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Parkinson Disease: HELP
Articles by Marjan Jahanshahi
Based on 68 articles published since 2008

Between 2008 and 2019, M. Jahanshahi wrote the following 68 articles about Parkinson Disease.
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Risky choices link the subthalamic nucleus with pathological gambling in Parkinson's disease. 2013

Jahanshahi, Marjan. ·UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, United Kingdom. ·Mov Disord · Pubmed #23843183.

ABSTRACT: -- No abstract --

2 Review Global scales for cognitive screening in Parkinson's disease: Critique and recommendations. 2018

Skorvanek, Matej / Goldman, Jennifer G / Jahanshahi, Marjan / Marras, Connie / Rektorova, Irena / Schmand, Ben / van Duijn, Erik / Goetz, Christopher G / Weintraub, Daniel / Stebbins, Glenn T / Martinez-Martin, Pablo / Anonymous2421195. ·Department of Neurology, Safarik University, Kosice, Slovakia. · Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovakia. · Rush University Medical Center, Department of Neurological Sciences, Section of Parkinson Disease and Movement Disorders, Chicago, Illinois, USA. · Sobell Department of Motor Neuroscience & Movement Disorders and the National Hospital for Neurology & Neurosurgery, London, UK. · Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Ontario, Canada. · Applied Neuroscience Research Group, Central European Institute of Technology, CEITEC, Masaryk University, Brno, Czech Republic. · Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands. · Department of Psychiatry, Leiden University Medical Centre, Leiden, and Centre of Mental Health Care Delfland, Delft, Netherlands. · Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania and Parkinson's Disease and Mental Health Research, Education and Clinical Centers (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. · National Centre of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain. ·Mov Disord · Pubmed #29168899.

ABSTRACT: BACKGROUND: Cognitive impairment is a common nonmotor manifestation of Parkinson's disease, with deficits ranging from mild cognitive difficulties in 1 or more of the cognitive domains to severe dementia. The International Parkinson and Movement Disorder Society commissioned the assessment of the clinimetric properties of cognitive rating scales measuring global cognitive performance in PD to make recommendations regarding their use. METHODS: A systematic literature search was conducted to identify the scales used to assess global cognitive performance in PD, and the identified scales were reviewed and rated as "recommended," "recommended with caveats," "suggested," or "listed" by the panel using previously established criteria. RESULTS: A total of 12 cognitive scales were included in this review. Three scales, the Montreal Cognitive Assessment, the Mattis Dementia Rating Scale Second Edition, and the Parkinson's Disease-Cognitive Rating Scale, were classified as "recommended." Two scales were classified as "recommended with caveats": the Mini-Mental Parkinson, because of limited coverage of executive abilities, and the Scales for Outcomes in Parkinson's Disease-Cognition, which has limited data on sensitivity to change. Six other scales were classified as "suggested" and 1 scale as "listed." CONCLUSIONS: Because of the existence of "recommended" scales for assessment of global cognitive performance in PD, this task force suggests that the development of a new scale for this purpose is not needed at this time. However, global cognitive scales are not a substitute for comprehensive neuropsychological testing. © 2017 International Parkinson and Movement Disorder Society.

3 Review Event-related potentials and cognition in Parkinson's disease: An integrative review. 2016

Seer, Caroline / Lange, Florian / Georgiev, Dejan / Jahanshahi, Marjan / Kopp, Bruno. ·Department of Neurology, Hannover Medical School, Hannover, Germany. Electronic address: seer.caroline@mh-hannover.de. · Department of Neurology, Hannover Medical School, Hannover, Germany. Electronic address: lange.florian@mh-hannover.de. · Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, UK; Department of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia. · Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, UK. · Department of Neurology, Hannover Medical School, Hannover, Germany. ·Neurosci Biobehav Rev · Pubmed #27498083.

ABSTRACT: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD), but the nature of cognitive changes varies considerably between individuals. According to the dual-syndrome hypothesis, one cluster of patients is characterized by deficits in executive function that may be related to fronto-striatal dysfunction. Other patients primarily show non-frontal cognitive impairments that progress rapidly to PD dementia (PDD). We provide a comprehensive review of event-related potential (ERP) studies to identify ERP measures substantiating the heterogeneity of cognitive impairment in PD. Our review revealed evidence for P3b and mismatch-negativity alterations in PDD, but not in non-demented PD, indicating that alterations of these ERPs constitute electrophysiological markers for PDD. In contrast, ERP correlates of executive functions, such as NoGo-P3, N2, and error(-related) negativity (N

4 Review Motor symptoms in Parkinson's disease: A unified framework. 2016

Moustafa, Ahmed A / Chakravarthy, Srinivasa / Phillips, Joseph R / Gupta, Ankur / Keri, Szabolcs / Polner, Bertalan / Frank, Michael J / Jahanshahi, Marjan. ·Department of Veterans Affairs, New Jersey Health Care System, East Orange, NJ, United States; School of Social Sciences and Psychology & Marcs Institute for Brain and Behaviour, Western Sydney University, Sydney, New South Wales, Australia; Marcs Institute for Brain and Behaviour, Western Sydney University, Sydney, New South Wales, Australia. Electronic address: a.moustafa@westernsydney.edu.au. · Department of Biotechnology, Indian Institute of Technology, Madras, Chennai, India. · School of Social Sciences and Psychology & Marcs Institute for Brain and Behaviour, Western Sydney University, Sydney, New South Wales, Australia. · Nyírő Gyula Hospital, National Institute of Psychiatry and Addictions, Budapest, Hungary; Department of Cognitive Science, Budapest University of Technology and Economics, Budapest, Hungary; Department of Physiology, Faculty of Medicine, University of Szeged, Hungary. · Nyírő Gyula Hospital, National Institute of Psychiatry and Addictions, Budapest, Hungary; Department of Cognitive Science, Budapest University of Technology and Economics, Budapest, Hungary. · Department of Cognitive, Linguistic Sciences and Psychological Sciences, Brown Institute for Brain Science, Brown University, Providence RI 02912, USA. · Cognitive Motor Neuroscience Group and Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery London, UK. ·Neurosci Biobehav Rev · Pubmed #27422450.

ABSTRACT: Parkinson's disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (akinesia and bradykinesia, tremor and rigidity), PD patients show additional motor deficits, including: gait disturbance, impaired handwriting, grip force and speech deficits, among others. Some of these motor symptoms (e.g., deficits of gait, speech, and handwriting) have similar clinical profiles, neural substrates, and respond similarly to dopaminergic medication and deep brain stimulation (DBS). Here, we provide an extensive review of the clinical characteristics and neural substrates of each of these motor symptoms, to highlight precisely how PD and its medical and surgical treatments impact motor symptoms. In conclusion, we offer a unified framework for understanding the range of motor symptoms in PD. We argue that various motor symptoms in PD reflect dysfunction of neural structures responsible for action selection, motor sequencing, and coordination and execution of movement.

5 Review Neural substrates and potential treatments for levodopa-induced dyskinesias in Parkinson's disease. 2016

Phillips, Joseph R / Eissa, Abeer M / Hewedi, Doaa H / Jahanshahi, Marjan / El-Gamal, Mohamed / Keri, Szabolcs / Moustafa, Ahmed A. · ·Rev Neurosci · Pubmed #27362959.

ABSTRACT: Parkinson's disease (PD) is primarily a motor disorder that involves the gradual loss of motor function. Symptoms are observed initially in the extremities, such as hands and arms, while advanced stages of the disease can effect blinking, swallowing, speaking, and breathing. PD is a neurodegenerative disease, with dopaminergic neuronal loss occurring in the substantia nigra pars compacta, thus disrupting basal ganglia functions. This leads to downstream effects on other neurotransmitter systems such as glutamate, γ-aminobutyric acid, and serotonin. To date, one of the main treatments for PD is levodopa. While it is generally very effective, prolonged treatments lead to levodopa-induced dyskinesia (LID). LID encompasses a family of symptoms ranging from uncontrolled repetitive movements to sustained muscle contractions. In many cases, the symptoms of LID can cause more grief than PD itself. The purpose of this review is to discuss the possible clinical features, cognitive correlates, neural substrates, as well as potential psychopharmacological and surgical (including nondopaminergic and deep brain stimulation) treatments of LID.

6 Review Movement-related potentials in Parkinson's disease. 2016

Georgiev, Dejan / Lange, Florian / Seer, Caroline / Kopp, Bruno / Jahanshahi, Marjan. ·Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, UK; Department of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia. · Department of Neurology, Hannover Medical School, Hannover, Germany. · Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, UK. Electronic address: m.jahanshahi@ucl.ac.uk. ·Clin Neurophysiol · Pubmed #27178872.

ABSTRACT: To date, many different approaches have been used to study the impairment of motor function in Parkinson's disease (PD). Event-related potentials (ERPs) are averaged amplitude fluctuations of the ongoing EEG activity that are time locked to specific sensory, motor or cognitive events, and as such can be used to study different brain processes with an excellent temporal resolution. Movement-related potentials (MRPs) are ERPs associated with processes of voluntary movement preparation and execution in different paradigms. In this review we concentrate on MRPs in PD. We review studies recording the Bereitschaftspotential, the Contingent Negative Variation, and the lateralized readiness potential in PD to highlight the contributions they have made to further understanding motor deficits in PD. Possible directions for future research are also discussed.

7 Review Interrelations between cognitive dysfunction and motor symptoms of Parkinson's disease: behavioral and neural studies. 2016

Moustafa, Ahmed A / Chakravarthy, Srinivasa / Phillips, Joseph R / Crouse, Jacob J / Gupta, Ankur / Frank, Michael J / Hall, Julie M / Jahanshahi, Marjan. · ·Rev Neurosci · Pubmed #26982614.

ABSTRACT: Parkinson's disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (tremor, bradykinesia/akinesia, and rigidity), PD patients also show other motor deficits, including gait disturbance, speech deficits, and impaired handwriting. However, along with these key motor symptoms, PD patients also experience cognitive deficits in attention, executive function, working memory, and learning. Recent evidence suggests that these motor and cognitive deficits of PD are not completely dissociable, as aspects of cognitive dysfunction can impact motor performance in PD. In this article, we provide a review of behavioral and neural studies on the associations between motor symptoms and cognitive deficits in PD, specifically akinesia/bradykinesia, tremor, gait, handwriting, precision grip, and speech production. This review paves the way for providing a framework for understanding how treatment of cognitive dysfunction, for example cognitive rehabilitation programs, may in turn influence the motor symptoms of PD.

8 Review Postural instability and falls in Parkinson's disease. 2016

Crouse, Jacob J / Phillips, Joseph R / Jahanshahi, Marjan / Moustafa, Ahmed A. · ·Rev Neurosci · Pubmed #26966928.

ABSTRACT: Postural instability (PI) is one of the most debilitating motor symptoms of Parkinson's disease (PD), as it is associated with an increased risk of falls and subsequent medical complications (e.g. fractures), fear of falling, decreased mobility, self-restricted physical activity, social isolation, and decreased quality of life. The pathophysiological mechanisms underlying PI in PD remain elusive. This short review provides a critical summary of the literature on PI in PD, covering the clinical features, the neural and cognitive substrates, and the effects of dopaminergic medications and deep brain stimulation. The delayed effect of dopaminergic medication combined with the success of extrastriatal deep brain stimulation suggests that PI involves neurotransmitter systems other than dopamine and brain regions extending beyond the basal ganglia, further challenging the traditional view of PD as a predominantly single-system neurodegenerative disease.

9 Review Parkinson's disease dementia: a neural networks perspective. 2015

Gratwicke, James / Jahanshahi, Marjan / Foltynie, Thomas. ·Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK, WC1N 3BG j.gratwicke@ucl.ac.uk. · Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK, WC1N 3BG. ·Brain · Pubmed #25888551.

ABSTRACT: In the long-term, with progression of the illness, Parkinson's disease dementia affects up to 90% of patients with Parkinson's disease. With increasing life expectancy in western countries, Parkinson's disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson's disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson's disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson's disease dementia, and discuss how this may offer new therapeutic opportunities.

10 Review Parkinson's disease, the subthalamic nucleus, inhibition, and impulsivity. 2015

Jahanshahi, Marjan / Obeso, Ignacio / Baunez, Christelle / Alegre, Manuel / Krack, Paul. ·Cognitive Motor Neuroscience Group and Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom. ·Mov Disord · Pubmed #25297382.

ABSTRACT: Although Parkinson's disease (PD) is primarily considered a disorder of initiation of actions, patients also have deficits in inhibitory control, both in the motor and cognitive domains. Impulse control disorders, which can develop in association with dopaminergic medication in a small proportion of patients with PD, are the symptoms most commonly considered as representing inhibitory deficits. However, there is now also a body of evidence suggesting a role for the subthalamic nucleus (STN), which is ordinarily hyperactive in PD, in inhibitory control. Here, we review evidence from animal studies, imaging studies, and investigations recording STN activity intra- or perioperatively in patients with PD having surgery for DBS of the STN (STN-DBS). We also highlight relevant hypotheses about the role of the STN and consider evidence from studies that have examined the effect of STN-DBS in patients with PD on performance of experimental tasks requiring inhibition of prepotent or habitual responses or decision making under conflict, as well as the psychiatric side effects of STN-DBS. Though the results are not always consistent, nevertheless, this body of evidence supports the role of the STN in inhibitory and executive control.

11 Review Motor and perceptual timing in Parkinson's disease. 2014

Jones, Catherine R G / Jahanshahi, Marjan. ·School of Psychology, Cardiff University, Cardiff, UK, jonescr10@cardiff.ac.uk. ·Adv Exp Med Biol · Pubmed #25358715.

ABSTRACT: Neuroimaging has been a powerful tool for understanding the neural architecture of interval timing. However, identifying the critical brain regions engaged in timing was initially driven by investigation of human patients and animals. This chapter draws on the important contribution that the study of patients with Parkinson's disease (PD) has made in identifying the basal ganglia as a key component of motor and perceptual timing. The chapter initially describes the experimental tasks that have been critical in PD (and non-PD) timing research before systematically discussing the results from behavioural studies. This is followed by a critique of neuroimaging studies that have given insight into the pattern of neural activity during motor and perceptual timing in PD. Finally, discussion of the effects of medical and surgical treatment on timing in PD enables further evaluation of the role of dopamine in interval timing.

12 Review Decision-making impairments in Parkinson's disease as a by-product of defective cost-benefit analysis and feedback processing. 2014

Ryterska, Agata / Jahanshahi, Marjan / Osman, Magda. ·Biological & Experimental Psychology Group, School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK. ·Neurodegener Dis Manag · Pubmed #25313988.

ABSTRACT: Studies examining decision-making in people with Parkinson's disease (PD) show impaired performance on a variety of tasks. However, there are also demonstrations that patients with PD can make optimal decisions just like healthy age-matched controls. We propose that the reason for these mixed findings is that PD does not produce a generalized impairment of decision-making, but rather affects sub-components of this process. In this review we evaluate this hypothesis by considering the empirical evidence examining decision-making in PD. We suggest that of the various stages of the decision-making process, the most affected in PD are (1) the cost-benefit analysis stage and (2) the outcome evaluation stage. We consider the implications of this proposal for research in this area.

13 Review What are people with Parkinson's disease really impaired on when it comes to making decisions? A meta-analysis of the evidence. 2013

Ryterska, Agata / Jahanshahi, Marjan / Osman, Magda. ·Biological and Experimental Psychology, School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK. ·Neurosci Biobehav Rev · Pubmed #24157725.

ABSTRACT: Parkinson's disease (PD) is associated with motor and cognitive impairment caused by dopamine dysregulation in the basal ganglia. Amongst a host of cognitive deficits, evidence suggests that decision-making is impaired in patients with PD, but the exact scope of this impairment is still unclear. The aim of this review was to establish which experimental manipulations commonly associated with studies involving decision-making tasks were most likely to generate impairments in performance in PD patients. This allowed us to address the question of the exact scope of the decision-making deficits in PD and to hypothesize about the role of the basal ganglia in decision-making processes. We conducted a meta-analysis of available literature, which revealed that the two key predictors of impairment in PD were the feedback structure of the decision-making task and the medication status of patients while performing the tasks. Rather than a global impairment in decision-making ability, these findings suggest that deficiencies in choice-behaviour in patients with PD stem from dysfunctions at the outcome evaluation stage of the decision-making process.

14 Review Executive dysfunction in Parkinson's disease: a review. 2013

Dirnberger, Georg / Jahanshahi, Marjan. ·Department of Clinical Neuroscience and Preventive Medicine, Danube University, Krems, Austria. m.jahanshahi@ucl.ac.uk ·J Neuropsychol · Pubmed #24007368.

ABSTRACT: Executive dysfunction can be present from the early stages of Parkinson's disease (PD). It is characterized by deficits in internal control of attention, set shifting, planning, inhibitory control, dual task performance, and on a range of decision-making and social cognition tasks. Treatment with dopaminergic medication has variable effects on executive deficits, improving some, leaving some unchanged, and worsening others. In this review, we start by defining the specific nature of executive dysfunction in PD and describe suitable neuropsychological tests. We then discuss how executive deficits relate to pathology in specific territories of the basal ganglia, consider the impact of dopaminergic treatment on executive function (EF) in this context, and review the changes in EFs with disease progression. In later sections, we summarize correlates of executive dysfunction in PD with motor performance (e.g., postural instability, freezing of gait) and a variety of psychiatric (e.g., depression, apathy) and other clinical symptoms, and finally discuss the implications of these for the patients' daily life.

15 Review Functional imaging of subthalamic nucleus deep brain stimulation in Parkinson's disease. 2011

Boertien, Tessel / Zrinzo, Ludvic / Kahan, Joshua / Jahanshahi, Marjan / Hariz, Marwan / Mancini, Laura / Limousin, Patricia / Foltynie, Thomas. ·Unit of Functional Neurosurgery, UCL Institute of Neurology, Queen Square, London, United Kingdom. ·Mov Disord · Pubmed #21674623.

ABSTRACT: Deep brain stimulation of the subthalamic nucleus is an accepted treatment for the motor complications of Parkinson's disease. The therapeutic mechanism of action remains incompletely understood. Although the results of deep brain stimulation are similar to the results that can be obtained by lesional surgery, accumulating evidence from functional imaging and clinical neurophysiology suggests that the effects of subthalamic nucleus-deep brain stimulation are not simply the result of inhibition of subthalamic nucleus activity. Positron emission tomography/single-photon emission computed tomography has consistently demonstrated changes in cortical activation in response to subthalamic nucleus-deep brain stimulation. However, the technique has limited spatial and temporal resolution, and therefore the changes in activity of subcortical projection sites of the subthalamic nucleus (such as the globus pallidus, substantia nigra, and thalamus) are not as clear. Clarifying whether clinically relevant effects from subthalamic nucleus-deep brain stimulation in humans are mediated through inhibition or excitation of orthodromic or antidromic pathways (or both) would contribute to our understanding of the precise mechanism of action of deep brain stimulation and may allow improvements in safety and efficacy of the technique. In this review we discuss the published evidence from functional imaging studies of patients with subthalamic nucleus-deep brain stimulation to date, together with how these data inform the mechanism of action of deep brain stimulation.

16 Review Gender distribution of patients with Parkinson's disease treated with subthalamic deep brain stimulation; a review of the 2000-2009 literature. 2011

Hariz, Gun-Marie / Nakajima, Takeshi / Limousin, Patricia / Foltynie, Tom / Zrinzo, Ludvic / Jahanshahi, Marjan / Hamberg, Katarina. ·Department of Community Medicine and Rehabilitation, Occupational Therapy, University of Umeå, Sweden. gun-marie.hariz@neuro.umu.se ·Parkinsonism Relat Disord · Pubmed #21195012.

ABSTRACT: PURPOSE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been the mainstream surgical procedure for advanced Parkinson's disease (PD) during the last decade. Reports from a few individual centres have hinted that women who receive STN DBS are under-represented. We aimed to evaluate the gender distribution of patients with PD who had received STN DBS during the last ten years, and to discuss the findings in relation to studies on gender prevalence of PD. METHODS: A search of the PubMed database of clinical papers in English language related to STN DBS between 2000 and 2009 was conducted. Care was taken to minimize redundancies in reporting of published patients. The proportion of men and women were expressed in total and according to pre-defined geographic regions. RESULTS: One hundred and thirty five papers were eligible for review. The gender of the patients was specified in 119 papers on a total of 3880 patients, of which 63% were men. According to geographic origin of publications, the percentage of men with STN DBS was 68% in North America, 62% in Europe, 69% in Australia and 50% in Asia. CONCLUSIONS: The proportion of male patients who undergo STN DBS seems to exceed the reported male/female ratio of patients with PD.

17 Review The substantia nigra, the basal ganglia, dopamine and temporal processing. 2009

Jones, Catherine R G / Jahanshahi, Marjan. ·Department of Psychology and Human Development, Institute of Education, University of London, London, UK. c.jones@ioe.ac.uk ·J Neural Transm Suppl · Pubmed #20411776.

ABSTRACT: It has been proposed that the basal ganglia are important to the temporal processing of milliseconds- and seconds-range intervals, both within the motor and perceptual domains. This review summarizes and discuses evidence from animal, pharmacological, clinical, and imaging research that supports this proposal, with particular reference to the role of the substantia nigra (SN).

18 Review Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms. 2009

Rodriguez-Oroz, Maria C / Jahanshahi, Marjan / Krack, Paul / Litvan, Irene / Macias, Raúl / Bezard, Erwan / Obeso, José A. ·Department of Neurology, Clinica Universitaria and Medical School and Neuroscience, CIMA, University of Navarra, Pamplona, Spain. ·Lancet Neurol · Pubmed #19909911.

ABSTRACT: A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.

19 Clinical Trial Deep brain stimulation of the subthalamic nucleus improves sense of well-being in Parkinson's disease. 2012

McDonald, Louise M / Page, Donna / Wilkinson, Leonora / Jahanshahi, Marjan. ·Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK. ·Mov Disord · Pubmed #22411848.

ABSTRACT: Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of Parkinson's disease. Although a range of psychiatric and behavioral problems have been documented following deep brain stimulation, the short-term effects of subthalamic nucleus stimulation on patients' mood have only been investigated in a few studies. Our aim was to compare self-reported mood in Parkinson's patients with deep brain stimulation of the subthalamic nucleus ON versus OFF. Twenty-three Parkinson's patients with bilateral deep brain stimulation of the subthalamic nucleus and 11 unoperated Parkinson's patients completed a mood visual analogue scale twice. Operated patients were tested with deep brain stimulation of the subthalamic nucleus both ON and OFF. All were assessed on medication. The operated Parkinson's group reported feeling significantly better coordinated, stronger, and more contented with deep brain stimulation ON compared to OFF. Fourteen of the 16 mood scales changed in a positive direction when deep brain stimulation of the subthalamic nucleus was ON. When changes in motor scores were taken into account, the operated patients still reported feeling better-coordinated, but also less gregarious with stimulation ON. Unoperated Parkinson's patients showed no differences on any of these measures between their 2 ratings. Short-term changes in deep brain stimulation of the subthalamic nucleus have a small and mostly positive effect on mood, which may be partly related to improvements in motor symptoms. The implications for day-to-day management of patients with deep brain stimulation of the subthalamic nucleus are discussed.

20 Clinical Trial Levodopa medication does not influence motor inhibition or conflict resolution in a conditional stop-signal task in Parkinson's disease. 2011

Obeso, Ignacio / Wilkinson, Leonora / Jahanshahi, Marjan. ·Cognitive-Motor Neuroscience Group, Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, University College London, 33 Queen Square, London, UK. ·Exp Brain Res · Pubmed #21796541.

ABSTRACT: Evidence from animal, clinical, and imaging studies suggests that the basal ganglia and their frontal connections mediate motor inhibition, but the role of dopamine remains unclear. The aim of our study was to investigate, for the first time, whether levodopa medication influences motor inhibition and conflict resolution on the conditional stop-signal reaction time task in patients with Parkinson's disease (PD) tested on or off their medication. Sixteen PD patients and 17 healthy controls performed the conditional stop-signal reaction time (SSRT) task, which requires inhibition of responses when a stop signal is presented on "critical" trials. Additionally, on "non-critical" trials, participants are instructed to ignore the stop signal and respond, thus generating conflict between motor inhibition and initiation; and conflict-induced slowing (CIS) on these "non-critical" trials. Levodopa medication did not significantly influence response initiation, inhibition (SSRT) or the measure of conflict resolution (CIS). Compared to healthy controls, PD patients showed significantly worse response initiation and inhibition both on and off their levodopa medication. Our results suggest that motor inhibition or conflict-induced slowing on the conditional stop-signal RT task are not altered by dopamine replacement in PD. This conclusion is consistent with evidence from animal studies and clinical pharmacological investigations suggesting a role for noradrenaline in motor inhibition and impulsivity.

21 Clinical Trial The effect of real and virtual visual cues on walking in Parkinson's disease. 2011

Griffin, H J / Greenlaw, R / Limousin, P / Bhatia, K / Quinn, N P / Jahanshahi, M. ·Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen's Square, London, WC1N 3BG, UK. ·J Neurol · Pubmed #21221626.

ABSTRACT: Patients with Parkinson's disease (PwPD) have a slow, shuffling gait, marked by sporadic freezing of gait (FoG) during which effective stepping ceases temporarily. As these gait problems are not commonly improved by medical and surgical treatments, alternative approaches to manage these problems have been adopted. The aim of this study was to evaluate the effect of real and virtual visual cues on walking in PD. We assessed 26 mid-stage PwPD, on and off medication, on a laboratory-based walking task which simulated real world challenges by incorporating FoG triggers and using appropriate placebo conditions. Cueing interventions were presented via virtual reality glasses (VRG rhythmic, visual flow and static placebo cues), and as transverse lines (TL) on the walkway. Objective measures of gait (task completion time; velocity, cadence, stride length; FoG frequency) and self-rated fear of falling (FoF) were recorded. Cueing intervention affected task completion time only off medication. Whereas placebo VRG cues provided no improvement in walking, visual flow VRG cues marginally reduced the task completion time. TL on the floor elicited more substantial improvements in gait with reduced cadence, increased stride length and reduced FoG frequency. VRG rhythmic cueing impaired overall walking. Notably, a final no-intervention condition yielded quicker task completion, greater walking velocity, increased stride length and less frequent FoG. Although the VRG produced modest improvements only in the visual flow condition, their flexibility is an advantage. These results endorse the use of TL and justify further testing and customisation of VRG cues for individual PwPD.

22 Article Deep Brain Stimulation of the Subthalamic Nucleus Does Not Affect the Decrease of Decision Threshold during the Choice Process When There Is No Conflict, Time Pressure, or Reward. 2018

Leimbach, Friederike / Georgiev, Dejan / Litvak, Vladimir / Antoniades, Chrystalina / Limousin, Patricia / Jahanshahi, Marjan / Bogacz, Rafal. ·University College London Institute of Neurology. · University of Oxford. · University of Electronic Science and Technology of China. ·J Cogn Neurosci · Pubmed #29488846.

ABSTRACT: During a decision process, the evidence supporting alternative options is integrated over time, and the choice is made when the accumulated evidence for one of the options reaches a decision threshold. Humans and animals have an ability to control the decision threshold, that is, the amount of evidence that needs to be gathered to commit to a choice, and it has been proposed that the subthalamic nucleus (STN) is important for this control. Recent behavioral and neurophysiological data suggest that, in some circumstances, the decision threshold decreases with time during choice trials, allowing overcoming of indecision during difficult choices. Here we asked whether this within-trial decrease of the decision threshold is mediated by the STN and if it is affected by disrupting information processing in the STN through deep brain stimulation (DBS). We assessed 13 patients with Parkinson disease receiving bilateral STN DBS six or more months after the surgery, 11 age-matched controls, and 12 young healthy controls. All participants completed a series of decision trials, in which the evidence was presented in discrete time points, which allowed more direct estimation of the decision threshold. The participants differed widely in the slope of their decision threshold, ranging from constant threshold within a trial to steeply decreasing. However, the slope of the decision threshold did not depend on whether STN DBS was switched on or off and did not differ between the patients and controls. Furthermore, there was no difference in accuracy and RT between the patients in the on and off stimulation conditions and healthy controls. Previous studies that have reported modulation of the decision threshold by STN DBS or unilateral subthalamotomy in Parkinson disease have involved either fast decision-making under conflict or time pressure or in anticipation of high reward. Our findings suggest that, in the absence of reward, decision conflict, or time pressure for decision-making, the STN does not play a critical role in modulating the within-trial decrease of decision thresholds during the choice process.

23 Article Connectivity derived thalamic segmentation in deep brain stimulation for tremor. 2018

Akram, Harith / Dayal, Viswas / Mahlknecht, Philipp / Georgiev, Dejan / Hyam, Jonathan / Foltynie, Thomas / Limousin, Patricia / De Vita, Enrico / Jahanshahi, Marjan / Ashburner, John / Behrens, Tim / Hariz, Marwan / Zrinzo, Ludvic. ·Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. · Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. · Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK. · Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. · Centre for Functional MRI of the Brain (FMRIB), John Radcliffe Hospital, Oxford OX3 9DU, UK. · Department of Clinical Neuroscience, Umeå University, Umeå, Sweden. ·Neuroimage Clin · Pubmed #29387530.

ABSTRACT: The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

24 Article GBA-Associated Parkinson's Disease: Progression in a Deep Brain Stimulation Cohort. 2017

Lythe, Vanessa / Athauda, Dilan / Foley, Jennifer / Mencacci, Niccolò E / Jahanshahi, Marjan / Cipolotti, Lisa / Hyam, Jonathan / Zrinzo, Ludvic / Hariz, Marwan / Hardy, John / Limousin, Patricia / Foltynie, Tom. ·Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK. · Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, London, UK. · Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. · Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. ·J Parkinsons Dis · Pubmed #28777757.

ABSTRACT: BACKGROUND: Recent evidence suggests that glucosidase beta acid (GBA) mutations predispose Parkinson's disease (PD) patients to a greater burden of cognitive impairment and non-motor symptoms. This emerging knowledge has not yet been considered in patients who have undergone deep brain stimulation (DBS); a surgery that is generally contraindicated in those with cognitive deficits. OBJECTIVE: To explore the long-term phenotypic progression of GBA-associated PD, in a DBS cohort. METHODS: Thirty-four PD patients who had undergone DBS surgery between 2002 and 2011 were included in this study; 17 patients with GBA mutations were matched to 17 non-carriers. Clinical evaluation involved the administration of four assessments: The Mattis Dementia Rating Scale was used to assess cognitive function; non-motor symptoms were assessed using the Non-Motor Symptom Assessment Scale for PD; quality of life was measured using the Parkinson's Disease Questionnaire; and motor symptoms were evaluated using part III of the Movement Disorders Society Unified Parkinson's Disease Rating Scale, in on-medication/on-stimulation conditions. Levodopa equivalent doses (LED) and DBS settings were compared with clinical outcomes. RESULTS: At a mean follow-up of 7.5 years after DBS, cognitive impairment was more prevalent (70% vs 19%) and more severe in GBA mutation carriers compared to non-carriers (60% vs 6% were severely impaired). Non-motor symptoms were also more severe and quality of life more impaired in GBA-associated PD. Motor symptoms, LED, and stimulation settings were not significantly different between groups at follow-up. CONCLUSIONS: GBA status appears to be an important predictor for non-motor symptom disease progression, after deep brain stimulation surgery.

25 Article Unilateral subthalamotomy in Parkinson's disease: Cognitive, psychiatric and neuroimaging changes. 2017

Obeso, Ignacio / Casabona, Enrique / Rodríguez-Rojas, Rafael / Bringas, Maria Luisa / Macías, Raúl / Pavón, Nancy / Obeso, Jose A / Jahanshahi, Marjan. ·HM Hospitales - HM CINAC, Mostoles and CEU-San Pablo University, Madrid, Spain; CIBERNED, Instituto Carlos III, Madrid, Spain. Electronic address: iobeso.hmcinac@hmhospitales.com. · Centro Internacional de Restauración Neurológica (CIREN), La Habana, Cuba. · HM Hospitales - HM CINAC, Mostoles and CEU-San Pablo University, Madrid, Spain; CIBERNED, Instituto Carlos III, Madrid, Spain. · Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK. Electronic address: m.jahanshahi@ucl.ac.uk. ·Cortex · Pubmed #28711816.

ABSTRACT: Unilateral subthalamotomy is an effective treatment for the cardinal motor features of Parkinson's disease (PD). However, non-motor changes possibly associated with right or left subthalamotomy remain unknown. Our aim was to assess cognitive, psychiatric and neuroimaging changes after treatment with unilateral subthalamotomy. Fourteen medicated patients with PD were evaluated before and after (mean 6 months after operation) unilateral subthalamotomy (5 right, 9 left). In addition to motor assessments, cognitive (global cognition and executive functions), psychiatric (apathy, depression, anxiety, mania, hypo- and hyperdopaminergic behaviours, impulsivity), quality of life evaluations and volume of lesions were obtained. After surgery, significant improvement of motor signs was observed. Unilateral subthalamotomy improved general cognitive status, but left subthalamotomy reduced semantic verbal fluency compared to the pre-operative state. Depression and quality of life were improved with both right and left subthalamotomy. However, hyper-emotionality was present after surgery and right subthalamotomy increased impulsivity and disinhibition (on NeuroPsychiatric Inventory and Ardouin Scale for Behaviour in PD), a result linked to larger lesion volumes. We conclude that unilateral subthalamotomy is effective for treating the cardinal motor features of PD and improves mood. Right subthalamotomy is associated with greater risk of impulsivity and disinhibition, while left subthalamotomy induces further impairment of semantic verbal fluency.