Hypokinetic Movement Disorders Research Articles

Symptomatic Treatment of Huntington Disease

Huntington disease (HD) is a progressive heredoneurodegenerative disease manifested by chorea and other hyperkinetic (dystonia, myoclonus, tics) and hypokinetic (parkinsonism) movement disorders. In addition, a variety of psychiatric and behavioral symptoms, along with cognitive decline, contribute significantly to the patient's disability. Because there are no effective neuroprotective therapies that delay the progression of the disease, symptomatic treatment remains the cornerstone of medical management. Several classes of medications have been used to ameliorate the various symptoms of HD, including typical and atypical neuroleptics, dopamine depleters, antidepressants, antiglutamatergic drugs, GABA agonists, antiepileptic medications, acetylcholinesterase inhibitors, and botulinum toxin. Recently, surgical approaches including pallidotomy, deep brain stimulation, and fetal cell transplants have been used for the symptomatic treatment of HD. The selected therapy must be customized to the needs of each patient, minimizing the potential adverse effects. The primary aim of this article is to review the role of the different therapies, both available and investigational, for the treatment of the motor, psychiatric, behavioral, and cognitive symptoms of HD, and to examine their impact on the patient's functionality and quality of life.

脳内埋め込み電極と体内埋設型刺激デバイスを用いた不随意運動の治療

In an attempt to control hypokinetic and hyperkinetic movement disorders, deep brain stimulation (DBS) has been developed during the last two decades by several investigators. In 1987, Benabid and his colleagues suggested the usefulness of high-frequency stimulation of the ventral intermediate nucleus of the thalamus for treating drug-resistant tremors and avoiding the adverse effects of thalamotomy. Since then, DBS has been used as an alternative to functional neurosurgery for movement disorders, and more recently, it has been applied to the treatment of epilepsy, obsessive-compulsive disorders and cluster headache, in addition to other applications in experimental models. In regard to the treatment of movement disorders, recent clinical studies have demonstrated that DBS affords great benefits in terms of improvement of the activities of daily living in patients with Parkinson's disease (PD), essential tremor, dystonia and poststroke hyperkinetic movement disorders. We have treated patients with movement disorders by DBS of the thalamic nuclei ventralis oralis (Voa/Vop) et intermedius (Vim), globus pallidus internus (GPi), and subthalamic nucleus (STN). The site of permanent electrode placement was identified using magnetic resonance imaging and multiunit extracellular recording. The implantable pulse generator was internalized after postoperative test stimulation for one week. The stimulation parameters were modified by physicians at each follow-up visit on the basis of the findings on neurological examination, as well as the patient's report concerning the activities of daily living. The advantages of DBS include reversibility and controllability of stimulation. In addition, DBS carries a smaller risk of side effects, particularly when employed bilaterally. Thalamic DBS is useful for controlling tremor that is unresponsive to medication. DBS of the STN and GPi improves the motor functions in PD patients, mainly during the off-period. Moreover, STN-DBS attenuates levodopa-induced dyskinesia through reducing the requirement of DOPA, whereas GPi-DBS directly attenuates DOPA-induced dyskinesia. In addition, GPi-DBS is very useful for controlling the symptoms of idiopatic generalized dystonia. According to reports, DBS is associated with few serious adverse effects associated with DBS. In general, the operative mortality is less than 1%. The incidences of hemorrhage are in the range of about 1-6%, and the incidences of device-related complications, such as infection or skin erosion, are in the range of 3-26%. DBS is clinically effective in well-selected patients and should be considered as a treatment option for patients with medically refractory movement disorders. Despite its clinical usefulness, the mechanism underlying the efficacy of DBS is still unclear. There is no proof currently that long-term DBS can reset neural networks or induce profound modifications of functional organization. Several researchers have proposed hypotheses concerning the mechanism underlying the efficacy of DBS, including 1) jamming of neural transmission, 2) direct inhibition of spike initiation at the level of the membrane that may be due to the activation of inhibitory terminals, 3) functional changes due to a decrease or increase in the amount of neurotransmitter released, and 4) retrograde activation of upstream neural structures. From the viewpoint of basic neuroscience, the development of DBS is intriguing. Investigation regarding the mechanism underlying the efficacy of DBS may provide clues for further clarification of various processes in the central nervous system.

Psychopathology in Verified Huntington's Disease Gene Carriers

Psychopathology in Verified Huntington's Disease Gene Carriers

Long-term prognosis of patients with psychogenic movement disorders

Psychogenic movement disorders (PMD) are hyper- or hypokinetic movement disorders associated with underlying psychological or psychiatric disorders. Structured telephone interview was administered to 228 patients with PMD seen in our clinic between 1990 and 2003. The mean age of the subjects was 42.3±14.3 years (range 14–70 years), mean duration of symptoms was 4.7±8.1 years (range 2–14 years), and mean duration of follow-up was 3.4±2.8 years (6 months–12 years). Improvement of symptoms was noted in 56.6% patients; while 22.1% were worse, and 21.3% remained the same at the time of follow-up. In this longitudinal study of patients with PMD we found that indices of strong physical health, positive social life perceptions, patient's perception of effective treatment by the physician, elimination of stressors, and treatment with a specific medication contributed to a favorable outcome.

Fragile X-associated tremor/ataxia syndrome and movements disorders

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a multiple-system neurologic disorder caused by expansion of 55-200 CGG repeats in the FMR1 (fragile site mental retardation 1) gene. The presence of both hyperkinetic and hypokinetic movement disorders such as ataxia, tremor, and parkinsonism are clinical features of FXTAS. The purpose of this review is to summarize the description of movement disorders associated with FXTAS and to discuss recent observations regarding the relationship between abnormal expansion in the FMR1 gene and development of neurodegenerative disorders. The clinical expression of FXTAS occasionally resembles the phenotypes of other idiopathic neurodegenerative disorders. However, the unique pathological feature - appearance of the intranuclear inclusions in the neurons and astrocytes, is discriminatory from those in other neurodegenerative disorders. Several studies found no association between the FMR1 gene premutation and development of other neurodegenerative disorders with similar movement disorders to FXTAS. However, a premutation expansion in the FMR1 gene may be a frequent genetic cause of late-onset sporadic ataxia with magnetic-resonance-image abnormality. FXTAS exhibits various movement-disorder phenotypes. However, the FMR1 gene premutation is unlikely to be a common genetic cause of neurodegenerative disorders with tremor or ataxia. Patients with sporadic late-onset ataxia associated with magnetic-resonance-image abnormality should be considered for testing for a CGG-repeat expansion in the FMR1 gene.

Borrowing from models of motor control to translate cognitive processes: Evidence for hypokinetic–hyperkinetic linguistic homologues?

In relation to motor control, the basal ganglia have been implicated in both the scaling and focusing of movement. Hypokinetic and hyperkinetic movement disorders manifest as a consequence of overshooting and undershooting GPi (globus pallidus internus) activity thresholds, respectively. Recently, models of motor control have been borrowed to translate cognitive processes relating to the overshooting and undershooting of GPi activity, including attention and executive function. Linguistic correlates, however, are yet to be extrapolated in sufficient detail. The aims of the present investigation were to: (1) characterise cognitive–linguistic processes within hypokinetic and hyperkinetic neural systems, as defined by motor disturbances; (2) investigate the impact of surgically-induced GPi lesions upon language abilities. Two Parkinsonian cases with opposing motor symptoms (akinetic versus dystonic/dyskinetic) served as experimental subjects in this research. Assessments were conducted both prior to as well as 3 and 12 months following bilateral posteroventral pallidotomy (PVP). Reliable changes in performance (i.e. both improvements and decrements) were typically restricted to tasks demanding complex linguistic operations across subjects. Hyperkinetic motor symptoms were associated with an initial overall improvement in complex language function as a consequence of bilateral PVP, which diminished over time, suggesting a decrescendo effect relative to surgical beneficence. In contrast, hypokinetic symptoms were associated with a more stable longitudinal linguistic profile, albeit defined by higher proportions of reliable decline versus improvement in postoperative assessment scores. The above findings endorsed the integration of the GPi within cognitive mechanisms involved in the arbitration of complex language functions. In relation to models of motor control, ‘focusing’ was postulated to represent the neural processes underpinning lexical-semantic manipulation, and ‘scaling’ the potential allocation of cognitive resources during the mediation of high-level linguistic tasks.

Psychogenic movement disorders: diagnosis and management.

Psychogenic movement disorders (PMDs) are best defined as hyper- or hypo-kinetic movement disorders, often associated with gait disorders, that cannot be directly attributed to a lesion or dysfunction of the nervous system and which are derived in most cases from psychological or psychiatric causes. There are a variety of PMDs including tremor, dystonia, parkinsonism, gait disorders and, even, unusual forms including paroxysmal dyskinesias. As has been recognised in the recent literature, PMDs cannot be strictly classified into clearly defined psychiatric disorders such as somatoform, dissociative or conversion disorders. In this review, we discuss the diagnosis of various PMDs (including hyper- and hypo-kinetic disorders; and current evidence for underlying comorbid disorders) and the current therapeutic approach to them. The therapy of PMDs is not well established, is very challenging to the clinician, and a better outcome can be achieved in the setting of a team approach involving movement disorders specialists, psychiatrists and therapists who specialise in cognitive-behavioural techniques. Current pharmacological and non-pharmacological approaches to treatment focus on therapy of underlying comorbid psychiatric and psychological issues, although compliance is a major concern.

A review of the cognitive and behavioral sequelae of Parkinson's disease: relationship to frontostriatal circuitry.

Parkinson's disease is a neurodegenerative hypokinetic movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with Parkinson's disease can also exhibit cognitive and behavioral impairments. These impairments may be attributed to dysfunction of multiple systems associated with the disease process in Parkinson's disease that are not necessarily related to motor symptoms. In recent years, considerable attention has addressed the circuits connecting the frontal cortical regions and the basal ganglia (i.e., frontostriatal circuits) and how they mediate cognition and behavior in humans. It has been suggested that these same circuits are disrupted in Parkinson's disease and may be responsible for the frontal/executive deficits predominantly reported in this patient population. The current survey of the literature provides a critique and analysis of the neuropsychological profile of Parkinson's disease, including cognitive impairments, behavioral alterations, and emotional processing deficits. A special feature of this paper is to ascertain how frontostriatal circuitry might provide the substrate for the neuropsychological impairments exhibited in Parkinson's disease. In so doing, studies involving nonhuman subjects, neurologically healthy adults, brain-lesioned individuals, and patients with Parkinson's disease are reviewed to provide a novel perspective in conceptualizing and categorizing the cognitive and behavioral sequelae concomitant to specific frontostriatal circuit dysfunction in Parkinson's disease. The current review suggests that the neuropsychological profile of Parkinson's disease, which predominantly reflects frontal/executive dysfunction, may be attributed to disruption of the frontostriatal circuitry. The information generated from this review can serve as a guide in the assessment of frontal/executive dysfunction in Parkinson's disease with suggestions for a clinical neuropsychological test battery.

Movement Disorders in Children

1. Bradley L. Schlaggar, MD, PhD* 2. Jonathan W. Mink, MD, PhD† 1. *Assistant Professor of Neurology, Radiology, and Pediatrics, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, MO 2. †Associate Professor of Neurology, Neurobiology & Anatomy, and Pediatrics; Chief, Child Neurology, University of Rochester School of Medicine and Dentistry and Golisano Children’s Hospital at Strong, Rochester, NY. After completing this article, readers should be able to: 1. Describe the prevalence of tic disorder 2. Characterize the treatment of tic disorder 3. Explain how movement disorders can differ from autism and mental retardation 4. Describe the use of stimulant medication in the treatment of attention-deficit/hyperactivity disorder associated with a tic disorder 5. Compare and contrast dopa-responsive dystonia and cerebral palsy Supreme Court Justice Potter Stewart, in 1964, while trying to define “obscenity,” articulated the now well-known “I shall not today attempt to define the kinds of material I understand to be embraced … [b]ut I know it when I see it ….” In some respects, a similar comment can be made about movement disorders. A movement disorder typically is defined as dysfunction in the implementation of appropriate targeting and velocity of intended movements, dysfunction of posture, the presence of abnormal involuntary movements, or the performance of normal-appearing movements at inappropriate or unintended times. The movement abnormalities are not due to weakness or abnormal muscle tone, but may be accompanied by weakness or abnormal tone By convention, movement disorders are divided into two major categories. The first is hyperkinetic movement disorders, sometimes referred to as dyskinesias. This term refers to abnormal, repetitive involuntary movements and encompasses most of the childhood movement disorders, including tics, chorea/ballismus, dystonia, myoclonus, stereotypies, and tremor. The second category is hypokinetic movement disorders, sometimes referred to as akinetic/rigid disorders. The primary movement disorder in this category is parkinsonism, manifested primarily in adulthood as Parkinson disease or one of many forms of secondary parkinsonism. Hypokinetic disorders are relatively uncommon in children. Although ataxia, weakness, and spasticity are characterized by motor dysfunction, by common convention these entities are not included among “movement disorders.” This review focuses on dyskinesias because they represent the bulk of movement disorders in children The components of the …

Pathophysiology of dystonia: a neuronal model.

Dystonia has commonly been thought to represent a disorder of basal ganglia function. Although long considered a hyperkinetic movement disorder, the evidence to support such a classification was based on the presence of excessive involuntary movement, not on physiological data. Only recently, with the return of surgical procedures using microelectrode guidance for the treatment of dystonia, has electrophysiological data demonstrated an alteration in mean discharge rate, somatosensory responsiveness and the pattern of neuronal activity in the basal ganglia thalamocortical motor circuit. Previous models of dystonia suggested that reduced mean discharge rates in the globus pallidus internus (GPi) led to unopposed increases in activity in the thalamocortical circuit that precipitated the development of involuntary movement associated with dystonia. This model has subsequently been modified given the clear improvement in dystonic symptoms following lesions in the GPi, a procedure that is associated with a further reduction in pallidal output. The improvement in dystonia following pallidal lesions is difficult to reconcile with the "rate" hypothesis for hypokinetic and hyperkinetic movement disorders and has led to the development of alternative models that, in addition to rate, incorporate changes in pattern, somatosensory responsiveness and degree of synchronization of neuronal activity. Present models of dystonia, however, must not only take these changes into account but must reconcile these changes with the reported changes in cortical excitability reported with transcranial magnetic stimulation, the changes in metabolic activity in cortical and subcortical structures documented by positron emission tomography (PET), and the alterations in spinal and brainstem reflexes. A model incorporating these changes together with the reported changes in neuronal activity in the basal ganglia and thalamus is presented.

Parkinson's disease

Parkinson's disease (PD) is a hypokinetic movement disorder. The features of classicidiopathic PD are typified by bradykinesia, tremors, muscular rigidity, and postural instability. In PD, interest in the role of mitochondria initially revolved around respiratory-chain dysfunction. The biochemical changes observed in PD would suggest that mitochondria may be involved in other diverse but interrelated ways, including increased oxidative stress, excitotoxicity, and apoptosis. The description of rare mutations in the alpha synuclein and parkin genes confirmed the impression that PD may have a variety of causes in different patients. . A description of mitochondrial involvement in PD pathogenesis encompasses a number of processes at different points of the pathways leading to cell death. The description of mutations in the alpha-synuclein gene in autosomal dominant PD prompted renewed interest in the role of protein aggregation in the pathogenesis of PD. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model provided a significant advance in the understanding of the biochemical mechanisms involved in a parkinsonian syndrome and prompted investigation of whether these changes are present in idiopathic PD.

Compactotomy in Huntington's chorea

Advances in neuroradiological and neurosurgical techniques have lead to a growing interest in functional neurosurgical interventions for medically intractable movement disorders. The majority of these procedures are performed in patients with hypokinetic movement disorders, especially Parkinson's disease. However, relatively few interventions were done in hyperkinetic disorders such as Huntington's disease (HD), mainly owing to the lack of an adequate target nucleus. We have recently described the case of a reversible chorea in a genetically confirmed HD patient. We subsequently identified a marked bilateral degeneration of the substantia nigra as the probable reason for choreatic cessation. We therefore suggest that primary striatal atrophy causing hyperkinesia and secondary substantia nigra atrophy favouring hypokinesia were balanced in this patient, thus resulting in a close-to-physiologic GABAergic basal ganglia output. We postulate that deep brain stimulation of the substantia nigra pars compacta may ameliorate hyperkinesia in choreatic movement disorders, thus representing the first effective therapy in Huntington's chorea. Several lines of evidence in recent neurophysiological research support our hypothesis and are discussed below.

Movement disorders and normal aging

As the population continues to age, it has become increasingly important for clinicians to recognize the clinical characteristics of normal aging. Impaired mobility is one of the most frequent effects of normal aging, and this necessitates a specific understanding of the effects of normal aging on the motor system. This article reviews the physiological basis and clinical manifestations of normal aging as related to movement disorders. The impact of normal aging on major hypokinetic and hyperkinetic movement disorders is also discussed.

Transcranial Magnetic Stimulation in Neuropsychiatry

Back to table of contents Previous article Next article Book ReviewsFull AccessTranscranial Magnetic Stimulation in NeuropsychiatryShirlene M. Sampson, M.D.Shirlene M. SampsonSearch for more papers by this author, M.D.Published Online:1 Nov 2000AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Transcranial magnetic stimulation (TMS) is an exciting new technology in which a rapid, brief magnetic pulse induces a secondary current in brain tissue. In addition to being a novel means of brain stimulation, it is unique in that it can be used to study brain neurophysiology and may have therapeutic applications for a number of neuropsychiatric disorders. TMS has been a rapidly growing subject of research since its initial development in 1985 and has been used by researchers from multiple disciplines (e.g., neurologists, neuroscientists, physicists, psychiatrists, and psychologists).Because TMS is a technology with multiple applications, any book reviewing this topic has the challenge of meeting the needs of readers with differing interests. This book is a comprehensive yet basic and readable TMS primer covering a broad spectrum of issues in TMS research, and it will likely serve the needs of readers from multiple disciplines.The book progresses logically from the historical origins of TMS, reviewed by the editors, to the physics involved in this technology, reviewed by Dr. Bohning. The overview of TMS physics begins with the basics; however, the discussion of complex mathematics is likely more than most readers require. Clearly there was an attempt to combine information for those wishing to become proficient in using TMS and those seeking a basic understanding of this technology and its potential future role in neuropsychiatry.Drs. Ziemann and Hallett have authored an impressive, clearly presented review of the basic neurophysiological studies that are possible with TMS. Although much of the current interest in TMS has focused on potential therapeutic benefits, this chapter is very important in describing the range of applications for TMS in studying basic brain physiology. These techniques can be useful in increasing our understanding of neurophysiology in both normal subjects and those with neurologic and psychiatric disorders.Dr. Belmaker and colleagues review the use of TMS to study mood disorder models in animals. Responses to TMS stimulation are compared with those of electroconvulsive shock studies (an animal model for ECT in humans). This review is brief, owing to the limited number of studies to date. In a separate chapter, the significant potential role of TMS in cognitive neuroscience is addressed in a review of TMS as a brain mapping tool.Drs. Lorberbaum and Wasserman offer an essential, practical review of safety issues for both single-pulse and repetitive TMS (rTMS). Seizure induction, the primary safety concern in using rTMS, is reviewed in terms of experience to date and guidelines for minimizing seizure risk.The use of TMS in clinical disorders is reviewed for hypokinetic movement disorders (primarily Parkinson's disease), epilepsy, depression, bipolar disorder, anxiety disorders, developmental stuttering and Tourette's syndrome, and schizophrenia.To date, the therapeutic role of TMS has been best studied in depression. However, many of the studies have varied in design, stimulation parameters, and type of TMS used. The reference charts provided in the review of TMS in major depression by Drs. Lisanby and Sackeim are very useful for comparing this broad range of studies. Another practical feature of this review is a figure displaying the various sham conditions that have been employed, since these are difficult to understand through a verbal description alone. Understanding the type of sham used in controlled studies is important because more recent data suggest that some sham manipulations may be partially active.The remaining chapters review TMS in other clinical disorders. The authors clearly present the limited research available in these areas and discuss future directions for research.Dr. George and colleagues review the use of TMS in combination with various neuroimaging procedures and discuss the outlook for combining these technologies. The book concludes with a discussion of rTMS and future therapeutic applications by Drs. Post and Speer.This book is very readable, is authored by leading researchers in multiple areas of TMS research, and has thorough listings of TMS references, most very recent. It is an excellent resource for understanding the broad range of TMS research performed to date and will likely be useful to both experienced researchers and interested novices.Dr. Sampson is Instructor and Associate Director for TMS in the Neuropsychiatric Therapeutic Procedures Program, Mayo Medical School, Rochester, MN.Edited by Mark S. George and Robert H. Belmaker, Washington, DC, American Psychiatric Press, 2000, 320 pages, ISBN 0-88048-948-0, $44.00 FiguresReferencesCited byDetailsCited ByRevista Brasileira de Psiquiatria, Vol. 40, No. 1 Volume 12Issue 4 November 2000Pages 512-513 Metrics History Published online 1 November 2000 Published in print 1 November 2000

Hypokinetic movement disorders.

Hypokinesis is the term used to refer to slow or reduced movement. Hypokinetic movement disorders are often referred to as parkinsonisms because they display clinical features of idiopathic Parkinson's disease (IPD). As a result, distinguishing other parkinsonian syndromes from IPD is difficult, and it is often not until post mortem that a misdiagnosis is realized. Conditions displaying features of parkinsonism are extensive. The more commonly encountered are IPD, multiple system atrophy, and progressive supranuclear palsy.

Course of motor and associative pallidothalamic projections in monkeys

As a result of the frequent performance of lesioning and electrical stimulation procedures targeting the globus pallidus internus (GPi) to treat medically intractable hypokinetic and hyperkinetic movement disorders, the course of the pallidothalamic projections originating, in particular, from the motor territory of GPi has important clinical relevancy. To assess the organization of pallidothalamic projections originating from motor and associative portions of GPi, small quantities of the anterograde/ retrograde tracer, biotinylated dextran amine (BDA) were injected into localized regions of the caudal GPi in squirrel monkeys. The localization to motor and associative territories in GPi was confirmed by examining the corresponding regions of retrograde labeling in the striatum and subthalamic nucleus (STN). The labeled pallidothalamic fibers projected principally medially across the inferior edge of the internal capsule. The fiber bundle ventral to the caudal GPi was mainly devoid of labeling. Fibers labeled along the medial and inferior borders of GPi at centrorostral levels were traceable to the medial edge of the injections. The densest fiber labeling at rostral levels was produced by those injections with the greatest extent of rostral labeling of neurons. In opposition to generally accepted schemes, the findings from this study suggest that the pallidothalamic fibers originating from the caudal portions of GPi, including the motor territory, do not course ventromedially to form the ansa lenticularis, but rather, travel predominately medially through the lenticular fasciculus en route to the thalamus. Thus, proposed surgical schemes to target fibers ventral to the caudal GPi or at the rostral pole of GPi appear to be misguided.

Pathophysiology of chorea and bradykinesia in Huntington's disease

This article reviews the neurophysiological abnormalities described in Huntington's disease. Among the typical features of choreic movements are variable and random patterns of electromyographic (EMG) activity, including cocontraction of agonist and antagonist muscles. Studies of premotor potentials show that choreic movements are not preceded by a Bereitschaftspotential, therefore demonstrating that choreic movement is involuntary. Early cortical median-nerve somatosensory-evoked potentials have reduced amplitudes and the reduction correlates with reduced glucose consumption in the caudate nucleus. Long-latency stretch reflexes evoked in the small hand muscles are depressed. These findings may reflect failed thalamocortical relay of sensory information. In Huntington's disease, the R2 response of the blink reflex has prolonged latencies, diminished amplitudes, and greater habituation than normal. These abnormalities correlate with the severity of chorea in the face. Patients with Huntington's disease perform simple voluntary movements more slowly than normal subjects and with an abnormal triphasic EMG pattern. Bradykinesia is also present during their performance of simultaneous and sequential movements. Eye movements show abnormalities similar to those seen in arm movements. In Huntington's disease, arm movement execution is associated with reduced PET activation of cortical frontal areas. Studies using transcranial magnetic stimulation show that patients with Huntington's disease have normal corticospinal conduction but some patients have a prolonged cortical silent period. Bradykinesia results from degeneration of the basal ganglia output to the supplementary motor areas concerned with the initiation and maintenance of sequential movements. The coexisting hyperkinetic and hypokinetic movement disorders in patients with Huntington's disease probably reflect the involvement of direct and indirect pathways in the basal ganglia-thalamus-cortical motor circuit.

Neuropsychiatric assessment of patients with hyperkinetic and hypokinetic movement disorders.

The role of the basal ganglia in neuropsychiatric behaviors is not well known. Anatomical, neurophysiological, and neurochemical evidence supports the notion of parallel direct and indirect basal ganglia thalamocortical motor systems, the differential involvement of which accounts for the hypokinesia or hyperkinesia observed in basal ganglia disorders. To evaluate the neuropsychiatric manifestations of patients with a hyperkinetic movement disorder, such as Huntington disease (HD), vs a hypokinetic disease, such as progressive supranuclear palsy (PSP). To verify if patients with HD show a greater frequency of hyperactive behaviors (eg, agitation, irritation, euphoria, or anxiety), while those with PSP exhibit hypoactive behaviors (eg, apathy). The Neuropsychiatric Inventory, a tool with established validity and reliability, was administered to 29 patients with HD (mean +/- SD age, 43.8 +/- 2 years) and 34 with PSP (mean +/- SD age, 66.6 +/- 1.2 years), matched for education, symptom duration, and overall degree of dementia. There was no difference between the groups in the total Neuropsychiatric Inventory scores. However, there was a double dissociation in behaviors: patients with HD exhibited significantly more agitation (45%), irritability (38%), and anxiety (34%), whereas patients with PSP exhibited more apathy (82%) (P < .01). Euphoria was present only in patients with HD. We found that patients with HD manifested predominantly hyperactive behaviors, while those with PSP manifested hypoactive behaviors. Based on our findings and the anatomical lesions known to occur in these disorders, we suggest that the hyperactive behaviors in HD are secondary to an excitatory subcortical output through the medial and orbitofrontal cortical circuits, while in PSP the hypoactive behaviors are secondary to hypostimulation.

WS-31-1 Subthalamic recording of tremor-like activity

In relation to motor control, the basal ganglia have been implicated in both the scaling and focusing of movement. Hypokinetic and hyperkinetic movement disorders manifest as a consequence of overshooting and undershooting GPi (globus pallidus internus) activity thresholds, respectively. Recently, models of motor control have been borrowed to translate cognitive processes relating to the overshooting and undershooting of GPi activity, including attention and executive function. Linguistic correlates, however, are yet to be extrapolated in sufficient detail. The aims of the present investigation were to: (1) characterise cognitive–linguistic processes within hypokinetic and hyperkinetic neural systems, as defined by motor disturbances; (2) investigate the impact of surgically-induced GPi lesions upon language abilities.Two Parkinsonian cases with opposing motor symptoms (akinetic versus dystonic/dyskinetic) served as experimental subjects in this research. Assessments were conducted both prior to as well as 3 and 12 months following bilateral posteroventral pallidotomy (PVP). Reliable changes in performance (i.e. both improvements and decrements) were typically restricted to tasks demanding complex linguistic operations across subjects. Hyperkinetic motor symptoms were associated with an initial overall improvement in complex language function as a consequence of bilateral PVP, which diminished over time, suggesting a decrescendo effect relative to surgical beneficence. In contrast, hypokinetic symptoms were associated with a more stable longitudinal linguistic profile, albeit defined by higher proportions of reliable decline versus improvement in postoperative assessment scores.The above findings endorsed the integration of the GPi within cognitive mechanisms involved in the arbitration of complex language functions. In relation to models of motor control, ‘focusing’ was postulated to represent the neural processes underpinning lexical-semantic manipulation, and ‘scaling’ the potential allocation of cognitive resources during the mediation of high-level linguistic tasks.

Output architecture of the primate putamen

The basal ganglia act through direct and indirect striatopallidal output pathways that have different effects on cortical activity. This division has been proposed to underlie the fundamental distinction between hyperkinetic and hypokinetic movement disorders such as Parkinson's disease and Huntington's disease. Evidence to date does not favor a relationship between this dual organization and the division of the striatum into striosome and matrix compartments. However, the possibility has been raised that the division of striatopallidal output paths reflects a compartmentalization of the matrix itself into clusters of different striatopallidal projection neurons. We directly tested this hypothesis in squirrel monkeys by comparing the distributions of striatal output neurons retrogradely labeled from the two pallidal segments. Striatopallidal neurons labeled by small injections confined to either the external pallidum (GPe) or the internal pallidum (GPi) formed small clusters ("matrisomes") in the matrix compartment of the putamen. However, contrary to previous predictions, labeled matrisomes projecting to GPe were not systematically separated from those projecting to GPi. They could overlap extensively, and within individual matrisomes GPe-projecting neurons and GPi-projecting neurons were extensively intermixed. Double-retrograde labeling analysis in single sections demonstrated that only 2.1 +/- 2.7% of labeled striatal neurons were doubly labeled from both GPe and GPi--a number not significantly different from zero. GPe-projecting and GPi-projecting neurons in the putamen also differed sharply in their expression of enkephalin-like immunoreactivity: 71.3 +/- 7.6% of the neurons labeled by GPe injections were enkephalin positive, in contrast to 10.0 +/- 3.6% of the neurons labeled by GPi injections. These results suggest that in the primate, populations of striatopallidal output neurons are grouped in clusters in the matrix, but that individual neurons in any given cluster project either to GPe or to GPi. Matrisomal clustering may thus coordinate signals sent into the direct and indirect pathways of the basal ganglia from distributed populations of projection neurons in the striatum.