Cerebellar Pathways Research Articles

Cerebellar Mutism after posterior fossa tumor surgery: is it predictable, preventable, treatable?

Introduction: Posterior fossa tumors pose challenges in pediatric neurosurgery and can lead to complications such as cerebellar mutism, affecting speech and motor abilities. This study aims to describe the evolution of cerebellar mutism and identify relevant factors in its pathophysiology and prognosis. Methods: A review was conducted on three cases of children who underwent surgery for posterior fossa tumors by the same surgical team and developed postoperative cerebellar mutism. The study analyzed preoperative clinical presentation, mutism manifestation, and recovery. Additionally, a literature review was performed on the emergence, evolution, and prognosis. Results: Case 1 involved a 3-year-old girl with medulloblastoma who experienced mutism, behavioral changes, and self-mutilation after surgery. Symptoms resolved after one month but recurred with a subsequent operation, resolving again after a month. Case 2 featured a 15-year-old girl who developed severe posterior fossa syndrome, including mutism, dysarthria, aphasia, and motor impairments. With support care, she gradually improved over a year. Case 3 involved a 4-year-old boy with cerebral palsy and a posterior fossa tumor. He experienced akinetic mutism, resolved over time with rehabilitation therapies. Discussion: Cerebellar mutism following posterior fossa surgery has implications for patient recovery. It primarily involves impairment of cerebellar outflow pathways rather than direct brainstem or cortical lesions. Identifying at-risk patients remains challenging, though younger age and specific tumor characteristics may increase the likelihood of mutism. Rehabilitation, including physical and speech therapies, plays a crucial role in promoting recovery. Effective communication and support for patients and their families are essential during the recovery process.

Cerebellar deep brain stimulation for the treatment of movement disorders in cerebral palsy.

Cerebral palsy (CP) represents the most common childhood physical disability that encompasses disorders of movement and posture attributed to nonprogressive disturbances that occurred in the developmental fetal or infant brain. Dyskinetic CP (DCP), the second most common type of CP after spastic forms, refers to a subset of patients in whom dystonia and choreoathetosis are the predominant motor manifestations. Most children with CP have abnormal brain MRI studies indicative of cortical and deep gray matter damage consistent with hypoxic ischemic encephalopathy, which may preclude or suggest decreased efficacy of standard deep brain stimulation (DBS) targets. The cerebellum has been posited as an attractive target for treatment of DCP because it is frequently spared from hypoxic ischemic damage and has shown promise in alleviating patient symptoms both in early work in the 1970s and in more recent case series with DBS. The authors performed bilateral cerebellar DBS implantation, targeting the dentate nucleus (DN) and cerebellar outflow pathway, in 3 patients with DCP. Leads were connected to a pulse generator that senses local field potentials during chronic continuous DBS. The authors report their surgical methods, examples of chronic cerebellar local field potential recordings, and preliminary clinical outcomes. Motor outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale. Three patients 14-22 years old with DCP and MRI evidence of structural damage to the basal ganglia were offered cerebellar stimulation targeting the DN. All patients tolerated the procedure well and demonstrated improvement in subjective motor function as well as objective improvement in the Burke-Fahn-Marsden Dystonia Rating Scale movement subscale, although the range of responses was variable (19%-40%). Patients experienced subjective improvement in motor function including ease of hand movements and coordination, gait, head control, speech, decreased overflow, and diminished muscle tightness. DBS of the dentate nuclei in patients with DCP appears to be safe and shows preliminary evidence of clinical benefit. New chronic sensing technology may allow for determination of in vivo mechanisms of network disruption in DCP and allow for further understanding of the effects of neuromodulation on brain physiology. Larger studies with long-term follow up will be required to further elucidate the clinical benefits of this therapy. This report addresses a gap in the literature regarding the technical approach to image-based stereotactic targeting and chronic neural recording in the DN.

Cerebellar and cerebral white matter changes in Parkinson's disease with resting tremor.

Cerebellum modulates the amplitude of resting tremor in Parkinson's disease (PD) via cerebello-thalamo-cortical (CTC) circuit. Tremor-related white matter alterations have been identified in PD patients by pathological studies, but in vivo evidence is limited; the influence of such cerebellar white matter alterations on tremor-related brain network, including CTC circuit, is also unclear. In this study, we investigated the cerebral and cerebellar white matter alterations in PD patients with resting tremor using diffusion tensor imaging (DTI). In this study, 30 PD patients with resting tremor (PDWR), 26 PD patients without resting tremor (PDNR), and 30 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort were included. Tract-based spatial statistics (TBSS) and region of interest-based analyses were conducted to determine white matter difference. Correlation analysis between DTI measures and clinical characteristics was also performed. In the whole brain, TBSS and region of interest-based analyses identified higher fractional anisotropy (FA) value, lower mean diffusivity (MD) value, and lower radial diffusivity (RD) in multiple fibers. In the cerebellum, TBSS analysis revealed significantly higher FA value, decreased RD value as well as MD value in multiple cerebellar tracts including the inferior cerebellar peduncle (ICP) and middle cerebellar peduncle (MCP) when comparing the PDWR with HC, and higher FA value in the MCP when compared with PDNR. We identified better white matter integrity in the cerebrum and cerebellum in PDWR indicating a potential association between the cerebral and cerebellar white matter and resting tremor in PD.

Excitation and Inhibition Delays within a Feedforward Inhibitory Pathway Modulate Cerebellar Purkinje Cell Output in Mice.

The cerebellar cortex computes sensorimotor information from many brain areas through a feedforward inhibitory (FFI) microcircuit between the input stage, the granule cell (GC) layer, and the output stage, the Purkinje cells (PCs). Although in other brain areas FFI underlies a precise excitation versus inhibition temporal correlation, recent findings in the cerebellum highlighted more complex behaviors at GC-molecular layer interneuron (MLI)-PC pathway. To dissect the temporal organization of this cerebellar FFI pathway, we combined ex vivo patch-clamp recordings of PCs in male mice with a viral-based strategy to express Channelrhodopsin2 in a subset of mossy fibers (MFs), the major excitatory inputs to GCs. We show that although light-mediated MF activation elicited pairs of excitatory and inhibitory postsynaptic currents in PCs, excitation (E) from GCs and inhibition (I) from MLIs reached PCs with a wide range of different temporal delays. However, when GCs were directly stimulated, a low variability in E/I delays was observed. Our results demonstrate that in many recordings MF stimulation recruited different groups of GCs that trigger E and/or I, and expanded PC temporal synaptic integration. Finally, using a computational model of the FFI pathway, we showed that this temporal expansion could strongly influence how PCs integrate GC inputs. Our findings show that specific E/I delays may help PCs encoding specific MF inputs.SIGNIFICANCE STATEMENT Sensorimotor information is conveyed to the cerebellar cortex by mossy fibers. Mossy fiber inputs activate granule cells that excite molecular interneurons and Purkinje cells, the sole output of the cerebellar cortex, leading to a sequence of synaptic excitation and inhibition in Purkinje cells, thus defining a feedforward inhibitory pathway. Using electrophysiological recordings, optogenetic stimulation, and mathematical modeling, we demonstrated that different groups of granule cells can elicit synaptic excitation and inhibition with various latencies onto Purkinje cells. This temporal variability controls how granule cells influence Purkinje cell discharge and may support temporal coding in the cerebellar cortex.

Integrative bioinformatics and artificial intelligence analyses of transcriptomics data identified genes associated with major depressive disorders including NRG1

Major depressive disorder (MDD) is a common mental disorder and is amongst the most prevalent psychiatric disorders. MDD remains challenging to diagnose and predict its onset due to its heterogeneous phenotype and complex etiology. Hence, early detection using diagnostic biomarkers is critical for rapid intervention. In this study, a mixture of AI and bioinformatics were used to mine transcriptomic data from publicly available datasets including 170 MDD patients and 121 healthy controls. Bioinformatics analysis using gene set enrichment analysis (GSEA) and machine learning (ML) algorithms were applied. The GSEA revealed that differentially expressed genes in MDD patients are mainly enriched in pathways related to immune response, inflammatory response, neurodegeneration pathways and cerebellar atrophy pathways. Feature selection methods and ML provided predicted models based on MDD-altered genes with ≥75% of accuracy. The integrative analysis between the bioinformatics and ML approaches identified ten key MDD-related biomarkers including NRG1, CEACAM8, CLEC12B, DEFA4, HP, LCN2, OLFM4, SERPING1, TCN1 and THBS1. Among them, NRG1, active in synaptic plasticity and neurotransmission, was the most robust and reliable to distinguish between MDD patients and healthy controls amongst independent external datasets consisting of a mixture of populations. Further evaluation using saliva samples from an independent cohort of MDD and healthy individuals confirmed the upregulation of NRG1 in patients with MDD compared to healthy controls. Functional mapping to the human brain regions showed NRG1 to have high expression in the main subcortical limbic brain regions implicated in depression. In conclusion, integrative bioinformatics and ML approaches identified putative non-invasive diagnostic MDD-related biomarkers panel for the onset of depression.

Psychosis Following a Cerebellar Stroke Revealing a Vertebral Artery Dissection

ABSTRACT The cerebellum plays a role not only in the control of balance and intentional voluntary movement but also plays an important role in the control of cognitive and emotional processes. We report a 62-year-old man who developed persistent persecutory delusions, hallucinations, cognitive impairment and flattened affect following a left bilateral cerebellar stroke. This is the second case reported of psychosis secondary to cerebellar vascular infarction due to vertebral dissection. Based on the distribution of the patient’s lesions, we suggest that his corresponding symptoms are a result of a disruption to cerebellar pathways. There is no consensus on the preferred pharmacological treatment of psychotic symptoms secondary to cerebellar lesions.

Cerebellar mutism is linked to midbrain volatility and desynchronization from speech cortices.

Cerebellar mutism syndrome is a disorder of speech, movement and affect that can occur after tumour removal from the posterior fossa. Projections from the fastigial nuclei to the periaqueductal grey area were recently implicated in its pathogenesis, but the functional consequences of damaging these projections remain poorly understood. Here, we examine functional MRI data from patients treated for medulloblastoma to identify functional changes in key brain areas that comprise the motor system for speech, which occur along the timeline of acute speech impairment in cerebellar mutism syndrome. One hundred and twenty-four participants, all with medulloblastoma, contributed to the study: 45 with cerebellar mutism syndrome, 11 patients with severe postoperative deficits other than mutism, and 68 without either (asymptomatic). We first performed a data-driven parcellation to spatially define functional nodes relevant to the cohort that align with brain regions critical for the motor control of speech. We then estimated functional connectivity between these nodes during the initial postoperative imaging sessions to identify functional deficits associated with the acute phase of the disorder. We further analysed how functional connectivity changed over time within a subset of participants that had suitable imaging acquired over the course of recovery. Signal dispersion was also measured in the periaqueductal grey area and red nuclei to estimate activity in midbrain regions considered key targets of the cerebellum with suspected involvement in cerebellar mutism pathogenesis. We found evidence of periaqueductal grey dysfunction in the acute phase of the disorder, with abnormal volatility and desynchronization with neocortical language nodes. Functional connectivity with periaqueductal grey was restored in imaging sessions that occurred after speech recovery and was further shown to be increased with left dorsolateral prefrontal cortex. The amygdalae were also broadly hyperconnected with neocortical nodes in the acute phase. Stable connectivity differences between groups were broadly present throughout the cerebrum, and one of the most substantial differences-between Broca's area and the supplementary motor area-was found to be inversely related to cerebellar outflow pathway damage in the mutism group. These results reveal systemic changes in the speech motor system of patients with mutism, centred on limbic areas tasked with the control of phonation. These findings provide further support for the hypothesis that periaqueductal grey dysfunction (following cerebellar surgical injury) contributes to the transient postoperative non-verbal episode commonly observed in cerebellar mutism syndrome but highlights a potential role of intact cerebellocortical projections in chronic features of the disorder.

Cerebellar structural, astrocytic, and neuronal abnormalities in the SMNΔ7 mouse model of spinal muscular atrophy.

Spinalmuscular atrophy (SMA) is a neuromuscular disease that affects as many as 1 in 6000 individuals at birth, making it the leading genetic cause of infant mortality. A growing number of studies indicate that SMA is a multi-system disease. The cerebellum has received little attention even though it plays an important role in motor function and widespread pathology has been reported in the cerebella of SMA patients. In this study, we assessed SMA pathology in the cerebellum using structural and diffusion magnetic resonance imaging, immunohistochemistry, and electrophysiology with the SMNΔ7 mouse model. We found a significant disproportionate loss in cerebellar volume, decrease in afferent cerebellar tracts, selective lobule-specific degeneration of Purkinje cells, abnormal lobule foliation and astrocyte integrity, and a decrease in spontaneous firing of cerebellar output neurons in the SMA mice compared to controls. Our data suggest that defects in cerebellar structure and function due to decreased survival motor neuron (SMN) levels impair the functional cerebellar output affecting motor control, and that cerebellar pathology should be addressed to achieve comprehensive treatment and therapy for SMA patients.

Chronic aphasias after left-hemisphere resective surgery

Surgical resection of brain tumours is associated with an increased risk of aphasia. However, relatively little is known about outcomes in the chronic phase (i.e., >6 months). Using voxel-based lesion symptom mapping (VLSM) in 46 patients, we investigated whether chronic language impairments are related to the location of surgical resection, residual tumour characteristics (e.g., peri-resection treatment effects, progressive infiltration, oedema) or both. Approximately 72% of patients scored below the cut-off for aphasia. Action naming and spoken sentence comprehension deficits were associated with lesions in the left anterior temporal and inferior parietal lobes, respectively. Voxel-wise analyses revealed significant associations between ventral language pathways and action naming deficits. Reading impairments were also associated with increasing disconnection of cerebellar pathways. The results indicate chronic post-surgical aphasias reflect a combination of resected tissue and tumour infiltration of language-related white matter tracts, implicating progressive disconnection as the critical mechanism of impairment.

Reduced cerebello-cerebral functional connectivity correlates with disease severity and impaired white matter integrity in Friedreich ataxia

Friedreich ataxia (FRDA) is a rare, inherited neurodegenerative disease characterised in most cases by progressive and debilitating motor dysfunction. Degeneration of cerebellar white matter pathways have been previously reported, alongside indications of cerebello-cerebral functional alterations. In this work, we examine resting-state functional connectivity changes within cerebello-cerebral circuits, and their associations with disease severity (Scale for the Assessment and Rating of Ataxia [SARA]), psychomotor function (speeded and paced finger tapping), and white matter integrity (diffusion tensor imaging) in 35 adults with FRDA and 45 age and sex-matched controls. Voxel-wise seed-based functional connectivity was assessed for three cerebellar cortical regions (anterior lobe, lobules I-V; superior posterior lobe, lobules VI-VIIB; inferior posterior lobe, lobules VIIIA-IX) and two dentate nucleus seeds (dorsal and ventral). Compared to controls, people with FRDA showed significantly reduced connectivity between the anterior cerebellum and bilateral pre/postcentral gyri, and between the superior posterior cerebellum and left dorsolateral PFC. Greater disease severity correlated with lower connectivity in these circuits. Lower anterior cerebellum-motor cortex functional connectivity also correlated with slower speeded finger tapping and less fractional anisotropy in the superior cerebellar peduncles, internal capsule, and precentral white matter in the FRDA cohort. There were no significant between-group differences in inferior posterior cerebellar or dentate nucleus connectivity. This study indicates that altered cerebello-cerebral functional connectivity is associated with functional status and white matter damage in cerebellar efferent pathways in people with FRDA, particularly in motor circuits.

Static Subjective Visual Vertical (SVV) in Patients with Vestibular Migraine.

Vestibular migraine (VM) is one of the common causes of episodic dizziness, but it is underdiagnosed and poorly understood. Previous research suggests that otolith reflex pathway performance is often impaired in this patient group, leading to altered perception of roll plane stimuli. Clinically, this perception can be measured with subjective visual vertical (SVV) testing. The aim of this study is to compare static SVV performance (absolute mean SVV tilt, variance) in a cohort of patients diagnosed with VM to results obtained from clinically derived normative data. Retrospective case review. Ninety-four consecutive patients between 18 and 65 years of age diagnosed with VM were included in this comparison to clinically derived normative data. Retrospective chart review was completed. Demographic data, symptom report, and vestibular laboratory results were documented. SVV performance was documented in terms of absolute mean SVV tilt and response variance. Abnormal mean SVV tilt was described in 54% (n = 51) of patients with VM. Including abnormal response variance increased those identified with abnormal presentation to 67% (n = 63). Laboratory findings were insignificant for semicircular canal function, but of those with abnormal ocular vestibular myogenic potential results (n = 30), 77% (n = 23) demonstrated both abnormal SVV and utriculo-ocular reflex performance. There were no associations noted for SVV performance and demographic or other self-report variables. Absolute mean SVV tilt and response variance are often abnormal in patients diagnosed with VM. These findings support theories suggesting atypical intralabyrinthine integration within the vestibular nuclei and cerebellar nodular pathways.

Changes in White Matter Microstructure Over 3 Years in People With and Without Stroke.

Cerebral white matter health can be estimated by MRI-derived indices of microstructure. White matter dysfunction is increasingly recognized as a contributor to neurodegenerative disorders affecting cognition and to functional outcomes after stroke. Reduced indices of white matter microstructure have been demonstrated cross-sectionally in stroke survivors compared with stroke-free participants, but longitudinal changes in the structure of white matter after stroke remain largely unexplored. We aimed to characterize white matter micro- and macrostructure over 3 years after stroke and study associations with white matter metrics and cognitive functions. Patients with first-ever or recurrent ischemic stroke of any etiology in any vascular territory were compared with stroke-free age- and sex-matched controls. Those diagnosed with hemorrhagic stroke, TIA, venous infarction, or significant medical comorbidities, psychiatric and neurodegenerative disorders, substance abuse, or history of dementia were excluded. Diffusion-weighted MRI data at 3, 12, and 36 months were analyzed using a longitudinal fixel-based analysis, sensitive to fiber tract-specific differences within a voxel. It was used to examine whole-brain white matter degeneration in stroke compared with control participants. We studied microstructural differences in fiber density and macrostructural changes in fiber-bundle cross-section, in relation to cognitive performance. Analyses were performed controlling for age, intracranial volume, and education (family-wise error-corrected p < 0.05, nonparametric testing over 5,000 permutations). We included 71 participants with stroke (age 66 ± 12 years, 22 women) and 36 controls (age 69 ± 5 years, 13 women). We observed extensive white matter structural degeneration across the whole brain, particularly affecting the thalamic, cerebellar, striatal, and superior longitudinal tracts and corpus callosum. Importantly, follow-up regression analyses in 72 predefined tracts showed that the decline in fiber density and cross-section from 3 months to 3 years was associated with worse cognitive performance at 3 years after stroke, especially affecting visuospatial processing, processing speed, language, and recognition memory. We conclude that white matter neurodegeneration in ipsi- and contralesional thalamic, striatal, and cerebellar tracts continues to be greater in stroke survivors compared with stroke-free controls. White matter degeneration persists even years after stroke and is associated with poststroke cognitive impairment. ClinicalTrails.gov NCT02205424.

Cerebellar and basal ganglia structural connections in humans: Effect of aging and relation with memory and learning.

The 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. In 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. Tractography 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. We 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.

Capacidade de deglutição e gravidade do risco de aspiração laringotraqueal no Acidente Vascular Encefálico atípico em via cerebelar: relato de caso

ABSTRACT This case report aimed to evaluate the swallowing capacity and the severity of the risk of laryngotracheal aspiration of a 52-year-old female patient with atypical and rare stroke, with major injury in the cerebellar pathway. In order to measure swallowing capacity and risk of aspiration a routine clinical assessment used in the speech therapy clinic was performed and two valid clinical tests were used: Massey Bedside Swallowing Screen (MBSS) and Gugging Swallowing Screen (GUSS). After evaluation with the clinical tests, it was observed that the patient had reduced swallowing capacity, performance characterized as pathological, 100% dysfunction in the water swallowing test (MBSS), presence of choking, coughing, change in vocal quality and anterior escape. In the assessment of risk of aspiration with the GUSS, the patient presented moderate dysphagia and risk of laryngotracheal aspiration.This case report demonstrated that moderate dysphagia is found in a stroke patient with lesions that affect the cerebellum. Standardized and validated clinical tests such as GUSS and MBSS should also be used to assess the risk of dysphagia after stroke at ambulatory care.

Preservation of cerebellar afferent pathway may be related to good hand function in patients with stroke

Preservation of cerebellar afferent pathway may be related to good hand function in patients with stroke

Deep Brain Stimulation of the Interposed Cerebellar Nuclei in a Conditional Genetic Mouse Model with Dystonia.

Dystonia is a neurological disease that is currently ranked as the third most common motor disorder. Patients exhibit repetitive and sometimes sustained muscle contractions that cause limb and body twisting and abnormal postures that impair movement. Deep brain stimulation (DBS) of the basal ganglia and thalamus can be used to improve motor function when other treatment options fail. Recently, the cerebellum has garnered interest as a DBS target for treating dystonia and other motor disorders. Here, we describe a procedure for targeting DBS electrodes to the interposed cerebellar nuclei to correct motor dysfunction in a mouse model with dystonia. Targeting cerebellar outflow pathways with neuromodulation opens new possibilities for using the expansive connectivity of the cerebellum to treat motor and non-motor diseases.

Cerebellar mutism syndrome: From pathophysiology to rehabilitation.

Cerebellar mutism syndrome (CMS) is a common complication following surgical resection of childhood tumors arising in the posterior fossa. Alteration of linguistic production, up to muteness and emotional lability, generally reported at least 24h after the intervention, is the hallmark of post-operative CMS. Other associated traits include hypotonia and other cerebellar motor signs, cerebellar cognitive-affective syndrome, motor deficits from the involvement of the long pathways, and cranial neuropathies. Recovery usually takes 6 months, but most children are burdened with long-term residual deficits. The pathogenic mechanism is likely due to the damage occurring to the proximal efferent cerebellar pathway, including the dentate nucleus, the superior cerebellar peduncle, and its decussation in the mesencephalic tegmentum. Proven risk factors include brain stem invasion, diagnosis of medulloblastoma, midline localization, tumor size, invasion of the fourth ventricle, invasion of the superior cerebellar peduncle, left-handedness, and incision of the vermis. Currently, rehabilitation is the cornerstone of the treatment of patients with cerebellar mutism syndrome, and it must consider the three main impaired domains, namely speech, cognition/behavior, and movement.

Neurophysiological mechanisms of gait disturbance in advanced Parkinson's disease patients

AbstractThis review considers pathophysiological mechanisms of posture‐gait disturbances in Parkinson's disease (PD). Clinical studies have shown that posture‐gait disturbance attributes to the dysfunction of the whole neuraxis in addition to the musculoskeletal system. The cerebral cortex, basal ganglia (BG), cerebellum, brainstem, and spinal cord temporally and spatially integrate and coordinate multisensory feedback and efferent copies of the motor command. Therefore, the extensive repertoire of voluntary movements can be coupled with anticipatory and reactive postural adjustments to provide the framework for supporting and stabilizing the goal‐directed gait activity. Redundancies in the system allow adaptation and compensation through reward‐oriented and error‐based learning processes implemented through the BG and cerebellar pathways, respectively. However, the impairment of these systems in PD may considerably compromise the capacity to adapt and lead to maladaptive changes impairing posture‐gait control. When these impairments occur, the risk of falls can significantly increase, and interventions are required to reduce morbidity. The damage in dopamine (DA) neurons is the primary cause of PD. Insufficient DA supply in the striatum disturbs the operation of intrinsic networks in the BG. This also pathologically increases GABAergic BG output to the cerebral cortex and brainstem, resulting in functional disconnection of other structures from the BG. The disconnection makes PD patients disable to achieve habitually acquired automatized gait control. Moreover, Lewy body degeneration in most brain areas, particularly in cholinergic and other monoaminergic systems vulnerable to neurodegeneration, further disturbs posture‐gait control and alters non‐motor symptoms of PD.

Differential changes in somatosensory evoked potentials and motor performance: pursuit movement task versus force matching tracking task.

Force modulation relies on accurate proprioception, and force-matching tasks alter corticocerebellar connectivity. Corticocerebellar (N24) and corticomotor pathways are impacted following the acquisition of a motor tracing task (MTT), measured using both somatosensory evoked potentials (SEPs) and transcranial magnetic stimulation. This study compared changes in early SEP peak amplitudes and motor performance following a force-matching tracking task (FMTT) to an MTT. Thirty (18 females) right-handed participants, aged 21.4 ± 2.76, were electrically stimulated over the right-median nerve at 2.47 Hz and 4.98 Hz (averaged 1,000 sweeps/rate) to elicit SEPs, recorded via a 64-channel electroencephalography cap, before, and after task acquisition using the right abductor pollicis brevis muscle. Retention was measured 24 h later. Significant time-by-group interactions occurred for the N20 SEP: 6.3% decrease post-FMTT versus 5.5% increase post-MTT (P = 0.013); P25 SEP: 4.0% decrease post-FMTT versus 10.3% increase post-MTT (P = 0.006); and N18 SEP: 113.4% increase post-FMTT versus 4.4% decrease post-MTT (P = 0.006). N18 and N30 showed significant effect of time (both P < 0.001). Motor performance: significant time-by-group interactions-postacquisition: FMTT improved 15.3% versus 24.3% for MTT (P = 0.025), retention: FMTT improved 17.4% and MTT by 30.1% (P = 0.004). Task-dependent differences occurred in SEP peaks associated with cortical somatosensory processing (N20 and P25), and cerebellar input (N18), with similar changes in sensorimotor integration (N30), with differential improvements in motor performance, indicating important differences in cerebellar and sensory processing for tasks reliant on proprioception.NEW & NOTEWORTHY This study demonstrates neurophysiological differences in cerebellar and somatosensory cortex pathways when learning a motor task requiring visuomotor tracking versus a task that requires force-matching modulation, in healthy individuals. The clear neurophysiological differences in early somatosensory evoked potentials associated with cortical somatosensory processing, cerebellar input, and sensorimotor integration between these two tasks demonstrate some of the neural correlates of force modulation and validate the force-matching task for use in future work.

Microstructural Properties of Brain White Matter Tracts in Breast Cancer Survivors: A Diffusion Tensor Imaging Study.

Complex breast cancer (BC) treatment can cause various neurological and psychiatric complications, such as postmastectomy pain syndrome, vestibulocerebellar ataxia, and depression, which can lead to microstructural damage of the white matter tracts of the brain. The purpose of the study is to assess microstructural changes in the white matter tracts of the brain in BC survivors using diffusion tensor imaging (DTI). Single DTI scans were performed on patients (n = 84) after complex BC treatment (i.e., surgery, chemotherapy and/or radiation therapy) and on the control group (n = 40). According to the results, a decrease in the quantitative anisotropy (FDR ≤ 0.05) was revealed in the bilateral corticospinal tracts, cerebellar tracts, corpus callosum, fornix, left superior corticostriatal and left corticopontine parietal in patients after BC treatment in comparison to the control group. A decrease in the quantitative anisotropy (FDR ≤ 0.05) was also revealed in the corpus callosum and right cerebellar tracts in patients after BC treatment with the presence of postmastectomy pain syndrome and vestibulocerebellar ataxia. The use of DTI in patients after BC treatment reveals microstructural properties of the white matter tracts in the brain. The results will allow for the improvement of treatment and rehabilitation approaches in patients receiving treatment for breast cancer.