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Zhang, Xu, et Sabato Santaniello. « Role of cerebellar GABAergic dysfunctions in the origins of essential tremor ». Proceedings of the National Academy of Sciences 116, no 27 (17 juin 2019) : 13592–601. http://dx.doi.org/10.1073/pnas.1817689116.
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Essential tremor (ET) is among the most prevalent movement disorders, but its origins are elusive. The inferior olivary nucleus (ION) has been hypothesized as the prime generator of tremor because of the pacemaker properties of ION neurons, but structural and functional changes in ION are unlikely under ET. Abnormalities have instead been reported in the cerebello-thalamo-cortical network, including dysfunctions of the GABAergic projections from the cerebellar cortex to the dentate nucleus. It remains unclear, though, how tremor would relate to a dysfunction of cerebellar connectivity. To address this question, we built a computational model of the cortico-cerebello-thalamo-cortical loop. We simulated the effects of a progressive loss of GABAA α1-receptor subunits and up-regulation of α2/3-receptor subunits in the dentate nucleus, and correspondingly, we studied the evolution of the firing patterns along the loop. The model closely reproduced experimental evidence for each structure in the loop. It showed that an alteration of amplitudes and decay times of the GABAergic currents to the dentate nucleus can facilitate sustained oscillatory activity at tremor frequency throughout the network as well as a robust bursting activity in the thalamus, which is consistent with observations of thalamic tremor cells in ET patients. Tremor-related oscillations initiated in small neural populations and spread to a larger network as the synaptic dysfunction increased, while thalamic high-frequency stimulation suppressed tremor-related activity in thalamus but increased the oscillation frequency in the olivocerebellar loop. These results suggest a mechanism for tremor generation under cerebellar dysfunction, which may explain the origin of ET.
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Brinkmann, Pia, Sonja A. Kotz, Jasper V. Smit, Marcus L. F. Janssen et Michael Schwartze. « Auditory thalamus dysfunction and pathophysiology in tinnitus : a predictive network hypothesis ». Brain Structure and Function 226, no 6 (2 mai 2021) : 1659–76. http://dx.doi.org/10.1007/s00429-021-02284-x.
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AbstractTinnitus is the perception of a ‘ringing’ sound without an acoustic source. It is generally accepted that tinnitus develops after peripheral hearing loss and is associated with altered auditory processing. The thalamus is a crucial relay in the underlying pathways that actively shapes processing of auditory signals before the respective information reaches the cerebral cortex. Here, we review animal and human evidence to define thalamic function in tinnitus. Overall increased spontaneous firing patterns and altered coherence between the thalamic medial geniculate body (MGB) and auditory cortices is observed in animal models of tinnitus. It is likely that the functional connectivity between the MGB and primary and secondary auditory cortices is reduced in humans. Conversely, there are indications for increased connectivity between the MGB and several areas in the cingulate cortex and posterior cerebellar regions, as well as variability in connectivity between the MGB and frontal areas regarding laterality and orientation in the inferior, medial and superior frontal gyrus. We suggest that these changes affect adaptive sensory gating of temporal and spectral sound features along the auditory pathway, reflecting dysfunction in an extensive thalamo-cortical network implicated in predictive temporal adaptation to the auditory environment. Modulation of temporal characteristics of input signals might hence factor into a thalamo-cortical dysrhythmia profile of tinnitus, but could ultimately also establish new directions for treatment options for persons with tinnitus.
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Hughes, Shelby, Daniel O. Claassen, Wery P. M. van den Wildenberg, Fenna T. Phibbs, Elise B. Bradley, Scott A. Wylie et Nelleke C. van Wouwe. « Action Control Deficits in Patients With Essential Tremor ». Journal of the International Neuropsychological Society 25, no 2 (3 décembre 2018) : 156–64. http://dx.doi.org/10.1017/s1355617718001054.
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AbstractObjectives: Essential tremor (ET) is a movement disorder characterized by action tremor which impacts motor execution. Given the disrupted cerebellar-thalamo-cortical networks in ET, we hypothesized that ET could interfere with the control mechanisms involved in regulating motor performance. The ability to inhibit or stop actions is critical for navigating many daily life situations such as driving or social interactions. The current study investigated the speed of action initiation and two forms of action control, response stopping and proactive slowing in ET. Methods: Thirty-three ET patients and 25 healthy controls (HCs) completed a choice reaction task and a stop-signal task, and measures of going speed, proactive slowing and stop latencies were assessed. Results: Going speed was significantly slower in ET patients (649 ms) compared to HCs (526 ms; F(1,56) = 42.37; p <.001; η2 = .43), whereas proactive slowing did not differ between groups. ET patients exhibited slower stop signal reaction times (320 ms) compared to HCs (258 ms, F(1,56) = 15.3; p <.00; η2 = .22) and more severe motor symptoms of ET were associated with longer stopping latencies in a subset of patients (Spearman rho = .48; p <.05). Conclusions: In line with previous studies, ET patients showed slower action initiation. Additionally, inhibitory control was impaired whereas proactive slowing remained intact relative to HCs. More severe motor symptoms of ET were associated with slower stopping speed, and may reflect more progressive changes to the cerebellar-thalamo-cortical network. Future imaging studies should specify which structural and functional changes in ET can explain changes in inhibitory action control. (JINS, 2019, 25, 156–164)
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Ekmen, Asya, Aurelie Meneret, Romain Valabregue, Benoit Beranger, Yulia Worbe, Jean-Charles Lamy, Sofien Mehdi et al. « Cerebellum Dysfunction in Patients With PRRT2-Related Paroxysmal Dyskinesia ». Neurology 98, no 10 (20 janvier 2022) : e1077-e1089. http://dx.doi.org/10.1212/wnl.0000000000200060.
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Background and ObjectivesThe main culprit gene for paroxysmal kinesigenic dyskinesia, characterized by brief and recurrent attacks of involuntary movements, is PRRT2. The location of the primary dysfunction associated with paroxysmal dyskinesia remains a matter of debate and may vary depending on the etiology. While striatal dysfunction has often been implicated in these patients, evidence from preclinical models indicates that the cerebellum could also play a role. We aimed to investigate the role of the cerebellum in the pathogenesis of PRRT2-related dyskinesia in humans.MethodsWe enrolled 22 consecutive right-handed patients with paroxysmal kinesigenic dyskinesia with a pathogenic variant of PRRT2 and their matched controls. Participants underwent a multimodal neuroimaging protocol. We recorded anatomic and diffusion-weighted MRI, as well as resting-state fMRI, during which we tested the aftereffects of sham and repetitive transcranial magnetic stimulation applied to the cerebellum on endogenous brain activity. We quantified the structural integrity of gray matter using voxel-based morphometry, the structural integrity of white matter using fixel-based analysis, and the strength and direction of functional cerebellar connections using spectral dynamic causal modeling.ResultsPatients with PRRT2 had decreased gray matter volume in the cerebellar lobule VI and in the medial prefrontal cortex, microstructural alterations of white matter in the cerebellum and along the tracts connecting the cerebellum to the striatum and the cortical motor areas, and dysfunction of cerebellar motor pathways to the striatum and the cortical motor areas, as well as abnormal communication between the associative cerebellum (Crus I) and the medial prefrontal cortex. Cerebellar stimulation modulated communication within the motor and associative cerebellar networks and tended to restore this communication to the level observed in healthy controls.DiscussionPatients with PRRT2-related dyskinesia have converging structural alterations of the motor cerebellum and related pathways with a dysfunction of cerebellar output toward the cerebello-thalamo-striato-cortical network. We hypothesize that abnormal cerebellar output is the primary dysfunction in patients with a PRRT2 pathogenic variant, resulting in striatal dysregulation and paroxysmal dyskinesia. More broadly, striatal dysfunction in paroxysmal dyskinesia might be secondary to aberrant cerebellar output transmitted by thalamic relays in certain disorders.Trial Registration Information:ClinicalTrials.gov identifier: NCT03481491.
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Tuleasca, Constantin, Thomas A. W. Bolton, Jean Régis, Elena Najdenovska, Tatiana Witjas, Nadine Girard, Francois Delaire et al. « Normalization of aberrant pretherapeutic dynamic functional connectivity of extrastriate visual system in patients who underwent thalamotomy with stereotactic radiosurgery for essential tremor : a resting-state functional MRI study ». Journal of Neurosurgery 132, no 6 (juin 2020) : 1792–801. http://dx.doi.org/10.3171/2019.2.jns183454.
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OBJECTIVE The tremor circuitry has commonly been hypothesized to be driven by one or multiple pacemakers within the cerebello-thalamo-cortical pathway, including the cerebellum, contralateral motor thalamus, and primary motor cortex. However, previous studies, using multiple methodologies, have advocated that tremor could be influenced by changes within the right extrastriate cortex, at both the structural and functional level. The purpose of this work was to evaluate the role of the extrastriate cortex in tremor generation and further arrest after left unilateral stereotactic radiosurgery thalamotomy (SRS-T). METHODS The authors considered 12 healthy controls (HCs, group 1); 15 patients with essential tremor (ET, right-sided, drug-resistant; group 2) before left unilateral SRS-T; and the same 15 patients (group 3) 1 year after the intervention, to account for delayed effects. Blood oxygenation level–dependent functional MRI during resting state was used to characterize the dynamic interactions of the right extrastriate cortex, comparing HC subjects against patients with ET before and 1 year after SRS-T. In particular, the authors applied coactivation pattern analysis to extract recurring whole-brain spatial patterns of brain activity over time. RESULTS The authors found 3 different sets of coactivating regions within the right extrastriate cortex in HCs and patients with pretherapeutic ET, reminiscent of the “cerebello-visuo-motor,” “thalamo-visuo-motor” (including the targeted thalamus), and “basal ganglia and extrastriate” networks. The occurrence of the first pattern was decreased in pretherapeutic ET compared to HCs, whereas the other two patterns showed increased occurrences. This suggests a misbalance between the more prominent cerebellar circuitry and the thalamo-visuo-motor and basal ganglia networks. Multiple regression analysis showed that pretherapeutic standard tremor scores negatively correlated with the increased occurrence of the thalamo-visuo-motor network, suggesting a compensatory pathophysiological trait. Clinical improvement after SRS-T was related to changes in occurrences of the basal ganglia and extrastriate cortex circuitry, which returned to HC values after the intervention, suggesting that the dynamics of the extrastriate cortex had a role in tremor generation and further arrest after the intervention. CONCLUSIONS The data in this study point to a broader implication of the visual system in tremor generation, and not only through visual feedback, given its connections to the dorsal visual stream pathway and the cerebello-thalamo-cortical circuitry, with which its dynamic balance seems to be a crucial feature for reduced tremor. Furthermore, SRS-T seems to bring abnormal pretherapeutic connectivity of the extrastriate cortex to levels comparable to those of HC subjects.
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Walia, Pushpinder, Abhishek Ghosh, Shubhmohan Singh et Anirban Dutta. « Portable Neuroimaging-Guided Noninvasive Brain Stimulation of the Cortico-Cerebello-Thalamo-Cortical Loop—Hypothesis and Theory in Cannabis Use Disorder ». Brain Sciences 12, no 4 (26 mars 2022) : 445. http://dx.doi.org/10.3390/brainsci12040445.
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Background: Maladaptive neuroplasticity-related learned response in substance use disorder (SUD) can be ameliorated using noninvasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation. Objective: Our first objective was to develop a hypothesis for NIBS for learned response in SUD based on a competing neurobehavioral decision systems model. The next objective was to develop the theory by conducting a computational simulation of NIBS of the cortico-cerebello-thalamo-cortical (CCTC) loop in cannabis use disorder (CUD)-related dysfunctional “cue-reactivity”—a construct closely related to “craving”—that is a core symptom. Our third objective was to test the feasibility of a neuroimaging-guided rational NIBS approach in healthy humans. Methods: “Cue-reactivity” can be measured using behavioral paradigms and portable neuroimaging, including functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG) metrics of sensorimotor gating. Therefore, we conducted a computational simulation of NIBS, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) of the cerebellar cortex and deep cerebellar nuclei (DCN) of the CCTC loop for its postulated effects on fNIRS and EEG metrics. We also developed a rational neuroimaging-guided NIBS approach for the cerebellar lobule (VII) and prefrontal cortex based on a healthy human study. Results: Simulation of cerebellar tDCS induced gamma oscillations in the cerebral cortex, while transcranial temporal interference stimulation induced a gamma-to-beta frequency shift. A preliminary healthy human study (N = 10) found that 2 mA cerebellar tDCS evoked similar oxyhemoglobin (HbO) response in the range of 5 × 10−6 M across the cerebellum and PFC brain regions (α = 0.01); however, infra-slow (0.01–0.10 Hz) prefrontal cortex HbO-driven phase–amplitude-coupled (PAC; 4 Hz, ±2 mA (max)) cerebellar tACS evoked HbO levels in the range of 10−7 M that were statistically different (α = 0.01) across these brain regions. Conclusion: Our healthy human study showed the feasibility of fNIRS of cerebellum and PFC and closed-loop fNIRS-driven ctACS at 4 Hz, which may facilitate cerebellar cognitive function via the frontoparietal network. Future work needs to combine fNIRS with EEG for multi-modal imaging for closed-loop NIBS during operant conditioning.
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Van der Walt, A., K. Buzzard, S. Sung, T. Spelman, SC Kolbe, M. Marriott, H. Butzkueven et A. Evans. « The occurrence of dystonia in upper-limb multiple sclerosis tremor ». Multiple Sclerosis Journal 21, no 14 (26 mai 2015) : 1847–55. http://dx.doi.org/10.1177/1352458515577690.
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Background: The pathophysiology of multiple sclerosis (MS) tremor is uncertain with limited phenotypical studies available. Objective: To investigate whether dystonia contributes to MS tremor and its severity. Methods: MS patients ( n = 54) with and without disabling uni- or bilateral upper limb tremor were recruited (39 limbs per group). We rated tremor severity, writing and Archimedes spiral drawing; cerebellar dysfunction (SARA score); the Global Dystonia Scale (GDS) for proximal and distal upper limbs, dystonic posturing, mirror movements, geste antagoniste, and writer’s cramp. Results: Geste antagoniste, mirror dystonia, and dystonic posturing were more frequent and severe ( p < 0.001) and dystonia scores were correlated with tremor severity in tremor compared to non-tremor patients. A 1-unit increase in distal dystonia predicted a 0.52-Bain unit (95% confidence interval (CI) 0.08–0.97), p = 0.022) increase in tremor severity and a 1-unit (95% CI 0.48–1.6, p = 0.001) increase in drawing scores. A 1-unit increase in proximal dystonia predicted 0.93-Bain unit increase (95% CI 0.45–1.41, p < 0.001) in tremor severity and 1.5-units (95% CI 0.62–2.41, p = 0.002) increase in the drawing score. Cerebellar function in the tremor limb and tremor severity was correlated ( p < 0.001). Conclusions: Upper limb dystonia is common in MS tremor suggesting that MS tremor pathophysiology involves cerebello-pallido-thalamo-cortical network dysfunction.
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Pollok, Bettina, Markus Butz, Joachim Gross et Alfons Schnitzler. « Intercerebellar Coupling Contributes to Bimanual Coordination ». Journal of Cognitive Neuroscience 19, no 4 (avril 2007) : 704–19. http://dx.doi.org/10.1162/jocn.2007.19.4.704.
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Compared to unimanual task execution, simultaneous bimanual tapping tasks are associated with a significantly reduced intertap variability. It has been suggested that this bimanual advantage is based on the integration of timing signals which otherwise control each hand independently. Although its functional and anatomic foundations are poorly understood, functional coupling between cerebellar hemispheres might be behind this process. Because the execution of fast alternating fingertaps increases intertap variability, it is hypothesized that intercerebellar coupling is reduced in such tasks. To shed light on the functional significance of intercerebellar coupling, 14 right-handed subjects performed unimanual right, bimanual simultaneous, and bimanual alternating synchronization tasks with respect to a regular auditory pacing signal. In all conditions, within-hand intertap interval was 500 msec. Continuous neuromagnetic activity, using a 122-channel wholehead neuromagnetometer and surface electromyograms of the first dorsal interosseus muscle of both hands, were recorded. For data analysis, we used the analysis tool Dynamic Imaging of Coherent Sources, which provides a tomographic map of cerebromuscular and cerebrocerebral coherence. Analysis revealed a bilateral cerebello-thalamo-cortical network oscillating at alpha (8–12 Hz) and beta (13–24 Hz) frequencies associated with bimanual synchronization. In line with our hypothesis, coupling between cerebellar hemispheres was restricted to simultaneous task execution. This result implies that intercerebellar coupling is key for the execution of simultaneous bimanual movements. Although the criticality of a specific magneto-encephalography pattern for behavioral changes should be interpreted with caution, data suggest that intercerebellar coupling possibly represents the functional foundation of the bimanual advantage.
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Biagi, Laura, Sara Lenzi, Emilio Cipriano, Simona Fiori, Paolo Bosco, Paola Cristofani, Guia Astrea et al. « Neural substrates of neuropsychological profiles in dystrophynopathies : A pilot study of diffusion tractography imaging ». PLOS ONE 16, no 5 (3 mai 2021) : e0250420. http://dx.doi.org/10.1371/journal.pone.0250420.
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Introduction Cognitive difficulties and neuropsychological alterations in Duchenne and Becker muscular dystrophy (DMD, BMD) boys are not yet sufficiently explored, although this topic could have a relevant impact, finding novel biomarkers of disease both at genetics and neuroimaging point of view. The current study aims to: 1) analyze the neuropsychological profile of a group of DMD and BMD boys without cognitive impairment with an assessment of their executive functions; 2) explore the structural connectivity in DMD, BMD, and age-matched controls focusing on cortico-subcortical tracts that connect frontal cortex, basal ganglia, and cerebellum via the thalamus; 3) explore possible correlations between altered structural connectivity and clinical neuropsychological measures. Materials and methods This pilot study included 15 boys (5 DMD subjects, 5 BMD subjects, and 5 age-matched typically developing, TD). They were assessed using a neuropsychological assessment protocol including cognitive and executive functioning assessment and performed a 1.5T MRI brain exam including advance Diffusion Weighted Imaging (DWI) method for tractography. Structural connectivity measurements were extracted along three specific tracts: Cortico-Ponto-Cerebellar Tract (CPCT), Cerebellar-Thalamic Tract (CTT), and Superior Longitudinal Fasciculus (SLF). Cortical-Spinal Tract (CST) was selected for reference, as control tract. Results Regarding intellectual functioning, a major impairment in executive functions compared to the general intellectual functioning was observed both for DMD (mean score = 86.20; SD = 11.54) and for BMD children (mean score = 88; SD = 3.67). Mean FA resulted tendentially always lower in DMD compared to both BMD and TD groups for all the examined tracts. The differences in FA were statistically significant for the right CTT (DMD vs BMD, p = 0.002, and DMD vs TD, p = 0.0015) and the right CPCT (DMD vs TD, p = 0.008). Concerning DMD, significant correlations emerged between FA-R-CTT and intellectual quotients (FIQ, p = 0.044; ρs = 0.821), and executive functions (Denomination Total, p = 0.044, ρs = 0.821; Inhibition Total, p = 0.019, ρs = 0.900). BMD showed a significant correlation between FA-R-CPCT and working memory index (p = 0.007; ρs = 0.949). Discussion and conclusion In this pilot study, despite the limitation of sample size, the findings support the hypothesis of the involvement of a cerebellar-thalamo-cortical loop for the neuropsychological profile of DMD, as the CTT and the CPCT are involved in the network and the related brain structures are known to be implied in executive functions. Our results suggest that altered WM connectivity and reduced fibre organization in cerebellar tracts, probably due to the lack of dystrophin in the brain, may render less efficient some neuropsychological functions in children affected by dystrophinopathies. The wider multicentric study could help to better establish the role of cerebellar connectivity in neuropsychological profile for dystrophinopathies, identifying possible novel diagnostic and prognostic biomarkers.
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Hoebeek, F. E. « Cerebellar impact on pathological oscillations in thalamo-cortical networks ». Brain Stimulation 10, no 2 (mars 2017) : 433. http://dx.doi.org/10.1016/j.brs.2017.01.290.
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Giannì, Costanza, Gabriele Pasqua, Gina Ferrazzano, Silvia Tommasin, Maria Ilenia De Bartolo, Nikolaos Petsas, Daniele Belvisi, Antonella Conte, Alfredo Berardelli et Patrizia Pantano. « Focal Dystonia ». Neurology 98, no 14 (15 février 2022) : e1499-e1509. http://dx.doi.org/10.1212/wnl.0000000000200022.
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Background and ObjectivesNeuroimaging studies suggest that changes in the cerebellar-basal ganglia-thalamo-cortical sensorimotor circuit are a pathophysiologic feature of focal dystonia. However, it remains unclear whether structural and functional alterations vary in different forms of focal dystonia. Thus, in patients with cervical dystonia (CD) and blepharospasm (BSP), we aimed to investigate structural damage and resting-state functional alterations using whole-brain and seed-based approaches to test the hypothesis of possible functional connectivity (FC) alterations in specific circuits, including the cerebellum, basal ganglia, and cerebral cortex, in the context of preserved global FC.MethodsIn this cross-sectional study, we applied a multimodal 3T MRI protocol, including 3-dimensional T1-weighted images to extract brain volumes and cortical thickness, and fMRI at rest to study FC of the dentate nucleus and globus pallidus with a seed-based approach and whole-brain FC with a graph theory approach.ResultsThis study included 33 patients (17 with CD [14 female] age 55.7 ± 10.1 years, 16 with BSP [11 female] age 62.9 ± 8.8 years) and 16 age- and sex-matched healthy controls (HC) (7 female) 54.3 ± 14.3 years if age. Patients with CD, patients with BSP, and HC did not differ in terms of cortical or subcortical volume. Compared to HC, both patients with CD and patients with BSP had a loss of dentate FC anticorrelation with the sensorimotor cortex. Patients with CD and those with BSP showed increased pallidal FC with the cerebellum, supplementary motor area, and prefrontal cortices with respect to HC. Increased dentate FC with the cerebellum and thalamus and increased pallidal FC with the bilateral thalamus, sensorimotor and temporo-occipital cortices, and right putamen were present in patients with CD but not patients with BSP compared to HC. Measures of global FC, that is, global efficiency and small-worldness, did not differ between patients and HC.DiscussionBoth patients with CD and those with BSP showed altered dentate and pallidal FC with regions belonging to the integrated cerebellar-basal ganglia-thalamo-cortical sensorimotor circuit, supporting the concept that focal dystonia is a disorder of specific networks and not merely a result of basal ganglia alterations in the context of a preserved whole-brain functional architecture. Differences in functional interplay among specific brain structures may distinguish CD and BSP.
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Georgescu Margarint, Elena Laura, Ioana Antoaneta Georgescu, Carmen-Denise-Mihaela Zahiu, Alexandru Răzvan Șteopoaie, Stefan-Alexandru Tirlea, Daniela Popa, Ana-Maria Zagrean et Leon Zagrean. « Reduced Interhemispheric Coherence after Cerebellar Vermis Output Perturbation ». Brain Sciences 10, no 9 (8 septembre 2020) : 621. http://dx.doi.org/10.3390/brainsci10090621.
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Motor coordination and motor learning are well-known roles of the cerebellum. Recent evidence also supports the contribution of the cerebellum to the oscillatory activity of brain networks involved in a wide range of disorders. Kainate, a potent analog of the excitatory neurotransmitter glutamate, can be used to induce dystonia, a neurological movement disorder syndrome consisting of sustained or repetitive involuntary muscle contractions, when applied on the surface of the cerebellum. This research aims to study the interhemispheric cortical communication between the primary motor cortices after repeated kainate application on cerebellar vermis for five consecutive days, in mice. We recorded left and right primary motor cortices electrocorticograms and neck muscle electromyograms, and quantified the motor behavior abnormalities. The results indicated a reduced coherence between left and right motor cortices in low-frequency bands. In addition, we observed a phenomenon of long-lasting adaptation with a modification of the baseline interhemispheric coherence. Our research provides evidence that the cerebellum can control the flow of information along the cerebello-thalamo-cortical neural pathways and can influence interhemispheric communication. This phenomenon could function as a compensatory mechanism for impaired regional networks.
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Schaller-Paule, Martin A., Peter Baumgarten, Volker Seifert, Marlies Wagner, Eike Steidl, Elke Hattingen, Felix Wicke, Joachim P. Steinbach, Christian Foerch et Juergen Konczalla. « A Paravermal Trans-Cerebellar Approach to the Posterior Fossa Tumor Causes Hypertrophic Olivary Degeneration by Dentate Nucleus Injury ». Cancers 13, no 2 (12 janvier 2021) : 258. http://dx.doi.org/10.3390/cancers13020258.
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Background: In brain tumor surgery, injury to cerebellar connectivity pathways can induce a neurodegenerative disease called hypertrophic olivary degeneration (HOD), along with a disabling clinical syndrome. In children, cerebellar mutism syndrome (CMS) is another consequence of damage to cerebello–thalamo–cortical networks. The goal of this study was to compare paravermal trans-cerebellar to other more midline or lateral operative approaches in their risk of causing HOD on MR-imaging and CMS. Methods: We scanned our neurosurgical database for patients with surgical removal of pilocytic astrocytoma, ependymoma and medulloblastoma in the posterior fossa. Fifty patients with a mean age of 22.7 (±16.9) years were identified and analyzed. Results: HOD occurred in n = 10/50 (20%) patients within four months (median), always associated with contralateral dentate nucleus (DN)-lesions (p < 0.001). Patients with paravermal trans-cerebellar approach significantly more often developed HOD (7/11; 63.6%) when compared to other approaches (3/39; 7.7%; p < 0.001). Injury to the DN occurred more frequently after a paravermal approach (8/11 vs. 13/39 patients; p < 0.05). CMS was described for n = 12/50 patients (24%). Data indicated no correlation of radiological HOD and CMS development. Conclusions: A paravermal trans-cerebellar approach more likely causes HOD due to DN-injury when compared to more midline or lateral approaches. HOD is a radiological indicator for surgical disruption of cerebellar pathways involving the DN. Neurosurgeons should consider trajectories and approaches in the planning of posterior fossa surgery that spare the DN, whenever feasible.
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Dumas, Daniël B., Simona V. Gornati, Youri Adolfs, Tomomi Shimogori, R. Jeroen Pasterkamp et Freek E. Hoebeek. « Anatomical Development of the Cerebellothalamic Tract in Embryonic Mice ». Cells 11, no 23 (27 novembre 2022) : 3800. http://dx.doi.org/10.3390/cells11233800.
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The main connection from cerebellum to cerebrum is formed by cerebellar nuclei axons that synapse in the thalamus. Apart from its role in coordinating sensorimotor integration in the adult brain, the cerebello-thalamic tract (CbT) has also been implicated in developmental disorders, such as autism spectrum disorders. Although the development of the cerebellum, thalamus and cerebral cortex have been studied, there is no detailed description of the ontogeny of the mammalian CbT. Here we investigated the development of the CbT at embryonic stages using transgenic Ntsr1-Cre/Ai14 mice and in utero electroporation of wild type mice. Wide-field, confocal and 3D light-sheet microscopy of immunohistochemical stainings showed that CbT fibers arrive in the prethalamus between E14.5 and E15.5, but only invade the thalamus after E16.5. We quantified the spread of CbT fibers throughout the various thalamic nuclei and found that at E17.5 and E18.5 the ventrolateral, ventromedial and parafascicular nuclei, but also the mediodorsal and posterior complex, become increasingly innervated. Several CbT fiber varicosities express vesicular glutamate transporter type 2 at E18.5, indicating cerebello-thalamic synapses. Our results provide the first quantitative data on the developing murine CbT, which provides guidance for future investigations of the impact that cerebellum has on thalamo-cortical networks during development.
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Woodward, Kathryn, Richard Apps, Marc Goodfellow et Nadia L. Cerminara. « Cerebello-Thalamo-Cortical Network Dynamics in the Harmaline Rodent Model of Essential Tremor ». Frontiers in Systems Neuroscience 16 (28 juillet 2022). http://dx.doi.org/10.3389/fnsys.2022.899446.
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Essential Tremor (ET) is a common movement disorder, characterised by a posture or movement-related tremor of the upper limbs. Abnormalities within cerebellar circuits are thought to underlie the pathogenesis of ET, resulting in aberrant synchronous oscillatory activity within the thalamo-cortical network leading to tremors. Harmaline produces pathological oscillations within the cerebellum, and a tremor that phenotypically resembles ET. However, the neural network dynamics in cerebellar-thalamo-cortical circuits in harmaline-induced tremor remains unclear, including the way circuit interactions may be influenced by behavioural state. Here, we examined the effect of harmaline on cerebello-thalamo-cortical oscillations during rest and movement. EEG recordings from the sensorimotor cortex and local field potentials (LFP) from thalamic and medial cerebellar nuclei were simultaneously recorded in awake behaving rats, alongside measures of tremor using EMG and accelerometery. Analyses compared neural oscillations before and after systemic administration of harmaline (10 mg/kg, I.P), and coherence across periods when rats were resting vs. moving. During movement, harmaline increased the 9–15 Hz behavioural tremor amplitude and increased thalamic LFP coherence with tremor. Medial cerebellar nuclei and cerebellar vermis LFP coherence with tremor however remained unchanged from rest. These findings suggest harmaline-induced cerebellar oscillations are independent of behavioural state and associated changes in tremor amplitude. By contrast, thalamic oscillations are dependent on behavioural state and related changes in tremor amplitude. This study provides new insights into the role of cerebello-thalamo-cortical network interactions in tremor, whereby neural oscillations in thalamocortical, but not cerebellar circuits can be influenced by movement and/or behavioural tremor amplitude in the harmaline model.
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Nicoletti, Valentina, Paolo Cecchi, Ilaria Pesaresi, Daniela Frosini, Mirco Cosottini et Roberto Ceravolo. « Cerebello-thalamo-cortical network is intrinsically altered in essential tremor : evidence from a resting state functional MRI study ». Scientific Reports 10, no 1 (7 octobre 2020). http://dx.doi.org/10.1038/s41598-020-73714-9.
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Abstract Cerebello-thalamo-cortical network is suggested to be involved in the pathophysiology of Essential Tremor (ET). 23 patients with ET and 23 matched HC underwent a 3T-MRI with acquisition of a resting state sequence. Connectivity was investigated using a seed-based regression analyses approach. In ET patients were observed: Reduced connectivity between left primary motor cortex (M1) seed and right premotor cortex and cerebellum and bilateral premotor, parietal areas, supplementary motor area (SMA); Increased connectivity between left somatosensory cortex (S1) seed and parietal areas, M1, premotor cortex, SMA; reduced connectivity of this seed with cerebellum. Increased connectivity of SMA seed with premotor cortex and decreased with parietal and precentral areas; Increased connectivity between left thalamus seed and cerebellum; Reduced connectivity between right cerebellum seeds and other cerebellar areas, precentral and premotor areas. ET showed altered connectivity within the cortical sensory-motor network and between cerebral cortex and cerebellum. The increased connectivity between cerebellum and thalamus is consistent with their crucial role in tremor generation. These findings support the dynamical entrainment of multiple central oscillators throughout the cerebello-thalamo-cortical network in ET. This evidence is strengthened by the finding that this network is altered also when the core symptom is absent.
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Radhakrishnan, Vineeth, Cecile Gallea, Romain Valabregue, Syam Krishnan, Chandrasekharan Kesavadas, Bejoy Thomas, Praveen James, Ramshekhar Menon et Asha Kishore. « Cerebellar and basal ganglia structural connections in humans : Effect of aging and relation with memory and learning ». Frontiers in Aging Neuroscience 15 (26 janvier 2023). http://dx.doi.org/10.3389/fnagi.2023.1019239.
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IntroductionThe cerebellum and basal ganglia were initially considered anatomically distinct regions, each connected via thalamic relays which project to the same cerebral cortical targets, such as the motor cortex. In the last two decades, transneuronal viral transport studies in non-human primates showed bidirectional connections between the cerebellum and basal ganglia at the subcortical level, without involving the cerebral cortical motor areas. These findings have significant implications for our understanding of neurodevelopmental and neurodegenerative diseases. While these subcortical connections were established in smaller studies on humans, their evolution with natural aging is less understood.MethodsIn this study, we validated and expanded the previous findings of the structural connectivity within the cerebellum-basal ganglia subcortical network, in a larger dataset of 64 subjects, across different age ranges. Tractography and fixel-based analysis were performed on the 3 T diffusion-weighted dataset using Mrtrix3 software, considering fiber density and cross-section as indicators of axonal integrity. Tractography of the well-established cerebello-thalamo-cortical tract was conducted as a control. We tested the relationship between the structural white matter integrity of these connections with aging and with the performance in different domains of Addenbrooke’s Cognitive Examination.ResultsTractography analysis isolated connections from the dentate nucleus to the contralateral putamen via the thalamus, and reciprocal tracts from the subthalamic nucleus to the contralateral cerebellar cortex via the pontine nuclei. Control tracts of cerebello-thalamo-cortical tracts were also isolated, including associative cerebello-prefrontal tracts. A negative linear relationship was found between the fiber density of both the ascending and descending cerebellum-basal ganglia tracts and age. Considering the cognitive assessments, the fiber density values of cerebello-thalamo-putaminal tracts correlated with the registration/learning domain scores. In addition, the fiber density values of cerebello-frontal and subthalamo-cerebellar (Crus II) tracts correlated with the cognitive assessment scores from the memory domain.ConclusionWe validated the structural connectivity within the cerebellum-basal ganglia reciprocal network, in a larger dataset of human subjects, across wider age range. The structural features of the subcortical cerebello-basal ganglia tracts in human subjects display age-related neurodegeneration. Individual morphological variability of cerebellar tracts to the striatum and prefrontal cortex was associated with different cognitive functions, suggesting a functional contribution of cerebellar tracts to cognitive decline with aging. This study offers new perspectives to consider the functional role of these pathways in motor learning and the pathophysiology of movement disorders involving the cerebellum and striatum.
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Zhu, Long, Hongxi Yin, Yanxin Wang, Wenming Yang, Ting Dong, Lei Xu, Zhifeng Hou et al. « Disrupted topological organization of the motor execution network in Wilson's disease ». Frontiers in Neurology 13 (21 novembre 2022). http://dx.doi.org/10.3389/fneur.2022.1029669.
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ObjectiveThere are a number of symptoms associated with Wilson's disease (WD), including motor function damage. The neuropathological mechanisms underlying motor impairments in WD are, however, little understood. In this study, we explored changes in the motor execution network topology in WD.MethodsWe conducted resting-state functional magnetic resonance imaging (fMRI) on 38 right-handed individuals, including 23 WD patients and 15 healthy controls of the same age. Based on graph theory, a motor execution network was constructed and analyzed. In this study, global, nodal, and edge topological properties of motor execution networks were compared.ResultsThe global topological organization of the motor execution network in the two groups did not differ significantly across groups. In the cerebellum, WD patients had a higher nodal degree. At the edge level, a cerebello-thalamo-striato-cortical circuit with altered functional connectivity strength in WD patients was observed. Specifically, the strength of the functional connections between the cerebellum and thalamus increased, whereas the cortical-thalamic, cortical-striatum and cortical-cerebellar connections exhibited a decrease in the strength of the functional connection.ConclusionThere is a disruption of the topology of the motor execution network in WD patients, which may be the potential basis for WD motor dysfunction and may provide important insights into neurobiological research related to WD motor dysfunction.
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Peng, Jiaxin, Jing Yang, Nannan Li, Du Lei, Junying Li, Liren Duan, Chaolan Chen et al. « Topologically Disrupted Gray Matter Networks in Drug-Naïve Essential Tremor Patients With Poor Sleep Quality ». Frontiers in Neurology 13 (26 avril 2022). http://dx.doi.org/10.3389/fneur.2022.834277.
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BackgroundSleep disturbances are widespread among patients with essential tremor (ET) and may have adverse effects on patients' quality of life. However, the pathophysiology underlying poor quality of sleep (QoS) in patients with ET remains unclear. Our study aimed to identify gray matter (GM) network alterations in the topological properties of structural MRI related to QoS in patients with ET.MethodWe enrolled 45 ET patients with poor QoS (SleET), 59 ET patients with normal QoS (NorET), and 66 healthy controls (HC), and they all underwent a three-dimensional T1-weighted MRI scan. We used a graph-theoretical approach to investigate the topological organization of GM morphological networks, and individual morphological brain networks were constructed according to the interregional similarity of GM volume distributions. Furthermore, we performed network-based statistics, and partial correlation analyses between topographic features and clinical characteristics were conducted.ResultsGlobal network organization was disrupted in patients with ET. Compared with the NorET group, the SleET group exhibited disrupted topological GM network organization with a shift toward randomization. Moreover, they showed altered nodal centralities in mainly the frontal, temporal, parietal, and cerebellar lobes. Morphological connection alterations within the default mode network (DMN), salience, and basal ganglia networks were observed in the SleET group and were generally more extensive than those in the NorET and HC groups. Alterations within the cerebello-thalamo-(cortical) network were only detected in the SleET group. The nodal degree of the left thalamus was negatively correlated with the Fahn-Tolosa-Marin Tremor Rating Scale score (r = −0.354, p =0.027).ConclusionOur findings suggest that potential complex interactions underlie tremor and sleep disruptions in patients with ET. Disruptions within the DMN and the cerebello-thalamo-(cortical) network may have a broader impact on sleep quality in patients with ET. Our results offer valuable insight into the neural mechanisms underlying poor QoS in patients with ET.
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Boscolo Galazzo, Ilaria, Francesca Magrinelli, Francesca Benedetta Pizzini, Silvia Francesca Storti, Federica Agosta, Massimo Filippi, Angela Marotta, Giancarlo Mansueto, Gloria Menegaz et Michele Tinazzi. « Voxel-based morphometry and task functional magnetic resonance imaging in essential tremor : evidence for a disrupted brain network ». Scientific Reports 10, no 1 (15 septembre 2020). http://dx.doi.org/10.1038/s41598-020-69514-w.
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Abstract The pathophysiology of essential tremor (ET) is controversial and might be further elucidated by advanced neuroimaging. Focusing on homogenous ET patients diagnosed according to the 2018 consensus criteria, this study aimed to: (1) investigate whether task functional MRI (fMRI) can identify networks of activated and deactivated brain areas, (2) characterize morphometric and functional modulations, relative to healthy controls (HC). Ten ET patients and ten HC underwent fMRI while performing two motor tasks with their upper limb: (1) maintaining a posture (both groups); (2) simulating tremor (HC only). Activations/deactivations were obtained from General Linear Model and compared across groups/tasks. Voxel-based morphometry and linear regressions between clinical and fMRI data were also performed. Few cerebellar clusters of gray matter loss were found in ET. Conversely, widespread fMRI alterations were shown. Tremor in ET (task 1) was associated with extensive deactivations mainly involving the cerebellum, sensory-motor cortex, and basal ganglia compared to both tasks in HC, and was negatively correlated with clinical tremor scales. Homogeneous ET patients demonstrated deactivation patterns during tasks triggering tremor, encompassing a network of cortical and subcortical regions. Our results point towards a marked cerebellar involvement in ET pathophysiology and the presence of an impaired cerebello-thalamo-cortical tremor network.
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Maleki, Nasim, Kayle S. Sawyer, Sarah Levy, Gordon J. Harris et Marlene Oscar-Berman. « Intrinsic brain functional connectivity patterns in alcohol use disorder ». Brain Communications, 4 novembre 2022. http://dx.doi.org/10.1093/braincomms/fcac290.
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Abstract Alcohol use disorder is associated with damaging effects to the brain. This study aimed to examine differences in static and dynamic intrinsic functional connectivity patterns in individuals with a history of alcohol use disorder in comparison to those with no history of alcohol abuse. A total of 55 participants consisting of 23 patients and 32 control individuals underwent neuropsychological assessments and resting-state functional magnetic resonance imaging on a 3 Tesla MRI scanner. Differences in functional connectivity between the two groups were determined using static and dynamic independent component analysis. Differences in static functional connectivity between the two groups were identified in the default mode network, attention network, frontoparietal network, frontal cortical network, and cerebellar network. Furthermore, the analyses revealed specific differences in the dynamic temporal characteristics of functional connectivity between the two groups of participants, in a cluster involving key regions in reward, sensorimotor, and frontal cortical functional networks, with some connections correlating with the length of sobriety and some others with the severity of drinking. The findings altogether suggest dysregulation in the intrinsic connectivity of cortico-basal ganglia-thalamo-cortical loops that may reflect persistent alcohol use disorder-related network abnormalities, compensatory recovery-related processes whereby additional neural resources are recruited to achieve normal levels of performance, or a predisposition toward developing alcohol use disorder.
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Loens, Sebastian, Julius Verrel, Vera-Maria Herrmann, Amrei Kienzle, Elinor Tzvi, Anne Weissbach, Johanna Junker, Alexander Münchau et Tobias Bäumer. « Motor learning deficits in cervical dystonia point to defective basal ganglia circuitry ». Scientific Reports 11, no 1 (1 avril 2021). http://dx.doi.org/10.1038/s41598-021-86513-7.
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AbstractDystonia is conceptualized as a network disorder involving basal ganglia, thalamus, sensorimotor cortex and the cerebellum. The cerebellum has been implicated in dystonia pathophysiology, but studies testing cerebellar function in dystonia patients have provided equivocal results. This study aimed to further elucidate motor network deficits in cervical dystonia with special interest in the role of the cerebellum. To this end we investigated motor learning tasks, that differ in their dependence on cerebellar and basal ganglia functioning. In 18 cervical dystonia patients and 18 age matched healthy controls we measured implicit motor sequence learning using a 12-item serial reaction time task mostly targeting basal ganglia circuitry and motor adaptation and eyeblink conditioning as markers of cerebellar functioning. ANOVA showed that motor sequence learning was overall impaired in cervical dystonia (p = 0.01). Moreover, unlike healthy controls, patients did not show a learning effect in the first part of the experiment. Visuomotor adaptation and eyeblink conditioning were normal. In conclusion, these data lend support to the notion that motor learning deficits in cervical dystonia relate to basal ganglia-thalamo-cortical loops rather than being a result of defective cerebellar circuitry.
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Metoki, Athanasia, Yin Wang et Ingrid R. Olson. « The Social Cerebellum : A Large-Scale Investigation of Functional and Structural Specificity and Connectivity ». Cerebral Cortex, 25 août 2021. http://dx.doi.org/10.1093/cercor/bhab260.
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Abstract The cerebellum has been traditionally disregarded in relation to nonmotor functions, but recent findings indicate it may be involved in language, affective processing, and social functions. Mentalizing, or Theory of Mind (ToM), is the ability to infer mental states of others and this skill relies on a distributed network of brain regions. Here, we leveraged large-scale multimodal neuroimaging data to elucidate the structural and functional role of the cerebellum in mentalizing. We used functional activations to determine whether the cerebellum has a domain-general or domain-specific functional role, and effective connectivity and probabilistic tractography to map the cerebello-cerebral mentalizing network. We found that the cerebellum is organized in a domain-specific way and that there is a left cerebellar effective and structural lateralization, with more and stronger effective connections from the left cerebellar hemisphere to the right cerebral mentalizing areas, and greater cerebello-thalamo-cortical and cortico-ponto-cerebellar streamline counts from and to the left cerebellum. Our study provides novel insights to the network organization of the cerebellum, an overlooked brain structure, and mentalizing, one of humans’ most essential abilities to navigate the social world.
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Zwir, I., C. Del-Val, M. Hintsanen, K. M. Cloninger, R. Romero-Zaliz, A. Mesa, J. Arnedo et al. « Evolution of genetic networks for human creativity ». Molecular Psychiatry, 21 avril 2021. http://dx.doi.org/10.1038/s41380-021-01097-y.
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AbstractThe genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and chimpanzees in their numbers of genes for both self-control and self-awareness. 95% of the 267 genes we found only in modern humans were not protein-coding, including many long-non-coding RNAs in the self-awareness network. These genes may have arisen by positive selection for the characteristics of human well-being and behavioral modernity, including creativity, prosocial behavior, and healthy longevity. The genes that cluster in association with those found only in modern humans are over-expressed in brain regions involved in human self-awareness and creativity, including late-myelinating and phylogenetically recent regions of neocortex for autobiographical memory in frontal, parietal, and temporal regions, as well as related components of cortico-thalamo-ponto-cerebellar-cortical and cortico-striato-cortical loops. We conclude that modern humans have more than 200 unique non-protein-coding genes regulating co-expression of many more protein-coding genes in coordinated networks that underlie their capacities for self-awareness, creativity, prosocial behavior, and healthy longevity, which are not found in chimpanzees or Neanderthals.
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Grami, F., G. de Marco, F. Bodranghien, M. Manto et C. Habas. « Cerebellar transcranial direct current stimulation reconfigurates static and dynamic functional connectivity of the resting-state networks ». Cerebellum & ; Ataxias 8, no 1 (24 février 2021). http://dx.doi.org/10.1186/s40673-021-00132-6.
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Abstract Background Transcranial direct current stimulation (tDCS) of the cerebellum dynamically modulates cerebello-thalamo-cortical excitability in a polarity-specific manner during motor, visuo- motor and cognitive tasks. It remains to be established whether tDCS of the cerebellum impact also on resting-state intrinsically connected networks (ICNs). Such impact would open novel research and therapeutical doors for the neuromodulation of ICNs in human. Method We combined tDCS applied over the right cerebellum and fMRI to investigate tDCS- induced resting-state intrinsic functional reconfiguration, using a randomized, sham-controlled design. fMRI data were recorded both before and after real anodal stimulation (2 mA, 20 min) or sham tDCS in 12 right-handed healthy volunteers. We resorted to a region-of-interest static correlational analysis and to a sliding window analysis to assess temporal variations in resting state FC between the cerebellar lobule VII and nodes of the main ICNs. Results After real tDCS and compared with sham tDCS, functional changes were observed between the cerebellum and ICNs. Static FC showed enhanced or decreased correlation between cerebellum and brain areas belonging to visual, default-mode (DMN), sensorimotor and salience networks (SN) (p-corrected < 0.05). The temporal variability (TV) of BOLD signal was significantly modified after tDCS displaying in particular a lesser TV between the whole lobule VII and DMN and central executive network and a greater TV between crus 2 and SN. Static and dynamic FC was also modified between cerebellar lobuli. Conclusion These results demonstrate short- and long-range static and majorly dynamic effects of tDCS stimulation of the cerebellum affecting distinct resting-state ICNs, as well as intracerebellar functional connectivity, so that tDCS of the cerebellum appears as a non-invasive tool reconfigurating the dynamics of ICNs.
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Kato, Sachiko, Satoshi Maesawa, Epifanio Bagarinao, Daisuke Nakatsubo, Takahiko Tsugawa, Satomi Mizuno, Kazuya Kawabata et al. « Magnetic resonance–guided focused ultrasound thalamotomy restored distinctive resting-state networks in patients with essential tremor ». Journal of Neurosurgery, 1 juillet 2022, 1–12. http://dx.doi.org/10.3171/2022.5.jns22411.
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OBJECTIVE Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy ameliorates symptoms in patients with essential tremor (ET). How this treatment affects canonical brain networks has not been elucidated. The purpose of this study was to clarify changes of brain networks after MRgFUS thalamotomy in ET patients by analyzing resting-state networks (RSNs). METHODS Fifteen patients with ET were included in this study. Left MRgFUS thalamotomy was performed in all cases, and MR images, including resting-state functional MRI (rsfMRI), were taken before and after surgery. MR images of 15 age- and sex-matched healthy controls (HCs) were also used for analysis. Using rsfMRI data, canonical RSNs were extracted by performing dual regression analysis, and the functional connectivity (FC) within respective networks was compared among pre-MRgFUS patients, post-MRgFUS patients, and HCs. The severity of tremor was evaluated using the Clinical Rating Scale for Tremor (CRST) score pre- and postoperatively, and its correlation with RSNs was examined. RESULTS Preoperatively, ET patients showed a significant decrease in FC in the sensorimotor network (SMN), primary visual network (VN), and visuospatial network (VSN) compared with HCs. The decrease in FC in the SMN correlated with the severity of tremor. After MRgFUS thalamotomy, ET patients still exhibited a significant decrease in FC in a small area of the SMN, but they exhibited an increase in the cerebellar network (CN). In comparison between pre- and post-MRgFUS patients, the FC in the SMN and the VSN significantly increased after treatment. Quantitative evaluation of the FCs in these three groups showed that the SMN and VSN increased postoperatively and demonstrated a trend toward those of HCs. CONCLUSIONS The SMN and CN, which are considered to be associated with the cerebello-thalamo-cortical loop, exhibited increased connectivity after MRgFUS thalamotomy. In addition, the FC of the visual network, which declined in ET patients compared with HCs, tended to normalize postoperatively. This could be related to the hypothesis that visual feedback is involved in tremor severity in ET patients. Overall, the analysis of the RSNs by rsfMRI reflected the pathophysiology with the intervention of MRgFUS thalamotomy in ET patients and demonstrated a possibility of a biomarker for successful treatment.
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Wu, Chengyuan, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo et Harith Akram. « Distributed Global Functional Connectivity Networks Predict Responsiveness to L-DOPA and Subthalamic Deep Brain Stimulation ». Neurosurgery 66, Supplement_1 (20 août 2019). http://dx.doi.org/10.1093/neuros/nyz310_147.
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Abstract INTRODUCTION Brain circuit dysfunction in Parkinson's disease (PD) involves an extensive global network. A distinctive basal ganglia resting-state functional connectivity (rsFC) pattern has been linked with the ranked response to L-DOPA. We therefore sought to investigate global rsFC patterns associated with response to L-DOPA and to subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced PD. METHODS A total of 19 patients underwent 3-Tesla resting-state functional magnetic resonance imaging (rsfMRI) in the ON-medication state prior to STN DBS. Improvement in UPDRS-III hemibody scores were assessed following L-DOPA therapy and STN DBS. Global rsFC was measured between regions-of-interest (ROIs) defined by the Automated Anatomical Labeling (AAL) atlas and the Montreal Neurologic Institute (MNI) PD25 subcortical atlas. Seed- and network-level correlations were made with an FDR-P < .005. Graph theoretical analysis was performed with an analysis threshold of FDR-P < .005; and then looking at the top 15% of edges. RESULTS Response to L-DOPA and to DBS displayed cerebellar desynchronization with bilateral thalami and synchronization with bilateral ventromedial prefrontal cortices (vmPFC). L-DOPA response was additionally associated with desynchronization between the vmPFC and the fusiform gyrus. Meanwhile, DBS response was associated with more widespread areas, which have been implicated in visuomotor control and planning. Graph theory analysis revealed that DBS response was inversely related to global efficiency of the thalamus and putamen bilaterally. No significant graph metrics were found relative to L-DOPA response. CONCLUSION Response to DBS and to L-DOPA share similar characteristics, particularly in cerebello-thalamo-cortical circuits, including those that play a role in planning, learning, decision-making, and reward-based behavior. Preservation of distributed networks involved in visuomotor control and network integration of striatothalamocortical circuits appear to predict DBS response. These findings shed a light on the mechanism of action of DBS and L-DOPA and may help serve as useful treatment response biomarkers.
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Klingbeil, Julian, Max Wawrzyniak, Anika Stockert, Max-Lennart Brandt, Hans-Ralf Schneider, Moritz Metelmann et Dorothee Saur. « Pathological laughter and crying : insights from lesion network-symptom-mapping ». Brain, 17 juin 2021. http://dx.doi.org/10.1093/brain/awab224.
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Abstract The study of pathological laughter and crying (PLC) allows insights into the neural basis of laughter and crying, two hallmarks of human nature. PLC is defined by brief, intense and frequent episodes of uncontrollable laughter or crying provoked by trivial stimuli. It occurs secondary to CNS disorders such as stroke, tumours or neurodegenerative diseases. Based on case studies reporting various lesions locations, PLC has been conceptualized as dysfunction in a cortico-limbic-subcortico-thalamo-ponto-cerebellar network. To test whether the heterogeneous lesion locations are indeed linked in a common network, we applied ‘lesion network-symptom-mapping’ (LNSM) to 70 focal lesions identified in a systematic literature search for case reports of PLC. In LNSM normative connectome data (resting state functional MRI, n = 100) is used to identify the brain regions which are likely affected by diaschisis based on the lesion locations. With LNSM we were able to identify a common network specific for PLC when compared with a control cohort (n = 270). This bilateral network is characterized by positive connectivity to the cingulate and temporomesial cortices, striatum, hypothalamus, mesencephalon and pons and negative connectivity to the primary motor and sensory cortices. In the most influential pathophysiological model of PLC, a center for the control and coordination of facial expressions, respiration and vocalization in the periaqueductal grey is assumed which is controlled via two pathways: an emotional system that exerts excitatory control of the periaqueductal grey descending from the temporal and frontal lobes, basal ganglia and hypothalamus and a volitional system descending from the lateral premotor cortices which can suppress laughter or crying. To test whether the positive and negative PLC subnetworks identified in our analyses can indeed be related to an emotional system and a volitional system, we identified lesions causing emotional (n = 15) or volitional facial paresis (n = 46) in a second literature search. Patients with emotional facial paresis show preserved volitional movements but cannot trigger emotional movements in the affected hemiface, while the reverse is true for volitional facial paresis. Importantly, these lesions map differentially onto the PLC subnetworks: the ‘positive PLC subnetwork’ is part of the emotional system and the ‘negative PLC subnetwork’ overlaps with the volitional system for the control of facial movements. Based on this network analysis we propose a two-hit model of PLC: a combination of direct lesion and indirect diaschisis effects cause PLC through the loss of inhibitory cortical control of a dysfunctional emotional system.
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Pidoux, Ludivine, Pascale Le Blanc, Carole Levenes et Arthur Leblois. « A subcortical circuit linking the cerebellum to the basal ganglia engaged in vocal learning ». eLife 7 (25 juillet 2018). http://dx.doi.org/10.7554/elife.32167.
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Speech is a complex sensorimotor skill, and vocal learning involves both the basal ganglia and the cerebellum. These subcortical structures interact indirectly through their respective loops with thalamo-cortical and brainstem networks, and directly via subcortical pathways, but the role of their interaction during sensorimotor learning remains undetermined. While songbirds and their song-dedicated basal ganglia-thalamo-cortical circuitry offer a unique opportunity to study subcortical circuits involved in vocal learning, the cerebellar contribution to avian song learning remains unknown. We demonstrate that the cerebellum provides a strong input to the song-related basal ganglia nucleus in zebra finches. Cerebellar signals are transmitted to the basal ganglia via a disynaptic connection through the thalamus and then conveyed to their cortical target and to the premotor nucleus controlling song production. Finally, cerebellar lesions impair juvenile song learning, opening new opportunities to investigate how subcortical interactions between the cerebellum and basal ganglia contribute to sensorimotor learning.
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Bernard, Jessica A., Hannah K. Ballard et Trevor Bryan Jackson. « Cerebellar Dentate Connectivity across Adulthood : A Large-Scale Resting State Functional Connectivity Investigation ». Cerebral Cortex Communications 2, no 3 (1 janvier 2021). http://dx.doi.org/10.1093/texcom/tgab050.
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Abstract Cerebellar contributions to behavior in advanced age are of interest and importance, given its role in motor and cognitive performance. There are differences and declines in cerebellar structure in advanced age and cerebellar resting state connectivity is lower. However, the work on this area to date has focused on the cerebellar cortex. The deep cerebellar nuclei provide the primary cerebellar inputs and outputs to the cortex, as well as the spinal and vestibular systems. Dentate networks can be dissociated such that the dorsal region is associated with the motor cortex, whereas the ventral aspect is associated with the prefrontal cortex. However, whether dentato-thalamo-cortical networks differ across adulthood remains unknown. Here, using a large adult sample (n = 590) from the Cambridge Center for Ageing and Neuroscience, we investigated dentate connectivity across adulthood. We replicated past work showing dissociable resting state networks in the dorsal and ventral aspects of the dentate. In both seeds, we demonstrated that connectivity is lower with advanced age, indicating that connectivity differences extend beyond the cerebellar cortex. Finally, we demonstrated sex differences in dentate connectivity. This expands our understanding of cerebellar circuitry in advanced age and underscores the potential importance of this structure in age-related performance differences.
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Tarrés-Gatius, Mireia, Lluís Miquel-Rio, Leticia Campa, Francesc Artigas et Anna Castañé. « Involvement of NMDA receptors containing the GluN2C subunit in the psychotomimetic and antidepressant-like effects of ketamine ». Translational Psychiatry 10, no 1 (décembre 2020). http://dx.doi.org/10.1038/s41398-020-01110-y.
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AbstractAcute ketamine administration evokes rapid and sustained antidepressant effects in treatment-resistant patients. However, ketamine also produces transient perceptual disturbances similarly to those evoked by other non-competitive NMDA-R antagonists like phencyclidine (PCP). Although the brain networks involved in both ketamine actions are not fully understood, PCP and ketamine activate thalamo-cortical networks after NMDA-R blockade in GABAergic neurons of the reticular thalamic nucleus (RtN). Given the involvement of thalamo-cortical networks in processing sensory information, these networks may underlie psychotomimetic action. Since the GluN2C subunit is densely expressed in the thalamus, including the RtN, we examined the dependence of psychotomimetic and antidepressant-like actions of ketamine on the presence of GluN2C subunits, using wild-type and GluN2C knockout (GluN2CKO) mice. Likewise, since few studies have investigated ketamine’s effects in females, we used mice of both sexes. GluN2C deletion dramatically reduced stereotyped (circling) behavior induced by ketamine in male and female mice, while the antidepressant-like effect was fully preserved in both genotypes and sexes. Despite ketamine appeared to induce similar effects in both sexes, some neurobiological differences were observed between male and female mice regarding c-fos expression in thalamic nuclei and cerebellum, and glutamate surge in prefrontal cortex. In conclusion, the GluN2C subunit may discriminate between antidepressant-like and psychotomimetic actions of ketamine. Further, the abundant presence of GluN2C subunits in the cerebellum and the improved motor coordination of GluN2CKO mice after ketamine treatment suggest the involvement of cerebellar NMDA-Rs in some behavioral actions of ketamine.
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Korostil, Michele, Gary Remington et Anthony Randal McIntosh. « Practice and Learning : Spatiotemporal Differences in Thalamo-Cortical-Cerebellar Networks Engagement across Learning Phases in Schizophrenia ». Frontiers in Psychiatry 7 (23 janvier 2017). http://dx.doi.org/10.3389/fpsyt.2016.00212.
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Anteraper, Sheeba, Xavier Guell et Susan Whitfield-Gabrieli. « Big contributions of the little brain for precision psychiatry ». Frontiers in Psychiatry 13 (17 octobre 2022). http://dx.doi.org/10.3389/fpsyt.2022.1021873.
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Our previous work using 3T functional Magnetic Resonance Imaging (fMRI) parcellated the human dentate nuclei (DN), the primary output of the cerebellum, to three distinct functional zones each contributing uniquely to default-mode, salience-motor, and visual brain networks. In this perspective piece, we highlight the possibility to target specific functional territories within the cerebellum using non-invasive brain stimulation, potentially leading to the refinement of cerebellar-based therapeutics for precision psychiatry. Significant knowledge gap exists in our functional understanding of cerebellar systems. Intervening early, gauging severity of illness, developing intervention strategies and assessing treatment response, are all dependent on our understanding of the cerebello-cerebral networks underlying the pathology of psychotic disorders. A promising yet under-examined avenue for biomarker discovery is disruptions in cerebellar output circuitry. This is primarily because most 3T MRI studies in the past had to exclude cerebellum from the field of view due to limitations in spatiotemporal resolutions. Using recent technological advances in 7T MRI (e.g., parallel transmit head coils) to identify functional territories of the DN, with a focus on dentato-cerebello-thalamo-cortical (CTC) circuitry can lead to better characterization of brain-behavioral correlations and assessments of co-morbidities. Such an improved mechanistic understanding of psychiatric illnesses can reveal aspects of CTC circuitry that can aid in neuroprognosis, identification of subtypes, and generate testable hypothesis for future studies.
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Wu, Yunhao, Chao Zhang, Yufei Li, Jie Feng, Ming Zhang, Hongxia Li, Tao Wang et al. « Imaging Insights of Isolated Idiopathic Dystonia : Voxel-Based Morphometry and Activation Likelihood Estimation Studies ». Frontiers in Neurology 13 (26 avril 2022). http://dx.doi.org/10.3389/fneur.2022.823882.
Texte intégralRésumé :
The understanding of brain structural abnormalities across different clinical forms of dystonia and their contribution to clinical characteristics remains unclear. The objective of this study is to investigate shared and specific gray matter volume (GMV) abnormalities in various forms of isolated idiopathic dystonia. We collected imaging data from 73 isolated idiopathic dystonia patients and matched them with healthy controls to explore the GMV alterations in patients and their correlations with clinical characteristics using the voxel-based morphometry (VBM) technique. In addition, we conducted an activation likelihood estimation (ALE) meta-analysis of previous VBM studies. Our study demonstrated widespread morphometry alterations in patients with idiopathic dystonia. Multiple systems were affected, which mainly included basal ganglia, sensorimotor, executive control, and visual networks. As the result of the ALE meta-analysis, a convergent cluster with increased GMV was found in the left globus pallidus. In subgroup VBM analyses, decreased putamen GMV was observed in all clinic forms, while the increased GMV was observed in parahippocampal, lingual, and temporal gyrus. GD demonstrated the most extensive GMV abnormalities in cortical regions, and the aberrant GMV of the posterior cerebellar lobe was prominent in CD. Moreover, trends of increased GMV regions of the left precuneus and right superior frontal gyrus were demonstrated in the moderate-outcome group compared with the superior-outcome group. Results of our study indicated shared pathophysiology of the disease-centered on the dysfunction of the basal ganglia-thalamo-cortical circuit, impairing sensorimotor integration, high-level motor execution, and cognition of patients. Dysfunction of the cerebello-thalamo-cortical circuit could also be involved in CD especially. Finally, the frontal-parietal pathway may act as a potential marker for predicting treatment outcomes such as deep brain stimulation.
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Wu, Yunhao, Chao Zhang, Yufei Li, Jie Feng, Ming Zhang, Hongxia Li, Tao Wang et al. « Imaging Insights of Isolated Idiopathic Dystonia : Voxel-Based Morphometry and Activation Likelihood Estimation Studies ». Frontiers in Neurology 13 (26 avril 2022). http://dx.doi.org/10.3389/fneur.2022.823882.
Texte intégralRésumé :
The understanding of brain structural abnormalities across different clinical forms of dystonia and their contribution to clinical characteristics remains unclear. The objective of this study is to investigate shared and specific gray matter volume (GMV) abnormalities in various forms of isolated idiopathic dystonia. We collected imaging data from 73 isolated idiopathic dystonia patients and matched them with healthy controls to explore the GMV alterations in patients and their correlations with clinical characteristics using the voxel-based morphometry (VBM) technique. In addition, we conducted an activation likelihood estimation (ALE) meta-analysis of previous VBM studies. Our study demonstrated widespread morphometry alterations in patients with idiopathic dystonia. Multiple systems were affected, which mainly included basal ganglia, sensorimotor, executive control, and visual networks. As the result of the ALE meta-analysis, a convergent cluster with increased GMV was found in the left globus pallidus. In subgroup VBM analyses, decreased putamen GMV was observed in all clinic forms, while the increased GMV was observed in parahippocampal, lingual, and temporal gyrus. GD demonstrated the most extensive GMV abnormalities in cortical regions, and the aberrant GMV of the posterior cerebellar lobe was prominent in CD. Moreover, trends of increased GMV regions of the left precuneus and right superior frontal gyrus were demonstrated in the moderate-outcome group compared with the superior-outcome group. Results of our study indicated shared pathophysiology of the disease-centered on the dysfunction of the basal ganglia-thalamo-cortical circuit, impairing sensorimotor integration, high-level motor execution, and cognition of patients. Dysfunction of the cerebello-thalamo-cortical circuit could also be involved in CD especially. Finally, the frontal-parietal pathway may act as a potential marker for predicting treatment outcomes such as deep brain stimulation.