Posttraumatic movement disorders: A clinical and imaging profile of 30 patients.

BACKGROUND: Posttraumatic movement disorders (PTMDs) are frequently associated with severe head injury. There are very few studies on the clinical phenomenology and radiological correlation of PTMD. AIMS: To study the clinical phenomenology of patients with PTMD and correlate it with the site of lesion on brain imaging. MATERIALS AND METHODS: This was a prospective study of patients with suspected PTMD. All of these patients underwent neurological evaluation to characterize the phenomenology and imaging, such as computed tomography/magnetic resonance imaging (CT/MRI), to localize the site of lesion. RESULTS: The age of the patients was 32.6 ± 16.4 years and the age at onset was 29.1 ± 16.0 years. Right upper limb was the initial body part affected in 36.7% patients. Tremor (alone or with dystonia) was the most common movement disorder (MD; 44.7%) followed by parkinsonism (17.2%), dystonia (13.8%), dystonia plus (dystonia associated with choreoathetosis: 10.3%), mixed MD (more than one MD: 10.3%), and myoclonus (3.4%). MRI was performed in 23 patients and the rest seven patients underwent CT brain. Normal MRI was observed in one patient with parkinsonism. Isolated, discrete lesions were found in six (27.3%) patients. Basal ganglia was the most common site of involvement (66.7%) followed by thalamus (16.7%) and brainstem (16.7%). Diffuse white matter involvement was the most common radiological lesion in patients with tremor. CONCLUSIONS: Our study describes the clinical phenomenology of patients with PTMDs and its radiological correlation. Tremor (alone or in combination with dystonia) was the most common MD observed and diffuse white matter lesions without affection of the basal ganglia was the most common site of lesion.

Basal ganglia contributions during the learning of a visuomotor rotation: Effect of dopamine, deep brain stimulation and reinforcement.

It is commonly thought that visuomotor adaptation is mediated by the cerebellum while reinforcement learning is mediated by the basal ganglia. In contrast to this strict dichotomy, we demonstrate a role for the basal ganglia in visuomotor adaptation (error-based motor learning) in patients with Parkinson's disease (PD) by comparing the degree of motor learning in the presence and absence of dopamine medication. We further show similar modulation of learning rates in the presence and absence of subthalamic deep brain stimulation. We also report that reinforcement is an essential component of visuomotor adaptation by demonstrating the lack of motor learning in patients with PD during the ON-dopamine state relative to the OFF-dopamine state in the absence of a reinforcement signal. Taken together, these results raise the possibility that the basal ganglia modulate the gain of visuomotor adaptation based on the reinforcement received at the end of the trial.

Phenotypic Variability of Essential Tremor Based on the Age at Onset.

BACKGROUND: Essential tremor (ET) is reported to have a bimodal distribution of age at onset (AAO) with phenotypic variability based on the AAO. This study aims to explore the distribution of AAO based on mathematical modeling and ascertain the differences, if any, in the clinical features of groups. METHODS: A chart review was conducted for 252 patients with ET diagnosed based on the Consensus statement of the Movement Disorder Society on Tremor. Finite mixture modeling was performed to identify groups of the cohort based on the AAO. RESULTS: Three groups were defined: early onset (EO): AAO ≤ 22 years, n = 63, intermediate onset (IO): 23 ≤ AAO ≤ 35 years, n = 43, and late onset (LO): AAO ≥ 36 years, n = 146. There were no significant differences related to family history or responsiveness to alcohol. The EO group had significantly higher prevalence of upper limb and lower limb tremor. Head tremor and voice tremor was more prevalent in the IO and LO groups. Cerebellar signs showed a significant increase with an increase in AAO. CONCLUSIONS: ET shows significant phenotypic variability based on the AAO. Patients with an early AAO are more likely to develop an appendicular tremor, whereas the probability of axial tremor and cerebellar signs increases with increasing AAO.

Clinical Utility of Longitudinal Measurement of Motor Threshold in Wilson's Disease.

This study describes the longitudinal changes of resting motor threshold (RMT) and central motor conduction time (CMCT) in 18 patients with Wilson's disease (WD). The RMT, CMCT, and Global Assessment Scale for Wilson Disease (GAS-WD) were measured at baseline and at follow-up after 12.94 ± 7.23 months. There was a significant decrease in the RMT (72.11 ± 18.62 vs. 63.7 ± 15.52%; p-value = 0.002) and GAS-WD scores (14.38 ± 5.35 vs. 9.77 ± 6.47 ms; p-value = 0.04). CMCT did not improve despite chelation therapy. Hence, RMT may serve as a marker of chelation efficacy in WD.

Implications of secondary unresponsiveness to dopaminergic drugs with preserved response to subthalamic nucleus stimulation in Parkinson's disease.

Improvement in motor symptoms with levodopa is one of the hallmark features of Parkinson's disease (PD). The response to levodopa may reduce during the course of the illness. Few studies have also reported reduced response to levodopa in patients with PD several years after deep brain stimulation (DBS) of the subthalamic nucleus (STN) on both the sides. In this study, we report an extreme unresponsiveness to levodopa in the presence of a good response to STN stimulation in a patient 5 years after the DBS proceudre had been carried out. The implications of this phenomenon are also discussed.

Shaky and unsteady: Dynamic posturography in essential tremor.

BACKGROUND: The spectrum of symptoms exhibited by patients with essential tremor (ET) extends far beyond the classical tremor. This study aims to explore and establish the presence of subtle balance abnormalities in ET using dynamic posturography (DP). METHODS: DP was performed on 18 patients with ET and 26 controls. Diagnosis of ET was based on the Consensus Statement of the Movement Disorder Society on Tremor. Dynamic stability which included the overall balance index, anterior-posterior index and mediolateral index, and limits of stability were measured. RESULTS: Patients with ET had significantly impaired balance indices. Impairment of dynamic stability revealed poor static balance control in all directions. Lower limits of stability scores indicated a smaller range of motion prior to which patients have to shift foot balance. No correlations were observed between age at evaluation, age at onset, duration of illness and the balance indices. CONCLUSIONS: Dynamic posturography reveals significant balance impairment in patients with ET which is unrelated to the age at onset, age at evaluation or duration of illness. This finding concurs with pre-existing reports and adds to the growing body evidence of cerebellar involvement in ET.

Experience of pallidal deep brain stimulation in dystonia at a tertiary care centre in India: An initial experience.

INTRODUCTION: Dystonia is one of the most prevalent forms of movement disorders and is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonia causes significant morbidity with an adverse impact on the quality of life. When dystonia is medically refractory, causing severe pain and impairment in activities of daily living, deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a potential option to reduce disability. MATERIALS AND METHODS: This is a chart review of patients who underwent DBS for dystonia (from 2009 to 2015) at our tertiary referral centre. A total of ten patients (7 males, 3 females) underwent DBS for non-parkinsonian conditions. The patients were selected after failure of adequate medical management. All the patients had a severe disability with normal cognitive (Mini-Mental State Examination) and psychiatric profile. They also had to have a suitable GPi for DBS based on magnetic resonance imaging. RESULTS: The mean baseline Burke-Fahn-Marsden dystonia movement score of the 10 patients selected for surgery was 60.3 ± 27.3 (ranging from 19 to 104). On repeated-measures analysis of variance, there was significant difference in the different time points (pre-DBS, post-DBS at 3 months, 6 months, and 1 year) F (3, 5) = 7.68, P = 0.026. The data showed that there was a maximum improvement after 1 year of stimulation (pre-DBS vs. 3 months 12.9 ± 1.9 vs 8.8 ± 2.1, P = 0.01; pre-DBS vs. 6 months 12.9 ± 1.9 vs 7.4 ± 1.6, P = 0.04; pre-DBS vs. 1 year, 12.9 ± 1.9 vs. 7 ± 2.4. CONCLUSION: In medically refractory primary or secondary dystonia patients, bilateral GPi DBS can be considered as an option. Patients with disabling symptoms that significantly deteriorate activities of daily life may consider DBS before these symptoms become fixed.

Abnormalities of Eye-Hand Coordination in Patients with Writer's Cramp: Possible Role of the Cerebellum.

Background: Writer's cramp (WC) is one of the commonly observed focal dystonias. The pathophysiology of WC has not been fully understood. The role of the cerebellum has been increasingly recognized in the pathogenesis of dystonia. As the cerebellum is crucial for maintaining accurate eye-hand coordination (EHC), its role in the pathogenesis of WC can be investigated by studying the EHC in patients with WC. Methods: Fifteen patients with WC (women:men, 3:12) and 15 age- and gender-matched controls performed oculomotor and EHC tasks. A visually guided stimulus (VGS) task was first performed with eye-only condition (EOC) and then with EHC. Results: A significant interaction between the groups (controls and patients) and tasks (EOC and EHC) with age as a covariate confirmed that the two groups reacted differently to the tasks in saccadic latency (F(1,27) = 4.8; p = 0.039) and average saccade acceleration (F(1,27) = 10.6; p = 0.003). The curvature index of acceleration of the hand was significantly more in patients compared to controls (patients vs. controls, 2.4±0.4 vs. 1.8±0.2, p = 0.01). While performing the EHC task, there was a significant correlation of the Writer's Cramp Rating Score with the average saccadic speed (-0.61, p = 0.016), peak saccadic deceleration (0.59, p = 0.019) and average saccadic acceleration (-0.63, p = 0.012). Discussion: Saccadic acceleration and latency are abnormal while performing EHC tasks in patients with WC. Our study gives further insights into the possible role of the cerebellum in the pathogenesis of WC.

Altered brain network measures in patients with primary writing tremor.

PURPOSE: Primary writing tremor (PWT) is a rare task-specific tremor, which occurs only while writing or while adopting the hand in the writing position. The basic pathophysiology of PWT has not been fully understood. The objective of this study is to explore the alterations in the resting state functional brain connectivity, if any, in patients with PWT using graph theory-based analysis. METHODS: This prospective case-control study included 10 patients with PWT and 10 age and gender matched healthy controls. All subjects underwent MRI in a 3-Tesla scanner. Several parameters of small-world functional connectivity were compared between patients and healthy controls by using graph theory-based analysis. RESULTS: There were no significant differences in age, handedness (all right handed), gender distribution (all were males), and MMSE scores between the patients and controls. The mean age at presentation of tremor in the patient group was 51.7 ± 8.6 years, and the mean duration of tremor was 3.5 ± 1.9 years. Graph theory-based analysis revealed that patients with PWT had significantly lower clustering coefficient and higher path length compared to healthy controls suggesting alterations in small-world architecture of the brain. The clustering coefficients were lower in PWT patients in left and right medial cerebellum, right dorsolateral prefrontal cortex (DLPFC), and left posterior parietal cortex (PPC). CONCLUSION: Patients with PWT have significantly altered small-world brain connectivity in bilateral medial cerebellum, right DLPFC, and left PPC. Further studies with larger sample size are required to confirm our results.

Imaging biomarker correlates with oxidative stress in Parkinson's disease.

BACKGROUND: While oxidative stress (OS) may be one of the crucial factors determining the initiation and progression of Parkinson's disease (PD), its correlation with gray matter (GM) atrophy is not known. AIMS: To determine the GM volume (GMV) changes using voxel-based morphometry (VBM) and correlation with OS marker serum malondialdehyde (MDA) in PD. MATERIALS AND METHODS: Seventy-two patients with PD were clinically evaluated and underwent magnetic resonance imaging (MRI) on a 3T MRI scanner using a 32-channel head coil. Lipid peroxidation product MDA levels were measured by spectrophotometry. MDA levels and regional GM differences using VBM were compared with 72 healthy controls. RESULTS: The mean age of the patients was 51.3 ± 10.6 years and that of controls was 50.8 ± 10.4 years. The mean age of onset of symptoms in PD was 45.2 ± 11.3 years. In PD, serum MDA level was significantly higher than that in controls (0.592 ± 0.89 µmol/l vs. 0.427 ± 0.055 µmol/l; P < 0.0001). Compared to controls, patients had greater regional GM atrophy in all the brain lobes (P < 0.001, uncorrected). A significant positive correlation was found between GMV and MDA in the caudate nucleus (CN) and posterior cingulate gyrus (PC) in the patient group (P < 0.001, uncorrected). CONCLUSIONS: We observed GM atrophy in all major brain lobes of patients when compared to controls. Only in the patient group, a significant positive correlation was observed in CN and PC with MDA. These findings suggest that, even though the whole brain is affected in PD, some of the non-substantia nigra regions of the brain, such as CN, may have some differential compensatory mechanism, which are preserved from oxidative damage.

Advanced structural neuroimaging in progressive supranuclear palsy: Where do we stand?

Progressive supranuclear palsy (PSP) is a progressive neurological disorder characterized by presence of supranuclear gaze palsy, early postural instability, parkinsonism and cognitive impairment. Advanced structural neuroimaging studies have demonstrated variable areas of grey and white matter involvement in PSP. Grey matter (GM) involvement is predominantly reported in the midbrain, subcortical structures such as thalamus and basal ganglia, and cerebellum. Most white matter (WM) tracts are also reported to be damaged in PSP. This review analyzes the published studies that have utilized advanced structural imaging techniques such as voxel based morphometry (VBM), diffusion tensor and diffusion weighted imaging (DTI, DWI), magnetic resonance volumetry (MRV), shape analysis, cortical thickness analysis and magnetic resonance morphometry in understanding the in vivo pathological changes in PSP and also discusses their clinical significance.

Role of altered cerebello-thalamo-cortical network in the neurobiology of essential tremor.

INTRODUCTION: Essential tremor (ET) is the most common movement disorder among adults. Although ET has been recognized as a mono-symptomatic benign illness, reports of non-motor symptoms and non-tremor motor symptoms have increased its clinical heterogeneity. The neural correlates of ET are not clearly understood. The aim of this study was to understand the neurobiology of ET using resting state fMRI. METHODS: Resting state functional MR images of 30 patients with ET and 30 age- and gender-matched healthy controls were obtained. The functional connectivity of the two groups was compared using whole-brain seed-to-voxel-based analysis. RESULTS: The ET group had decreased connectivity of several cortical regions especially of the primary motor cortex and the primary somatosensory cortex with several right cerebellar lobules compared to the controls. The thalamus on both hemispheres had increased connectivity with multiple posterior cerebellar lobules and vermis. Connectivity of several right cerebellar seeds with the cortical and thalamic seeds had significant correlation with an overall score of Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) as well as the subscores for head tremor and limb tremor. CONCLUSION: Seed-to-voxel resting state connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical network in patients with ET. These alterations correlated with the overall FTM scores as well as the subscores for limb tremor and head tremor in patients with ET. These results further support the previous evidence of cerebellar pathology in ET.

Role of Corpus Callosum Volumetry in Differentiating the Subtypes of Progressive Supranuclear Palsy and Early Parkinson's Disease.

BACKGROUND AND OBJECTIVE: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder. Classic PSP or Richardson-Steele phenotype (PSP-RS) and parkinsonian phenotype (PSP-P) are the common subtypes of PSP. At the early stage, differentiating the subtypes of PSP as well as differentiating PSP from other parkinsonian disorders, especially Parkinson's disease (PD) is challenging. Microstructural abnormalities of corpus callosum (CC) have been reported both in PSP and PD. The objective of this study was to compare the volumes of various segments of CC between patients with PSP-P, PSP-RS, and early PD. METHODOLOGY: This study included 32 patients with PSP (RS: 18, P: 14), 20 patients with early PD, and 25 controls. All subjects underwent 3-Tesla MRI. An automated surface-based analysis package (FreeSurfer) was used to divide CC into five segments: anterior (CC1), midanterior (CC2), central (CC3), midposterior (CC4), and posterior (CC5). Volumes of these segments were compared among the four groups. RESULTS: The PSP-RS group had significantly lower CC volume in all segments except in CC1 and CC5, whereas the volumes of the five segments of CC were comparable among PSP-P, PD and controls. The PSP-RS group had lower CC3 volume compared to the PSP-P group, and the PSP-RS group had lower volume of both CC2 and CC3 compared to the PD group. CONCLUSIONS: The lower volume of the central segment of CC (CC3) might help in differentiating PSP-RS from PSP-P. There is no significant difference in the pattern of CC atrophy in PSP-P and early PD. Studies with higher sample sizes are warranted to confirm the results of our study.

Exploring cortical atrophy and its clinical and biochemical correlates in Wilson's disease using voxel based morphometry.

OBJECTIVES: To determine cortical grey matter (GM) changes and their clinical and biochemical correlates in patients with Wilson's disease using voxel based morphometry (VBM). METHODS: Clinical and imaging data of 10 patients (all male, mean age 16.0 ± 6.3years) with Wilson's Disease were analyzed. T1W volumetric MRI data of patients without obvious cortical atrophy or signal changes on conventional MRI was compared with MRI of 11 matched control subjects using VBM analysis with Statistical Parametric Mapping 8. Results were expressed at statistical threshold of p < 0.05 (FWE corrected) and p < 0.001 (uncorrected). Multiple regression analysis was done to analyze possible relation between GM atrophy, duration of disease and biochemical abnormalities. RESULTS: Compared to controls, patients showed scattered areas of reduced GM volume in bilateral caudate head, medial part of right globus pallidus and body of right caudate (FWE corrected p < 0.05). At p < 0.001(uncorrected) widespread areas of cortical atrophy were also noted involving the frontal and temporal lobes, lentiform nuclei, cerebellum and thalamus. Significant positive correlation (uncorrected p < 0.001) were noted between (i) duration of disease and cortical GM volume of frontal, parietal and temporal lobes and cerebellum (ii) serum copper levels and GM volume of right medial frontal gyrus and paracentral lobule. CONCLUSIONS: To the best of our knowledge, this is the first VBM study in patients with Wilson's disease. In spite of apparently normal cortex on visual inspection of MRI, decreased cortical GM volume was detected using VBM. In addition, serum copper may act as surrogate marker of cortical abnormalities in Wilson's disease.

A preliminary study of the neuroanatomical correlates of primary writing tremor: role of cerebellum.

INTRODUCTION: To explore the neuroanatomical correlates of primary writing tremor (PWT) and the role of cerebellum, using advanced structural neuroimaging. Till date, there are no studies exploring the gray and white matter changes using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) in PWT. METHODS: Ten male patients with PWT were evaluated clinically and with magnetic resonance imaging. VBM and DTI images of patients were compared with that of 10 healthy male subjects. Spatially unbiased infra-tentorial template (SUIT) analysis was done to investigate the alterations of cerebellar gray matter. Region-of-interest analysis was performed on regions observed to be significantly different on DTI analysis. RESULTS: The mean duration of illness and mean age of the patients were 3.5 ± 1.9 and 51.7 ± 8.6 years, respectively. On VBM analysis, the cluster of gray matter atrophy was found in bilateral cerebellar areas of culmen and left declive, right superior and medial frontal gyrus, bilateral middle frontal gyrus, bilateral anterior cingulate gyrus, and bilateral parahippocampal gyrus. DTI showed significantly reduced fractional anisotrophy of the anterior thalamic radiation, cingulum, and inferior fronto-occipital fasciculus in PWT patients compared to controls. The axial diffusivity, mean diffusivity, and radial diffusivity maps did not reveal any significant differences. On SUIT analysis, significant atrophy was found in right uvula and semilunar lobule in patients with PWT compared to controls. CONCLUSIONS: Our study found that patients with PWT had predominant gray matter atrophy in parts of cerebellum and frontal lobe along with white matter changes of the cingulum and frontal lobe connections.

Research in Parkinson's disease in India: A review.

Parkinson's disease (PD) is a common neurodegenerative disorder affecting patients in large numbers throughout the world. In this article, we review all the published data on PD based on studies in Indian population. We have tried to consolidate the contribution of Indian studies in PD research. We found 95 articles, of which 92 were original research papers. This is a relatively less number, but in the last decade, there has been an increase in research on PD from this country. But most of them seem to be restricted to only a few research institutes. The nonmotor symptoms and genetics are the most commonly studied aspects. The systematic review of the articles reveals that the epidemiology in India may be different with relatively lesser incidence here. Most of the genetic mutations found to cause PD in other population are not found in India, revealing that other genetic factors may be involved. Further research needs to be encouraged to understand the disease in Indian patients better, as all the results cannot be extrapolated from the Western literature to this heterogeneous Indian population. There need to be more studies on therapeutic aspects of the disease.

Freezing of gait in Parkinson's disease is associated with altered functional brain connectivity.

BACKGROUND: Patients with Parkinson's disease (PD) may develop several gait disturbances during the course of illness and Freezing of gait (FOG) is one of them. Several neuroimaging studies have been conducted to identify the neural correlates of FOG but results have not been uniform. Resting state functional MRI (rs-fMRI) is relatively less explored in PD patients with FOG. This study aims to compare the whole brain resting state connectivity of PD patients with and without FOG using rs-fMRI. METHODS: rs-fMRI was obtained for 28 PD patients (15 with and 13 patients without FOG) who were matched for various demographic and clinical characteristics. Seed to voxel analysis was performed at whole brain level and compared between the two groups. RESULTS: When compared to patients without FOG, the patients with FOG had reduced functional connectivity across multiple seeds. Major finding was reduced inter-hemispheric connectivity of left parietal opercular cortex with multiple regions of the brain primarily involving the primary somatosensory and auditory areas, which also negatively correlated with the FOGQ scores. CONCLUSION: Our findings suggest that alterations in the resting state functional connectivity of the opercular parietal cortex may be one of the substrates of FOG. Reduced interhemispheric connectivity probably is the reason for impairment of control and coordination in bilateral leg movements while walking.

Interactions of visual hallucinations, rapid eye movement sleep behavior disorder and cognitive impairment in Parkinson's disease: A review.

Patients with Parkinson's disease may develop various non-motor symptoms during the course of the illness. Visual hallucinations (VH) and cognitive impairment (CI) are two common non-motor symptoms of Parkinson's disease. Studies have reported association of both VH and CI with presence of rapid eye movement sleep behavior disorder (RBD). Presence of visual hallucinations and cognitive impairment has been described as risk factors for emergence of each other. There is marked overlap in the risk factors for development of RBD, VH and CI in patients with PD. Results of clinical and epidemiological studies as well as studies based on neuroimaging, electrophysiology especially transcranial magnetic stimulation and neuropsycholgical evaluations in PD patients have suggested presence of certain common neurobiological process leading to emergence of RBD, VH and CI. Structural neuroimaging studies using voxel-based morphometry have often reported grey matter atrophy of hippocampus and parahippocampal cortices in PD patients with RBD, VH and CI. Cholinergic dysfunction is common in PD patients with RBD, VH and CI. This review explores the complex interactions of RBD, VH and CI in patients with PD and their potential implications.

Determinants of Onset of Huntington's Disease with Behavioral Symptoms: Insight from 92 Patients.

BACKGROUND: Huntington's disease (HD) is a genetically mediated neurodegenerative disorder characterized by presence of involuntary movements, behavioral problems and cognitive dysfunctions. Though few patients with HD may have behavioral symptoms at onset of the disease, studies comparing patients with behavioral symptoms at the onset of HD with those having motor symptoms are sparse. OBJECTIVE: Objective of this study is to determine the differences in the demographic and genetic characteristics of patients with behavioral symptom at the onset of HD from those with motor symptoms. METHODS: A chart review of 92 patients with HD who had attended the neurology outpatient clinics of National Institute of Mental Health and Neurosciences, India was done. Demographic and genetic characteristics of HD patients with onset of the disease with initial behavioral symptoms (HD-iB) were compared with patients with onset of the disease with initial motor symptoms (HD-iM). RESULTS: The principal findings in our study were (i) higher proportion of patients with HD-iB had a positive family history of HD, (ii) maternal inheritance of HD was more frequent among those with HD-iB, and (iii) There is no significant difference between the CAG repeat length between HD-iB and HD-iM groups. CONCLUSION: Presence of family history of HD especially inheritance of HD from mother may be associated with behavioral symptoms at the onset of HD. CAG repeat length in patients with HD-iB does not differ from those with HD-iM.

Neuropsychological and imaging profile of patients with Parkinson's disease and freezing of gait.

BACKGROUND: Neuropsychological evaluation with advanced neuroimaging may be a useful tool to determine the anatomical substrates that play crucial role in freezing of gait (FOG) in patients with Parkinson's Disease (PD). OBJECTIVES: To compare the cognitive profile and gray matter (GM) changes (using Voxel Based Morphometry - VBM) between patients with PD with and without FOG (FOG+ve and FOG-ve). METHODS: Seventeen FOG+ve (M:F = 11:6) and 21 FOG-ve (M:F = 11:10) were evaluated clinically and with a structured neuropsychological battery. All patients underwent 3 T MRI. In order to determine areas of GM atrophy, T1W volumetric MRI data of the two groups were compared using VBM and Statistical Parametric Mapping 8. RESULTS: The mean age of FOG+ve and FOG-ve patients were 56.9 ± 6.6 and 47.4 ± 9.1 years respectively. There was no significant difference in the duration (6.0 ± 4.9 vs 5.2 ± 3.5 years, p < 0.05) and stage of PD (Hoehn & Yahr stage: 1.96 ± 0.53 vs 1.78 ± 0.37) between the two groups. Compared to the FOG-ve group, the FOG+ve group had (i) significant impairment in memory, attention, executive and visuospatial functions on neuropsychological tests, and (ii) significant GM atrophy in the right cerebellum (pyramis, declive), left cerebrum (Brodmann area (BA) 21 and 22) and right cerebrum (BA 10 and 6) on VBM analysis. CONCLUSIONS: The FOG+ve group showed widespread involvement of cognition localizing to frontal, temporal (especially left) and parietal areas. VBM analysis showed significant GM atrophy in FOG+ve group in left temporal, right frontal areas (coinciding with that observed in neuropsychological tests) and significant involvement of right cerebellum.