Cerebellum: an explanation for dystonia?

Dystonia is a movement disorder that is characterized by involuntary muscle contractions, abnormal movements and postures, as well as by non-motor symptoms, and is due to abnormalities in different brain areas. In this article, we focus on the growing number of experimental studies aimed at explaining the pathophysiological role of the cerebellum in dystonia. Lastly, we highlight gaps in current knowledge and issues that future research studies should focus on as well as some of the potential applications of this research avenue. Clarifying the pathophysiological role of cerebellum in dystonia is an important concern given the increasing availability of invasive and non-invasive stimulation techniques and their potential therapeutic role in this condition

Effects of transcranial alternating current stimulation on repetitive finger movements in healthy humans

Transcranial alternating current stimulation (tACS) is a noninvasive neurophysiological technique that can entrain brain oscillations. Only few studies have investigated the effects of tACS on voluntary movements. We aimed to verify whether tACS, delivered over M1 at beta and gamma frequencies, has any effect on repetitive finger tapping as assessed by means of kinematic analysis. Eighteen healthy subjects were enrolled. Objective measurements of repetitive finger tapping were obtained by using a motion analysis system. M1 excitability was assessed by using single-pulse TMS and measuring the amplitude of motor-evoked potentials (MEPs). Movement kinematic measures and MEPs were collected during beta, gamma, and sham tACS and when the stimulation was off. Beta tACS led to an amplitude decrement (i.e., progressive reduction in amplitude) across the first ten movements of the motor sequence while gamma tACS had the opposite effect. The results did not reveal any significant effect of tACS on other movement parameters, nor any changes in MEPs. These findings demonstrate that tACS modulates finger tapping in a frequency-dependent manner with no concurrent changes in corticospinal excitability. The results suggest that cortical beta and gamma oscillations are involved in the motor control of repetitive finger movements

Cognitive behavioral group therapy versus psychoeducational intervention in Parkinson's disease

Objective: The aim of the current study was to evaluate whether cognitive behavioral group therapy has a positive impact on psychiatric, and motor and non-motor symptoms in Parkinson’s disease (PD). Methods: We assigned 20 PD patients with a diagnosis of psychiatric disorder to either a 12-week cognitive behavioral therapy (CBT) group or a psychoeducational protocol. For the neurological examination, we administered the Unified Parkinson’s Disease Rating Scale and the non-motor symptoms scale. The severity of psychiatric symptoms was assessed by means of the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Brief Psychiatric Rating Scale, and the Clinical Global Impressions. Results: Cognitive behavioral group therapy was effective in treating depression and anxiety symptoms as well as reducing the severity of non-motor symptoms in PD patients; whereas, no changes were observed in PD patients treated with the psychoeducational protocol. Conclusion: CBT offered in a group format should be considered in addition to standard drug therapy in PD patient

The Contribution of Neuroimaging to the Understanding of Essential Tremor Pathophysiology: a Systematic Review

Essential tremor (ET) is one of the most common movement disorders. Over the last 10 years, magnetic resonance imaging (MRI) has shed light on the structural and functional abnormalities possibly involved in ET pathophysiology. In this systematic review, we aimed to identify the cortical and subcortical structures involved and the role that different brain areas play in the pathophysiology of motor and non-motor ET features. We found that structural (grey and white matter) cerebellar damage and connectivity alterations between the cerebellum and various cortical areas play a role in both motor and non-motor symptoms of ET. In particular, many studies found an association between MRI findings and non-motor symptoms

Abnormal resting-state functional connectivity in progressive supranuclear palsy and corticobasal syndrome

Background: Pathological and MRI-based evidence suggests that multiple brain structures are likely to be involved in functional disconnection between brain areas. Few studies have investigated resting-state functional connectivity (rsFC) in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). In this study, we investigated within- and between-network rsFC abnormalities in these two conditions. Methods: Twenty patients with PSP, 11 patients with CBS, and 16 healthy subjects (HS) underwent a resting-state fMRI study. Resting-state networks (RSNs) were extracted to evaluate within- and between-network rsFC using the Melodic and FSLNets software packages. results: Increased within-network rsFC was observed in both PSP and CBS patients, with a larger number of RSNs being involved in CBS. Within-network cerebellar rsFC positively correlated with mini-mental state examination scores in patients with PSP. Compared to healthy volunteers, PSP and CBS patients exhibit reduced functional connectivity between the lateral visual and auditory RSNs, with PSP patients additionally showing lower functional connectivity between the cerebellar and insular RSNs. Moreover, rsFC between the salience and executive-control RSNs was increased in patients with CBS compared to HS. conclusion: This study provides evidence of functional brain reorganization in both PSP and CBS. Increased within-network rsFC could represent a higher degree of synchronization in damaged brain areas, while between-network rsFC abnormalities may mainly reflect degeneration of long-range white matter fibers

Congenital mirror movements in a new Italian family

Mirror movements (MMs) occur on the contralateral side of a limb being used intentionally. Because few families with congenital MMs and no other neurological signs have been reported, the underlying mechanisms of MMs are still not entirely clear. We report on the clinical, genetic, neurophysiological and neuroimaging findings of 10 of 26 living members of a novel four-generation family with congenital MMs. DCC and RAD51 were sequenced in affected members of the family. Five of the ten subjects with MMs underwent neurophysiological and neuroimaging evaluations. The neurophysiological evaluation consisted of electromyographic (EMG) mirror recordings, investigations of corticospinal excitability, and analysis of interhemispheric inhibition using transcranial magnetic stimulation techniques. The neuroimaging evaluation included functional MRI during finger movements. Eight (all females) of the ten members examined presented MMs of varying degrees at the clinical assessment. Transmission of MMs appears to have occurred according to an autosomal-dominant fashion with variable expression. No mutation in DCC or RAD51 was identified. EMG mirror activity was higher in MM subjects than in healthy controls. Short-latency interhemispheric inhibition was reduced in MM subjects. Ipsilateral motor-evoked potentials were detectable in the most severe case. The neuroimaging evaluation did not disclose any significant abnormalities in MM subjects. The variability of the clinical features of this family, and the lack of known genetic abnormalities, suggests that MMs are heterogeneous disorders. The pathophysiological mechanisms of MMs include abnormalities of transcallosal inhibition and corticospinal decussatio

Bradykinesia and dystonia

Background: Bradykinesia has been reported in patients with dystonia. Despite this, the pathophysiological mechanisms of bradykinesia in dystonia remain largely unknown. Methods: We here performed a comprehensive literature search and reviewed clinical and experimental studies on bradykinesia in patients with dystonia. Results: Many studies have documented the presence of bradykinesia in patients with idiopathic and inherited isolated dystonia, regardless of the presence of parkinsonism. In addition, bradykinesia has been observed as a side effect in dystonic patients who have undergone deep brain stimulation, in those with functional dystonia as well as in those with combined dystonia, e.g., dystonia-parkinsonism. These clinical and experimental findings support the hypothesis that dysfunction in a brain network involving the basal ganglia, primary sensorimotor cortex, and cerebellum may play a key role in the pathophysiology of both bradykinesia and dystonia. Conclusion: Bradykinesia is frequently observed in dystonia. We may gain insights into the pathophysiological underpinnings of two distinct movement disorders by investigating this issue. Furthermore, a deeper understanding of bradykinesia in dystonia may have terminological implications in this field

Changes in Corticospinal Circuits During Premovement Facilitation in Physiological Conditions.

Changes in corticospinal excitability have been well documented in the preparatory period before movement, however, their mechanisms and physiological role have not been entirely elucidated. We aimed to investigate the functional changes of excitatory corticospinal circuits during a reaction time (RT) motor task (thumb abduction) in healthy subjects (HS). 26 HS received single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). After a visual go signal, we calculated RT and delivered TMS at three intervals (50, 100, and 150 ms) within RT and before movement onset, recording motor evoked potentials (MEP) from the abductor pollicis brevis (APB) and the task-irrelevant abductor digiti minimi (ADM). We found that TMS increased MEPAPB amplitude when delivered at 150, 100, and 50 ms before movement onset, demonstrating the occurrence of premovement facilitation (PMF). MEP increase was greater at the shorter interval (MEP50) and restricted to APB (no significant effects were detected recording from ADM). We also reported time-dependent changes of the RT and a TMS side-dependent effect on MEP amplitude (greater on the dominant side). In conclusion, we here report changes of RT and side-dependent, selective and facilitatory effects on the MEPAPB amplitude when TMS is delivered before movement onset (PMF), supporting the role of excitatory corticospinal mechanisms at the basis of the selective PMF of the target muscle during the RT protocol

May Bradykinesia Features Aid in Distinguishing Parkinson's Disease, Essential Tremor, And Healthy Elderly Individuals?

Background: Bradykinesia is the hallmark feature of Parkinson's disease (PD); however, it can manifest in other conditions, including essential tremor (ET), and in healthy elderly individuals. Objective: Here we assessed whether bradykinesia features aid in distinguishing PD, ET, and healthy elderly individuals. Methods: We conducted simultaneous video and kinematic recordings of finger tapping in 44 PD patients, 69 ET patients, and 77 healthy elderly individuals. Videos were evaluated blindly by expert neurologists. Kinematic recordings were blindly analyzed. We calculated the inter-raters agreement and compared data among groups. Density plots assessed the overlapping in the distribution of kinematic data. Regression analyses and receiver operating characteristic curves determined how the kinematics influenced the likelihood of belonging to a clinical score category and diagnostic group. Results: The inter-rater agreement was fair (Fleiss K = 0.32). Rater found the highest clinical scores in PD, and higher scores in ET than healthy elderly individuals (p < 0.001). In regard to kinematic analysis, the groups showed variations in movement velocity, with PD presenting the slowest values and ET displaying less velocity than healthy elderly individuals (all ps < 0.001). Additionally, PD patients showed irregular rhythm and sequence effect. However, kinematic data significantly overlapped. Regression analyses showed that kinematic analysis had high specificity in differentiating between PD and healthy elderly individuals. Nonetheless, accuracy decreased when evaluating subjects with intermediate kinematic values, i.e., ET patients. Conclusion: Despite a considerable degree of overlap, bradykinesia features vary to some extent in PD, ET, and healthy elderly individuals. Our findings have implications for defining bradykinesia and categorizing patients