Showing papers by "Mark Hallett published in 2011"
TL;DR: 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.
Abstract: 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.
950 citations
TL;DR: On behalf of all coauthors of the safety paper, they apologize to the scientific community, and provide a revised 13-item screening questionnaire, which should replace the previous one.
439 citations
TL;DR: The pathophysiology of dystonia has been best studied in patients with focal hand dySTONia, and a possible hypothesis is that there is a genetic loss of inhibitory interneurons in Dystonia and that this deficit is a substrate on which other factors can act to produce dystonIA.
306 citations
TL;DR: It is 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, and 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.
Abstract: 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.
212 citations
TL;DR: Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum, providing a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals.
Abstract: Impulse control disorders are common in Parkinson's; 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 Parkinson's; 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 Parkinson's; 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 Parkinson's; 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 Parkinson's; 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.
209 citations
TL;DR: 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 is proposed.
Abstract: 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.
201 citations
TL;DR: The findings highlight a biopsychosocial approach toward the pathophysiology of psychogenic movement disorder, although the association with psychological issues is much less prominent than expected compared with the nonepileptic seizure population.
Abstract: Psychogenic movement disorder is defined as abnormal movements unrelated to a medical cause and presumed related to underlying psychological factors. Although psychological factors are of both clinical and pathophysiological relevance, very few studies to date have systematically assessed their role in psychogenic movement disorder. We sought to assess the role of previous life stress using validated quantitative measures in patients with psychogenic movement disorder compared with age- and sex-matched healthy volunteers as well as a convenience sample of patients with focal hand dystonia. Sixty-four patients with psychogenic movement disorder (72% female; mean age, 45.2 years [standard deviation, 15.2 years]), 38 healthy volunteers (74% female; mean age, 49 years [standard deviation, 13.7 years]), and 39 patients with focal hand dystonia (37% female; mean age, 48.7 years [standard deviation, 11.7 years]) were evaluated using a standardized psychological interview as well as validated quantitative scales to assess trauma and previous stressors, depression, anxiety, and personality traits. Patients with psychogenic movement disorder reported higher rates of childhood trauma, specifically greater emotional abuse and physical neglect, greater fear associated with traumatic events, and a greater number of traumatic episodes compared with healthy volunteers and patients with focal hand dystonia controlled for depressive symptoms and sex (Bonferroni corrected P < .005). There were no differences in categorical psychiatric diagnoses or scores on childhood physical or sexual abuse subscales, personality traits, or the dissociative experience scale. Our findings highlight a biopsychosocial approach toward the pathophysiology of psychogenic movement disorder, although the association with psychological issues is much less prominent than expected compared with the nonepileptic seizure population. A careful psychological assessment is indicated to optimize therapeutic modalities.
191 citations
TL;DR: Functional MRI and psychophysiological interaction methods demonstrate that the pattern of interactions of brain networks is disrupted in PD during performance of self-initiated movements, and the striatum-cortical andstriatum-cerebellar connections are weakened.
190 citations
TL;DR: There are more connectivity changes of networks related to motor preparation and initiation than to networks of motor execution in PD, and disrupted connections indicate a lack of readiness for movement and may be partly responsible for difficulty in initiating movements in PD.
Abstract: Parkinson's disease (PD) patients have difficulty in initiating movements. Previous studies have suggested that the abnormal brain activity may happen not only during performance of self-initiated movements but also in the before movement (baseline or resting) state. In the current study, we investigated the functional connectivity of brain networks in the resting state in PD. We chose the rostral supplementary motor area (pre-SMA) and bilateral primary motor cortex (M1) as “seed” regions, because the pre-SMA is important in motor preparation, whereas the M1 is critical in motor execution. FMRIs were acquired in 18 patients and 18 matched controls. We found that in the resting state, the pattern of connectivity with both the pre-SMA or the M1 was changed in PD. Connectivity with the pre-SMA in patients with PD compared to normal subjects was increased connectivity to the right M1 and decreased to the left putamen, right insula, right premotor cortex, and left inferior parietal lobule. We only found stronger connectivity in the M1 with its own local region in patients with PD compared to controls. Our findings demonstrate that the interactions of brain networks are abnormal in PD in the resting state. There are more connectivity changes of networks related to motor preparation and initiation than to networks of motor execution in PD. We postulate that these disrupted connections indicate a lack of readiness for movement and may be partly responsible for difficulty in initiating movements in PD. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.
190 citations
Book•
01 Jan 2011
TL;DR: This chapter discusses the clinical overview and phenomenology of movement disorders and current concepts on the etiology and pathogenesis of Parkinson disease.
Abstract: Section I: Overview 1. Clinical overview and phenomenology of movement disorders 2. Motor control: Physiology of voluntary and involuntary movements 3. Functional neuroanatomy of the basal ganglia Section II: Hypokinetic disorders 4. Parkinsonism: Clinical features and differential diagnosis 5. Current concepts on the etiology and pathogenesis of Parkinson disease 6. Medical treatment of Parkinson disease 7. Surgical treatment of Parkinson disease and other movement disorders 8. Nonmotor problems in Parkinson disease 9. Atypical parkinsonism, parkinsonism-plus syndromes, and secondary parkinsonian disorders 10. Gait disorders: Pathophysiology and clinical syndromes 11. Stiffness syndromes Section III: Hyperkinetic disorders 12. Dystonia: Phenomenology, classification, etiology, pathology, biochemistry, and genetics 13. Treatment of dystonia 14. Huntington disease 15. Chorea, ballism, and athetosis 16. Tics and Tourette syndrome 17. Stereotypies 18. Tremors 19. The tardive syndromes: Phenomenology, concepts on pathophysiology and treatment, and other neuroleptic-induced syndromes 20. Myoclonus: Phenomenology, etiology, physiology, and treatment 21. Ataxia: Pathophysiology and clinical syndromes 22. The paroxysmal dyskinesias 23. Restless legs and peripheral movement disorders 24. Wilson disease 25. Psychogenic movement disorders: Phenomenology, diagnosis, and treatment Index
185 citations
TL;DR: The successful prediction of human movement intention will provide further insight into how the brain prepares for movement, as well as the potential for direct cortical control of a device which may be faster than normal physical control.
TL;DR: Recent large-scale studies and converging findings are beginning to provide an understanding of mechanisms underlying ICDs in Parkinson's disease, which can guide prevention of these behaviours and optimize therapeutic approaches.
Abstract: Purpose of review—To review the recent advances in the epidemiology and pathophysiology of impulse control disorders (ICD) in Parkinson’s disease (PD). Recent findings—Large cross-sectional and case-control multicentre studies show that ICDs in PD are common with a frequency of 13.6%. These behaviours are associated with impaired functioning and with depressive, anxiety and obsessive symptoms, novelty seeking and impulsivity. Behavioural subtypes demonstrate differences in novelty seeking and impulsivity suggesting pathophysiological differences. Observational and neurophysiological studies point towards a potential mechanistic overlap between the behavioural (ICDs) and motor (dyskinesias) dopaminergic sequelae. Converging data suggest dopamine agonists in ICDs appear to enhance learning from rewarding outcomes and impulsive choice. ICD patients also have enhanced risk preference and impaired working memory. Neuroimaging data points towards enhanced bottomup ventral striatal dopamine release to incentive cues, gambling tasks and reward prediction, and possibly inhibition of top-down orbitofrontal influences. Dopamine agonist-related ventral striatal hypoactivity to risk is consistent with impaired risk evaluation. Summary—Recent large scale studies and converging findings are beginning to provide an understanding of mechanisms underlying ICDs in PD which can guide prevention of these behaviours and optimize therapeutic approaches.
TL;DR: Major findings clearly indicate that functional brain alterations in the acute phase of injury are overlooked when conventional clinical and neuropsychological examinations are used, and may reveal subtle alterations of functional brain connections in asymptomatic mTBI subjects.
TL;DR: A novel, ecologically valid, virtual-reality experiment using blood oxygen level-dependent functional magnetic resonance imaging (fMRI) where SA could be modulated in real-time while subjects performed voluntary finger movements demonstrated paradigm validity along with the identification of a bias that led subjects to over- or underestimate the amount of control they had.
Abstract: Self-agency (SA) is the individual's perception that an action is the consequence of his/her own intention. The neural networks underlying SA are not well understood. We carried out a novel, ecologically valid, virtual-reality experiment using blood oxygen level–dependent functional magnetic resonance imaging (fMRI) where SA could be modulated in real-time while subjects performed voluntary finger movements. Behavioral testing was also performed to assess the explicit judgment of SA. Twenty healthy volunteers completed the experiment. Results of the behavioral testing demonstrated paradigm validity along with the identification of a bias that led subjects to over- or underestimate the amount of control they had. The fMRI experiment identified 2 discrete networks. These leading and lagging networks likely represent a spatial and temporal flow of information, with the leading network serving the role of mismatch detection and the lagging network receiving this information and mediating its elevation to conscious awareness, giving rise to SA.
TL;DR: The process is enhanced with handedness and task difficulty indicating that it may be an important mechanism for the performance of individuated finger movements, and several intracortical inhibitory networks are modulated differently in FHD compared with healthy subjects, and these may contribute to the loss of surround inhibition.
Abstract: Surround inhibition is a physiological mechanism to focus neuronal activity in the central nervous system. This so-called center-surround organization is well known in sensory systems, where central signals are facilitated and eccentric signals are inhibited in order to sharpen the contrast between them. There is evidence that this mechanism is relevant to skilled motor behavior, and it is deficient, for example, in the affected primary motor cortex of patients with focal hand dystonia (FHD). While it is still not fully elucidated how surround inhibition is generated in healthy subjects, the process is enhanced with handedness and task difficulty indicating that it may be an important mechanism for the performance of individuated finger movements. In FHD, where involuntary overactivation of muscles interferes with precise finger movements, a loss of intracortical inhibition likely contributes to the loss of surround inhibition. Several intracortical inhibitory networks are modulated differently in FHD compared with healthy subjects, and these may contribute to the loss of surround inhibition. Surround inhibition can be observed and assessed in the primary motor cortex. It remains unclear, however, if the effects are created in the cortex or if they are derived from, or supported by, motor signals that come from the basal ganglia.
TL;DR: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.
Abstract: Objective: To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Background: Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. Methods: In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson9s Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. Results: We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. Conclusion: iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. Classification of evidence: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.
TL;DR: The findings provide the first evidence for plasticity of interhemispheric connections to mediate cross education produced by a simple motor task.
Abstract: Introduction: Chronic unimanual motor practice increases the motor output not only in the trained but also in the nonexercised homologous muscle in the opposite limb. We examined the hypothesis that adaptations in motor cortical excitability of the nontrained primary motor cortex (iM1) and in interhemispheric inhibition from the trained to the nontrained M1 mediate this interlimb cross education. Methods: Healthy, young volunteers (n = 12) performed 1000 submaximal voluntary contractions (MVC) of the right first dorsal interosseus (FDI) at 80% MVC during 20 sessions. Results: Trained FDI's MVC increased 49.9%, and the untrained FDI's MVC increased 28.1%. Although corticospinal excitability in iM1, measured with transcranial magnetic stimulation (TMS) before and after every fifth session, increased 6% at rest, these changes, as those in intracortical inhibition and facilitation, did not correlate with cross education. When weak and strong TMS of iM1 were delivered on a background of a weak and strong muscle contraction, respectively, of the right FDI, excitability of iM1 increased dramatically after 20 sessions. Interhemispheric inhibition decreased 8.9% acutely within sessions and 30.9% chronically during 20 sessions and these chronic reductions progressively became more strongly associated with cross education. There were no changes in force or TMS measures in the trained group's left abductor minimi digiti and there were no changes in the nonexercising control group (n = 8). Conclusions: The findings provide the first evidence for plasticity of interhemispheric connections to mediate cross education produced by a simple motor task.
TL;DR: It is indicated that patients' perceived sensitivity derives from altered central processing rather than enhanced peripheral detection, and one aspect of processing: the perception of intensity.
Abstract: Lastly, 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 compared with healthy volunteers. Future research is necessary to define the anatomical and physiological basis of the patients’ experience of heightened sensitivity.
TL;DR: This prospective within-subject VBM study in task-specific hand dystonia shows that the grey matter density of M1(HAND) is dynamically shaped by the level of manual activity, which is functionally relevant as local grey matter changes are mirrored by changes in regional excitability.
TL;DR: Using a standardized treatment approach, it is demonstrated 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.
Abstract: 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 Findley's 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.
TL;DR: Seven neurologists independently reviewed YouTube videos of patients described as having dystonia, Parkinsonism, chorea, myoclonus, tics, or tremor and rated 19 of 29 popular videos as actually showing psychogenic movement disorders rather the conditions listed.
Abstract: Seven neurologists independently reviewed YouTube videos of patients described as having dystonia, Parkinsonism, chorea, myoclonus, tics, or tremor These experts rated 19 of 29 popular videos as actually showing psychogenic movement disorders rather the conditions listed
TL;DR: In this paper, the authors explored the efficacy and safety of BoNT treatment for FHD, but none have followed a large number of patients for 10 or more years, and none have evaluated the safety of the treatment.
Abstract: Background
Prior studies have explored the efficacy and safety of BoNT treatment for FHD, but none have followed a large number of patients for 10 or more years.
TL;DR: Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp, and subjective worsening remained unexplained, leading to premature study termination.
Abstract: The treatment of writer's cramp, a task-specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double-blind, sham-controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2-week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp.
TL;DR: The abnormal beta‐band functional connectivity in focal hand dystonia patients suggests deficient brain connectivity and mutual information differences were from linear connectivity.
Abstract: The aim of the present study was to investigate functional connectivity in focal hand dystonia patients to understand the pathophysiology underlying their abnormality in movement. We recorded EEGs from 58 electrodes in 15 focal hand dystonia patients and 15 healthy volunteers during rest and a simple finger-tapping task that did not induce any dystonic symptoms. We investigated mutual information, which provides a quantitative measure of linear and nonlinear coupling, in the alpha, beta, and gamma bands. Mean mutual information of all 58 channels and mean of the channels of interest representative of regional functional connectivity over sensorimotor areas (C3, CP3, C4, CP4, FCz, and Cz) were evaluated. For both groups, we found enhanced mutual information during the task compared with the rest condition, specifically in the beta and gamma bands for mean mutual information of all channels, and in all bands for mean mutual information of channels of interest. Comparing the focal hand dystonia patients with the healthy volunteers for both rest and task, there was reduced mutual information in the beta band for both mean mutual information of all channels and mean mutual information of channels of interest. Regarding the properties of the connectivity in the beta band, we found that the majority of the mutual information differences were from linear connectivity. The abnormal beta-band functional connectivity in focal hand dystonia patients suggests deficient brain connectivity.
TL;DR: Patients with benign essential blepharospasm are characterized by diagnosis, environmental risk factors, and family history.
Abstract: Background and purpose:To characterize patients with benign essential blepharospasm (BEB) by diagnosis, environmental risk factors, and family history. Methods:Two hundred and forty patients with BEB were evaluated through a clinical examination and questionnaire. The questionnaire reviewed personal medical history, demographic factors, risk factors for the development of blepharospasm and family history of dystonia and other neurological conditions. Results:Benign essential blepharospasm was more commonly found in women (2.8:1) and 93% of the patients were Caucasian. Fifty percent had pure BEB, 31% had BEB/Meige!s syndrome, and 4% had BEB and eyelid opening apraxia (+/)Meige!s syndrome). A minority of patients reported preceding photophobia (25%) or other eye conditions (22%). The majority were non-smokers, had no exposure to anti-emetic or antipsychotic agents, had a normal birth history, and had no history of head trauma. Seventy-two percent did report a stressful event immediately prior to the development of symptoms. Treatments reported included botulinum toxin (BoNT), oral medications, surgical procedures, and acupuncture. Thirty-two percent of patients reported a family history of focal dystonia, and BEB was the most commonly reported. Conclusion:This study confirms previous reports of usual age, sex, ca!eine and tobacco use, and family history in patients with blepharospasm. New findings include a report on occupation, lower reports of preceding eye conditions and photophobia, and higher reported stressful events. Further, this study shows a change in treatment with an increase in BoNT use and decrease in surgical procedures.
TL;DR: Progress in pathophysiology includes improved knowledge about bradykinesia in Parkinson's disease, loss of inhibition and increased plasticity in dystonia, abnormal startle in hyperekplexia, and various features of psychogenic movement disorders that can aid diagnosis.
Abstract: 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 Parkinson's 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.
TL;DR: The present study provides the first evidence with graph theory for abnormal reconfiguration of brain functional networks in FHD during motor task, and finds that FHD patients have economical small-world properties in their brainfunctional networks in the alpha and beta bands.
Abstract: 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.
TL;DR: The neuroimaging and neurophysiologic evidence for dysfunctional neural networks in PMD is described, the diagnostic potential of clinical neurophysiological testing is explained, the promising if increasingly complex role of neuropsychiatric genetics is discussed, and current treatment strategies are reviewed.
Abstract: 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.
TL;DR: The approach to patients with psychogenic movement disorders from the perspective of neurology and psychiatry is described, illustrating the differences in terminology and categorization.
TL;DR: The most significant finding was the identification of octanoic acid as the product of rapid 1-octanol metabolism, which provides preliminary evidence for a new class of compound that may be effective in the treatment of ET.