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Find video protocols related to scientific articles indexed in Pubmed.
Short apraxia screening test.
J Clin Exp Neuropsychol
PUBLISHED: 10-31-2014
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Limb apraxia comprises many different and common disorders, which are largely unrecognized essentially because there is no easy-to-use screening test sensitive enough to identify all types of limb praxis deficits.
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Effects of subconcussive head trauma on the default mode network of the brain.
J. Neurotrauma
PUBLISHED: 10-16-2014
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Abstract Although they are less severe than a full blown concussive episodes, subconcussive impacts happen much more frequently and current research has suggested this form of head trauma may have an accumulative effect and lead to neurological impairment later in life. To investigate the acute effects that subconcussive head trauma may have on the default mode network of the brain resting-state, functional magnetic resonance was performed. Twenty-four current collegiate rugby players were recruited and all subjects underwent initial scanning 24?h prior to a scheduled full contact game to provide a baseline. Follow-up scanning of the rugby players occurred within 24?h following that game to assess acute effects from subconcussive head trauma. Differences between pre-game and post-game scans showed both increased connectivity from the left supramarginal gyrus to bilateral orbitofrontal cortex and decreased connectivity from the retrosplenial cortex and dorsal posterior cingulate cortex. To assess whether or not a history of previous concussion may lead to a differential response following subconcussive impacts, subjects were further divided into two subgroups based upon history of previous concussion. Individuals with a prior history of concussion exhibited only decreased functional connectivity following exposure to subconcussive head trauma, while those with no history showed increased connectivity. Even acute exposure to subconcussive head trauma demonstrates the ability to alter functional connectivity and there is possible evidence of a differential response in the brain for those with and without a history of concussion.
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Post-traumatic shoulder movement disorders: A challenging differential diagnosis between organic and functional.
Mov Disord Clin Pract (Hoboken)
PUBLISHED: 09-09-2014
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Peripheral trauma may be a trigger for the development of various movement disorders though the pathophysiology remains controversial and some of these patients have a functional (psychogenic) disorder. We report 3 cases of shoulder movement disorders following trauma to the shoulder region. Physiology was done in all the patients to extend the physical examination. Two patients had history of recurrent shoulder dislocation and were diagnosed with Ehlers-Danlos syndrome. One patient had shoulder injury following repeated falls while performing as a cheerleader. In two patients there were some clinical features suggesting a functional etiology, but physiological studies in all three failed to produce objective evidence of a functional nature. Shoulder movement following trauma is uncommon. Diagnosis in such cases is challenging considering the complex pathophysiology. The movements can be associated with prolonged pain and handicap, and once established they appear resistant to treatment.
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Functional neuroimaging of acute oculomotor deficits in concussed athletes.
Brain Imaging Behav
PUBLISHED: 09-02-2014
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In the pursuit to better understand the neural underpinnings of oculomotor deficits following concussion we performed a battery of oculomotor tests while performing simultaneous functional magnetic resonance imaging (fMRI). Based on the increasing evidence that concussion can disrupt multiple brain functional networks, including the oculomotor control networks, a series of classic saccadic and smooth pursuit tasks were implemented. Nine concussed athletes were tested within seven days of injury along with nine age and sex matched healthy normal volunteers. Both behavioral and fMRI data revealed differential results between the concussed and normal volunteer groups. Concussed subjects displayed longer latency time in the saccadic tasks, worse position errors, and fewer numbers of self-paced saccades compared to normal volunteer subjects. Furthermore, the concussed group showed recruitment of additional brain regions and larger activation sites as evidenced by fMRI. As a potential diagnostic and management tool for concussion, oculomotor testing shows promise, and here we try to understand the reasons for this disrupted performance with the aide of advanced neuroimaging tools.
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Tremor: pathophysiology.
Parkinsonism Relat. Disord.
PUBLISHED: 07-12-2014
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The precise way that tremors emerge is not well known, but there is some good information and hypotheses. This review will focus on the classic ("rest") tremor of Parkinson disease and essential tremor. Both have their genesis in central oscillators, which appear to be malfunctioning networks. With classic Parkinson tremor, there appears to be dysfunction of the basal ganglia network and the cerebello-thalamo-cortical network. There is evidence that the basal ganglia network triggers the onset of tremor and the cerebellar network is responsible for the amplitude. Since it is a tremor of stability, the beta activity of the basal ganglia may be the trigger. With essential tremor, the cerebello-thalamo-cortical network itself is dysfunctional and perhaps the inferior olive-cerebellar network as well. This is a tremor of action, and the associated ataxia suggests that delays in motor control processing may set up the oscillation.
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Drooling in Parkinson's disease: A review.
Parkinsonism Relat. Disord.
PUBLISHED: 07-10-2014
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Parkinson's disease (PD) is a neurodegenerative disease causing both motor and non-motor symptoms. Drooling, an excessive pooling and spillover of saliva out of the oral cavity, is one of the non-motor symptoms in PD patients that produces various negative physical and psychosocial consequences for patients and their caregivers. At present, the pathophysiology of drooling in PD is not completely certain; however, impaired intra-oral salivary clearance is likely the major contributor. There are neither standard diagnostic criteria nor standard severity assessment tools for evaluating drooling in PD. In accordance with the possible pathophysiology, dopaminergic agents have been used to improve salivary clearance; however, these agents are not completely effective in controlling drooling. Various pharmacological and non-pharmacological treatment options have been studied. Local injection with botulinum toxin serotypes A and B into major salivary glands is most effective to reduce drooling. Future research to explore the exact pathophysiology and develop standard diagnostic criteria and standard severity assessment tools are needed to formulate specific treatment options and improve patient care.
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Botulinum toxin and blink rate in patients with blepharospasm and increased blinking.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 06-26-2014
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The aim of the study was to investigate the effect of botulinum toxin (BoNT) on blink rate (BR) in patients with blepharospasm (BSP) and increased blinking (IB).
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Attention to Automatic Movements in Parkinson's Disease: Modified Automatic Mode in the Striatum.
Cereb. Cortex
PUBLISHED: 06-14-2014
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We investigated neural correlates when attending to a movement that could be made automatically in healthy subjects and Parkinson's disease (PD) patients. Subjects practiced a visuomotor association task until they could perform it automatically, and then directed their attention back to the automated task. Functional MRI was obtained during the early-learning, automatic stage, and when re-attending. In controls, attention to automatic movement induced more activation in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex, and rostral supplementary motor area. The motor cortex received more influence from the cortical motor association regions. In contrast, the pattern of the activity and connectivity of the striatum remained at the level of the automatic stage. In PD patients, attention enhanced activity in the DLPFC, premotor cortex, and cerebellum, but the connectivity from the putamen to the motor cortex decreased. Our findings demonstrate that, in controls, when a movement achieves the automatic stage, attention can influence the attentional networks and cortical motor association areas, but has no apparent effect on the striatum. In PD patients, attention induces a shift from the automatic mode back to the controlled pattern within the striatum. The shifting between controlled and automatic behaviors relies in part on striatal function.
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Dynamics of functional and effective connectivity within human cortical motor control networks.
Clin Neurophysiol
PUBLISHED: 06-06-2014
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Praxis, the performance of complex motor gestures, is crucial to the development of motor and social/communicative capacities. Praxis relies on a network consisting of inferior parietal and premotor regions, particularly on the left, and is thought to require transformation of spatio-temporal representations (parietal) into movement sequences (premotor).
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Efficient and reliable characterization of the corticospinal system using transcranial magnetic stimulation.
J Clin Neurophysiol
PUBLISHED: 06-03-2014
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The purpose of this study is to develop a method to reliably characterize multiple features of the corticospinal system in a more efficient manner than typically done in transcranial magnetic stimulation studies.
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Role of the sensorimotor cortex in tourette syndrome using multimodal imaging.
Hum Brain Mapp
PUBLISHED: 04-08-2014
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Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics. Most patients describe uncomfortable premonitory sensations preceding the tics and a subjective experience of increased sensitivity to tactile stimuli. These reports indicate that a sensory processing disturbance is an important component of TS together with motor phenomena. Thus, we focused our investigation on the role of the sensorimotor cortex (SMC) in TS using multimodal neuroimaging techniques. We measured the gamma-aminobutyric acid (GABA)+/Creatine (Cre) ratio in the SMC using GABA (1) H magnetic resonance spectroscopy. We recorded the baseline beta activity in the SMC using magnetoencephalography and correlated GABA+/Cre ratio with baseline beta band power. Finally, we examined the resting state functional connectivity (FC) pattern of the SMC using functional magnetic resonance imaging (fMRI). GABA+/Cre ratio in the SMC did not differ between patients and controls. Correlation between the baseline beta band power and GABA+/Cre ratio was abnormal in patients. The anterior insula showed increased FC with the SMC in patients. These findings suggest that altered limbic input to the SMC and abnormal GABA-mediated beta oscillations in the SMC may underpin some of the sensorimotor processing disturbances in TS and contribute to tic generation. Hum Brain Mapp 35:5834-5846, 2014. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
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Sensory aspects of movement disorders.
Lancet Neurol
PUBLISHED: 02-12-2014
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Movement disorders, which include disorders such as Parkinson's disease, dystonia, Tourette's syndrome, restless legs syndrome, and akathisia, have traditionally been considered to be disorders of impaired motor control resulting predominantly from dysfunction of the basal ganglia. This notion has been revised largely because of increasing recognition of associated behavioural, psychiatric, autonomic, and other non-motor symptoms. The sensory aspects of movement disorders include intrinsic sensory abnormalities and the effects of external sensory input on the underlying motor abnormality. The basal ganglia, cerebellum, thalamus, and their connections, coupled with altered sensory input, seem to play a key part in abnormal sensorimotor integration. However, more investigation into the phenomenology and physiological basis of sensory abnormalities, and about the role of the basal ganglia, cerebellum, and related structures in somatosensory processing, and its effect on motor control, is needed.
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Frequency-dependent neural activity in Parkinson's disease.
Hum Brain Mapp
PUBLISHED: 02-05-2014
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The brainstem and basal ganglia are important in the pathophysiology of Parkinson's disease (PD). Reliable and sensitive detection of neural activity changes in these regions should be helpful in scientific and clinical research on PD. In this study, we used resting state functional MRI and amplitude of low frequency fluctuation (ALFF) methods to examine spontaneous neural activity in 109 patients with PD. We examined activity in two frequency bands, slow-4 (between 0.027 and 0.073 Hz) and slow-5 (0.010-0.027 Hz). Patients had decreased ALFF in the striatum and increased ALFF in the midbrain, and changes were more significant in slow-4. Additionally, changes in slow-4 in both basal ganglia and midbrain correlated with the severity of the parkinsonism. The ALFF in the caudate nucleus positively correlated with the dose of levodopa, while the ALFF in the putamen negatively correlated with the disease duration in both slow-4 and slow-5 bands. In addition, the ALFF in the rostral supplementary motor area negatively correlated with bradykinesia subscale scores. Our findings show that with a large cohort of patients and distinguishing frequency bands, neural modulations in the brainstem and striatum in PD can be detected and may have clinical relevance. The physiological interpretation of these changes needs to be determined. Hum Brain Mapp 35:5815-5833, 2014. © 2014 Wiley Periodicals, Inc.
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Tricks in dystonia: ordering the complexity.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 01-31-2014
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Sensory tricks are various manoeuvres that can ameliorate dystonia. Common characteristics are well known, but their variety is wide, sensory stimulation is not necessarily the critical feature, and their physiology is unknown. To enumerate the various forms of sensory tricks and describe their nature, research findings and theories that may elucidate their neurophysiologic mechanism, we reviewed the literature pertaining to sensory tricks, including variants like motor tricks, imaginary tricks, forcible tricks and reverse sensory tricks. On the basis of this information, we propose a new classification of sensory tricks to include its variants. We highlight neurophysiologic evidence suggesting that sensory tricks work by decreasing abnormal facilitation. We tie this with established dystonia pathogenesis and postulate that sensory tricks decrease abnormally increased facilitation to inhibition ratios in the dystonic brain. It appears worthwhile for patients to search for possible sensory tricks.
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Restless legs syndrome and pregnancy: a review.
Parkinsonism Relat. Disord.
PUBLISHED: 01-20-2014
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Restless legs syndrome (RLS) is a common sensorimotor neurological disorder that is diagnosed according to the revised criteria of the International RLS Study Group (IRLSSG). The pathophysiology of RLS is still unknown and its prevalence is influenced by ethnicity, age, and gender. RLS is divided into two types by etiology: primary or idiopathic and secondary. Primary RLS is strongly influenced by a genetic component while secondary RLS is caused by other associated conditions such as end-stage renal disease or peripheral neuropathy. Another common condition associated with RLS is pregnancy. The prevalence of RLS during pregnancy is two to three times higher than in the normal population and is influenced by the trimester and the number of parity. The main mechanisms that may contribute to the pathophysiology of RLS during pregnancy are hormonal changes and iron and folate status. Standard medications for treating RLS during pregnancy are not established. Most medications have been used according to the evidence from non-pregnant patients. Therefore, consideration of the medical treatment for treating RLS during pregnancy should be balanced between the benefit of relieving the symptoms and maternal and fetal risk. In general, the prognosis of RLS during pregnancy is good and symptoms are usually relieved after delivery.
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Abnormal dorsal premotor-motor inhibition in writer's cramp.
Mov. Disord.
PUBLISHED: 01-13-2014
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The authors hypothesized that a deficient premotor-motor inhibitory network contributes to the unwanted involuntary movements in dystonia. The authors studied nine controls and nine patients with writer's cramp (WC). Dorsal premotor-motor cortical inhibition (dPMI) was tested by applying conditioning transcranial magnetic stimulation (TMS) to the dorsal premotor cortex and then a test pulse to the ipsilateral motor cortex at an interval of 6 ms. The authors used an H-reflex in flexor carpi radialis paired with TMS over the premotor cortex to assess for spinal cord excitability change. Finally, the authors interrupted a choice reaction time task with TMS over dorsal premotor cortex to assess performance in a nondystonic task. The results showed that WC patients exhibited dPMI at rest (88.5%, the ratio of conditioned to unconditioned test pulse), in contrast to controls, who did not show dPMI (109.6%) (P?=?0.0198). This difference between patients and controls persisted during contraction (100% vs. 112%) and pen-holding (95.6% vs. 111%). The H-reflex in the arm was not modulated by the premotor cortex stimulation. The WC patients made more errors, and the error rate improved with TMS over the premotor cortex. These results suggest that abnormal premotor-motor interactions may play a role in the pathophysiology of focal dystonia. The dPMI was not modulated by task in either group, but was constantly greater in the patients. The significance of the increased inhibition is likely to be compensatory. It appears to be a robust finding and, in combination with other features, could be further explored as a biomarker.
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Characteristics of bilateral hand function in individuals with unilateral dystonia due to perinatal stroke: sensory and motor aspects.
J. Child Neurol.
PUBLISHED: 01-05-2014
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The authors assessed bilateral motor and sensory function in individuals with upper limb dystonia due to unilateral perinatal stroke and explored interrelationships of motor function and sensory ability. Reach kinematics and tactile sensation were measured in 7 participants with dystonia and 9 healthy volunteers. The dystonia group had poorer motor (hold time, reach time, shoulder/elbow correlation) and sensory (spatial discrimination, stereognosis) outcomes than the control group on the nondominant side. On the dominant side, only sensation (spatial discrimination, stereognosis) was poorer in the dystonia group compared with the control group. In the dystonia group, although sensory and motor outcomes were uncorrelated, dystonia severity was related to poorer stereognosis, longer hold and reach times, and decreased shoulder/elbow coordination. Findings of bilateral sensory deficits in dystonia can be explained by neural reorganization. Visual compensation for somatosensory changes in the nonstroke hemisphere may explain the lack of bilateral impairments in reaching.
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Treatment of essential tremor with long-chain alcohols: still experimental or ready for prime time?
Tremor Other Hyperkinet Mov (N Y)
PUBLISHED: 01-01-2014
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To review current literature on long-chain alcohols and their derivatives as novel pharmacotherapy for the treatment of essential tremor (ET).
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Striatal dopaminergic dysfunction at rest and during task performance in writers cramp.
Brain
PUBLISHED: 10-21-2013
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Writers cramp is a task-specific focal hand dystonia characterized by involuntary excessive muscle contractions during writing. Although abnormal striatal dopamine receptor binding has been implicated in the pathophysiology of writers cramp and other primary dystonias, endogenous dopamine release during task performance has not been previously investigated in writers cramp. Using positron emission tomography imaging with the D2/D3 antagonist (11)C-raclopride, we analysed striatal D2/D3 availability at rest and endogenous dopamine release during sequential finger tapping and speech production tasks in 15 patients with writers cramp and 15 matched healthy control subjects. Compared with control subjects, patients had reduced (11)C-raclopride binding to D2/D3 receptors at rest in the bilateral striatum, consistent with findings in previous studies. During the tapping task, patients had decreased dopamine release in the left striatum as assessed by reduced change in (11)C-raclopride binding compared with control subjects. One cluster of reduced dopamine release in the left putamen during tapping overlapped with a region of reduced (11)C-raclopride binding to D2/D3 receptors at rest. During the sentence production task, patients showed increased dopamine release in the left striatum. No overlap between altered dopamine release during speech production and reduced (11)C-raclopride binding to D2/D3 receptors at rest was seen. Striatal regions where D2/D3 availability at rest positively correlated with disease duration were lateral and non-overlapping with striatal regions showing reduced D2/D3 receptor availability, except for a cluster in the left nucleus accumbens, which showed a negative correlation with disease duration and overlapped with striatal regions showing reduced D2/D3 availability. Our findings suggest that patients with writers cramp may have divergent responses in striatal dopamine release during an asymptomatic motor task involving the dystonic hand and an unrelated asymptomatic task, sentence production. Our voxel-based results also suggest that writers cramp may be associated with reduced striatal dopamine release occuring in the setting of reduced D2/D3 receptor availability and raise the possibility that basal ganglia circuits associated with premotor cortices and those associated with primary motor cortex are differentially affected in primary focal dystonias.
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Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia.
J. Neurosci.
PUBLISHED: 09-13-2013
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Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia-thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [(11)C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ?BP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ?BP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ?BP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ?BP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.
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Induction of Motor Associative Plasticity in the Posterior Parietal Cortex-Primary Motor Network.
Cereb. Cortex
PUBLISHED: 08-24-2013
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There is anatomical and functional connectivity between the primary motor cortex (M1) and posterior parietal cortex (PPC) that plays a role in sensorimotor integration. In this study, we applied corticocortical paired-associative stimuli to ipsilateral PPC and M1 (parietal ccPAS) in healthy right-handed subjects to test if this procedure could modulate M1 excitability and PPC-M1 connectivity. One hundred and eighty paired transcranial magnetic stimuli to the PPC and M1 at an interstimulus interval (ISI) of 8 ms were delivered at 0.2 Hz. We found that parietal ccPAS in the left hemisphere increased the excitability of conditioned left M1 assessed by motor evoked potentials (MEPs) and the input-output curve. Motor behavior assessed by the Purdue pegboard task was unchanged compared with controls. At baseline, conditioning stimuli over the left PPC potentiated MEPs from left M1 when ISI was 8 ms. This interaction significantly attenuated at 60 min after left parietal ccPAS. Additional experiments showed that parietal ccPAS induced plasticity was timing-dependent, was absent if ISI was 100 ms, and could also be seen in the right hemisphere. Our results suggest that parietal ccPAS can modulate M1 excitability and PPC-M1 connectivity and is a new approach to modify motor excitability and sensorimotor interaction.
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Development and validation of a clinical guideline for diagnosing blepharospasm.
Neurology
PUBLISHED: 06-14-2013
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To design and validate a clinical diagnostic guideline for aiding physicians in confirming or refuting suspected blepharospasm.
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Is increased blinking a form of blepharospasm?
Neurology
PUBLISHED: 06-12-2013
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The aim of this study was to investigate whether increased blink rate (BR) is part of the clinical spectrum of primary blepharospasm (BSP).
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Alcohol challenge and sensitivity to change of the essential tremor rating assessment scale.
Mov. Disord.
PUBLISHED: 05-07-2013
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The ability of the Essential Tremor (ET) Rating Assessment Scale (TETRAS) to detect changes in tremor severity is unknown.
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Emerging concepts in the physiological basis of dystonia.
Mov. Disord.
PUBLISHED: 04-30-2013
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Work over the past 2 decades has led to substantial changes in our understanding of dystonia pathophysiology. Three general abnormalities appear to underlie the pathophysiological substrate. The first is a loss of inhibition. This makes sense considering that it may be responsible for the excess of movement and for the overflow phenomena seen in dystonia. A second abnormality is sensory dysfunction which is related to the mild sensory complaints in patients with focal dystonias and may be responsible for some of the motor dysfunction. Third, evidence from animal models of dystonia as well as from patients with primary dystonia has revealed significant alterations of synaptic plasticity characterized by a disruption of homeostatic plasticity, with a prevailing facilitation of synaptic potentiation, together with the loss of synaptic inhibitory processes. We speculate that during motor learning this abnormal plasticity may lead to an abnormal sensorimotor integration, leading to consolidation of abnormal motor engrams. If so, then removing this abnormal plasticity might have little immediate effect on dystonic movements because bad motor memories have already been learned and are difficult to erase. These considerations might explain the delayed clinical effects of deep brain stimulation (DBS) in patients with generalized dystonia. Current lines of research will be discussed from a network perspective. © 2013 Movement Disorder Society.
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Role of posterior parietal cortex in reaching movements in humans: clinical implication for optic ataxia.
Clin Neurophysiol
PUBLISHED: 04-12-2013
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To clarify the spatio-temporal profile of cortical activity related to reaching movement in the posterior parietal cortex (PPC) in humans.
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Absent movement-related cortical potentials in children with primary motor stereotypies.
Mov. Disord.
PUBLISHED: 04-04-2013
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The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown, with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about 1 second before the onset of a voluntary movement. Early MRCPs preceded self-paced arm movements in 8 of 10 children with motor stereotypies and in 6 of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. © 2013 International Parkinson and Movement Disorder Society.
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The focal dystonias: current views and challenges for future research.
Mov. Disord.
PUBLISHED: 03-31-2013
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The most common forms of dystonia are those that develop in adults and affect a relatively isolated region of the body. Although these adult-onset focal dystonias are most prevalent, knowledge of their etiologies and pathogenesis has lagged behind some of the rarer generalized dystonias, in which the identification of genetic defects has facilitated both basic and clinical research. This summary provides a brief review of the clinical manifestations of the adult-onset focal dystonias, focusing attention on less well understood clinical manifestations that need further study. It also provides a simple conceptual model for the similarities and differences among the different adult-onset focal dystonias as a rationale for lumping them together as a class of disorders while at the same time splitting them into subtypes. The concluding section outlines some of the most important research questions for the future. Answers to these questions are critical for advancing our understanding of this group of disorders and for developing novel therapeutics.
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Octanoic acid in alcohol-responsive essential tremor: a randomized controlled study.
Neurology
PUBLISHED: 02-13-2013
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To assess safety and efficacy of an oral, single, low dose of octanoic acid (OA) in subjects with alcohol-responsive essential tremor (ET).
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The cerebellum in Parkinsons disease.
Brain
PUBLISHED: 02-11-2013
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Parkinsons disease is a chronic progressive neurodegenerative disorder characterized by resting tremor, slowness of movements, rigidity, gait disturbance and postural instability. Most investigations on Parkinsons disease focused on the basal ganglia, whereas the cerebellum has often been overlooked. However, increasing evidence suggests that the cerebellum may have certain roles in the pathophysiology of Parkinsons disease. Anatomical studies identified reciprocal connections between the basal ganglia and cerebellum. There are Parkinsons disease-related pathological changes in the cerebellum. Functional or morphological modulations in the cerebellum were detected related to akinesia/rigidity, tremor, gait disturbance, dyskinesia and some non-motor symptoms. It is likely that the major roles of the cerebellum in Parkinsons disease include pathological and compensatory effects. Pathological changes in the cerebellum might be induced by dopaminergic degeneration, abnormal drives from the basal ganglia and dopaminergic treatment, and may account for some clinical symptoms in Parkinsons disease. The compensatory effect may help maintain better motor and non-motor functions. The cerebellum is also a potential target for some parkinsonian symptoms. Our knowledge about the roles of the cerebellum in Parkinsons disease remains limited, and further attention to the cerebellum is warranted.
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Long-term depression-like plasticity of the blink reflex for the treatment of blepharospasm.
Mov. Disord.
PUBLISHED: 02-11-2013
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Our previous work showed a beneficial therapeutic effect on blepharospasm using slow repetitive transcranial magnetic stimulation, which produces a long-term depression (LTD)-like effect. High-frequency supraorbital electrical stimulation, asynchronous with the R2 component of the blink reflex, can also induce LTD-like effects on the blink reflex circuit in healthy subjects. Patients with blepharospasm have reduced inhibition of their blink recovery curves; therefore, a LTD-like intervention might normalize the blink reflex recovery (BRR) and have a favorable therapeutic effect. This is a randomized, sham-controlled, observer-blinded prospective study. In 14 blepharospasm patients, we evaluated the effects of high-frequency supraorbital stimulation on three separate treatment days. We applied 28 trains of nine stimuli, 400 Hz, either before or after the R2 or used sham stimulation. The primary outcome was the blink rate, number of spasms rated by a blinded physician and patient rating before, immediately after and 1 hour after stimulation while resting, reading, and talking; secondary outcome was the BRR. Stimulation "before" and "after" the R2 both showed a similar improvement as sham stimulation in physician rating, but patients felt significantly better with the before condition. Improvement in recovery of the blink reflex was noted only in the before condition. Clinical symptoms differed in the three baseline conditions (resting, reading, and talking). Stimulation before R2 increased inhibition in trigeminal blink reflex circuits in blepharospasm toward normal values and produced subjective, but not objective, improvement. Inhibition of the blink reflex pathway by itself appeared to be insufficient for a useful therapeutic effect.
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Botulinum neurotoxin treatment improves force regulation in writers cramp.
Parkinsonism Relat. Disord.
PUBLISHED: 02-05-2013
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Writers cramp patients show poor force regulation during handwriting, but also in other experimental tasks requiring fine motor control. Botulinum neurotoxin (BoNT) treatment is clinically effective in a substantial portion of writers cramp patients, but the full mechanism of action remains enigmatic. BoNT possibly influences ?- and ?-motoneurons through chemodenervation not only of extra-, but also intrafusal muscle fibres and might thus influence muscle spindle afferents. Hence, BoNT weakens injected muscles, but may also modulate sensory aspects of force control. Ten patients and 18 controls pressed their index finger on a force sensor tracking two visual targets: The first target consisted of five plateaus with successively higher force levels and alternated with ascending ramps. In the second target condition the same successive plateaus were to be reached by abrupt jumps. The generated force displayed as a time dependant curve. Root mean square of the difference between target and produced force level was calculated for each plateau/ramp/jump. Patients were treated with BoNT at week 4 and measured at baseline, weeks 2, 4, 6 and 8. Disturbed force regulation in patients for the plateaus and the second jump at baseline resolved after BoNT treatment, and the root mean square of force deviation decreased for the ramps. Fine force control was within the 95% confidence interval of the control group after treatment. In conclusion, force regulation was disturbed in patients and improved after BoNT treatment. This is not compatible with a simple muscle weakening and might thus reflect improved sensorimotor integration.
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Evidence-based review and assessment of botulinum neurotoxin for the treatment of movement disorders.
Toxicon
PUBLISHED: 02-04-2013
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Botulinum neurotoxin (BoNT) can be injected to achieve therapeutic benefit across a large range of clinical conditions. To assess the efficacy and safety of BoNT injections for the treatment of certain movement disorders, including blepharospasm, hemifacial spasm, oromandibular dystonia, cervical dystonia, focal limb dystonias, laryngeal dystonia, tics, and essential tremor, an expert panel reviewed evidence from the published literature. Data sources included English-language studies identified via MEDLINE, EMBASE, CINAHL, Current Contents, and the Cochrane Central Register of Controlled Trials. Evidence tables generated in the 2008 Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) review of the use of BoNT for movement disorders were also reviewed and updated. The panel evaluated evidence at several levels, supporting BoNT as a class, the serotypes BoNT-A and BoNT-B, as well as the four individual commercially available formulations: abobotulinumtoxinA (A/Abo), onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), and rimabotulinumtoxinB (B/Rima). The panel ultimately made recommendations for each therapeutic indication, based upon the strength of clinical evidence and following the AAN classification scale. For the treatment of blepharospasm, the evidence supported a Level A recommendation for BoNT-A, A/Inco, and A/Ona; a Level B recommendation for A/Abo; and a Level U recommendation for B/Rima. For hemifacial spasm, the evidence supported a Level B recommendation for BoNT-A and A/Ona, a Level C recommendation for A/Abo, and a Level U recommendation for A/Inco and B/Rima. For the treatment of oromandibular dystonia, the evidence supported a Level C recommendation for BoNT-A, A/Abo, and A/Ona, and a Level U recommendation for A/Inco and B/Rima. For the treatment of cervical dystonia, the published evidence supported a Level A recommendation for all four BoNT formulations. For limb dystonia, the available evidence supported a Level B recommendation for both A/Abo and A/Ona, but no published studies were identified for A/Inco or B/Rima, resulting in a Level U recommendation for these two formulations. For adductor laryngeal dystonia, evidence supported a Level C recommendation for the use of A/Ona, but a Level U recommendation was warranted for B/Rima, A/Abo, and A/Inco. For the treatment of focal tics, a Level U recommendation was warranted at this time for all four formulations. For the treatment of tremor, the published evidence supported a level B recommendation for A/Ona, but no published studies were identified for A/Abo, A/Inco, or B/Rima, warranting a Level U recommendation for these three formulations. Further research is needed to address evidence gaps and to evaluate BoNT formulations where currently there is insufficient or conflicting clinical data.
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Clinical utility of different botulinum neurotoxin preparations.
Toxicon
PUBLISHED: 01-30-2013
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Comparative literature assessing the relative safety and efficacy of different BoNT products is limited. The quantity and quality of data vary by preparation and indication. Clinicians seeking data relevant to the care of patients with specific conditions may find only reports about small numbers of patients with varying symptoms. While a literature search for "botulinum neurotoxins" will yield a large number of publications; only a fraction of these meet criteria for an academic evidence-based review. Patients may have been treated with a different BoNT formulation than that with which the physician is familiar, or there may be little or no clinical data on the use of a specific BoNT product for the proposed intervention. This paper is an introduction to a series of papers (which follow) in which an expert panel reviewed the BoNT clinical trial literature in order to provide evidence-based recommendations regarding the clinical use and efficacy of available BoNT preparations for four major therapeutic areas: movement disorders, spasticity, urology, and secretory disorders. Expert opinion is also included to address practical issues where more evidence and further research is needed.
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What we think before a voluntary movement.
J Cogn Neurosci
PUBLISHED: 01-30-2013
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A central feature of voluntary movement is the sense of volition, but when this sense arises in the course of movement formulation and execution is not clear. Many studies have explored how the brain might be actively preparing movement before the sense of volition; however, because the timing of the sense of volition has depended on subjective and retrospective judgments, these findings are still regarded with a degree of scepticism. EEG events such as beta event-related desynchronization and movement-related cortical potentials are associated with the brains programming of movement. Using an optimized EEG signal derived from multiple variables, we were able to make real-time predictions of movements in advance of their occurrence with a low false-positive rate. We asked participants what they were thinking at the time of prediction: Sometimes they were thinking about movement, and other times they were not. Our results indicate that the brain can be preparing to make voluntary movements while participants are thinking about something else.
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Criteria for the diagnosis of corticobasal degeneration.
Neurology
PUBLISHED: 01-30-2013
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Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ? 50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed.
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Response inhibition in motor conversion disorder.
Mov. Disord.
PUBLISHED: 01-26-2013
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Conversion disorders (CDs) are unexplained neurological symptoms presumed to be related to a psychological issue. Studies focusing on conversion paralysis have suggested potential impairments in motor initiation or execution. Here we studied CD patients with aberrant or excessive motor movements and focused on motor response inhibition. We also assessed cognitive measures in multiple domains. We compared 30 CD patients and 30 age-, sex-, and education-matched healthy volunteers on a motor response inhibition task (go/no go), along with verbal motor response inhibition (color-word interference) and measures of attention, sustained attention, processing speed, language, memory, visuospatial processing, and executive function including planning and verbal fluency. CD patients had greater impairments in commission errors on the go/no go task (P?
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Exercise-induced strengthening of inter-digital connections in musicians.
Clin Neurophysiol
PUBLISHED: 01-24-2013
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To investigate whether finger exercise affects surround inhibition in professional musicians as it was previously observed in non-musicians, we performed a transcranial magnetic stimulation (TMS) study in 13 healthy right-handed professional musicians.
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Action-effect binding is decreased in motor conversion disorder: implications for sense of agency.
Mov. Disord.
PUBLISHED: 01-23-2013
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The abnormal movements seen in motor conversion disorder are affected by distraction and entrainment, similar to voluntary movement. Unlike voluntary movement, however, patients lack a sense of control for the abnormal movements, a failure of "self-agency." The action-effect binding paradigm has been used to quantify the sense of self-agency, because subjective contraction of time between an action and its effect only occurs if the patient feels that they are the agent responsible for the action. We used this paradigm, coupled with emotional stimuli, to investigate the sense of agency with voluntary movements in patients with motor conversion disorder. Twenty patients with motor conversion disorder and 20 age-matched and sex-matched healthy volunteers used a rotating clock to judge the time of their own voluntary key presses (action) and a subsequent auditory tone (effect) after they completed conditioning blocks in which high, medium, and low tones were coupled to images of happy, fearful, and neutral faces. The results replicated those produced previously: it was reported that an effect after a voluntary action occurred earlier, and the preceding action occurred later, compared with trials that used only key presses or tones. Patients had reduced overall binding scores relative to healthy volunteers, suggesting a reduced sense of agency. There was no effect of the emotional stimuli (faces) or other interaction effects. Healthy volunteers with subclinical depressive symptoms had higher overall binding scores. We demonstrate that patients with motor conversion disorder have decreased action-effect binding for normal voluntary movements compared with healthy volunteers, consistent with the greater experience of lack of control.
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Phenomenology and classification of dystonia: a consensus update.
Mov. Disord.
PUBLISHED: 01-21-2013
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This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during 3 in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along 2 axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features); and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. © 2013 Movement Disorder Society.
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Neurology of volition.
Exp Brain Res
PUBLISHED: 01-18-2013
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Neurological disorders of volition may be characterized by deficits in willing and/or agency. When we move our bodies through space, it is the sense that we intended to move (willing) and that our actions were a consequence of this intention (self-agency) that gives us the sense of voluntariness and a general feeling of being "in control." While it is possible to have movements that share executive machinery ordinarily used for voluntary movement but lack a sense of voluntariness, such as psychogenic movement disorders, it is also possible to claim volition for presumed involuntary movements (early chorea) or even when no movement is produced (anosognosia). The study of such patients should enlighten traditional models of how the percepts of volition are generated in the brain with regard to movement. We discuss volition and its components as multi-leveled processes with feedforward and feedback information flow, and dependence on prior expectations as well as external and internal cues.
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Microvascular decompression for hemifacial spasm in patients >65 years of age: an analysis of outcomes and complications.
Muscle Nerve
PUBLISHED: 01-17-2013
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Few data are available to quantify the risks and benefits of microvascular decompression (MVD) in elderly patients with hemifacial spasm.
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Repetitive transcranial magnetic stimulation attenuates the perception of force output production in non-exercised hand muscles after unilateral exercise.
PLoS ONE
PUBLISHED: 01-01-2013
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We examined whether unilateral exercise creates perception bias in the non-exercised limb and ascertained whether rTMS applied to the primary motor cortex (M1) interferes with this perception. All participants completed 4 interventions: 1) 15-min learning period of intermittent isometric contractions at 35% MVC with the trained hand (EX), 2) 15-min learning period of intermittent isometric contractions at 35% MVC with the trained hand whilst receiving rTMS over the contralateral M1 (rTMS+EX); 3) 15-min of rTMS over the trained M1 (rTMS) and 4) 15-min rest (Rest). Pre and post-interventions, the error of force output production, the perception of effort (RPE), motor evoked potentials (MEPs) and compound muscle action potentials (CMAPs) were measured in both hands. EX did not alter the error of force output production in the trained hand (?3%; P>0.05); however, the error of force output production was reduced in the untrained hand (?12%; P<0.05). rTMS+EX and rTMS alone did not show an attenuation in the error of force output production in either hand. EX increased RPE in the trained hand (9.1±0.5 vs. 11.3±0.7; P<0.01) but not the untrained hand (8.8±0.6 vs. 9.2±0.6; P>0.05). RPE was significantly higher after rTMS+EX in the trained hand (9.2±0.5 vs. 10.7±0.7; P<0.01) but ratings were unchanged in the untrained hand (8.5±0.6 vs. 9.2±0.5; P>0.05). The novel finding was that exercise alone reduced the error in force output production by over a third in the untrained hand. Further, when exercise was combined with rTMS the transfer of force perception was attenuated. These data suggest that the contralateral M1 of the trained hand might, in part, play an essential role for the transfer of force perception to the untrained hand.
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Modulation of functionally localized right insular cortex activity using real-time fMRI-based neurofeedback.
Front Hum Neurosci
PUBLISHED: 01-01-2013
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The capacity for subjects to learn to volitionally control localized brain activity using neurofeedback is actively being investigated. We aimed to investigate the ability of healthy volunteers to quickly learn to use visual feedback during real-time functional MRI (rtfMRI) to modulate brain activity within their anterior right insular cortex (RIC) localized during a blink suppression task, an approach of possible interest in the use of rtfMRI to reduce urges. The RIC region of interest (RIC-ROI) was functionally localized using a blink suppression task, and blood-oxygen level dependent (BOLD) signal changes within RIC-ROI used to create a constantly updating display fed back to the subject in the scanner. Subjects were instructed to use emotional imagery to try and increase activity within RIC-ROI during four feedback training runs (FB1-FB4). A "control" run (CNTRL) before training and a "transfer" run (XSFR) after training were performed without feedback to assess for baseline abilities and learning effects. Fourteen participants completed all neurofeedback training runs. At the group-level, increased BOLD activity was seen in the anterior RIC during all the FB runs, but a significant increase in the functionally defined RIC-ROI was only attained during FB2. In atlas-defined insular cortex ROIs, significant increases were seen bilaterally during the CNTRL, FB1, FB2, and FB4 runs. Increased activity within the insular cortices did not show lateralization. Training did, however, result in a significant increase in functional connectivity between the RIC-ROI and the medial frontal gyrus when comparing FB4 to FB1. Since neurofeedback training did not lead to an increase in BOLD signal across all feedback runs, we suggest that learning to control ones brain activity in this fashion may require longer or repeated rtfMRI training sessions.
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What is It? Difficult to Pigeon Hole Tremor: a Clinical-Pathological Study of a Man with Jaw Tremor.
Tremor Other Hyperkinet Mov (N Y)
PUBLISHED: 01-01-2013
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The phenomenology of tremor is broad and its classification is complicated. Furthermore, the full range of tremor phenomenology with respect to specific neurological and neurodegenerative diseases has not been fully elaborated.
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Functional anatomy of writing with the dominant hand.
PLoS ONE
PUBLISHED: 01-01-2013
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While writing performed by any body part is similar in style, indicating a common program, writing with the dominant hand is particularly skilled. We hypothesized that this skill utilizes a special motor network supplementing the motor equivalence areas. Using functional magnetic resonance imaging in 13 normal subjects, we studied nine conditions: writing, zigzagging and tapping, each with the right hand, left hand and right foot. We identified brain regions activated with the right (dominant) hand writing task, exceeding the activation common to right-hand use and the writing program, both identified without right-hand writing itself. Right-hand writing significantly differed from the other tasks. First, we observed stronger activations in the left dorsal prefrontal cortex, left intraparietal sulcus and right cerebellum. Second, the left anterior putamen was required to initiate all the tested tasks, but only showed sustained activation during the right-hand writing condition. Lastly, an exploratory analysis showed clusters in the left ventral premotor cortex and inferior and superior parietal cortices were only significantly active for right-hand writing. The increased activation with right-hand writing cannot be ascribed to increased effort, since this is a well-practiced task much easier to perform than some of the other tasks studied. Because parietal-premotor connections code for particular skills, it would seem that the parietal and premotor regions, together with basal ganglia-sustained activation likely underlie the special skill of handwriting with the dominant hand.
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Middle ear myoclonus: two informative cases and a systematic discussion of myogenic tinnitus.
Tremor Other Hyperkinet Mov (N Y)
PUBLISHED: 01-01-2013
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THE TERM MIDDLE EAR MYOCLONUS (MEM) HAS BEEN INVOKED TO EXPLAIN SYMPTOMS OF TINNITUS PRESUMABLY CAUSED BY THE DYSFUNCTIONAL MOVEMENT OF EITHER OF THE TWO MUSCLES THAT INSERT IN THE MIDDLE EAR: tensor tympani and stapedius. MEM has been characterized through heterogeneous case reports in the otolaryngology literature, where clinical presentation is variable, phenomenology is scarcely described, the pathogenic muscle is usually not specified, natural history is unknown, and the presumptive definitive treatment, tensor tympani or stapedius tendon lysis, is inconsistently effective. It is not surprising that no unique acoustogenic mechanism or pathophysiologic process has been identified to explain MEM, one of several descriptive diagnoses associated with the complicated disorders of myogenic tinnitus.
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A finite element analysis of the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in tDCS.
J Neural Eng
PUBLISHED: 11-15-2011
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We investigated the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in transcranial direct current stimulation (tDCS). For this purpose, we used the finite element method to compute the distribution of the current density in a four-layered spherical head model using various electrode montages, corresponding to a range of electrode sizes and inter-electrode distances. We found that smaller electrodes required slightly less current to achieve a constant value of the current density at a reference point on the brain surface located directly under the electrode center. Under these conditions, smaller electrodes also produced a more focal current density distribution in the brain, i.e. the magnitude of the current density fell more rapidly with distance from the reference point. The combination of two electrodes with different areas produced an asymmetric current distribution that could lead to more effective and localized neural modulation under the smaller electrode than under the larger one. Focality improved rapidly with decreasing electrode size when the larger electrode sizes were considered but the improvement was less marked for the smaller electrode sizes. Also, focality was not affected significantly by inter-electrode distance unless two large electrodes were placed close together. Increasing the inter-electrode distance resulted in decreased shunting of the current through the scalp and the cerebrospinal fluid, and decreasing electrode area resulted in increased current density on the scalp under the edges of the electrode. Our calculations suggest that when working with conventional electrodes (25-35 cm(2)), one of the electrodes should be placed just behind the target relative to the other electrode, for maximum current density on the target. Also electrodes with areas in the range 3.5-12 cm(2) may provide a better compromise between focality and current density in the scalp than the traditional electrodes. Finally, the use of multiple small return electrodes may be more efficient than the use of a single large return electrode.
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Cerebellum and processing of negative facial emotions: cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness.
Cogn Emot
PUBLISHED: 11-14-2011
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Some evidence suggests that the cerebellum participates in the complex network processing emotional facial expression. To evaluate the role of the cerebellum in recognising facial expressions we delivered transcranial direct current stimulation (tDCS) over the cerebellum and prefrontal cortex. A facial emotion recognition task was administered to 21 healthy subjects before and after cerebellar tDCS; we also tested subjects with a visual attention task and a visual analogue scale (VAS) for mood. Anodal and cathodal cerebellar tDCS both significantly enhanced sensory processing in response to negative facial expressions (anodal tDCS, p=.0021; cathodal tDCS, p=.018), but left positive emotion and neutral facial expressions unchanged (p>.05). tDCS over the right prefrontal cortex left facial expressions of both negative and positive emotion unchanged. These findings suggest that the cerebellum is specifically involved in processing facial expressions of negative emotion.
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Development of a VR-based treadmill control interface for gait assessment of patients with Parkinsons disease.
IEEE Int Conf Rehabil Robot
PUBLISHED: 10-07-2011
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Freezing of gait (FOG) is a commonly observed phenomenon in Parkinsons disease, but its causes and mechanisms are not fully understood. This paper presents the development of a virtual reality (VR)-based body-weight supported treadmill interface (BWSTI) designed and applied to investigate FOG. The BWSTI provides a safe and controlled walking platform which allows investigators to assess gait impairments under various conditions that simulate real life. In order to be able to evoke FOG, our BWSTI employed a novel speed adaptation controller, which allows patients to drive the treadmill speed. Our interface responsively follows the subjects intention of changing walking speed by the combined use of feedback and feedforward controllers. To provide realistic visual stimuli, a three dimensional VR system is interfaced with the speed adaptation controller and synchronously displays realistic visual cues. The VR-based BWSTI was tested with three patients with PD who are known to have FOG. Visual stimuli that might cause FOG were shown to them while the speed adaptation controller adjusted treadmill speed to follow the subjects intention. Two of the three subjects showed FOG during the treadmill walking.
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Metabolic alterations in corpus callosum may compromise brain functional connectivity in MTBI patients: an 1H-MRS study.
Neurosci. Lett.
PUBLISHED: 10-03-2011
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After clinical resolution of signs and symptoms of mild traumatic brain injury (MTBI) it is still not clear if there are residual abnormalities of structural or functional brain networks. We have previously documented disrupted interhemispheric functional connectivity in asymptomatic concussed individuals during the sub-acute phase of injury. Testing of 15 normal volunteers (NV) and 15 subacute MTBI subjects was performed within 24h of clinical symptoms resolution and medical clearance for the first stage of aerobic activity. In this MRS study we report: (a) both in the genu and splenium of the corpus callosum NAA/Cho and NAA/Cr ratios were significantly (p<0.05) lower in MTBI subjects shortly after the injury compared to NVs, and (b) the metabolic ratio NAA/Cho in the splenium significantly correlated with the magnitude of inter-hippocampal functional connectivity in normal volunteers, but not in MTBI. This novel finding supports our hypothesis that the functional disruption of interhemispheric brain networks in MTBI subjects results from compromised metabolic integrity of the corpus callosum and that this persists despite apparent clinical return to baseline.
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The non-motor syndrome of primary dystonia: clinical and pathophysiological implications.
Brain
PUBLISHED: 09-20-2011
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Dystonia is typically considered a movement disorder characterized by motor manifestations, primarily involuntary muscle contractions causing twisting movements and abnormal postures. However, growing evidence indicates an important non-motor component to primary dystonia, including abnormalities in sensory and perceptual functions, as well as neuropsychiatric, cognitive and sleep domains. Here, we review this evidence and discuss its clinical and pathophysiological implications.
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Similarities and differences between normal urges and the urge to tic.
Cogn Neurosci
PUBLISHED: 09-01-2011
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Abstract Investigations into the neurobiological substrates underlying urge are important for developing better understanding and treatment for impulse-control disorders. We characterize the phenomenon based on normal bodily (interoceptive) urges. Features include the following: a preceding awareness of an uncomfortable bodily sensation, a sense of urgency that action must be taken, rising distress when action is delayed, a temporary (e.g., a few minutes in length) ability to suppress or manifest the action voluntarily, subsequent relief once action is taken, association with an action that is necessary to survival. We compare and contrast these characteristics with those described by Tourette syndrome patients as the urge to tic, and highlight several unknowns which merit further investigation.
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Abnormal reorganization of functional cortical small-world networks in focal hand dystonia.
PLoS ONE
PUBLISHED: 08-08-2011
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We investigated the large-scale functional cortical connectivity network in focal hand dystonia (FHD) patients using graph theoretic measures to assess efficiency. High-resolution EEGs were recorded in 15 FHD patients and 15 healthy volunteers at rest and during a simple sequential finger tapping task. Mutual information (MI) values of wavelet coefficients were estimated to create an association matrix between EEG electrodes, and to produce a series of adjacency matrices or graphs, G, by thresholding with network cost. Efficiency measures of small-world networks were assessed. As a result, we found that FHD patients have economical small-world properties in their brain functional networks in the alpha and beta bands. During a motor task, in the beta band network, FHD patients have decreased efficiency of small-world networks, whereas healthy volunteers increase efficiency. Reduced efficient beta band network in FHD patients during the task was consistently observed in global efficiency, cost-efficiency, and maximum cost-efficiency. This suggests that the beta band functional cortical network of FHD patients is reorganized even during a task that does not induce dystonic symptoms, representing a loss of long-range communication and abnormal functional integration in large-scale brain functional cortical networks. Moreover, negative correlations between efficiency measures and duration of disease were found, indicating that the longer duration of disease, the less efficient the beta band network in FHD patients. In regional efficiency analysis, FHD patients at rest have high regional efficiency at supplementary motor cortex (SMA) compared with healthy volunteers; however, it is diminished during the motor task, possibly reflecting abnormal inhibition in FHD patients. The present study provides the first evidence with graph theory for abnormal reconfiguration of brain functional networks in FHD during motor task.
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Freezing of gait: moving forward on a mysterious clinical phenomenon.
Lancet Neurol
PUBLISHED: 07-23-2011
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Freezing of gait (FoG) is a unique and disabling clinical phenomenon characterised by brief episodes of inability to step or by extremely short steps that typically occur on initiating gait or on turning while walking. Patients with FoG, which is a feature of parkinsonian syndromes, show variability in gait metrics between FoG episodes and a substantial reduction in step length with frequent trembling of the legs during FoG episodes. Physiological, functional imaging, and clinical-pathological studies point to disturbances in frontal cortical regions, the basal ganglia, and the midbrain locomotor region as the probable origins of FoG. Medications, deep brain stimulation, and rehabilitation techniques can alleviate symptoms of FoG in some patients, but these treatments lack efficacy in patients with advanced FoG. A better understanding of the phenomenon is needed to aid the development of effective therapeutic strategies.
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Impulse control disorders in Parkinsons disease: recent advances.
Curr. Opin. Neurol.
PUBLISHED: 07-05-2011
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The aim is to review the recent advances in the epidemiology and pathophysiology of impulse control disorders (ICDs) in Parkinsons disease.
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Milestones in clinical neurophysiology.
Mov. Disord.
PUBLISHED: 06-01-2011
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Over the last 25 years, clinical neurophysiology has made many advances in the understanding, diagnosis, and even treatment of different movement disorders. Transcranial magnetic stimulation has been the biggest technical advance. Progress in pathophysiology includes improved knowledge about bradykinesia in Parkinsons disease, loss of inhibition and increased plasticity in dystonia, abnormal startle in hyperekplexia, and various features of psychogenic movement disorders that can aid diagnosis. Studies have been done looking at the use of noninvasive brain stimulation for therapy, but effects are generally small.
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Dopamine agonists and risk: impulse control disorders in Parkinsons disease.
Brain
PUBLISHED: 05-21-2011
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Impulse control disorders are common in Parkinsons disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinsons disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a Sure choice and a Gamble choice of moderate risk. To commence each trial, in the Gain condition, individuals started at $0 and in the Loss condition individuals started at -$50 below the Sure amount. The difference between the maximum and minimum outcomes from each gamble (i.e. range) was used as an index of risk (Gamble Risk). Sixteen healthy volunteers were behaviourally tested. Fourteen impulse control disorder (problem gambling or compulsive shopping) and 14 matched Parkinsons disease controls were tested ON and OFF dopamine agonists. Patients with impulse control disorder made more risky choices in the Gain relative to the Loss condition along with decreased orbitofrontal cortex and anterior cingulate activity, with the opposite observed in Parkinsons disease controls. In patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk along with decreased ventral striatal activity again with the opposite in Parkinsons disease controls. Patients with impulse control disorder appear to have a bias towards risky choices independent of the effect of loss aversion. Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum. Our results provide a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals.
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An open-label, single-dose, crossover study of the pharmacokinetics and metabolism of two oral formulations of 1-octanol in patients with essential tremor.
Neurotherapeutics
PUBLISHED: 05-20-2011
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Existing therapeutic options for management of essential tremor are frequently limited by poor efficacy and adverse effects. Likely the most potent tremor suppressant used is ethanol, although its use is prohibitive due to a brief therapeutic window, and the obvious implications of excessive alcohol use. Longer-chain alcohols have been shown to suppress tremor in harmaline animal models, and appear to be safe and well tolerated in 2 prior studies in humans. Here we report on the findings of a phase I/II study of 1-octanol designed to explore pharmacokinetics, efficacy, and safety. The most significant finding was the identification of octanoic acid as the product of rapid 1-octanol metabolism. Furthermore, the temporal profile of efficacy closely matches the plasma concentration of octanoic acid. Therefore, these findings identify a novel class of compound (e.g., carboxylic acids) with tremor suppressive properties in ET. Administration of 1-octanol also appears to be safe based on various measures collected. Essential tremor (ET) is the most common tremor disorder, with tremors occurring during static posturing or movement. These tremors are known to briefly improve in many cases after alcohol (ethanol) consumption. Two previous studies of a longer chain alcohol, 1-octanol, have demonstrated longer duration tremor-suppressive effects without the occurrence of intoxication. The aim of this study was to characterize the pharmacokinetics of 1-octanol and its primary metabolite octanoic acid using two formulations, along with additional safety and efficacy measures. Participants with proven ethanol-responsive ET were recruited into 1 of 2 parts: (part A) a dose escalation study (1-64 mg/kg; n?=?4), and (part B) a fixed dose (64 mg/kg; n?=?10) balanced, open-label crossover design. Two participants in part B then completed an exploratory part C evaluating 128 mg/kg.Plasma samples were collected at 10 intervals during a 6-hour period postingestion. Efficacy was assessed using spirography, whereas safety was assessed with electrocardiograms, vital signs, adverse effects surveys, and an intoxication assessment. Plasma concentrations of 1-octanol were detectable at low levels whereas octanoic acid (OA) concentrations were approximately 100-fold higher. The half-life of OA was 87.6 minutes. This was matched by a clinical reduction in tremor severity of 32% at 90 minutes, assessed using spirography. The safety profile was favorable, with the most commonly reported adverse effect being dysgeusia (38%). Early detection and higher plasma concentrations of OA are a product of rapid metabolism of 1-octanol.OA pharmacokinetics mirrored the timing of clinical improvement. These findings provide preliminary evidence for a new class of compound that may be effective in the treatment of ET.
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An update on psychogenic movement disorders.
Curr Neurol Neurosci Rep
PUBLISHED: 05-12-2011
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Psychogenic movement disorders (PMD) and other conversion disorders (CD) with apparent neurologic signs (neurologic CD) plague patients and perplex physicians. Due to a lack of objective evidence of underlying brain lesions, CD were largely abandoned by neurologists and remained poorly understood psychiatric diagnoses throughout most of the 20th century. Modern neuroscience now supports increasingly comprehensive biological models for these complex disorders, definitively establishing their place in both neurology and psychiatry. Although it is often clinically useful to distinguish a movement disorder as either "organic" or "psychogenic," this dichotomy is difficult to defend scientifically. Here we describe the neuroimaging and neurophysiologic evidence for dysfunctional neural networks in PMD, explain the diagnostic potential of clinical neurophysiologic testing, discuss the promising if increasingly complex role of neuropsychiatric genetics, and review current treatment strategies.
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Sensory sensitivity to external stimuli in Tourette syndrome patients.
Mov. Disord.
PUBLISHED: 05-11-2011
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Patients with Tourette Syndrome often state that their sensitivity to sensations is equally or more disruptive than are motor tics. However, their sensory sensitivity is not addressed by standard clinical assessments nor is it a focus of research. This lapse likely results from our limited awareness and understanding of the symptom. In this study (1) we defined the patients experience of sensitivity to external stimuli in detail, and (2) we tested 2 hypotheses regarding its origin. First, we interviewed in depth and administered a lengthy questionnaire to adult Tourette patients (n = 19) and age-matched healthy volunteers (n = 19). Eighty percent of patients described heightened sensitivity to external stimuli, with examples among all 5 sensory modalities. Bothersome stimuli were characterized as faint, repetitive or constant, and nonsalient, whereas intense stimuli were well tolerated. We then determined whether the sensitivity could be the result of an increased ability to detect faint stimuli. After measuring the threshold of detection for olfactory and tactile stimuli among the patients and healthy volunteers, we found no significant differences between them for either sensory modality. These results indicate that patients perceived sensitivity derives from altered central processing rather than enhanced peripheral detection. Last, we assessed one aspect of processing: the perception of intensity. When subjects rated the intensity of near-threshold tactile and olfactory stimuli, there was a surprising difference: Tourette patients more frequently used the lowest range of the scale than did healthy volunteers. Future research is necessary to define the anatomical and physiological basis of the patients experience of heightened sensitivity. © 2011 Movement Disorder Society.
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Neural correlates of blink suppression and the buildup of a natural bodily urge.
Neuroimage
PUBLISHED: 05-09-2011
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Neuroimaging studies have elucidated some of the underlying physiology of spontaneous and voluntary eye blinking; however, the neural networks involved in eye blink suppression remain poorly understood. Here we investigated blink suppression by analyzing fMRI data in a block design and event-related manner, and employed a novel hypothetical time-varying neural response model to detect brain activations associated with the buildup of urge. Blinks were found to activate visual cortices while our block design analysis revealed activations limited to the middle occipital gyri and deactivations in medial occipital, posterior cingulate and precuneus areas. Our model for urge, however, revealed a widespread network of activations including right greater than left insular cortex, right ventrolateral prefrontal cortex, middle cingulate cortex, and bilateral temporo-parietal cortices, primary and secondary face motor regions, and visual cortices. Subsequent inspection of BOLD time-series in an extensive ROI analysis showed that activity in the bilateral insular cortex, right ventrolateral prefrontal cortex, and bilateral STG and MTG showed strong correlations with our hypothetical model for urge suggesting these areas play a prominent role in the buildup of urge. The involvement of the insular cortex in particular, along with its function in interoceptive processing, helps support a key role for this structure in the buildup of urge during blink suppression. The right ventrolateral prefrontal cortex findings in conjunction with its known involvement in inhibitory control suggest a role for this structure in maintaining volitional suppression of an increasing sense of urge. The consistency of our urge model findings with prior studies investigating the suppression of blinking and other bodily urges, thoughts, and behaviors suggests that a similar investigative approach may have utility in fMRI studies of disorders associated with abnormal urge suppression such as Tourette syndrome and obsessive-compulsive disorder.
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Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder.
Mov. Disord.
PUBLISHED: 05-01-2011
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Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2-button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top-down regulation.
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Extreme task specificity in writers cramp.
Mov. Disord.
PUBLISHED: 04-27-2011
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Focal hand dystonia may be task specific, as is the case with writers cramp. In early stages, task specificity can be so specific that it may be mistaken for a psychogenic movement disorder.
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Alteration of brain default network in subacute phase of injury in concussed individuals: resting-state fMRI study.
Neuroimage
PUBLISHED: 04-26-2011
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There are a number of symptoms, both neurological and behavioral, associated with a single episode of r mild traumatic brain injury (mTBI). Neuropsychological testing and conventional neuroimaging techniques are not sufficiently sensitive to detect these changes, which adds to the complexity and difficulty in relating symptoms from mTBI to their underlying structural or functional deficits. With the inability of traditional brain imaging techniques to properly assess the severity of brain damage induced by mTBI, there is hope that more advanced neuroimaging applications will be more sensitive, as well as specific, in accurately assessing mTBI. In this study, we used resting state functional magnetic resonance imaging to evaluate the default mode network (DMN) in the subacute phase of mTBI. Fourteen concussed student-athletes who were asymptomatic based upon clinical symptoms resolution and clearance for aerobic exercise by medical professionals were scanned using resting state functional magnetic resonance imaging. Nine additional asymptomatic yet not medically cleared athletes were recruited to investigate the effect of a single episode of mTBI versus multiple mTBIs on the resting state DMN. In concussed individuals the resting state DMN showed a reduced number of connections and strength of connections in the posterior cingulate and lateral parietal cortices. An increased number of connections and strength of connections was seen in the medial prefrontal cortex. Connections between the left dorso-lateral prefrontal cortex and left lateral parietal cortex showed a significant reduction in magnitude as the number of concussions increased. Regression analysis also indicated an overall loss of connectivity as the number of mTBI episodes increased. Our findings indicate that alterations in the brain resting state default mode network in the subacute phase of injury may be of use clinically in assessing the severity of mTBI and offering some insight into the pathophysiology of the disorder.
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Validation of digital spiral analysis as outcome parameter for clinical trials in essential tremor.
Mov. Disord.
PUBLISHED: 04-21-2011
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Essential tremor, one of the most prevalent movement disorders, is characterized by kinetic and postural tremor affecting activities of daily living. Spiral drawing is commonly used to visually rate tremor intensity, as part of the routine clinical assessment of tremor and as a tool in clinical trials. We present a strategy to quantify tremor severity from spirals drawn on a digitizing tablet. We validate our method against a well-established visual spiral rating method and compare both methods on their capacity to capture a therapeutic effect, as defined by the change in clinical essential tremor rating scale after an ethanol challenge. Fifty-four Archimedes spirals were drawn using a digitizing tablet by nine ethanol-responsive patients with essential tremor before and at five consecutive time points after the administration of ethanol in a standardized treatment intervention. Quantitative spiral tremor severity was estimated from the velocity tremor peak amplitude after numerical derivation and Fourier transformation of pen-tip positions. In randomly ordered sets, spirals were scored by seven trained raters, using Bain and Findleys 0 to 10 rating scale. Computerized scores correlated with visual ratings (P < 0.0001). The correlation was significant at each time point before and after ethanol (P < 0.005). Quantitative ratings provided better sensitivity than visual rating to capture the effects of an ethanol challenge (P < 0.05). Using a standardized treatment approach, we were able to demonstrate that spirography time-series analysis is a valid, reliable method to document tremor intensity and a more sensitive measure for small effects than currently available visual spiral rating methods.
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Thalamic neuronal and EMG activity in psychogenic dystonia compared with organic dystonia.
Mov. Disord.
PUBLISHED: 04-15-2011
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This is a retrospective analysis of thalamic neuronal and electromyogram activities between subjects with organic dystonia and a subject with psychogenic dystonia in whom a thalamotomy was carried out before the diagnosis of psychogenic dystonia was made.
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Reorganization of brain functional small-world networks during finger movements.
Hum Brain Mapp
PUBLISHED: 04-11-2011
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A functional measure of brain organization is the efficiency of functional connectivity. The degree of functional connectivity can differ during a task compared to the rest, and to study this issue, we investigated the functional connectivity networks in healthy subjects during a simple, right-handed, sequential finger-tapping task using graph theoretic measures. EEGs were recorded from 58 channels in 15 healthy subjects at rest and during a motor task. We estimated mutual information values of wavelet coefficients to create an association matrix between EEG electrodes and produced a series of adjacency matrices or graphs, A, by thresholding with network cost. These graphs are called small-world networks, and we assessed their efficiency measures. We found economical small-world properties in brain functional connectivity networks in the alpha and beta band networks. The efficiency of the brain networks was enhanced during the task in the beta band networks, but not in the alpha band networks. A regional efficiency analysis during the task showed that the bilateral primary motor and left sensory areas showed increased nodal efficiency, Enodal, whereas decreased Enodal was found over the posterior parietal areas. The present study provides evidence for the reorganization of brain functional connectivity networks in a motor task with the greatest increase in Enodal in motor executive areas.
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Self-modulation of primary motor cortex activity with motor and motor imagery tasks using real-time fMRI-based neurofeedback.
Neuroimage
PUBLISHED: 04-05-2011
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Advances in fMRI data acquisition and processing have made it possible to analyze brain activity as rapidly as the images are acquired allowing this information to be fed back to subjects in the scanner. The ability of subjects to learn to volitionally control localized brain activity within motor cortex using such real-time fMRI-based neurofeedback (NF) is actively being investigated as it may have clinical implications for motor rehabilitation after central nervous system injury and brain-computer interfaces. We investigated the ability of fifteen healthy volunteers to use NF to modulate brain activity within the primary motor cortex (M1) during a finger tapping and tapping imagery task. The M1 hand area ROI (ROI(m)) was functionally localized during finger tapping and a visual representation of BOLD signal changes within the ROI(m) fed back to the subject in the scanner. Surface EMG was used to assess motor output during tapping and ensure no motor activity was present during motor imagery task. Subjects quickly learned to modulate brain activity within their ROI(m) during the finger-tapping task, which could be dissociated from the magnitude of the tapping, but did not show a significant increase within the ROI(m) during the hand motor imagery task at the group level despite strongly activating a network consistent with the performance of motor imagery. The inability of subjects to modulate M1 proper with motor imagery may reflect an inherent difficulty in activating synapses in this area, with or without NF, since such activation may lead to M1 neuronal output and obligatory muscle activity. Future real-time fMRI-based NF investigations involving motor cortex may benefit from focusing attention on cortical regions other than M1 for feedback training or alternative feedback strategies such as measures of functional connectivity within the motor system.
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