Project description:Dystonia involves sustained or repetitive muscle contractions, affects different skeletal muscles, and may be associated with tremor. Few studies have investigated if cortical pathophysiology is impaired even when dystonic muscles are not directly engaged and during the presence of dystonic tremor (DT). Here, we recorded high-density electroencephalography and time-locked behavioral data in 2 cohorts of patients and controls during the performance of head movements, upper limb movements, and grip force. Patients with cervical dystonia had reduced movement-related desynchronization in the alpha and beta bands in the bilateral sensorimotor cortex during head turning movements, produced by dystonic muscles. Reduced desynchronization in the upper beta band in the ipsilateral motor and bilateral sensorimotor cortex was found during upper limb planar movements, produced by non-dystonic muscles. In a precision grip task, patients with DT had reduced movement-related desynchronization in the alpha and beta bands in the bilateral sensorimotor cortex. We observed a general pattern of abnormal sensorimotor cortical desynchronization that was present across the head and upper limb motor tasks, in patients with and without DT when compared with controls. Our findings suggest that abnormal cortical desynchronization is a general feature of dystonia that should be a target of pharmacological and other therapeutic interventions.
Project description:ObjectiveTo investigate the performance of structural MRI cortical and subcortical morphometric data combined with blink-reflex recovery cycle (BRrc) values using machine learning (ML) models in distinguishing between essential tremor (ET) with resting tremor (rET) and classic ET.MethodsWe enrolled 47 ET, 43 rET patients and 45 healthy controls (HC). All participants underwent brain 3 T-MRI and BRrc examination at different interstimulus intervals (ISIs, 100-300 msec). MRI data (cortical thickness, volumes, surface area, roughness, mean curvature and subcortical volumes) were extracted using Freesurfer on T1-weighted images. We employed two decision tree-based ML classification algorithms (eXtreme Gradient Boosting [XGBoost] and Random Forest) combining MRI data and BRrc values to differentiate between rET and ET patients.ResultsML models based exclusively on MRI features reached acceptable performance (AUC: 0.85-0.86) in differentiating rET from ET patients and from HC. Similar performances were obtained by ML models based on BRrc data (AUC: 0.81-0.82 in rET vs. ET and AUC: 0.88-0.89 in rET vs. HC). ML models combining imaging data (cortical thickness, surface, roughness, and mean curvature) together with BRrc values showed the highest classification performance in distinguishing between rET and ET patients, reaching AUC of 0.94 ± 0.05. The improvement in classification performances when BRrc data were added to imaging features was confirmed by both ML algorithms.ConclusionThis study highlights the usefulness of adding a simple electrophysiological assessment such as BRrc to MRI cortical morphometric features for accurately distinguishing rET from ET patients, paving the way for a better classification of these ET syndromes.
Project description:Essential tremor (ET) presumably has a cerebellar origin. Imaging studies showed various cerebellar and also cortical structural changes. A number of pathology studies indicated cerebellar Purkinje cell pathology. ET is a heterogeneous disorder, possibly indicating different underlying disease mechanisms. Familial cortical myoclonic tremor with epilepsy (FCMTE), with evident Purkinje cell degeneration, can be an ET mimic. Here, we investigate whole brain and, more specifically, cerebellar morphological changes in hereditary ET, FCMTE, and healthy controls. Anatomical magnetic resonance images were preprocessed using voxel-based morphometry. Study 1 included voxel-wise comparisons of 36 familial, propranolol-sensitive ET patients, with subgroup analysis on age at onset and head tremor, and 30 healthy controls. Study 2 included voxel-wise comparisons in another nine ET patients, eight FCMTE patients, and nine healthy controls. Study 3 compared total cerebellar volume between 45 ET patients, 8 FCTME patients, and 39 controls. In our large sample of selected hereditary ET patients and ET subgroups, no local atrophy was observed compared to healthy controls or FCMTE. In ET patients with head tremor, a volume increase in cortical motor regions was observed. In FCMTE, a decrease in total cerebellar volume and in local cerebellar gray matter was observed compared to healthy controls and ET patients. The current study did not find local atrophy, specifically not in the cerebellum in hereditary ET, contrary to FCMTE. Volume increase of cortical motor areas in ET patients with head tremor might suggest cortical plasticity changes due to continuous involuntary head movements.
Project description:IntroductionTremor is a common side effect of treatment with lithium. Its characteristics can vary and when less rhythmical, distinction from myoclonus can be difficult.MethodsWe identified 8 patients on long-term treatment with lithium that developed upper limb tremor. All patients were assessed clinically and electrophysiologically, with jerk-locked averaging (JLA) and cross-correlation (CC) analysis, and five of them underwent brain MRI examination including spectroscopy (MRS) of the cerebellum.ResultsSeven patients (6 female) had action and postural myoclonus and one a regular postural and kinetic tremor that persisted at rest. Mean age at presentation was 58 years (range 42-77) after lengthy exposure to lithium (range 7-40 years). During routine monitoring all patients had lithium levels within the recommended therapeutic range (0.4-1 mmol/l). There was clinical and/or radiological evidence (on cerebellar MRS) of cerebellar dysfunction in 6 patients. JLA and/or CC suggested a cortical generator of the myoclonus in seven patients. All seven were on antidepressants and three additionally on neuroleptics, four of them had gluten sensitivity and two reported alcohol abuse.ConclusionsA synergistic effect of different factors appears to be contributing to the development of cortical myoclonus after chronic exposure to lithium. We hypothesise that the cerebellum is involved in the generation of cortical myoclonus in these cases and factors aetiologically linked to cerebellar pathology like gluten sensitivity and alcohol abuse may play a role in the development of myoclonus. Despite the very limited evidence in the literature, lithium induced cortical myoclonus may not be so rare.
Project description:Globally, stroke is a leading cause of death and disability. Traditional risk factors like hypertension, diabetes, and obesity do not fully account for all stroke cases. Recent infection is regarded as changes in systemic immune signaling, which can increase thrombosis formation and other stroke risk factors. We have previously shown that administration of lipopolysaccharide (LPS) 30-minutes prior to stroke increases in infarct volume. In the current study, we found that animals intermittently exposed to LPS have larger cortical infarcts when compared to saline controls. To elucidate the mechanism behind this phenomenon, several avenues were investigated. We observed significant upregulation of tumor necrosis factor-alpha (TNF-α) mRNA, especially in the ipsilateral hemisphere of both saline and LPS exposed groups compared to sham surgery animals. We also observed significant reductions in expression of genes involved in autophagy in the ipsilateral hemisphere of LPS stroke animals. In addition, we assessed DNA methylation of autophagy genes and observed a significant increase in the ipsilateral hemisphere of LPS stroke animals. Intermittent exposure to LPS increases cortical infarct volume, downregulates autophagy genes, and induces hypermethylation of the corresponding CpG islands. These data suggest that intermittent immune activation may deregulate epigenetic mechanisms and promote neuropathological outcomes after stroke.
Project description:The prevalence of subcortical white matter strokes in elderly patients is on the rise, but these patients show mixed responses to conventional rehabilitative interventions. To examine whether cortical electrical stimulation can promote motor recovery after white matter stroke, we delivered stimulation to a small or wide region of sensory-parietal cortex for two weeks in a rodent model of circumscribed subcortical capsular infarct. The sham-operated group (SOG) showed persistent and severe motor impairments together with decreased activation in bilateral sensorimotor cortices and striatum. In contrast, sensory-parietal cortex stimulation significantly improved motor recovery: final recovery levels were 72.9% of prelesion levels in the wide stimulation group (WSG) and 37% of prelesion levels in the small stimulation group (SSG). The microPET imaging showed reversal of cortical diaschisis in both groups: in both hemispheres for the WSG, and in the hemisphere ipsilateral to stimulation in the SSG. In addition, we observed activation of the corpus callosum and subcortical corticostriatal structures after stimulation. The results from the c-Fos mapping study were grossly consistent with the microPET imaging. Sensory-parietal cortex stimulation may therefore be a useful strategy for overcoming the limits of rehabilitative training in patients with severe forms of subcortical capsular infarct.
Project description:High-intensity Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a recent, non-invasive line of treatment for medication-resistant tremor. We used MRgFUS to produce small lesions in the thalamic ventral intermediate nucleus (VIM), an important node in the cerebello-thalamo-cortical tremor network, in 13 patients with tremor-dominant Parkinson's disease or essential tremor. Significant tremor alleviation in the target hand ensued (t(12) = 7.21, p < 0.001, two-tailed), which was strongly associated with the functional reorganization of the brain's hand region with the cerebellum (r = 0.91, p < 0.001, one-tailed). This reorganization potentially reflected a process of normalization, as there was a trend of increase in similarity between the hand cerebellar connectivity of the patients and that of a matched, healthy control group (n = 48) after treatment. Control regions in the ventral attention, dorsal attention, default, and frontoparietal networks, in comparison, exhibited no association with tremor alleviation and no normalization. More broadly, changes in functional connectivity were observed in regions belonging to the motor, limbic, visual, and dorsal attention networks, largely overlapping with regions connected to the lesion targets. Our results indicate that MRgFUS is a highly efficient treatment for tremor, and that lesioning the VIM may result in the reorganization of the cerebello-thalamo-cortical tremor network.