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1
Vahdat, Shahabeddin, Arjun Vivek Pendharkar, Terrance Chiang, Sean Harvey, Haruto Uchino, Zhijuan Cao, Anika Kim, et al. "Brain-wide neural dynamics of poststroke recovery induced by optogenetic stimulation." Science Advances 7, no. 33 (August 2021): eabd9465. http://dx.doi.org/10.1126/sciadv.abd9465.
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Poststroke optogenetic stimulations can promote functional recovery. However, the circuit mechanisms underlying recovery remain unclear. Elucidating key neural circuits involved in recovery will be invaluable for translating neuromodulation strategies after stroke. Here, we used optogenetic functional magnetic resonance imaging to map brain-wide neural circuit dynamics after stroke in mice treated with and without optogenetic excitatory neuronal stimulations in the ipsilesional primary motor cortex (iM1). We identified key sensorimotor circuits affected by stroke. iM1 stimulation treatment restored activation of the ipsilesional corticothalamic and corticocortical circuits, and the extent of activation was correlated with functional recovery. Furthermore, stimulated mice exhibited higher expression of axonal growth–associated protein 43 in the ipsilesional thalamus and showed increased Synaptophysin+/channelrhodopsin+ presynaptic axonal terminals in the corticothalamic circuit. Selective stimulation of the corticothalamic circuit was sufficient to improve functional recovery. Together, these findings suggest early involvement of corticothalamic circuit as an important mediator of poststroke recovery.
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Cunningham, David A., Jayme S. Knutson, Vishwanath Sankarasubramanian, Kelsey A. Potter-Baker, Andre G. Machado, and Ela B. Plow. "Bilateral Contralaterally Controlled Functional Electrical Stimulation Reveals New Insights Into the Interhemispheric Competition Model in Chronic Stroke." Neurorehabilitation and Neural Repair 33, no. 9 (July 18, 2019): 707–17. http://dx.doi.org/10.1177/1545968319863709.
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Background. Upper-limb chronic stroke hemiplegia was once thought to persist because of disproportionate amounts of inhibition imposed from the contralesional on the ipsilesional hemisphere. Thus, one rehabilitation strategy involves discouraging engagement of the contralesional hemisphere by only engaging the impaired upper limb with intensive unilateral activities. However, this premise has recently been debated and has been shown to be task specific and/or apply only to a subset of the stroke population. Bilateral rehabilitation, conversely, engages both hemispheres and has been shown to benefit motor recovery. To determine what neurophysiological strategies bilateral therapies may engage, we compared the effects of a bilateral and unilateral based therapy using transcranial magnetic stimulation. Methods. We adopted a peripheral electrical stimulation paradigm where participants received 1 session of bilateral contralaterally controlled functional electrical stimulation (CCFES) and 1 session of unilateral cyclic neuromuscular electrical stimulation (cNMES) in a repeated-measures design. In all, 15 chronic stroke participants with a wide range of motor impairments (upper extremity Fugl-Meyer score: 15 [severe] to 63 [mild]) underwent single 1-hour sessions of CCFES and cNMES. We measured whether CCFES and cNMES produced different effects on interhemispheric inhibition (IHI) to the ipsilesional hemisphere, ipsilesional corticospinal output, and ipsilateral corticospinal output originating from the contralesional hemisphere. Results. CCFES reduced IHI and maintained ipsilesional output when compared with cNMES. We found no effect on ipsilateral output for either condition. Finally, the less-impaired participants demonstrated a greater increase in ipsilesional output following CCFES. Conclusions. Our results suggest that bilateral therapies are capable of alleviating inhibition on the ipsilesional hemisphere and enhancing output to the paretic limb.
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Kakinoki, Ryosuke, Scott F. M. Duncan, Ryosuke Ikeguchi, Souichi Ohta, Manabu Nankaku, Hiroshi Sakai, Takashi Noguchi, Yukitoshi Kaizawa, and Masao Akagi. "Motor and Sensory Cortical Changes after Contralateral Cervical Seventh Nerve Root (CC7) Transfer in Patients with Brachial Plexus Injuries." Journal of Hand Surgery (Asian-Pacific Volume) 22, no. 02 (May 15, 2017): 138–49. http://dx.doi.org/10.1142/s0218810417500162.
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Background: Previous animal studies demonstrated that the sensory and motor functions in ipsilesional upper limbs that had been reconstructed by CC7 transfer eventually associated with the contralesional brain cortices that had originally mediated the functions of the ipsilesional upper limbs before brachial plexus injury (BPI). Our hypothesis was that the same findings would be seen in humans.Methods: Four patients with total BPI treated with CC7 transfer were included. Changes in the locations of the activated areas in the primary motor (M1) and somatosensory (S1) cortices corresponding to the motor outputs to and sensory inputs from the ipsilesional limbs were investigated using functional near-infrared spectroscopy (fNIRS) 2–3 years and 6–7 years after surgery.Results: One patient was excluded from the evaluation of motor function after CC7 transfer. The motor and sensory functions of the ipsilesional upper limb in all patients were still controlled by the ipsilesional brain hemisphere 2–3 years after CC7 transfer. The reconstructed motions of the ipsilesional upper limbs correlated with the contralesional M1 in one patient and the bilateral M1s in another patient (both of whom demonstrated good motor recovery in the ipsilesional upper limbs) and with the ipsilesional M1 in a third patient with poor motor recovery in the ipsilesional upper limb. Sensory stimulation of the ipsilesional hands 6–7 years after CC7 transfer activated the contralesional S1 in two patients who achieved good sensory recovery in the ipsilesional hands but activated the ipsilesional S1 in the other two patients with poor sensory recovery of the ipsilesional hands.Conclusions: Transhemispheric transposition of the activated brain cortices associated with the recovery of motor and sensory functions of the ipsilesional upper limbs was seen in patients with CC7 transfer as has been reported for animal models of CC7 transfer.
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Juan Du, Weihe Yao, Jianrui Li, Fang Yang, Jingze Hu, Qiang Xu, Ling Liu, et al. "Motor Network Reorganization After Repetitive Transcranial Magnetic Stimulation in Early Stroke Patients: A Resting State fMRI Study." Neurorehabilitation and Neural Repair 36, no. 1 (October 28, 2021): 61–68. http://dx.doi.org/10.1177/15459683211054184.
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Objective To compare the effects of high-frequency (10 Hz) versus low-frequency (1 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) on motor recovery and functional reorganization of the cortical motor network during the early phase of stroke. Methods Forty-six hospitalized, first-ever ischemic stroke patients in early stage (within two weeks) with upper limb motor deficits were recruited. They were randomly allocated to three groups with 10 Hz ipsilesional rTMS, 1 Hz contralesional rTMS, and sham rTMS of five daily session. All patients underwent motor function (Upper Extremity Fugl–Meyer), neurophysiological and resting-state functional Magnetic Resonance Imaging (fMRI) (rs-fMRI) assessments before and after rTMS intervention. Motor recovery (△Fugl–Meyer Assessment) was defined as motor function changes before and after rTMS intervention. Motor function assessment was reevaluated at time point of three month follow-up. Results The two real rTMS groups manifested greater motor improvements than the sham group. The effect sustained for at least 3 months after the end of the treatment sessions. Compared with the sham group, 10 Hz ipsilesional rTMS group presented increased resting-state functional connectivity (FC) between ipsilesional primary motor cortex (M1) and contralesional M1 (P = .007), whereas 1 Hz contralesional rTMS group presented increased FC between contralesional M1 and ipsilesional supplementary motor area (P = .010), which were positively correlated with motor recovery (P < .05). Conclusion Beneficial effect of rTMS on motor recovery might be underlaid by increased FC between stimulating site and the remote motor areas, highlighting the motor network reorganization mechanism of rTMS in early post-stroke phase.
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Guo, Zhiwei, Yu Jin, Xi Bai, Binghu Jiang, Lin He, Morgan A. McClure, and Qiwen Mu. "Distinction of High- and Low-Frequency Repetitive Transcranial Magnetic Stimulation on the Functional Reorganization of the Motor Network in Stroke Patients." Neural Plasticity 2021 (January 20, 2021): 1–11. http://dx.doi.org/10.1155/2021/8873221.
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Objective. To investigate the functional reorganization of the motor network after repetitive transcranial magnetic stimulation (rTMS) in stroke patients with motor dysfunction and the distinction between high-frequency rTMS (HF-rTMS) and low-frequency rTMS (LF-rTMS). Methods. Thirty-three subcortical stroke patients were enrolled and assigned to the HF-rTMS group, LF-rTMS group, and sham group. Each patient of rTMS groups received either 10.0 Hz rTMS over the ipsilesional primary motor cortex (M1) or 1.0 Hz rTMS over the contralesional M1 for 10 consecutive days. A resting-state functional magnetic resonance imaging (fMRI) scan and neurological examinations were performed at baseline and after rTMS. The motor network and functional connectivities intramotor network with the core brain regions including the bilateral M1, premotor area (PMA), and supplementary motor area (SMA) were calculated. Comparisons of functional connectivities and Pearson correlation analysis between functional connectivity changes and behavioral improvement were calculated. Results. Significant motor improvement was found after rTMS in all groups which was larger in two rTMS groups than in the sham group. The functional connectivities of the motor network were significantly increased in bilateral M1, SMA, and contralesional PMA after real rTMS. These changes were only detected in the regions of the ipsilesional hemisphere in the HF-rTMS group and in the regions of the contralesional hemisphere in the LF-rTMS group. Significantly changed functional connectivities of the intramotor network were found between the ipsilesional M1 and SMA and contralesional PMA, between contralesional M1 and contralesional SMA, between contralesional SMA and ipsilesional SMA and contralesional PMA in the HF-rTMS group in which the changed connectivity between ipsilesional M1 and contralesional PMA was obviously correlated with the motor improvement. In addition, the functional connectivity of the intramotor network between ipsilesional M1 and contralesional PMA was significantly higher in the HF-rTMS group than in the LF-rTMS group. Conclusion. Both HF-rTMS and LF-rTMS have a positive effect on motor recovery in patients with subcortical stroke and could promote the reorganization of the motor network. HF-rTMS may contribute more to the functional connectivity reorganization of the ipsilesional motor network and realize greater benefit to the motor recovery.
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Guo, Xiaoli, Yongzhi He, Hongyang Lu, Yao Li, Xin Su, Ying Jiang, and Shanbao Tong. "Plastic Change along the Intact Crossed Pathway in Acute Phase of Cerebral Ischemia Revealed by Optical Intrinsic Signal Imaging." Neural Plasticity 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/1923160.
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The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours) after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input.
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Zou, Fei, Yi-Fang Lin, Shu-Geng Chen, Lei Cao, Hao-ran Wang, Bin Ye, Qiang Wang, He Jie-Ying, and Jie Jia. "The Impact of Electroacupuncture at Hegu, Shousanli, and Quchi Based on the Theory “Treating Flaccid Paralysis by Yangming Alone” on Stroke Patients’ EEG: A Pilot Study." Evidence-Based Complementary and Alternative Medicine 2020 (November 24, 2020): 1–9. http://dx.doi.org/10.1155/2020/8839491.
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Background. In China, electroacupuncture based on meridians theory “treating flaccid paralysis by Yangming alone” has been widely used for stroke rehabilitation in clinical practice. The aim of this study was to explore the electroencephalography change of electroacupuncture intervention on strokes patients with flaccid paralysis. Methods. Twenty-three stroke patients with flaccid paralysis and six stroke patients with spasticity accepted electroacupuncture with the acupoints Hegu [LI4], Shousanli [LI10], and Quchi [LI11] for 20 minutes and their EEG data were recorded before, during, and after the electroacupuncture intervention. Results. Compared with the baseline EEG signals before electroacupuncture, the ipsilesional and contralesional beta-band average power of patients with flaccid paralysis and spasticity were significantly increased during the needles retention stage and decreased slightly after removing the needles. The significant decrease of the ipsilesional and contralesional delta band average power in patients with flaccid paralysis occurred during the electroacupuncture stimulation, and they increased after the removal of the needles. The ipsilesional delta band average power of patients with spasticity significantly decreased during the electroacupuncture stimulation. Conclusion. From this pilot electrophysiological study, we provided a possible electrophysiological mechanism of the curative effect of electroacupuncture for stroke rehabilitation.
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Kim, Young R., In J. Huang, Seong-Ryong Lee, Emiri Tejima, Joseph B. Mandeville, Maurits PA van Meer, George Dai, et al. "Measurements of BOLD/CBV Ratio Show Altered fMRI Hemodynamics during Stroke Recovery in Rats." Journal of Cerebral Blood Flow & Metabolism 25, no. 7 (March 9, 2005): 820–29. http://dx.doi.org/10.1038/sj.jcbfm.9600084.
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Brain responses to external stimuli after permanent and transient ischemic insults have been documented using cerebral blood volume weighted (CBVw) functional magnetic resonance imaging (fMRI) in correlation with tissue damage and neurological recovery. Here, we extend our previous studies of stroke recovery in rat models of focal cerebral ischemia by comparing blood oxygen level-dependent (BOLD) and cerebral blood volume (CBV) changes. Responses to forepaw stimulation were measured in normal rats ( n = 5) and stroke rats subjected to 2 h of middle cerebral artery occlusion ( n = 6). Functional magnetic resonance imaging was performed 2 weeks after stroke to evaluate the recovery process. After stroke, animals showed variable degrees of fMRI activation in ipsilesional cortex, the extent of which did not correlate with structural damages as measured using apparent diffusion coefficient, fractional anisotropy, blood volume, and vessel size index. While the contralesional cortex showed good overlap between BOLD and CBV-activated regions, the ipsilesional cortex showed low covariance between significantly activated voxels by BOLD and CBVw techniques. In particular, the relative activation during contralateral stimuli in the ipsilesional somatosensory cortex was significantly higher for CBVw responses than BOLD, which might be due to stroke-related alterations in fMRI hemodynamic coupling. Aberrant subcortical activations were also observed. When unaffected forelimbs were stimulated, strong bilateral responses were observed. However, little thalamic responses accompanied stimulation of affected forelimbs despite significant activation in the ipsilesional somatosensory cortex. These results suggest that stroke affects not only local hemodynamics and coupling but also other factors including neural connectivity.
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Ahn, Sung Min, Da Hee Jung, Hong Ju Lee, Malk Eun Pak, Young Jin Jung, Yong-Il Shin, Hwa Kyoung Shin, and Byung Tae Choi. "Contralesional Application of Transcranial Direct Current Stimulation on Functional Improvement in Ischemic Stroke Mice." Stroke 51, no. 7 (July 2020): 2208–18. http://dx.doi.org/10.1161/strokeaha.120.029221.
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Background and Purpose: The therapeutic use of transcranial direct current stimulation (tDCS), an adjuvant tool for stroke, induces long-term changes in cortical excitability, for example, the secretion of activity-dependent growth factors. We assessed the proper therapeutic configuration of high-definition tDCS (HD-tDCS) in the subacute stage of ischemic stroke and its underlying expression profiling of growth factors to propose a new method for ensuring better therapeutic effects. Methods: Male C57BL/6J mice were subjected to middle cerebral artery occlusion, after which repetitive HD-tDCS (20 minutes, 55 µA/mm 2 , charge density 66 000 C/m 2 ) was applied from subacute phases of their ischemic insult. Behavioral tests assessing motor and cognitive functions were used to determine suitable conditions and HD-tDCS stimulation sites. Gene expression profiling of growth factors and their secretion and activation were analyzed to shed light on the underlying mechanisms. Results: Anodal HD-tDCS application over the contralesional cortex, especially the motor cortex, was more effective than ipsilesional stimulation in attenuating motor and cognitive deficits. In the HD-tDCS application over the contralesional motor cortex, positive changes in Bmp8b , Gdf5 , Il4 , Pdgfa , Pgf , and Vegfb were observed in the ipsilesional site. The expression of GDF5 (growth/differentiation factor 5) and PDGFA (platelet-derived growth factor subunit A) tended to similarly increase in both ipsi- and contralesional striata. However, higher expression levels of GDF5 and PDGFA and their receptors were observed in the peri-infarct regions of the striatum after HD-tDCS, especially in PDGFA expression. A higher number of proliferating or newly formed neuronal cells was detected in ipsilesional sites such as the subventricular zone. Conclusions: Application of anodal HD-tDCS over the contralesional cortex may enhance beneficial recovery through the expression of growth factors, such as GDF5 and PDGFA, in the ipsilesional site. Therefore, this therapeutic configuration may be applied in the subacute stage of ischemic stroke to ameliorate neurological impairments.
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Guo, Zhiwei, Yu Jin, Haitao Peng, Guoqiang Xing, Xiang Liao, Yunfeng Wang, Huaping Chen, Bin He, Morgan A. McClure, and Qiwen Mu. "Ipsilesional High Frequency Repetitive Transcranial Magnetic Stimulation Add-On Therapy Improved Diffusion Parameters of Stroke Patients with Motor Dysfunction: A Preliminary DTI Study." Neural Plasticity 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/6238575.
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Purpose. The aim of this study was to evaluate the effects of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) on stroke patients with motor dysfunction and to investigate the underlying neural mechanism.Methods. Fifteen stroke patients were assigned to the rTMS treatment (RT) group and conventional treatment (CT) group. Patients in the RT received 10 Hz rTMS stimulation on the ipsilesional primary motor cortex for 10 days plus conventional treatment of CT, which consisted of acupuncture and antiplatelet aggregation medication. Difference in fractional anisotropy (FA) between pretreatment and posttreatment and between two groups was determined. Correlations between FA values and neurological assessments were also calculated.Results. Both groups significantly improved the neurological function after treatment. rTMS-treated patients showed better improvement in Fugl-Meyer Assessment (FMA) score and increased FA value in motor-related white matter and gray matter cortices compared with CT-treated patients and pretreatment status. Besides, the increased FA value in the ipsilesional posterior limb of the internal capsule in RT group was significantly correlated with the improved FMA score.Significance. HF-rTMS could be a supplement therapy to CT in improving motor recovery in patients with stroke. And this benefit effect may be achieved through modulating the ipsilesional corticospinal tracts and motor-related gray matter cortices.
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Du, Juan, Jianping Hu, Jingze Hu, Qiang Xu, Qirui Zhang, Ling Liu, Minmin Ma, et al. "Aberrances of Cortex Excitability and Connectivity Underlying Motor Deficit in Acute Stroke." Neural Plasticity 2018 (October 21, 2018): 1–10. http://dx.doi.org/10.1155/2018/1318093.
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Purpose. This study was aimed at evaluating the motor cortical excitability and connectivity underlying the neural mechanism of motor deficit in acute stroke by the combination of functional magnetic resonance imaging (fMRI) and electrophysiological measures. Methods. Twenty-five patients with motor deficit after acute ischemic stroke were involved. General linear model and dynamic causal model analyses were applied to fMRI data for detecting motor-related activation and effective connectivity of the motor cortices. Motor cortical excitability was determined as a resting motor threshold (RMT) of motor evoked potential detected by transcranial magnetic stimulation (TMS). fMRI results were correlated with cortical excitability and upper extremity Fugl-Meyer assessment scores, respectively. Results. Greater fMRI activation likelihood and motor cortical excitability in the ipsilesional primary motor area (M1) region were associated with better motor performance. During hand movements, the inhibitory connectivity from the contralesional to the ipsilesional M1 was correlated with the degree of motor impairment. Furthermore, ipsilesional motor cortex excitability was correlated with an enhancement of promoting connectivity in ipsilesional M1 or a reduction of interhemispheric inhibition in contralesional M1. Conclusions. The study suggested that a dysfunction of the ipsilesional M1 and abnormal interhemispheric interactions might underlie the motor disability in acute ischemic stroke. Modifying the excitability of the motor cortex and correcting the abnormal motor network connectivity associated with the motor deficit might be the therapeutic target in early neurorehabilitation for stroke patients.
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Ferris, Jennifer K., Jason L. Neva, Beatrice A. Francisco, and Lara A. Boyd. "Bilateral Motor Cortex Plasticity in Individuals With Chronic Stroke, Induced by Paired Associative Stimulation." Neurorehabilitation and Neural Repair 32, no. 8 (July 4, 2018): 671–81. http://dx.doi.org/10.1177/1545968318785043.
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Background: In the chronic phase after stroke, cortical excitability differs between the cerebral hemispheres; the magnitude of this asymmetry depends on degree of motor impairment. It is unclear whether these asymmetries also affect capacity for plasticity in corticospinal tract excitability or whether hemispheric differences in plasticity are related to chronic sensorimotor impairment. Methods: Response to paired associative stimulation (PAS) was assessed bilaterally in 22 individuals with chronic hemiparesis. Corticospinal excitability was measured as the area under the motor-evoked potential (MEP) recruitment curve (AUC) at baseline, 5 minutes, and 30 minutes post-PAS. Percentage change in contralesional AUC was calculated and correlated with paretic motor and somatosensory impairment scores. Results: PAS induced a significant increase in AUC in the contralesional hemisphere ( P = .041); in the ipsilesional hemisphere, there was no significant effect of PAS ( P = .073). Contralesional AUC showed significantly greater change in individuals without an ipsilesional MEP ( P = .029). Percentage change in contralesional AUC between baseline and 5 m post-PAS correlated significantly with FM score ( r = −0.443; P = .039) and monofilament thresholds ( r = 0.444, P = .044). Discussion: There are differential responses to PAS within each cerebral hemisphere. Contralesional plasticity was increased in individuals with more severe hemiparesis, indicated by both the absence of an ipsilesional MEP and a greater degree of motor and somatosensory impairment. These data support a body of research showing compensatory changes in the contralesional hemisphere after stroke; new therapies for individuals with chronic stroke could exploit contralesional plasticity to help restore function.
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Arima, Michiko, Atsuko Ogata, Kazumi Kawahira, and Megumi Shimodozono. "Improvement and Neuroplasticity after Combined Rehabilitation to Forced Grasping." Case Reports in Neurological Medicine 2017 (2017): 1–7. http://dx.doi.org/10.1155/2017/1028390.
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The grasp reflex is a distressing symptom but the need to treat or suppress it has rarely been discussed in the literature. We report the case of a 17-year-old man who had suffered cerebral infarction of the right putamen and temporal lobe 10 years previously. Forced grasping of the hemiparetic left upper limb was improved after a unique combined treatment. Botulinum toxin type A (BTX-A) was first injected into the left biceps, wrist flexor muscles, and finger flexor muscles. Forced grasping was reduced along with spasticity of the upper limb. In addition, repetitive facilitative exercise and object-related training were performed under low-amplitude continuous neuromuscular electrical stimulation. Since this 2-week treatment improved upper limb function, we compared brain activities, as measured by near-infrared spectroscopy during finger pinching, before and after the combined treatment. Brain activities in the ipsilesional sensorimotor cortex (SMC) and medial frontal cortex (MFC) during pinching under electrical stimulation after treatment were greater than those before. The results suggest that training under electrical stimulation after BTX-A treatment may modulate the activities of the ipsilesional SMC and MFC and lead to functional improvement of the affected upper limb with forced grasping.
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Mooney, Ronan A., Suzanne J. Ackerley, Deshan K. Rajeswaran, John Cirillo, P. Alan Barber, Cathy M. Stinear, and Winston D. Byblow. "The Influence of Primary Motor Cortex Inhibition on Upper Limb Impairment and Function in Chronic Stroke: A Multimodal Study." Neurorehabilitation and Neural Repair 33, no. 2 (February 2019): 130–40. http://dx.doi.org/10.1177/1545968319826052.
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Background. Stroke is a leading cause of adult disability owing largely to motor impairment and loss of function. After stroke, there may be abnormalities in γ-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage. Objective. To quantify GABA neurotransmission and concentration within ipsilesional and contralesional M1 and determine if they relate to upper limb impairment and function at the chronic stage of stroke. Methods. Twelve chronic stroke patients and 16 age-similar controls were recruited for the study. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Threshold tracking paired-pulse transcranial magnetic stimulation protocols were used to examine short- and long-interval intracortical inhibition and late cortical disinhibition. Magnetic resonance spectroscopy was used to evaluate GABA concentration. Results. Short-interval intracortical inhibition was similar between patients and controls ( P = .10). Long-interval intracortical inhibition was greater in ipsilesional M1 compared with controls ( P < .001). Patients who did not exhibit late cortical disinhibition in ipsilesional M1 were those with greater upper limb impairment and worse function ( P = .002 and P = .017). GABA concentration was lower within ipsilesional ( P = .009) and contralesional ( P = .021) M1 compared with controls, resulting in an elevated excitation-inhibition ratio for patients. Conclusion. These findings indicate that ipsilesional and contralesional M1 GABAergic inhibition are altered in this small cohort of chronic stroke patients. Further study is warranted to determine how M1 inhibitory networks might be targeted to improve motor function.
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Hensel, Lukas, Christian Grefkes, Caroline Tscherpel, Corinna Ringmaier, Daria Kraus, Stefanie Hamacher, Lukas J. Volz, and Gereon R. Fink. "Intermittent theta burst stimulation applied during early rehabilitation after stroke: study protocol for a randomised controlled trial." BMJ Open 9, no. 12 (December 2019): e034088. http://dx.doi.org/10.1136/bmjopen-2019-034088.
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IntroductionIntermittent theta burst stimulation (iTBS) applied to primary motor cortex (M1) has been shown to modulate both the excitability and connectivity of the motor system. A recent proof-of-principle study, based on a small group of hospitalised patients with acute ischemic stroke, suggested that iTBS applied to the ipsilesional M1 combined with physical therapy early after stroke can amplify motor recovery with lasting after effects. A randomised controlled clinical trial using a double-blind design is warranted to justify the implementation of iTBS-assisted motor rehabilitation in neurorehabilitation from an acute ischaemic stroke.Methods/designWe investigate the effects of daily iTBS on early motor rehabilitation after stroke in an investigator-initiated, longitudinal randomised controlled trial. Patients (n=150) with hemiparesis receive either iTBS (600 pulses) applied to the ipsilesional motor cortex (M1) or a control stimulation (ie, coil placement over the parieto-occipital vertex in parallel to the interhemispheric fissure and with a tilt of 45°). On 8 consecutive workdays, a 45 min arm-centred motor training follows the intervention . The relative grip strength, defined as the grip force ratios of the affected and unaffected hands, serves as the primary outcome parameter. Secondary outcome parameters are measures of arm function (Action Research Arm Test, Fugl-Meyer Motor Scale), stroke severity (National Institutes of Health Stroke Scale), stroke-induced disability (modified Rankin Scale, Barthel Index), duration of inpatient rehabilitation, quality of life (EuroQol 5D), motor evoked potentials and the resting motor threshold of the ipsilesional M1.Ethics and disseminationThe study was approved by the Ethics Commission of the Medical Faculty, University of Cologne, Germany (reference number 15-343). Data will be disseminated through peer-reviewed publications and presentations at conferences. Study title: Theta-Burst Stimulation in Early Rehabilitation after Stroke (acronym: TheSiReS). Study registration at German Registry for Clinical Trials (DRKS00008963) and at ClinicalTrials.gov (NCT02910024).
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Sharma, Vivek, Divya Gupta, Harraman Kaur, and Nayeem Ul Zia. "Comparison of Contralesional and Ipsilesional Repetitive Transcranial Magnetic Stimulation in Stroke Patients." Archives of Physical Medicine and Rehabilitation 96, no. 10 (October 2015): e70-e71. http://dx.doi.org/10.1016/j.apmr.2015.08.238.
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Hammerbeck, Ulrike, Sarah F. Tyson, Prawin Samraj, Kristen Hollands, John W. Krakauer, and John Rothwell. "The Strength of the Corticospinal Tract Not the Reticulospinal Tract Determines Upper-Limb Impairment Level and Capacity for Skill-Acquisition in the Sub-Acute Post-Stroke Period." Neurorehabilitation and Neural Repair 35, no. 9 (July 4, 2021): 812–22. http://dx.doi.org/10.1177/15459683211028243.
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Background. Upper-limb impairment in patients with chronic stroke appears to be partly attributable to an upregulated reticulospinal tract (RST). Here, we assessed whether the impact of corticospinal (CST) and RST connectivity on motor impairment and skill-acquisition differs in sub-acute stroke, using transcranial magnetic stimulation (TMS)–based proxy measures. Methods. Thirty-eight stroke survivors were randomized to either reach training 3-6 weeks post-stroke (plus usual care) or usual care only. At 3, 6 and 12 weeks post-stroke, we measured ipsilesional and contralesional cortical connectivity (surrogates for CST and RST connectivity, respectively) to weak pre-activated triceps and deltoid muscles with single pulse TMS, accuracy of planar reaching movements, muscle strength (Motricity Index) and synergies (Fugl-Meyer upper-limb score). Results. Strength and presence of synergies were associated with ipsilesional (CST) connectivity to the paretic upper-limb at 3 and 12 weeks. Training led to planar reaching skill beyond that expected from spontaneous recovery and occurred for both weak and strong ipsilesional tract integrity. Reaching ability, presence of synergies, skill-acquisition and strength were not affected by either the presence or absence of contralesional (RST) connectivity. Conclusion. The degree of ipsilesional CST connectivity is the main determinant of proximal dexterity, upper-limb strength and synergy expression in sub-acute stroke. In contrast, there is no evidence for enhanced contralesional RST connectivity contributing to any of these components of impairment. In the sub-acute post-stroke period, the balance of activity between CST and RST may matter more for the paretic phenotype than RST upregulation per se.
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Mahmoudi Aqeel-Abadi, Abolfazl, Hamid-Reza Fateh, Saeed Masoudnia, Niloufar Shirzad, Milad Seyfi, Tayyebeh Ebrahimi, and Mohammad-Reza Nazem-Zadeh. "A Preliminary Study of Alterations in Iron Disposal and Neural Activity in Ischemic Stroke." BioMed Research International 2022 (August 6, 2022): 1–16. http://dx.doi.org/10.1155/2022/4552568.
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Purpose. The study aimed to evaluate the postrehabilitation changes in deep gray matter (DGM) nuclei, corticospinal tract (CST), and motor cortex area, involved in motor tasks in patients with ischemic stroke. Methods. Three patients participated in this study, who had experienced an ischemic stroke on the left side of the brain. They underwent a standard rehabilitation program for four consecutive weeks, including transcranial direct current stimulation (tDCS), neuromuscular electrical stimulation (NMES), and occupational therapy. The patients’ motor ability was evaluated by Fugl-Meyer assessment-upper extremity (FMA-UE) and Wolf motor function test (WMFT). Multimodal magnetic resonance imaging (MRI) was acquired from the patients by a 3 Tesla machine before and after the rehabilitation. The magnetic susceptibility changes were examined in DGM nuclei including the bilateral caudate (CA), putamen (PT), globus pallidus (GP), and thalamus (TH) using quantitative susceptibility mapping (QSM). Functional MRI (fMRI) in the motor cortex areas was acquired to evaluate the postrehab functional motor activity. The three-dimensional corticospinal tract (CST) was reconstructed using diffusion-weighted imaging (DWI) and diffusion tensor tractography (DTT), and the fractional anisotropy (FA) was measured along the tract. Ultimately, the relationship between the structural and functional changes was evaluated in CST and motor cortex. Results. Postrehabilitation FMA-UE and WMFT scores increased for all patients compared to the prerehabilitation. QSM analysis revealed increasing in susceptibility values in GP and CA in all patients at the ipsilesional hemisphere. By fMRI analysis, the ipsilesional hemisphere demonstrated an increase in functional activity in motor areas for all 3 patients. In the ipsilesional hemisphere, the fractional anisotropy (FA) was increased in CST in two patients, while the mean diffusivity (MD) was decreased in CA in a patient, in PT and TH in another patient, and in PT in two patients. Conclusion. This preliminary study demonstrates that the magnetic susceptibility may decrease at some ipsilesional DGM nuclei after tDCS, NMES, and occupational therapy for patients with ischemic stroke, suggesting a drop in the level of iron deposition, which may be associated with an increase in the level of activity in motor cortex after rehabilitation.
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Vatinno, Amanda A., Christian Schranz, Annie N. Simpson, Viswanathan Ramakrishnan, Leonardo Bonilha, and N. J. Seo. "Predicting upper extremity motor improvement following therapy using EEG-based connectivity in chronic stroke." NeuroRehabilitation 50, no. 1 (January 31, 2022): 105–13. http://dx.doi.org/10.3233/nre-210171.
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BACKGROUND: Uncertain prognosis presents a challenge for therapists in determining the most efficient course of rehabilitation treatment for individual patients. Cortical Sensorimotor network connectivity may have prognostic utility for upper extremity motor improvement because the integrity of the communication within the sensorimotor network forms the basis for neuroplasticity and recovery. OBJECTIVE: To investigate if pre-intervention sensorimotor connectivity predicts post-stroke upper extremity motor improvement following therapy. METHODS: Secondary analysis of a pilot triple-blind randomized controlled trial. Twelve chronic stroke survivors underwent 2-week task-practice therapy, while receiving vibratory stimulation for the treatment group and no stimulation for the control group. EEG connectivity was obtained pre-intervention. Motor improvement was quantified as change in the Box and Block Test from pre to post-therapy. The association between ipsilesional sensorimotor connectivity and motor improvement was examined using regression, controlling for group. For negative control, contralesional/interhemispheric connectivity and conventional predictors (initial clinical motor score, age, time post-stroke, lesion volume) were examined. RESULTS: Greater ipsilesional sensorimotor alpha connectivity was associated with greater upper extremity motor improvement following therapy for both groups (p < 0.05). Other factors were not significant. CONCLUSION: EEG connectivity may have a prognostic utility for individual patients’ upper extremity motor improvement following therapy in chronic stroke.
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Huo, Congcong, Xinglou Li, Jing Jing, Yanping Ma, Wenhao Li, Yanqin Wang, Wanlin Liu, et al. "Median Nerve Electrical Stimulation–Induced Changes in Effective Connectivity in Patients With Stroke as Assessed With Functional Near-Infrared Spectroscopy." Neurorehabilitation and Neural Repair 33, no. 12 (September 24, 2019): 1008–17. http://dx.doi.org/10.1177/1545968319875952.
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Background. The cortical plastic changes in response to median nerve electrical stimulation (MNES) in stroke patients have not been entirely illustrated. Objective. This study aimed to investigate MNES-related changes in effective connectivity (EC) within a cortical network after stroke by using functional near-infrared spectroscopy (fNIRS). Methods. The cerebral oxygenation signals in the bilateral prefrontal cortex (LPFC/RPFC), motor cortex (LMC/RMC), and occipital lobe (LOL/ROL) of 20 stroke patients with right hemiplegia were measured by fNIRS in 2 conditions: (1) resting state and (2) MNES applied to the right wrist. Coupling function together with dynamical Bayesian inference was used to assess MNES-related changes in EC among the cerebral low-frequency fluctuations. Results. Compared with the resting state, EC from LPFC and RPFC to LOL was significantly increased during the MNES state in stroke patients. Additionally, MNES triggered significantly higher coupling strengths from LMC and LOL to RPFC. The interregional main coupling direction was observed from LPFC to bilateral motor and occipital areas in responding to MNES, suggesting that MNES could promote the regulation function of ipsilesional prefrontal areas in the functional network. MNES can induce muscle twitch of the stroke-affected hand involving a decreased neural coupling of the contralesional motor area on the ipsilesional MC. Conclusions. MNES can trigger sensorimotor stimulations of the affected hand that sequentially involved functional reorganization of distant cortical areas after stroke. Investigating MNES-related changes in EC after stroke may help further our understanding of the neural mechanisms underlying MNES.
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Boddington, Laura J., Jason P. Gray, Jan M. Schulz, and John N. J. Reynolds. "Low-intensity contralesional electrical theta burst stimulation modulates ipsilesional excitability and enhances stroke recovery." Experimental Neurology 323 (January 2020): 113071. http://dx.doi.org/10.1016/j.expneurol.2019.113071.
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Fanini, Alessandra, and Carlo Alberto Marzi. "Unwanted reflex-like saccades in visual extinction patients." Behavioral and Brain Sciences 22, no. 4 (August 1999): 683. http://dx.doi.org/10.1017/s0140525x99312152.
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We studied patients with left visual extinction following right hemisphere damage in a simple manual reaction time task using brief visual stimuli. With unilateral lateralized stimuli the patients showed a high proportion of unwanted, reflex-like saccades to either side of stimulation. In contrast, with bilateral stimuli there was an overall decrease in the proportion of unwanted saccades, and the vast majority of them were directed toward the ipsilesional side. The implications of these results for the Findlay & Walker model are discussed.
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Keller, Ingo, Gudrun Lefin-Rank, Judith Lösch, and Georg Kerkhoff. "Combination of Pursuit Eye Movement Training With Prism Adaptation and Arm Movements in Neglect Therapy: A Pilot Study." Neurorehabilitation and Neural Repair 23, no. 1 (September 15, 2008): 58–66. http://dx.doi.org/10.1177/1545968308317438.
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Objective. The aim of the present study was to determine if a combination of pursuit eye movement training to optokinetic stimulation (OKSP) and prism adaptation leads to greater improvement of neglect symptoms than a single application of OKSP. Additionally, the effect of ipsilesional arm movements during OKSP was tested. Methods. Ten patients with left-sided neglect due to unilateral right-sided vascular brain lesions were studied between 2 and 4.5 months after their stroke. Each patient received 4 different single-session treatments (each lasting 30 minutes): visual scanning treatment (control condition), OKSP, OKSP in conjunction with wearing base-left prisms inducing a shift of the visual field to the right by 10°, and OKSP in conjunction with the right to the left side. Severity of visuospatial neglect was assessed before and directly after each treatment with 4 standard neglect tests. Results. Visual scanning training improved neglect symptoms only slightly. Single OKSP stimulation led to significant improvements in all tests. OKSP in conjunction with prism adaptation was superior to the control condition in the cancellation task. The treatment condition requiring arm movements aggravated neglect symptoms in all tests. A comparison between treatments indicates best improvements may be achieved with OKSP without any additional treatment. Conclusions . The present results give evidence that OKSP significantly reduces symptoms of visuospatial neglect within 1 treatment session. The results suggest that patients should be prevented from performing ipsilesional movements during OKSP.
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Cleland, Brice T., and Sangeetha Madhavan. "Ipsilateral Motor Pathways and Transcallosal Inhibition During Lower Limb Movement After Stroke." Neurorehabilitation and Neural Repair 35, no. 4 (March 11, 2021): 367–78. http://dx.doi.org/10.1177/1545968321999049.
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Background Stroke rehabilitation may be improved with a better understanding of the contribution of ipsilateral motor pathways to the paretic limb and alterations in transcallosal inhibition. Few studies have evaluated these factors during dynamic, bilateral lower limb movements, and it is unclear whether they relate to functional outcomes. Objective Determine if lower limb ipsilateral excitability and transcallosal inhibition after stroke depend on target limb, task, or number of limbs involved, and whether these factors are related to clinical measures. Methods In 29 individuals with stroke, ipsilateral and contralateral responses to transcranial magnetic stimulation were measured in the paretic and nonparetic tibialis anterior during dynamic (unilateral or bilateral ankle dorsiflexion/plantarflexion) and isometric (unilateral dorsiflexion) conditions. Relative ipsilateral excitability and transcallosal inhibition were assessed. Fugl-Meyer, ankle movement accuracy, and walking characteristics were assessed. Results Relative ipsilateral excitability was greater during dynamic than isometric conditions in the paretic limb ( P ≤ .02) and greater in the paretic than the nonparetic limb during dynamic conditions ( P ≤ .004). Transcallosal inhibition was greater in the ipsilesional than contralesional hemisphere ( P = .002) and during dynamic than isometric conditions ( P = .03). Greater ipsilesional transcallosal inhibition was correlated with better ankle movement accuracy ( R2 = 0.18, P = .04). Greater contralateral excitability to the nonparetic limb was correlated with improved walking symmetry ( R2 = 0.19, P = .03). Conclusions Ipsilateral pathways have increased excitability to the paretic limb, particularly during dynamic tasks. Transcallosal inhibition is greater in the ipsilesional than contralesional hemisphere and during dynamic than isometric tasks. Ipsilateral pathways and transcallosal inhibition may influence walking asymmetry and ankle movement accuracy.
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Làdavas, Elisabetta, Giuseppe di Pellegrino, Alessandro Farnè, and Gabriele Zeloni. "Neuropsychological Evidence of an Integrated Visuotactile Representation of Peripersonal Space in Humans." Journal of Cognitive Neuroscience 10, no. 5 (September 1998): 581–89. http://dx.doi.org/10.1162/089892998562988.
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Current interpretations of extinction suggest that the disorder is due to an unbalanced competition between ipsilesional and contralesional representations of space. The question addressed in this study is whether the competition between left and right representations of space in one sensory modality (i.e., touch) can be reduced or exacerbated by the activation of an intact spatial representation in a different modality that is functionally linked to the damaged representation (i.e., vision). This hypothesis was tested in 10 right-hemisphere lesioned patients who suffered from reliable tactile extinction. We found that a visual stimulus presented near the patient's ipsilesional hand (i.e., visual peripersonal space) inhibited the processing of a tactile stimulus delivered on the contralesional hand (cross-modal visuotactile extinction) to the same extent as did an ipsilesional tactile stimulation (unimodal tactile extinction). It was also found that a visual stimulus presented near the contralesional hand improved the detection of a tactile stimulus applied to the same hand. In striking contrast, less modulatory effects of vision on touch perception were observed when a visual stimulus was presented far from the space immediately around the patient's hand (i.e., extrapersonal space). This study clearly demonstrates the existence of a visual peripersonal space centered on the hand in humans and its modulatory effects on tactile perception. These findings are explained by referring to the activity of bimodal neurons in premotor and parietal cortex of macaque, which have tactile receptive fields on the hand and corresponding visual receptive fields in the space immediately adjacent to the tactile fields.
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Lee, Jungsoo, Eunhee Park, Ahee Lee, Won Hyuk Chang, Dae-Shik Kim, Yong-Il Shin, and Yun-Hee Kim. "Modulating Brain Connectivity by Simultaneous Dual-Mode Stimulation over Bilateral Primary Motor Cortices in Subacute Stroke Patients." Neural Plasticity 2018 (2018): 1–9. http://dx.doi.org/10.1155/2018/1458061.
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Repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has been used for the modulation of stroke patients’ motor function. Recently, more challenging approaches have been studied. In this study, simultaneous stimulation using both rTMS and tDCS (dual-mode stimulation) over bilateral primary motor cortices (M1s) was investigated to compare its modulatory effects with single rTMS stimulation over the ipsilesional M1 in subacute stroke patients. Twenty-four patients participated; 12 participants were assigned to the dual-mode stimulation group while the other 12 participants were assigned to the rTMS-only group. We assessed each patient’s motor function using the Fugl-Meyer assessment score and acquired their resting-state fMRI data at two times: prior to stimulation and 2 months after stimulation. Twelve healthy subjects were also recruited as the control group. The interhemispheric connectivity of the contralesional M1, interhemispheric connectivity between bilateral hemispheres, and global efficiency of the motor network noticeably increased in the dual-mode stimulation group compared to the rTMS-only group. Contrary to the dual-mode stimulation group, there was no significant change in the rTMS-only group. These data suggested that simultaneous dual-mode stimulation contributed to the recovery of interhemispheric interaction than rTMS only in subacute stroke patients. This trial is registered with NCT03279640.
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Chen, Qing-Mei, Fei-Rong Yao, Hai-Wei Sun, Zhi-Guo Chen, Jun Ke, Juan Liao, Xiu-Ying Cai, et al. "Combining inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) treatment improves motor function by modulating GABA in acute ischemic stroke patients." Restorative Neurology and Neuroscience 39, no. 6 (December 28, 2021): 419–34. http://dx.doi.org/10.3233/rnn-211195.
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Background: The combination of inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) can improve motor function of stroke patients with undefined mechanism. It has been demonstrated that rTMS exhibits a neuro-modulatory effect by regulating the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in other diseases. Objectives: To evaluate the effect of combined inhibitory and facilitatory rTMS on GABA in the primary motor cortex (M1) for treating motor dysfunction after acute ischemic stroke. Methods: 44 ischemic stroke patients with motor dysfunction were randomly divided into two groups. The treatment group was stimulated with 10 Hz rTMS at the ipsilesional M1 and 1 Hz rTMS at the contralesional M1. The sham group received bilateral sham stimulation at the motor cortices. The GABA level in the bilateral M1 was measured by proton magnetic resonance spectroscopy (1H-MRS) at 24 hours before and after rTMS stimulation. Motor function was measured using the Fugl-Meyer Assessment (FMA). The clinical assessments were performed before and after rTMS and after 3 months. Results: The treatment group exhibited a greater improvement in motor function 24 hours after rTMS compared to the sham group. The increased improvement in motor function lasted for at least 3 months after treatment. Following 4 weeks of rTMS, the GABA level in the ipsilesional M1 of the treatment group was significantly decreased compared to the sham group. Furthermore, the change of FMA score for motor function was negatively correlated to the change of the GABA:Cr ratio. Finally, the effect of rTMS on motor function outcome was partially mediated by GABA level change in response to the treatment (27.7%). Conclusions: Combining inhibitory and facilitatory rTMS can decrease the GABA level in M1, which is correlated to the improvement of motor function. Thus, the GABA level in M1 may be a potential biomarker for treatment strategy decisions regarding rTMS neuromodulatory interventions.
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Zhang, Chengliang, Xiuqin Zheng, Rulan Lu, Wenwei Yun, Huifang Yun, and Xianju Zhou. "Repetitive transcranial magnetic stimulation in combination with neuromuscular electrical stimulation for treatment of post-stroke dysphagia." Journal of International Medical Research 47, no. 2 (October 25, 2018): 662–72. http://dx.doi.org/10.1177/0300060518807340.
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Objective This study was performed to determine whether repetitive transcranial magnetic stimulation (rTMS) combined with neuromuscular electrical stimulation (NMES) effectively ameliorates dysphagia and how rTMS protocols (bilateral vs. unilateral) combined with NMES can be optimized. Methods Sixty-four patients were randomly divided into four groups using a random distribution table: the sham rTMS plus NMES (Sham-rTMS/NMES), ipsilesional 10-Hz rTMS plus NMES (Ipsi-rTMS/NMES), contralesional 1-Hz rTMS plus NMES (Contra-rTMS/NMES), and bilateral rTMS plus NMES (Bi-rTMS/NMES) groups. Cortical excitability as measured by the amplitude of the motor evoked potential at the mylohyoid muscle cortical representative area, swallowing function as measured by the Standardized Swallowing Assessment, and the degree of dysphagia were evaluated at baseline, after the stimulation course, and at the 1-month follow-up. Results Bi-rTMS/NMES produced higher cortical excitability and better swallowing function recovery. Compared with NMES alone, unilateral rTMS plus NMES had additional effects on cortical excitability and rehabilitation of dysphagia, but there were no differences between the Contra-rTMS/NMES and Ipsi-rTMS/NMES groups. No adverse events occurred. Conclusion The combination of rTMS with NMES was superior to NMES alone in improving the recovery of post-stroke dysphagia, and the combination of bilateral rTMS with NMES was more effective than unilateral rTMS combined with NMES.
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Tseng, Chia-Chen, Shou-Jen Wang, and Yi-Ho Young. "Comparison of Bone-Conducted Vibration for Eliciting Ocular Vestibular-Evoked Myogenic Potentials." Otolaryngology–Head and Neck Surgery 146, no. 2 (October 20, 2011): 289–94. http://dx.doi.org/10.1177/0194599811425884.
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Objective. This study compared bone-conducted vibration (BCV) stimuli at forehead (Fz) and mastoid sites for eliciting ocular vestibular-evoked myogenic potentials (oVEMPs). Study Design. Prospective study. Setting. University hospital. Methods. Twenty healthy subjects underwent oVEMP testing via BCV stimuli at Fz and mastoid sites. Another 50 patients with unilateral Meniere’s disease also underwent oVEMP testing. Results. All healthy subjects showed clear oVEMPs via BCV stimulation regardless of the tapping sites. The right oVEMPs stimulated by tapping at the right mastoid had earlier nI and pI latencies and a larger nI-pI amplitude compared with those stimulated by tapping at the Fz and left mastoid. Similar trends were also observed in left oVEMPs. However, the asymmetry ratio did not differ significantly between the ipsilateral mastoid and Fz sites. Clinically, tapping at the Fz revealed absent oVEMPs in 28% of Meniere’s ears, which decreased to 16% when tapping at the ipsilesional (hydropic) mastoid site, exhibiting a significant difference. Conclusion. Tapping at the ipsilateral mastoid site elicits earlier oVEMP latencies and larger oVEMP amplitudes when compared with tapping at the Fz site. Thus, tapping at the Fz site is suggested to screen for the otolithic function, whereas tapping at the ipsilesional mastoid site is suitable for evaluating residual otolithic function.
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Costa, Vanessa, Giuseppe Giglia, Filippo Brighina, Serena Indovino, and Brigida Fierro. "Ipsilesional and contralesional regions participate in the improvement of poststroke aphasia: a transcranial direct current stimulation study." Neurocase 21, no. 4 (June 24, 2014): 479–88. http://dx.doi.org/10.1080/13554794.2014.927508.
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Hsu, Ya-Fang, Ying-Zu Huang, Yung-Yang Lin, Chih-Wei Tang, Kwong-Kum Liao, Po-Lei Lee, Yun-An Tsai, et al. "Intermittent theta burst stimulation over ipsilesional primary motor cortex of subacute ischemic stroke patients: A pilot study." Brain Stimulation 6, no. 2 (March 2013): 166–74. http://dx.doi.org/10.1016/j.brs.2012.04.007.
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Kumar, Raj, Ramakant Yadav, Hanuman Prasad Prajapati, Suraj Kumar, GowriShankar Potturi, and Rahul Sharma. "Effect of Transcranial direct current stimulation (tDCS) on altered conscious patients after traumatic brain injury & cerebrovascular accident: A randomized clinical control trial." Neurology Asia 27, no. 2 (June 2022): 457–63. http://dx.doi.org/10.54029/2022nre.
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Background & Objective: Traumatic brain injury and cerebrovascular accidents can result in altered levels of consciousness. This study is aimed at finding the effect of transcranial direct current stimulation (tDCS) on the level of consciousness in these patients. Methods: A total of 100 patients admitted to the neurological ICU of the hospital were screened and 40 subjects after satisfying inclusion criteria were recruited within the first one to two weeks of injury. They were randomly divided into two groups after written consent from a caretaker, Group A (experimental) (n=20) and Group B (control) (n=20) by computerized randomization. Group A received Anodal tDCS to the motor area (C3/C4 ipsilesional), sensory area (P3/P4 ipsilesional) and left dorsolateral prefrontal cortex (F3) according to the 10/20 EEG montage for two sessions of 20min/day for 7 consecutive days and routine physiotherapy. Group B only received routine physiotherapy similar to Group A. Glasgow coma scale (GCS) and Rancho Los Amigos scale (RLAS) was taken pre and post- intervention to assess the level of consciousness. Results: The pretest and post- test GCS and RLAS scores in groups A and B showed statistical significance at p<0.01. The differences of mean GCS and RLAS between pretest and posttest in group A showed better improvement than that of group B. The results were statistically significant at p<0.01. The effect size was large, calculated by Cohen’s d. Conclusion: The tDCS can be effective in improving GCS and RLAS in altered consciousness patients in the acute period after injury. It is non-invasive, cost-effective with minimal contraindications, and doesnot interfere with other modalities in the intensive care unit.
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Nowak, Dennis A., Christian Grefkes, Mitra Ameli, and Gereon R. Fink. "Interhemispheric Competition After Stroke: Brain Stimulation to Enhance Recovery of Function of the Affected Hand." Neurorehabilitation and Neural Repair 23, no. 7 (June 16, 2009): 641–56. http://dx.doi.org/10.1177/1545968309336661.
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Background and purpose. Within the concept of interhemispheric competition, technical modulation of the excitability of motor areas in the contralesional and ipsilesional hemisphere has been applied in an attempt to enhance recovery of hand function following stroke. This review critically summarizes the data supporting the use of novel electrophysiological concepts in the rehabilitation of hand function after stroke. Summary of review. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are powerful tools to inhibit or facilitate cortical excitability. Modulation of cortical excitability may instantaneously induce plastic changes within the cortical network of sensorimotor areas, thereby improving motor function of the affected hand after stroke. No significant adverse effects have been noted when applying brain stimulation in stroke patients. To date, however, the clinical effects are small to moderate and short lived. Future work should elucidate whether repetitive administration of rTMS or tDCS over several days and the combination of these techniques with behavioral training (ie, physiotherapy) could result in an enhanced effectiveness. Conclusion. Brain stimulation is a safe and promising tool to induce plastic changes in the cortical sensorimotor network to improve motor behavior after stroke. However, several methodological issues remain to be answered to further improve the effectiveness of these new approaches.
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Schuhmann, Michael K., Guido Stoll, Lena Papp, Arne Bohr, Jens Volkmann, and Felix Fluri. "Electrical Stimulation of the Mesencephalic Locomotor Region Has No Impact on Blood–Brain Barrier Alterations after Cerebral Photothrombosis in Rats." International Journal of Molecular Sciences 20, no. 16 (August 19, 2019): 4036. http://dx.doi.org/10.3390/ijms20164036.
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Blood–brain barrier (BBB) disruption is a critical event after ischemic stroke, which results in edema formation and hemorrhagic transformation of infarcted tissue. BBB dysfunction following stroke is partly mediated by proinflammatory agents. We recently have shown that high frequency stimulation of the mesencephalic locomotor region (MLR-HFS) exerts an antiapoptotic and anti-inflammatory effect in the border zone of cerebral photothrombotic stroke in rats. Whether MLR-HFS also has an impact on BBB dysfunction in the early stage of stroke is unknown. In this study, rats were subjected to photothrombotic stroke of the sensorimotor cortex and implantation of a stimulating microelectrode into the ipsilesional MLR. Thereafter, either HFS or sham stimulation of the MLR was applied for 24 h. After scarifying the rats, BBB disruption was assessed by determining albumin extravasation and tight junction integrity (claudin 3, claudin 5, and occludin) using Western blot analyses and immunohistochemistry. In addition, by applying zymography, expression of pro-metalloproteinase-9 (pro-MMP-9) was analyzed. No differences were found regarding infarct size and BBB dysfunction between stimulated and unstimulated animals 24 h after induction of stroke. Our results indicate that MLR-HFS neither improves nor worsens the damaged BBB after stroke. Attenuating cytokines/chemokines in the perilesional area, as mediated by MLR-HFS, tend to play a less significant role in preventing the BBB integrity.
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Hordacre, Brenton, Duncan Austin, Katlyn E. Brown, Lynton Graetz, Isabel Pareés, Stefania De Trane, Ann-Maree Vallence, et al. "Evidence for a Window of Enhanced Plasticity in the Human Motor Cortex Following Ischemic Stroke." Neurorehabilitation and Neural Repair 35, no. 4 (February 12, 2021): 307–20. http://dx.doi.org/10.1177/1545968321992330.
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Background In preclinical models, behavioral training early after stroke produces larger gains compared with delayed training. The effects are thought to be mediated by increased and widespread reorganization of synaptic connections in the brain. It is viewed as a period of spontaneous biological recovery during which synaptic plasticity is increased. Objective To look for evidence of a similar change in synaptic plasticity in the human brain in the weeks and months after ischemic stroke. Methods We used continuous theta burst stimulation (cTBS) to activate synapses repeatedly in the motor cortex. This initiates early stages of synaptic plasticity that temporarily reduces cortical excitability and motor-evoked potential amplitude. Thus, the greater the effect of cTBS on the motor-evoked potential, the greater the inferred level of synaptic plasticity. Data were collected from separate cohorts (Australia and UK). In each cohort, serial measurements were made in the weeks to months following stroke. Data were obtained for the ipsilesional motor cortex in 31 stroke survivors (Australia, 66.6 ± 17.8 years) over 12 months and the contralesional motor cortex in 29 stroke survivors (UK, 68.2 ± 9.8 years) over 6 months. Results Depression of cortical excitability by cTBS was most prominent shortly after stroke in the contralesional hemisphere and diminished over subsequent sessions ( P = .030). cTBS response did not differ across the 12-month follow-up period in the ipsilesional hemisphere ( P = .903). Conclusions Our results provide the first neurophysiological evidence consistent with a period of enhanced synaptic plasticity in the human brain after stroke. Behavioral training given during this period may be especially effective in supporting poststroke recovery.
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Newlands, Shawn D., and Min Wei. "Responses of central vestibular neurons to sinusoidal yaw rotation in compensated macaques after unilateral labyrinthectomy." Journal of Neurophysiology 110, no. 8 (October 15, 2013): 1822–36. http://dx.doi.org/10.1152/jn.00365.2013.
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After vestibular labyrinth injury, behavioral measures of vestibular function partially recover through the process of vestibular compensation. The present study was performed to improve our understanding of the physiology of macaque vestibular nucleus neurons in the compensated state (>6 wk) after unilateral labyrinthectomy (UL). The responses of neurons to sinusoidal yaw rotation at a series of frequencies (0.1–2.0 Hz) and peak velocities (7.5–210°/s) were examined to determine how the behavior of these cells differed from those in animals with intact labyrinths. The sensitivity of neurons responding to ipsilateral rotation (type I) did not differ between the intact and injured sides after UL, although this sensitivity was lower bilaterally after lesion than before lesion. The sensitivity of neurons that increase firing with contralateral rotation (type II) was higher ipsilateral to the UL than before lesion or in the nucleus contralateral to the UL. UL did not increase asymmetry in the responses of individual type I or II neurons to ipsilateral vs. contralateral rotation, nor does it change the power law relationship between neuronal firing and level of stimulation. Increased sensitivities of contralesional type I neurons to the remaining vestibular nerve input and increased efficacy of inhibitory vestibular commissures projecting to the ipsilesional vestibular nucleus appear to be responsible for recovery of dynamic function of central vestibular neurons in compensated animals. The portion of type I neurons on the ipsilesional side is reduced in compensated animals, which likely accounts for the asymmetries in vestibular reflexes and perception that characterize vestibular function after UL.
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Battelli, Lorella, George A. Alvarez, Thomas Carlson, and Alvaro Pascual-Leone. "The Role of the Parietal Lobe in Visual Extinction Studied with Transcranial Magnetic Stimulation." Journal of Cognitive Neuroscience 21, no. 10 (October 2009): 1946–55. http://dx.doi.org/10.1162/jocn.2008.21149.
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Interhemispheric competition between homologous areas in the human brain is believed to be involved in a wide variety of human behaviors from motor activity to visual perception and particularly attention. For example, patients with lesions in the posterior parietal cortex are unable to selectively track objects in the contralesional side of visual space when targets are simultaneously present in the ipsilesional visual field, a form of visual extinction. Visual extinction may arise due to an imbalance in the normal interhemispheric competition. To directly assess the issue of reciprocal inhibition, we used fMRI to localize those brain regions active during attention-based visual tracking and then applied low-frequency repetitive transcranial magnetic stimulation over identified areas in the left and right intraparietal sulcus to asses the behavioral effects on visual tracking. We induced a severe impairment in visual tracking that was selective for conditions of simultaneous tracking in both visual fields. Our data show that the parietal lobe is essential for visual tracking and that the two hemispheres compete for attentional resources during tracking. Our results provide a neuronal basis for visual extinction in patients with parietal lobe damage.
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Khan, Fayaz, Chaturbhuj Rathore, Mahesh Kate, Josy Joy, George Zachariah, P. C. Vincent, Ravi Prasad Varma, and Kurupath Radhakrishnan. "The comparative efficacy of theta burst stimulation or functional electrical stimulation when combined with physical therapy after stroke: a randomized controlled trial." Clinical Rehabilitation 33, no. 4 (January 8, 2019): 693–703. http://dx.doi.org/10.1177/0269215518820896.
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Objective: To study the long-term effectiveness of Theta Burst Stimulation (TBS) or Functional Electrical Stimulation (FES) combined with Physical therapy (PT) as compared to PT alone for improving arm functions in patients with acute stroke. Design: Single blind randomized controlled trial. Setting: Outpatient clinics and inpatient wards at tertiary care neurology center. Subjects: Adult patients with acute middle cerebral artery territory ischemic stroke. Interventions: 60 patients were randomized into three groups of 20 each: TBS+PT; FES+PT; and PT alone. TBS group received intermittent TBS of ipsilesional hemisphere and continuous TBS of contralesional hemisphere while FES group received FES of paretic limb, both for four weeks. All groups received supervised physical therapy for four weeks followed by home physiotherapy for one year. Outcome measures: Fugl Meyer Assessment upper limb score (FMA-UL) was primary outcome measure. Patients were evaluated at baseline and subsequently at one, three and six months and one year. Results: Compared to PT group, mean FMA-UL scores were higher in TBS and FES groups at all follow-ups ( P < 0.001). From baseline to one year, mean (SD) FMA-UL scores increased from 14.9(2.1) to 55.55(2.46) in TBS group, 15.5(1.99) to 55.85(2.46) in FES group, and 14.3(2.2) to 43.3(4.22) in PT group indicating an increase of 273%, 260%, and 203% respectively. There was no difference between FES and TBS groups. Conclusion: A four-week intervention with TBS or FES combined with PT produces better long-term arm functions as compared to PT alone in patients with acute stroke.
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Revill, Kate Pirog, Marc W. Haut, Samir R. Belagaje, Fadi Nahab, Daniel Drake, and Cathrin M. Buetefisch. "Hebbian-Type Primary Motor Cortex Stimulation: A Potential Treatment of Impaired Hand Function in Chronic Stroke Patients." Neurorehabilitation and Neural Repair 34, no. 2 (January 24, 2020): 159–71. http://dx.doi.org/10.1177/1545968319899911.
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Background. Stroke often involves primary motor cortex (M1) and its corticospinal (CST) projections. As hand function is critically dependent on these structures, its recovery is often incomplete. Objective. To determine whether impaired hand function in patients with chronic ischemic stroke involving M1 or CST benefits from the enhancing effect of Hebbian-type stimulation (pairing M1 afferent stimulation and M1 activity in a specific temporal relationship) on M1 plasticity and hand function. Methods. In a double-blind, randomized, sham-controlled design, 20 patients with chronic ischemic stroke affecting M1 or CST were randomly assigned to 5 days of hand motor training that was combined with either Hebbian-type (trainingHebb) or sham stimulation (trainingsham) of the lesioned M1. Measures of hand function and task-based M1 functional magnetic resonance imaging (fMRI) activity were collected prior to, immediately following, and 4 weeks after the intervention. Results. Both interventions were effective in improving affected hand function at the completion of training, but only participants in the trainingHebb group maintained functional gains. Changes in hand function and fMRI activity were positively correlated in both ipsilesional and contralesional M1. Compared with trainingsham, participants in the trainingHebb group showed a stronger relationship between improved hand function and changes in M1 functional activity. Conclusions. Only when motor training was combined with Hebbian-type stimulation were functional gains maintained over time and correlated with measures of M1 functional plasticity. As hand dexterity is critically dependent on M1 function, these results suggest that functional reorganization in M1 is facilitated by Hebbian-type stimulation. ClinicalTrials.gov Identifier: NCT01569607.
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Wadden, K. P., S. Peters, M. R. Borich, J. L. Neva, K. S. Hayward, C. S. Mang, N. J. Snow, et al. "White Matter Biomarkers Associated with Motor Change in Individuals with Stroke: A Continuous Theta Burst Stimulation Study." Neural Plasticity 2019 (February 4, 2019): 1–15. http://dx.doi.org/10.1155/2019/7092496.
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Continuous theta burst stimulation (cTBS) is a form of noninvasive repetitive brain stimulation that, when delivered over the contralesional hemisphere, can influence the excitability of the ipsilesional hemisphere in individuals with stroke. cTBS applied prior to skilled motor practice interventions may augment motor learning; however, there is a high degree of variability in individual response to this intervention. The main objective of the present study was to assess white matter biomarkers of response to cTBS paired with skilled motor practice in individuals with chronic stroke. We tested the effects of stimulation of the contralesional hemisphere at the site of the primary motor cortex (M1c) or primary somatosensory cortex (S1c) and a third group who received sham stimulation. Within each stimulation group, individuals were categorized into responders or nonresponders based on their capacity for motor skill change. Baseline diffusion tensor imaging (DTI) indexed the underlying white matter microstructure of a previously known motor learning network, named the constrained motor connectome (CMC), as well as the corticospinal tract (CST) of lesioned and nonlesioned hemispheres. Across practice, there were no differential group effects. However, when categorized as responders vs. nonresponders using change in motor behaviour, we demonstrated a significant difference in CMC microstructural properties (as measured by fractional anisotropy (FA)) for individuals in M1c and S1c groups. There were no significant differences between responders and nonresponders in clinical baseline measures or microstructural properties (FA) in the CST. The present study identifies a white matter biomarker, which extends beyond the CST, advancing our understanding of the importance of white matter networks for motor after stroke.
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Schuhmann, Michael K., Guido Stoll, Arne Bohr, Jens Volkmann, and Felix Fluri. "Electrical Stimulation of the Mesencephalic Locomotor Region Attenuates Neuronal Loss and Cytokine Expression in the Perifocal Region of Photothrombotic Stroke in Rats." International Journal of Molecular Sciences 20, no. 9 (May 11, 2019): 2341. http://dx.doi.org/10.3390/ijms20092341.
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Deep brain stimulation of the mesencephalic locomotor region (MLR) improves the motor symptoms in Parkinson’s disease and experimental stroke by intervening in the motor cerebral network. Whether high-frequency stimulation (HFS) of the MLR is involved in non-motor processes, such as neuroprotection and inflammation in the area surrounding the photothrombotic lesion, has not been elucidated. This study evaluates whether MLR-HFS exerts an anti-apoptotic and anti-inflammatory effect on the border zone of cerebral photothrombotic stroke. Rats underwent photothrombotic stroke of the right sensorimotor cortex and the implantation of a microelectrode into the ipsilesional MLR. After intervention, either HFS or sham stimulation of the MLR was applied for 24 h. The infarct volumes were calculated from consecutive brain sections. Neuronal apoptosis was analyzed by TUNEL staining. Flow cytometry and immunohistochemistry determined the perilesional inflammatory response. Neuronal apoptosis was significantly reduced in the ischemic penumbra after MLR-HFS, whereas the infarct volumes did not differ between the groups. MLR-HFS significantly reduced the release of cytokines and chemokines within the ischemic penumbra. MLR-HFS is neuroprotective and it reduces pro-inflammatory mediators in the area that surrounds the photothrombotic stroke without changing the number of immune cells, which indicates that MLR-HFS enables the function of inflammatory cells to be altered on a molecular level.
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Vabalaite, Birute, Laura Petruseviciene, Raimondas Savickas, Raimondas Kubilius, Povilas Ignatavicius, and Egle Lendraitiene. "Effects of High-Frequency (HF) Repetitive Transcranial Magnetic Stimulation (rTMS) on Upper Extremity Motor Function in Stroke Patients: A Systematic Review." Medicina 57, no. 11 (November 7, 2021): 1215. http://dx.doi.org/10.3390/medicina57111215.
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Background and Objectives: Repetitive transcranial magnetic stimulation (rTMS) is being widely used for treating upper extremity paresis after stroke, however, evidence of applying high-frequency rTMS (HF-rTMS) on the ipsilesional hemisphere for upper extremity motor recovery remains limited. This systematic review aimed to investigate the effect of high-frequency repetitive transcranial magnetic stimulation for upper extremity motor function recovery after a first-time ischaemic stroke. Materials and Methods: This systematic review was prepared according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A comprehensive literature search was performed to identify all studies published before 12 February 2021. The search was performed on the following databases: PubMed, Ovid, The Cochrane Library. Results: A total of 6440 studies were found in the databases and four trials were included in the review. Three of the studies were randomized control trials (RCT), and one was a pseudo-RCT. Three of the studies showed good methodological quality and one study was rated as excellent. Fugl-Meyer Assessment (FMA) was performed in three out of four studies and the score significantly increased in the HF-rTMS treatment group compared with sham stimulation in all trials. Other measures used in the studies were handgrip strength, shoulder abduction, Motricity Index, Wolf Motor Function Test (WMFT), and Box and Block, although these tests did not show unanimous results. Overall, all four studies conveyed significantly better results in at least one test that was performed for hand motor function evaluation in a 10 Hz stimulation group while none of the tests showed any advantage for sham stimulation groups. Two studies reported headache as an adverse event (six patients in total). Conclusion: The overall results showed that HF-rTMS may increase impaired upper extremity motor function better than sham stimulation in stroke patients.
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van Lieshout, Eline C. C., Johanna M. A. Visser-Meily, Sebastiaan F. W. Neggers, H. Bart van der Worp, and Rick M. Dijkhuizen. "Brain stimulation for arm recovery after stroke (B-STARS): protocol for a randomised controlled trial in subacute stroke patients." BMJ Open 7, no. 8 (August 2017): e016566. http://dx.doi.org/10.1136/bmjopen-2017-016566.
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IntroductionMany patients with stroke have moderate to severe long-term sensorimotor impairments, often including inability to execute movements of the affected arm or hand. Limited recovery from stroke may be partly caused by imbalanced interaction between the cerebral hemispheres, with reduced excitability of the ipsilesional motor cortex while excitability of the contralesional motor cortex is increased. Non-invasive brain stimulation with inhibitory repetitive transcranial magnetic stimulation (rTMS) of the contralesional hemisphere may aid in relieving a post-stroke interhemispheric excitability imbalance, which could improve functional recovery. There are encouraging effects of theta burst stimulation (TBS), a form of TMS, in patients with chronic stroke, but evidence on efficacy and long-term effects on arm function of contralesional TBS in patients with subacute hemiparetic stroke is lacking.Methods and analysisIn a randomised clinical trial, we will assign 60 patients with a first-ever ischaemic stroke in the previous 7–14 days and a persistent paresis of one arm to 10 sessions of real stimulation with TBS of the contralesional primary motor cortex or to sham stimulation over a period of 2 weeks. Both types of stimulation will be followed by upper limb training. A subset of patients will undergo five MRI sessions to assess post-stroke brain reorganisation. The primary outcome measure will be the upper limb function score, assessed from grasp, grip, pinch and gross movements in the action research arm test, measured at 3 months after stroke. Patients will be blinded to treatment allocation. The primary outcome at 3 months will also be assessed in a blinded fashion.Ethics and disseminationThe study has been approved by the Medical Research Ethics Committee of the University Medical Center Utrecht, The Netherlands. The results will be disseminated through (open access) peer-reviewed publications, networks of scientists, professionals and the public, and presented at conferences.Trial registration numberNTR6133
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Lee, Yookyung, Byung-Mo Oh, Sung-Hye Park, and Tai Ryoon Han. "Low-Frequency Repetitive Transcranial Magnetic Stimulation in the Early Subacute Phase of Stroke Enhances Angiogenic Mechanisms in Rats." Annals of Rehabilitation Medicine 46, no. 5 (October 31, 2022): 228–36. http://dx.doi.org/10.5535/arm.22040.
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Objective To characterize the repetitive transcranial magnetic stimulation (rTMS) induced changes in angiogenic mechanisms across different brain regions.Methods Seventy-nine adult male Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (day 0) and then treated with 1-Hz, 20-Hz, or sham stimulation of their lesioned hemispheres for 2 weeks. The stimulation intensity was set to 100% of the motor threshold. The neurological function was assessed on days 3, 10, and 17. The infarct volume and angiogenesis were measured by histology, immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR) assays. Brain tissue was harvested from the ischemic core (IC), ischemic border zone (BZ), and contralateral homologous cortex (CH).Results Optical density of angiopoietin1 and synaptophysin in the IC was significantly greater in the low-frequency group than in the sham group (p=0.03 and p=0.03, respectively). The 1-Hz rTMS significantly increased the level of Akt phosphorylation in the BZ (p<0.05 vs. 20 Hz). Endothelial nitric oxide synthase phosphorylation was increased in the IC (p<0.05 vs. 20 Hz), BZ (p<0.05 vs. 20 Hz), and CH (p<0.05 vs. 20 Hz and p<0.05 vs. sham). Real-time PCR demonstrated that low-frequency stimulation significantly increased the transcriptional activity of the <i>TIE2</i> gene in the IC (p<0.05).Conclusion Low-frequency rTMS of the ipsilesional hemisphere in the early subacute phase of stroke promotes the expression of angiogenic factors and related genes in the brain, particularly in the injured area.
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Yuan, Xiaoxia, Yuan Yang, Na Cao, and Changhao Jiang. "Promotion of Poststroke Motor-Function Recovery with Repetitive Transcranial Magnetic Stimulation by Regulating the Interhemispheric Imbalance." Brain Sciences 10, no. 9 (September 18, 2020): 648. http://dx.doi.org/10.3390/brainsci10090648.
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Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain-stimulation technique that transiently modulates cerebral cortex excitability, achieving overall positive results in poststroke motor-function recovery. Excessive inhibition of the ipsilesional-affected hemisphere by the contralesional-unaffected hemisphere has seriously hindered poststroke motor-function recovery. Hence, intracortical disinhibition can be used as an approach to managing poststroke brain injury. This technique promotes neural plasticity for faster motor-function recovery. rTMS relieves unilateral inhibition of the brain function by regulatinga interhemispheric-imbalanced inhibition. This paper summarized 12 studies from 2016 to date, focusing on rTMS on motor function after acute and chronic stroke by regulating the interhemispheric imbalance of inhibitory inputs. Although rTMS studies have shown promising outcomes on recovery of motor functions in stroke patients, different intervention methods may lead to discrepancies in results. A uniform optimal stimulus model cannot routinely be used, mainly due to the stimulus schemes, stroke types and outcome-measuring differences among studies. Thus, the effect of rTMS on poststroke motor-function recovery should be investigated further to standardize the rTMS program for optimal poststroke motor-function recovery. More randomized, placebo-controlled clinical trials with standardized rTMS protocols are needed to ensure the effectiveness of the treatment.
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Hamoudi, Manuela, Heidi M. Schambra, Brita Fritsch, Annika Schoechlin-Marx, Cornelius Weiller, Leonardo G. Cohen, and Janine Reis. "Transcranial Direct Current Stimulation Enhances Motor Skill Learning but Not Generalization in Chronic Stroke." Neurorehabilitation and Neural Repair 32, no. 4-5 (April 2018): 295–308. http://dx.doi.org/10.1177/1545968318769164.
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Background. Motor training alone or combined with transcranial direct current stimulation (tDCS) positioned over the motor cortex (M1) improves motor function in chronic stroke. Currently, understanding of how tDCS influences the process of motor skill learning after stroke is lacking. Objective. To assess the effects of tDCS on the stages of motor skill learning and on generalization to untrained motor function. Methods. In this randomized, sham-controlled, blinded study of 56 mildly impaired chronic stroke patients, tDCS (anode over the ipsilesional M1 and cathode on the contralesional forehead) was applied during 5 days of training on an unfamiliar, challenging fine motor skill task (sequential visual isometric pinch force task). We assessed online and offline learning during the training period and retention over the following 4 months. We additionally assessed the generalization to untrained tasks. Results. With training alone (sham tDCS group), patients acquired a novel motor skill. This skill improved online, remained stable during the offline periods and was largely retained at follow-up. When tDCS was added to training (real tDCS group), motor skill significantly increased relative to sham, mostly in the online stage. Long-term retention was not affected by tDCS. Training effects generalized to untrained tasks, but those performance gains were not enhanced further by tDCS. Conclusions. Training of an unfamiliar skill task represents a strategy to improve fine motor function in chronic stroke. tDCS augments motor skill learning, but its additive effect is restricted to the trained skill.
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Lee, Jungsoo, Ahee Lee, Heegoo Kim, Mina Shin, Sang Moon Yun, Youngjin Jung, Won Hyuk Chang, and Yun-Hee Kim. "Different Brain Connectivity between Responders and Nonresponders to Dual-Mode Noninvasive Brain Stimulation over Bilateral Primary Motor Cortices in Stroke Patients." Neural Plasticity 2019 (April 7, 2019): 1–10. http://dx.doi.org/10.1155/2019/3826495.
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Noninvasive brain stimulation (NBS), such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS), has been used in stroke patients with motor impairment. NBS can help recovery from brain damage by modulating cortical excitability. However, the efficacy of NBS varies among individuals. To obtain insights of responsiveness to the efficacy of NBS, we investigated characteristic changes of the motor network in responders and nonresponders of NBS over the primary motor cortex (M1). A total of 21 patients with subacute stroke (13 males, mean age 59.6±11.5 years) received NBS in the same manner: 1 Hz rTMS on the contralesional M1 and anodal tDCS on the ipsilesional M1. Participants were classified into responders and nonresponders based on the functional improvement of the affected upper extremity after applying NBS. Twelve age-matched healthy controls (8 males, mean age 56.1±14.3 years) were also recruited. Motor networks were constructed using resting-state functional magnetic resonance imaging. M1 intrahemispheric connectivity, interhemispheric connectivity, and network efficiency were measured to investigate differences in network characteristics between groups. The motor network characteristics were found to differ between both groups. Specifically, M1 intrahemispheric connectivity in responders showed a noticeable imbalance between affected and unaffected hemispheres, which was markedly restored after NBS. The responders also showed greater interhemispheric connectivity and higher efficiency of the motor network than the nonresponders. These results may provide insight on patient-specific NBS treatment based on the brain network characteristics in neurorehabilitation of patients with stroke. This trial is registered with trial registration number NCT03390192.
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Inguaggiato, Emanuela, Nadia Bolognini, Simona Fiori, and Giovanni Cioni. "Transcranial Direct Current Stimulation (tDCS) in Unilateral Cerebral Palsy: A Pilot Study of Motor Effect." Neural Plasticity 2019 (January 14, 2019): 1–10. http://dx.doi.org/10.1155/2019/2184398.
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Transcranial Direct Current Stimulation (tDCS) is an emerging tool to improve upper limb motor functions after stroke acquired in adulthood; however, there is a paucity of reports on its efficacy for upper limb motor rehabilitation in congenital or early-acquired stroke. In this pilot study we have explored, for the first time, the immediate effects, and their short-term persistence, of a single application of anodal tDCS on chronic upper limb motor disorders in children and young individuals with Unilateral Cerebral Palsy (UCP). To this aim, in a crossover sham-controlled study, eight subjects aged 10-28 years with UCP underwent two sessions of active and sham tDCS. Anodal tDCS (1.5 mA, 20 min) was delivered over the primary motor cortex (M1) of the ipsilesional hemisphere. Results showed, only following the active stimulation, an immediate improvement in unimanual gross motor dexterity of hemiplegic, but not of nonhemiplegic, hand in Box and Block test (BBT). Such improvement remained stable for at least 90 minutes. Performance of both hands in Hand Grip Strength test was not modified by anodal tDCS. Improvement in BBT was unrelated to participants’ age or lesion size, as revealed by MRI data analysis. No serious adverse effects occurred after tDCS; some mild and transient side effects (e.g., headache, tingling, and itchiness) were reported in a limited number of cases. This study provides an innovative contribution to scientific literature on the efficacy and safety of anodal tDCS in UCP. This trial is registered with NCT03137940.
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Zhang, Jack Jiaqi, and Kenneth N. K. Fong. "Effects of priming intermittent theta burst stimulation on upper limb motor recovery after stroke: study protocol for a proof-of-concept randomised controlled trial." BMJ Open 10, no. 3 (March 2020): e035348. http://dx.doi.org/10.1136/bmjopen-2019-035348.
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IntroductionIntermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS), delivered to the ipsilesional primary motor cortex (M1), appears to enhance the brain’s response to rehabilitative training in patients with stroke. However, its clinical utility is highly subject to variability in different protocols. New evidence has reported that preceding iTBS, with continuous theta burst stimulation (cTBS) may stabilise and even boost the facilitatory effect of iTBS on the stimulated M1, via metaplasticity. The aim of this study is to investigate the effects of iTBS primed with cTBS (ie, priming iTBS), in addition to robot-assisted training (RAT), on the improvement of the hemiparetic upper limb functions of stroke patients and to explore potential sensorimotor neuroplasticity using electroencephalography (EEG).Methods and analysisA three-arm, subjects and assessors-blinded, randomised controlled trial will be performed with patients with chronic stroke. An estimated sample of 36 patients will be needed based on the prior sample size calculation. All participants will be randomly allocated to receive 10 sessions of rTMS with different TBS protocols (cTBS+iTBS, sham cTBS+iTBS and sham cTBS+sham iTBS), three to five sessions per week, for 2–3 weeks. All participants will receive 60 min of RAT after each stimulation session. Primary outcomes will be assessed using Fugl-Meyer Assessment-Upper Extremity scores and Action Research Arm Test. Secondary outcomes will be assessed using kinematic outcomes generated during RAT and EEG.Ethics and disseminationEthical approval has been obtained from The Human Subjects Ethics Sub-committee, University Research Committee of The Hong Kong Polytechnic University (reference number: HSEARS20190718003). The results yielded from this study will be presented at international conferences and sent to a peer-review journal to be considered for publication.Trial registration numberNCT04034069.
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Cheng, Michelle Y., Shahabeddin Vahdat, Arjun V. Pendharkar, Sean Harvey, Terrance Chiang, Hyun Joo Lee, Jin Hyung Lee, and Gary K. Steinberg. "Abstract 177: Brain-Wide Circuit Dynamics of Post-Stroke Recovery After Optogenetic Stimulation." Stroke 51, Suppl_1 (February 2020). http://dx.doi.org/10.1161/str.51.suppl_1.177.
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Background: Post-stroke optogenetic stimulations have been shown to promote functional recovery. However, the cellular and circuit mechanisms underlying such recovery remain unclear. Elucidating key neural circuits in post-stroke recovery will be invaluable for translation of neuromodulation for stroke. Here we used optogenetic functional magnetic response imaging (ofMRI) to examine brain-wide circuit dynamics induced by optogenetic stimulation treatment (OST). Method: Male mice expressing channelrhodopsin (ChR2) in ipsilesional M1 (iM1) layer V excitatory neurons were used. ofMRI were performed on pre-stroke and post-stroke days (PD) 3, 15 and 29. OST were given daily from PD5-15. Sensorimotor tests were conducted one day prior to each ofMRI session. Mice underwent transient middle cerebral artery occlusion (intraluminal suture model, 30 minutes). Two groups were assigned: stim group (mice with 10 days of OST, n=9) and no stim group (mice without OST, n=9). Activation maps were compared between stim and no stim groups to reveal key brain circuits recovered by OST. The expression of plasticity marker GAP43 was examined using western blot. Result: Our results show that 1) Optogenetic excitatory neuronal stimulations in iM1 promotes motor function at PD 14 (P<0.01). 2) At pre-stroke, iM1 stimulations activate expected network including ipsilesional M1, M2, S1, striatum, thalamus, contralateral M1 and cerebellum. 3) At PD3, all mice exhibit a depressed response throughout the brain. 4) At PD15, ipsilesional thalamus and S1 circuits are significantly recovered by OST. Moreover, restoration of thalamic activation is correlated with behavioral recovery in the stim group. 5) At PD15, stimulated mice exhibited higher level of plasticity marker (GAP43) in the ipsilesional thalamus (P<0.05). 6) At PD29, iS1 activation remains stronger in the stim group when compared to no stim group. Conclusion: Our findings revealed key circuits underlying stimulation-induced post-stroke recovery. We found that restoration of cortico-thalamic projections is important in stimulation-induced recovery at early phase post-stroke, while sustained strengthening of ipsilesional cortico-cortical connections may be critical in the later phase of recovery.