Majority of movements in everyday situations are complex and involve volition, planning of the movement and selection of the motor programme, all occurring before movement execution. Higher order ...motor disorders may be defined as abnormal motor behaviours resulting from disruption of any of the cortical processes that precede execution of the motor act. They are common in patients with neurodegenerative disorders, psychiatric diseases and structural brain lesions. These abnormal behaviours may be overlooked in the clinic, unless specifically evoked by the examiner. We discuss clinical and pathophysiological aspects of higher order motor disorders including: (1) disorders of disinhibition, such as grasp reflex and grasping behaviour, utilisation and imitation behaviour, motor preservations and paratonia; (2) disorders of motor intention such as motor neglect and motor impersistence; (3) alien limb syndrome; and (4) motor overflow phenomena, such as mirror movements and synkinesias. A video illustration of each phenomenon is provided. We place the findings from recent neurophysiological studies within the framework of theories of motor control to provide better insight into pathophysiology of different disorders.
fMRI studies show activation of cerebellum during transcutaneous auricular vagal nerve stimulation (taVNS); however, there is no evidence whether taVNS induced activation of the cerebellum translates ...to the cerebellar closed loops involved in motor functions. We assessed the propensity of taVNS at 25 Hz (taVNS25) and 100 Hz (taVNS100) to modulate cerebello-thalamo-cortical pathways using transcranial magnetic stimulation. In our double blind within-subjects study thirty-two participants completed one visit during which cerebellar brain inhibition (CBI) was assessed at baseline (no stimulation) and in a randomized order during taVNS100, taVNS25, and sham taVNS (xVNS). Generalized linear mixed models with gamma distribution were built to assess the effect of taVNS on CBI. The estimated marginal means of linear trends during each taVNS condition were computed and compared in a pairwise fashion with Benjamini-Hochberg correction for multiple comparisons. CBI significantly increased during taVNS100 compared to taVNS25 and xVNS (
p
= 0.0003 and
p
= 0.0465, respectively). The taVNS current intensity and CBI conditioning stimulus intensity had no significant effect on CBI. taVNS has a frequency dependent propensity to modulate the cerebello-thalamo-cortical pathway. The cerebellum participates in closed-loop circuits involved in motor, cognitive, and affective operations and may serve as an entry for modulating effects of taVNS.
Pseudodystonia represents a wide range of conditions that mimic dystonia, including disorders of the peripheral nervous system, spinal cord, brainstem, thalamus, cortex and non-neurological ...conditions such as musculoskeletal diseases. Here, we propose a definition of pseudodystonia and suggest a classification based on underlying pathophysiological mechanisms. We describe phenomenology of different forms of pseudodystonia and point to distinctions between dystonia and pseudodystonia as well as challenging issues that may arise in clinical practice. The term pseudodystonia can be used to describe abnormal postures, repetitive movements or both, in which results of clinical, imaging, laboratory or electrophysiological investigations provide definite explanation of symptoms which is not compatible with dystonia. Pseudodystonia can be classified into non-neurological disorders of the musculoskeletal system, disorders of sensory pathways, disorders of motor pathways and compensatory postures in other neurological diseases. Presence of associated neurological findings in the affected body part is the key towards diagnosis of pseudodystonia. Additional supporting features are the presence of fixed postures, the absence of sensory trick, acute mode of onset and severe pain. Worsening on eye closure, traditionally considered typical for pseudodystonia, is not always present and can also appear in dystonia. It is challenging to separate dystonia and pseudodystonia in patients with thalamic lesions or corticobasal syndrome, where abnormal postures coexist with sensory loss. Many cases of pseudodystonia are treatable. Therefore, it is essential to consider pseudodystonia in a differential diagnosis of abnormal postures until a detailed neurological examination rules it out.
•Pseudodystonia represents a wide range of conditions that mimic dystonia.•Causes of pseudodystonia include musculoskeletal disease, sensory or motor pathway disorders and compensatory postures.•The clues towards diagnosis of pseudodystonia are associated neurological findings in affected body parts.•Specific clinical features further support the diagnosis of pseudodystonia.•Clinical suspicion needs to be high, as many cases of pseudodystonia are treatable.
Neurophysiological evidence that transcutaneous auricular vagal nerve stimulation (taVNS) affects neuronal signalling at the cortical level is sparse. We used transcranial magnetic stimulation to ...assess the effect of taVNS on the excitability of intracortical GABAergic and cholinergic circuits.
In this within‐subject, double‐blind study on 30 healthy participants, we used TMS paradigms to assess the effect of a single session of taVNS at 100 Hz and sham earlobe VNS (sVNS) on short‐interval intracortical inhibition (SICI) curve and short‐latency afferent inhibition (SAI). Control experiment was performed on additional 15 participants using the same experimental settings, but delivering no stimulation (xVNS). Bayesian statistics were used to assess the differences, producing % values that reflect the certainty that the values of interest were decreased during or after stimulation compared with baseline. taVNS increased SICI (96.3%), whereas sVNS decreased SICI (1.2%). SAI was not affected by taVNS, although it was decreased during sVNS (1.34% and 9.1%, for interstimulus intervals 20 and 24 ms, respectively). The changes in TMS parameters detected during sVNS were present in the same direction in the control experiment with no stimulation.
Our study provides evidence that taVNS increases the activity of cortical GABAAergic system, leaving cortical cholinergic circuits unaffected. Changes in intracortical cortical excitability during sVNS, which were also observed in the control experiment with no stimulation were likely the effect of expectation related to participation in an interventional study.
We used TMS to obtain neurophysiological evidence of taVNS‐induced neuromodulation. Activity of the intracortical GABAAergic circuit was increased by taVNS at 100 Hz. Activity of motor cortex cholinergic circuits was unchanged during taVNS at 100 Hz.
Dopaminergic pathway is the most disrupted pathway in the pathogenesis of Parkinson's disease. Several studies reported associations of dopaminergic genes with the occurrence of adverse events of ...dopaminergic treatment. However, none of these studies adopted a pathway based approach. The aim of this study was to comprehensively evaluate the influence of selected single nucleotide polymorphisms of key dopaminergic pathway genes on the occurrence of motor and non-motor adverse events of dopaminergic treatment in Parkinson's disease. In total, 231 Parkinson's disease patients were enrolled. Demographic and clinical data were collected. Genotyping was performed for 16 single nucleotide polymorphisms from key dopaminergic pathway genes. Logistic and Cox regression analyses were used for evaluation. Results were adjusted for significant clinical data. We observed that carriers of at least one
rs165815 C allele had lower odds for developing visual hallucinations (OR = 0.34; 95% CI = 0.16-0.72;
= 0.004), while carriers of at least one
rs6280 C allele and CC homozygotes had higher odds for this adverse event (OR = 1.88; 95% CI = 1.00-3.54;
= 0.049 and OR = 3.31; 95% CI = 1.37-8.03;
= 0.008, respectively). Carriers of at least one
rs921451 C allele and CT heterozygotes had higher odds for orthostatic hypotension (OR = 1.86; 95% CI = 1.07-3.23;
= 0.028 and OR = 2.30; 95% CI = 1.26-4.20;
= 0.007, respectively). Heterozygotes for
rs3837091 and
rs628031 AA carriers also had higher odds for orthostatic hypotension (OR = 1.94; 95% CI = 1.07-3.51;
= 0.028 and OR = 2.57; 95% CI = 1.11-5.95;
= 0.028, respectively). Carriers of the
rs628031 AA genotype had higher odds for peripheral edema and impulse control disorders (OR = 4.00; 95% CI = 1.62-9.88;
= 0.003 and OR = 3.16; 95% CI = 1.03-9.72;
= 0.045, respectively). Finally, heterozygotes for
rs628031 and carriers of at least one
rs628031 A allele had lower odds for dyskinesia (OR = 0.48; 95% CI = 0.24-0.98,
= 0.043 and OR = 0.48; 95% CI = 0.25-0.92;
= 0.027, respectively). Gene-gene interactions, more specifically
, and
, also significantly influenced the occurrence of some adverse events. Additionally, haplotypes of
and
were associated with the occurrence of visual hallucinations (AT vs. GC: OR = 0.34; 95% CI = 0.16-0.72;
= 0.005) and orthostatic hypotension (ATG vs. ACG: OR = 2.48; 95% CI: 1.01-6.07;
= 0.047), respectively. Pathway based approach allowed us to identify new potential candidates for predictive biomarkers of adverse events of dopaminergic treatment in Parkinson's disease, which could contribute to treatment personalization.
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