White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study

Background

Some gray and white matter regions of the brain are sexually dimorphic. The best MRI technique for identifying subtle differences in white matter is diffusion tensor imaging (DTI). The purpose of this paper is to investigate whether white matter patterns in female to male (FtM) transsexuals before commencing cross-sex hormone treatment are more similar to that of their biological sex or to that of their gender identity.

Method

DTI was performed in 18 FtM transsexuals and 24 male and 19 female heterosexual controls scanned with a 3 T Trio Tim Magneton. Fractional anisotropy (FA) was performed on white matter fibers of the whole brain, which was spatially analyzed using Tract-Based Spatial Statistics.

Results

In controls, males have significantly higher FA values than females in the medial and posterior parts of the right superior longitudinal fasciculus (SLF), the forceps minor, and the corticospinal tract. Compared to control females, FtM showed higher FA values in posterior part of the right SLF, the forceps minor and corticospinal tract. Compared to control males, FtM showed only lower FA values in the corticospinal tract.

Conclusions

Our results show that the white matter microstructure pattern in untreated FtM transsexuals is closer to the pattern of subjects who share their gender identity (males) than those who share their biological sex (females). Our results provide evidence for an inherent difference in the brain structure of FtM transsexuals.     

A meta-analysis of whole-brain diffusion tensor imaging studies in bipolar disorder

Objectives

White matter abnormalities are one of the most consistently reported findings in neuroimaging studies of bipolar disorder (BD). We conducted an anatomical likelihood estimation meta-analysis of BD whole-brain diffusion tensor imaging (DTI) studies, with the aim of identifying statistically consistent fractional anisotropy (FA) changes reflecting microstructural modifications to white matter in BD.

Methods

We performed online searches of the PUBMED and EMBASE databases in January 2011. Studies were considered for inclusion if they used diffusion tensor MRI, compared a group of subjects with BD with healthy controls and involved whole-brain white matter analysis of FA. The analyses were conducted in Talairach space, using the activation likelihood estimation technique. We carried out a meta-analysis restricted to studies reporting a lower FA in patients with BD than in healthy controls.

Results

Ten studies were included. We identified two significant clusters of decreased FA on the right side of the brain. The first was located in the right white matter, close to the parahippocampal gyrus. Four of the ten studies included contributed to this cluster. The second cluster was located close to the right anterior and subgenual cingulate cortex. These two clusters of decreased FA in BD are crossed by several white matter tracts.

Conclusions

These two clusters of altered FA may underlie the abnormal emotional processing and altered functional limbic connectivity in BD. Explorations based on DTI-based tractography are required to identify the tracts involved in the pathophysiology of BD.     

Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis

Background

Individual structural imaging studies in the pre-psychotic phases deliver contrasting findings and are unable to definitively characterize the neuroanatomical correlates of an increased liability to psychosis and to predict transition to psychosis.

Method

Ninenteen voxel-based morphometry (VBM) studies of subjects at enhanced risk for psychosis and healthy controls were included in an activation likelihood estimation (ALE) meta-analysis.

Results

The overall sample consisted of 701 controls and 896 high risk subjects. Subjects at high risk for psychosis showed reduced gray matter (GM) volume as compared to controls in the right superior temporal gyrus, left precuneus, left medial frontal gyrus, right middle frontal gyrus, bilateral parahippocampal/hippocampal regions and bilateral anterior cingulate. High risk subjects who later developed a psychotic episode showed baseline GM volume reductions in the right inferior frontal gyrus and in the right superior temporal gyrus.

Conclusions

GM volume reductions in temporo-parietal, bilateral prefrontal and limbic cortex are neuroanatomical correlates of an enhanced vulnerability to psychosis. Baseline GM reductions in superior temporal and inferior frontal areas are associated with later transition to psychosis.     

Initial evidence for the role of CACNA1C on subcortical brain morphology in patients with bipolar disorder

Background

The polymorphism rs1006737 within the CACNA1C gene is associated with increased risk for bipolar disorder (BD) and variations in brain morphology and function of subcortical regions. Here we sought to investigate the influence of CACNA1C polymorphism on key subcortical brain structures implicated in the pathophysiology of BD.

Methods

Structural magnetic resonance imaging scans were acquired from 41 euthymic patients with BD and 40 healthy controls, who were also genotyped for the CACNA1C rs1006737 polymorphism. The effect of diagnosis, genotype and their interaction was examined in predefined volumes of interest in the basal ganglia, hypothalamus and amygdala extracted using SPM5.

Results

Carriers of the CACNA1C rs1006737 risk allele showed increased grey matter density in the right amygdala and right hypothalamus irrespective of diagnosis. An interaction between genotype and diagnosis was observed in the left putamen which was smaller in BD patients carrying the risk allele than in healthy controls.

Conclusions

: The CACNA1C rs1006737 polymorphism influences anatomical variation within subcortical regions involved in emotional processing.     

A voxel-based morphometric MRI study of stabilized obsessive-compulsive adolescent patients

Background

The aim of this study was to determine whether treated stabilized adolescents with obsessive-compulsive disorder (OCD) present brain structure differences in comparison with healthy control subjects.

Methods

Twenty-seven adolescents with already-treated OCD and 27 healthy controls matched by age, sex and estimated intellectual level were assessed by means of psychopathological scales and magnetic resonance imaging (MRI). Axial three-dimensional T1-weighted images were obtained in a 1.5 T scanner and analyzed using optimized voxel-based morphometry (VBM).

Results

Compared with controls, stabilized patients with OCD did not present any statistical differences in the whole brain. However, a small volume correction analysis yielded significant results that survived correction for multiple comparisons, showing decreased white matter (WM) volume in a small area of the parietal cortex (t = 3.39, p = 0.045 FWE (family wise error)-corrected) of OCD patients in comparison with healthy controls. There was no significant correlation between decreased WM volume in the parietal cortex and obsessive-compulsive symptomatology.

Conclusion

There were no global significant differences in either gray matter (GM) or WM. Small differences were found between adolescent patients with stabilized OCD and healthy controls as regards in WM volume in right parietal areas. The parietal lobe may play a role in the pathophysiology of OCD, even in clinically stabilized patients.     

Diffusion tensor imaging patterns differ in bulbar and limb onset amyotrophic lateral sclerosis

Background

Amyotrophic lateral sclerosis (ALS) is characterized by pronounced clinical heterogeneity in terms of onset and disease progression. Widespread changes in white matter fibres could be observed by diffusion tensor imaging (DTI), which detects alterations in the degree (diffusivity, ADC) and directedness (fractional anisotropy, FA) of proton movement. The aim of the current study was to determine whether different ALS onset types were reflected in different DTI brain patterns.

Methods

Seventeen patients with a diagnosis of ALS (6 bulbar, 11 limb onset) and seventeen age-matched controls received 1.5T DTI, where FA and ADC were analyzed using statistical parametric mapping.

Results

In ALS patients, an increased diffusivity in the white matter was found below the precentral gyrus and along the corticospinal tract (CST) right into the internal capsule. The FA was decreased in the posterior limb of internal capsule and in the subcortical white matter in the precentral gyrus. In bulbar onset increased diffusivity was found in the CST, whilst in limb onset, frontal subcortical areas displayed an increased diffusivity.

Conclusion

DTI changes can be regarded as prominent features in ALS. Herein we were able to demonstrate discriminating brain DTI patterns due to bulbar or limb onset.     

A primary study of diffusion tensor imaging-based histogram analysis in vascular cognitive impairment with no dementia

Purpose

This study performed diffusion tensor imaging (DTI) histogram analysis and voxel-based analysis (VBA) to detect white matter (WM) damage in patients with vascular cognitive impairment with no dementia (VCIND) and to determine correlations between DTI histogram-derived measures and cognitive dysfunction in these patients.

Materials and methods

Among patients with subcortical ischemic vascular disease, 18 patients with VCIND were selected along with 18 age- and sex-matched cognitive-normal subjects. Both groups underwent magnetic resonance and DTI scans, and fractional anisotropy (FA) changes in VBA between the two groups were assessed. Further, mean diffusivity (MD) and FA histograms of WM and normal-appearing WM (NAWM) in each subject were evaluated.

Results

Compared to control, the VCIND group showed lower FA values throughout the brain. FA and MD histogram patterns of WM and NAWM were significantly different between the groups. Significant differences were found in all DTI histogram-derived measures, except in the mean FA peak height of WM and mean MD peak location of NAWM. Neuropsychological results (z-scores) were found to be significantly correlated with mean FA peak location, average MD, mean MD peak location of WM, and mean FA peak height, average MD, mean MD peak location of NAWM.

Conclusions

Results of VBA and diffusion tensor imaging-based histogram analysis suggest that VCIND patients have more severe damage in WM and NAWM than the control. Thus, the severity of damage in WM and NAWM may be related with cognitive dysfunction in VCIND patients, and DTI histogram analysis can help in further understanding VCIND.     

Voxelwise meta-analysis of gray matter reduction in major depressive disorder

Background

Voxel-based morphometry (VBM) has been widely used in studies of major depressive disorder (MDD) and has provided cumulative evidence of gray matter abnormalities in patients relative to controls. Thus we performed a meta-analysis to integrate the reported studies to determine the consistent gray matter alterations in MDD.

Methods

A systematic search was conducted to identify VBM studies which contrasted MDD patients against a comparison group. The coordinates of gray matter change across studies were meta-analyzed using the activation likelihood estimation (ALE) method hybridized with the rank-based Genome Scan Meta-Analysis (GSMA) to quantitatively estimate regional gray matter reductions in MDD.

Results

A total of 20 VBM studies comparing 543 major depressive patients with 750 healthy control subjects were included. Consistent gray matter reductions in all MDD patients relative to healthy controls were identified in the bilateral anterior cingulate cortex (ACC), right middle and inferior frontal gyrus, right hippocampus and left thalamus.

Conclusions

Meta-analysis of all primary VBM studies indicates that significant gray matter reductions in MDD are localized in a distributed neural network which includes frontal, limbic and thalamic regions. Future studies will benefit from the use of a longitudinal approach to examine anatomical and functional abnormalities within this network and their relationship to clinical profile, particularly in first-episode and drug-naive MDD patients.     

Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD

Background

Many studies using diffusion tensor imaging (DTI) have demonstrated impaired white matter integrity in patients with major depressive disorder (MDD), with significant results found in diverse brain regions. We sought to identify whether there are consistent changes of regional white matter integrity in patients with MDD, as shown by decreased fractional anisotropy in DTI.

Method

A systematic search strategy was used to identify relevant whole brain voxel-based DTI studies of patients with MDD in relation to comparison groups. Relevant databases were searched for studies published between January 1994 and February 2011 using combinations of the terms “DTI” or “diffusion tensor;” “whole brain” or “voxel-based;” and “depress^*.” Using the studies that met our inclusion criteria, we performed a meta-analysis of the coordinates of decreased fractional anisotropy using the activation likelihood estimation (ALE) method, which detects 3-dimensional conjunctions of coordinates from multiple studies, weighted by sample size. We then used DTIquery software for fibre tracking to locate the fascicles involved in each region.

Results

We included 11 studies with a combined sample of 231 patients with MDD and 261 comparison participants, providing 50 coordinates of decreased fractional anisotropy. Our meta-analysis identified 4 consistent locations of decreased fractional anisotropy in patients with MDD: white matter in the right frontal lobe, right fusiform gyrus, left frontal lobe and right occipital lobe. Fibre tracking showed that the main fascicles involved were the right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, right posterior thalamic radiation and interhemispheric fibres running through the genu and body of the corpus callosum.

Limitations

The number of studies included was relatively small, and the DTI data acquisition and analysis techniques were heterogeneous. The ALE method cannot handle studies with no significant group differences.

Conclusion

Voxel-based analysis of DTI studies of patients with MDD consistently identified decreased fractional anisotropy in the white matter fascicles connecting the prefrontal cortex within cortical (frontal, temporal and occipital lobes) and subcortical areas (amygdala and hippocampus). This is strong evidence for the involvement of these neural circuits in the pathology of MDD.     

Correlating 3T MRI and histopathology in patients undergoing epilepsy surgery

Purpose

To investigate whether specific semi-quantitative 3T MRI parameters are associated with particular histological features in temporal lobe specimens in epilepsy surgery patients whose conventional MRI scan appeared normal. These MRI techniques have the potential to visualise subtle structural abnormalities currently undetected on conventional MRI; but correlation between pre-operative in vivo MRI and histopathology is needed to understand the basis of these MRI abnormalities. Predicting subtle histopathology with semi-quantitative MRI techniques could contribute to pre-surgical evaluation of epilepsy patients.

Materials and methods

MRI techniques: normalised FLAIR signal intensity (nFSI), grey matter probability and diffusion tensor imaging (DTI) were correlated with quantitative histopathological measures: NeuN (neuronal nuclear antigen); GFAP (glial fibrillary acidic protein) and MBP (myelin basic protein) field fractions and stereological neuronal densities obtained in grey and white matter regions in twenty-four patients who underwent anterior temporal lobe resections.

Results

There were no significant correlations between the histopathological measurements and MRI values in grey or white matter in macroscopically normal appearing tissue.

Conclusion

Findings suggest that in macroscopically normal appearing tissue, the studied semiquantitative MRI measurements are not significantly related to the measures of gliosis, neuronal loss/gain and myelin used in the current study. Studies of macroscopically abnormal tissue as well as improvements to the MRI techniques may increase the sensitivity of future correlative studies to improve our understanding of the histopathological basis of MRI signal characteristics.     

A polymorphism of the ABCA1 gene confers susceptibility to schizophrenia and related brain changes

Objective

The ATP-binding cassette transporter A1 (ABCA1) mediates cellular cholesterol efflux through the transfer of cholesterol from the inner to the outer layer of the cell membrane and regulates extracellular cholesterol levels in the central nervous system. Several lines of evidence have indicated lipid and myelin abnormalities in schizophrenia.

Method

Initially, we examined the possible association of the polymorphisms of the ABCA1 gene (ABCA1) with susceptibility to schizophrenia in 506 patients with schizophrenia (DSM-IV) and 941 controls. The observed association was then subject to a replication analysis in an independent sample of 511 patients and 539 controls. We further examined the possible effect of the risk allele on gray matter volume assessed with magnetic resonance imaging (MRI) in 86 patients with schizophrenia (49 males) and 139 healthy controls (47 males).

Results

In the initial association study, the 1587 K allele (rs2230808) was significantly more common in male patients with schizophrenia than in male controls. Although such a significant difference was not observed in the second sample alone, the increased frequency of the 1587 K allele in male patients remained to be significant in the combined male sample of 556 patients and 594 controls. Male schizophrenia patients carrying the 1587 K allele had a smaller amount of gray matter volume than those who did not carry the allele.

Conclusion

Our data suggest a male-specific association of the 1587 K allele of ABCA1 with susceptibility to schizophrenia and smaller gray matter volume in schizophrenia.     

Effect of median-nerve electrical stimulation on BOLD activity in acute ischemic stroke patients

Objective

To investigate blood oxygenation level-dependent (BOLD) activation during somatosensory electrical stimulation of the median nerve in acute stroke patients and to determine its correlation with ischemic damage and clinical recovery over time.

Methods

Fourteen acute stroke patients underwent functional magnetic resonance imaging (fMRI) during contralesional median-nerve electrical stimulation 12-48 h after stroke. Findings were then validated by diffusion tensor imaging (DTI) and motor evoked potential by transcranial magnetic stimulation (TMS).

Results

Poor clinical recovery at three months was noted in four patients with no activation in the early days after stroke, whereas good clinical recovery was observed in eight patients with a normal activation pattern in the primary sensory motor area in the acute phase. In two patients BOLD activation correlated weakly with clinical recovery. Findings from TMS and DTI partially correlated with clinical recovery and functional scores.

Conclusions

Clinically relevant insights into the “functional reserve” of stroke patients gained with peripheral nerve stimulation during fMRI may carry prognostic value already in the acute period of a cerebrovascular accident.

Significance

BOLD activation maps could provide insights into the functional organization of the residual systems and could contribute to medical decision making in neurological and rehabilitative treatment.     

Progressive alterations of the auditory association areas in young non-psychotic offspring of schizophrenia patients

Background

Schizophrenia may involve progressive alterations of structure and hemispheric lateralization of auditory association areas (AAA) within the superior temporal gyrus. These alterations may be greater in male patients. It is unclear if these deficits are state-dependent or whether they predate illness onset and reflect familial diathesis.

Aims

We sought to compare AAA cortical thickness, surface area and lateralization across adolescent and young adult non-psychotic offspring of schizophrenia patients (OS) and healthy controls at baseline and one year follow-up. We also assessed the moderating effect of gender on these measures.

Methods

Fifty-six OS and thirty-six control subjects were assessed at baseline and at follow-up on AAA surface area and thickness using FreeSurfer to process T1-MRI-images. We used repeated measures ANCOVAs, controlling intra cranial volume and age with assessment-time and side as within-subject factors and gender and study group as between-subject factors.

Results

Surface area deficit in OS was greater on the left than on the right, as reflected in a lower surface area laterality-index (left-right/left + right  × 100) in OS compared to controls. Left, but not right surface area and surface area laterality-index showed a longitudinal decline in OS compared to controls. Male OS declined more than controls on surface area and thickness.

Conclusions

Left AAA surface area may progressively decline in young non-psychotic offspring at familial diathesis for schizophrenia causing a continuing reversal of the leftward AAA lateralization. Progressive surface area reduction and thinning of AAA may be more prominent in young non-psychotic male offspring at risk for schizophrenia.     

Elevated leukocyte count in asymptomatic subjects is associated with a higher risk for cerebral white matter lesions

Objective

Cerebral white matter lesions (WMLs) are radiologic markers of small vessel disease in brain, and inflammatory processes were related to WMLs. We propose to determine if elevated leukocyte count was associated with a higher risk of WMLs.

Methods

1586 asymptomatic subjects who visited our hospital for a routine health check-up were enrolled. Leukocyte counts were measured and the presence of moderate to severe WMLs was determined by brain MRI.

Results

Thirty (1.9%) had moderate to severe WMLs, and a significant greater proportion (4.1%) of subjects in the highest leukocyte count quartile had moderate to severe WMLs. After adjusting by C-reactive protein, aspirin use and cardiovascular risk factors, the highest quartile of leukocyte count (≥6.7 × 10⁹/L) was significantly associated with moderate to severe WMLs compared with the lowest quartile [adjusted odds ratio, 4.03; 95% confidence interval, 1.05-15.5].

Conclusion

The authors report for the first time that an elevated leukocyte count is independently associated with moderate to severe WMLs.     

Hippocampal volume in borderline personality disorder with and without comorbid posttraumatic stress disorder: A meta-analysis

Background

Several studies have found a reduction in hippocampal volume in borderline personality disorder (BPD) patients.

Methods

In order to investigate the degree to which comorbid posttraumatic stress disorder (PTSD) could account for reduction in hippocampal volume in these patients, we conducted a systematic review and meta-analysis of studies that compared hippocampal volume in BPD patients with and without PTSD relative to healthy controls.

Results

Seven articles, involving 124 patients and 147 controls, were included. We found a statistically significant reduction for the left and right hippocampus. Data from the four studies that discriminated BPD patients with and without PTSD indicate that hippocampal volumes were reduced bilaterally in BPD patients with PTSD, relative to healthy controls, but that results were mixed for BPD patients without PTSD, relative to healthy controls.

Conclusions

Results from this meta-analysis suggest that hippocampal volumes are reduced in patients with BPD, relative to healthy controls, but particularly in cases in which patients are diagnosed with comorbid PTSD.     

Progressive paraparesis with sensorineural deafness and leukoencephalopathy revealing neurobrucellosis

Introduction

Brucellosis is a rare disease with variable neurological and imaging manifestations.

Case report

A 54-year-old woman presented with progressive paraparesis and sensorineural hearing loss over 18 months. The presence of diffuse white matter changes on brain magnetic resonance imaging (MRI) and cerebrospinal fluid findings led to the diagnosis of neurobrucellosis. Spinal MRI did not show any lesion that could explain the paraparesis that was finally attributed to the leukoencephalopathic lesions. The patient improved clinically after three months of antibiotic treatment but no significant changes were noticed on brain imaging.

Discussion and conclusion

Neurobrucellosis is a treatable disease which should be discussed when a patient presents with the triade progressive paraparesis, sensorineural hearing loss and leukoencephalopathy on MRI. Outcome can be favorable if adapted treatment is given early.     

Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use

Background

There is growing evidence that adolescence is a key period for neuronal maturation. Despite the high prevalence of marijuana use among adolescents and young adults in the United States and internationally, very little is known about its impact on the developing brain. Based on neuroimaging literature on normal brain developmental during adolescence, we hypothesized that individuals with heavy cannabis use (HCU) would have brain structure abnormalities in similar brain regions that undergo development during late adolescence, particularly the fronto-temporal connection.

Method

Fourteen young adult males in residential treatment for cannabis dependence and 14 age-matched healthy male control subjects were recruited. Patients had a history of HCU throughout adolescence; 5 had concurrent alcohol abuse. Subjects underwent structural and diffusion tensor magnetic resonance imaging. White matter integrity was compared between subject groups using voxelwise and fiber tractography analysis.

Results

Voxelwise and tractography analyses revealed that adolescents with HCU had reduced fractional anisotropy, increased radial diffusivity, and increased trace in the homologous areas known to be involved in ongoing development during late adolescence, particularly in the fronto-temporal connection via arcuate fasciculus.

Conclusions

Our results support the hypothesis that heavy cannabis use during adolescence may affect the trajectory of normal brain maturation. Due to concurrent alcohol consumption in five HCU subjects, conclusions from this study should be considered preliminary, as the DTI findings reported here may be reflective of the combination of alcohol and marijuana use. Further research in larger samples, longitudinal in nature, and controlling for alcohol consumption is needed to better understand the pathophysiology of the effect of cannabis on the developing brain.     

Effects of androgenization on the white matter microstructure of female-to-male transsexuals. A diffusion tensor imaging study

Diffusion tensor imaging (DTI) can sensitively detect white matter sex differences and the effects of pharmacological treatments. Before cross-sex hormone treatment, the white matter microstructure of several brain bundles in female-to-male transsexuals (FtMs) differs from those in females but not from that in males. The purpose of this study was to investigate whether cross-sex hormone treatment (androgenization) affects the brain white matter microstructure. Using a Siemens 3 T Trio Tim Magneton, DTI was performed twice, before and during cross-sex hormonal treatment with testosterone in 15 FtMs scanned. Fractional anisotropy (FA) was analyzed on white matter of the whole brain, and the latter was spatially analyzed using Tract-Based Spatial Statistics. Before each scan the subjects were assessed for serum testosterone, sex hormone binding globulin level (SHBG), and their free testosterone index. After at least seven months of cross-gender hormonal treatment, FA values increased in the right superior longitudinal fasciculus (SLF) and the right corticospinal tract (CST) in FtMs compared to their pre-treatment values. Hierarchical regression analyses showed that the increments in the FA values in the SLF and CST are predicted by the free testosterone index before hormonal treatment. All these observations suggest that testosterone treatment changes white matter microstructure in FtMs.     

Reduced interhemispheric coherence in dyslexic adults

Introduction

Developmental dyslexia has been associated with reduced interhemispheric neural connectivity in children. The present study investigated functional interhemispheric connectivity in male dyslexic adults.

Methods

A group of 19 dyslexic men were compared to a group of 15 controls on interhemispheric coherence of the dominant frequency in the power spectrum during a visuo-spatial attention task. The coherence between a left hemisphere central-parietal electrode and the respective right hemisphere electrode and surrounding sites was analysed.

Results

Compared to controls, the dyslexic group demonstrated reduced, and more diffuse, interhemispheric coherence of alpha activity in the central-parietal cortex. No group differences in interhemispheric coherence were found on frontal, temporal or central sites.

Conclusions

The deviant pattern of functional connectivity in dyslexics is suggestive of an altered development of neural circuitry that may lead to deficits in magnocellular processing.     

Visuomotor integration deficits precede clinical onset in Huntington's disease

Objectives

Visuomotor integration deficits have been documented in Huntington disease (HD), with disproportionately more impairment when direct visual feedback is unavailable. Visuomotor integration under direct and indirect visual feedback conditions has not been investigated in the stage before clinical onset (‘premanifest’). However, given evidence of posterior cortical atrophy in premanifest HD, we predicted visuomotor integration would be adversely affected, with greater impairment under conditions of indirect visual feedback.

Methods

239 subjects with the HD CAG expansion, ranging from more than a decade before predicted clinical onset until early stage disease, and 122 controls, completed a circle-tracing task, which included both direct and indirect visual feedback conditions. Measures included accuracy, speed, and speed of error detection and correction. Using brain images acquired with 3T magnetic resonance imaging (MRI), we generated grey and white matter volumes with voxel-based morphometry, and analyzed correlations with circle-tracing performance.

Results

Compared with controls, early HD was associated with lower accuracy and slower performance in both circle-tracing conditions. Premanifest HD was associated with lower accuracy in both conditions and fewer rotations in the direct condition. Comparing performance in the indirect condition with the direct condition, HD gene expansion-carriers exhibited a disproportionate increase in errors relative to controls. Premanifest and early HD groups required longer to detect and correct errors, especially in the indirect condition. Slower performance in the indirect condition was associated with lower grey matter volumes in the left somatosensory cortex in VBM analyses.

Conclusions

Visuomotor integration deficits are evident many years before the clinical onset of HD, with deficits in speed, accuracy, and speed of error detection and correction. The visuomotor transformation demands of the indirect condition result in a disproportionate decrease in accuracy in the HD groups. Slower performance under indirect visual feedback was associated with atrophy of the left-hemisphere somatosensory cortex, which may reflect the proprioceptive demands of the task.