Multiple mechanisms underpin cerebral and cerebellar white matter deficits in Friedreich ataxia: The IMAGE‐FRDA study

Friedreich ataxia is a progressive neurodegenerative disorder with reported abnormalities in cerebellar, brainstem, and cerebral white matter. White matter structure can be measured using in vivo neuroimaging indices sensitive to different white matter features. For the first time, we examined the relative sensitivity and relationship between multiple white matter indices in Friedreich ataxia to more richly characterize disease expression and infer possible mechanisms underlying the observed white matter abnormalities. Diffusion‐tensor, magnetization transfer, and T1‐weighted structural images were acquired from 31 individuals with Friedreich ataxia and 36 controls. Six white matter indices were extracted: fractional anisotropy, diffusivity (mean, axial, radial), magnetization transfer ratio (microstructure), and volume (macrostructure). For each index, whole‐brain voxel‐wise between‐group comparisons and correlations with disease severity, onset age, and gene triplet‐repeat length were undertaken. Correlations between pairs of indices were assessed in the Friedreich ataxia cohort. Spatial similarities in the voxel‐level pattern of between‐group differences across the indices were also assessed. Microstructural abnormalities were maximal in cerebellar and brainstem regions, but evident throughout the brain, while macroscopic abnormalities were restricted to the brainstem. Poorer microstructure and reduced macrostructural volume correlated with greater disease severity and earlier onset, particularly in peri‐dentate nuclei and brainstem regions. Microstructural and macrostructural abnormalities were largely independent. Reduced fractional anisotropy was most strongly associated with axial diffusivity in cerebral tracts, and magnetization transfer in cerebellar tracts. Multiple mechanisms likely underpin white matter abnormalities in Friedreich ataxia, with differential impacts in cerebellar and cerebral pathways.     

Regional alterations of brain microstructure in Parkinson's disease using diffusion tensor imaging

This study tested the hypothesis that diffusion tensor imaging can detect alteration in microscopic integrity of white matter and basal ganglia regions known to be involved in Parkinson's disease (PD) pathology. It was also hypothesized that there is an association between diffusion abnormality and PD severity and subtype. Diffusion tensor imaging at 4 Tesla was obtained in 12 PD and 20 control subjects, and measures of fractional anisotropy and mean diffusivity were evaluated using both region‐of‐interest and voxel‐based methods. Movement deficits and subtypes in PD subjects were assessed using the Motor Subscale (Part III) of the Unified Parkinson's Disease Rating Scale. Reduced fractional anisotropy (P < .05, corrected) was found in PD subjects in regions related to the precentral gyrus, substantia nigra, putamen, posterior striatum, frontal lobe, and the supplementary motor areas. Reduced fractional anisotropy in the substantia nigra correlated (P < .05, corrected) with the increased rating scale motor scores. Significant spatial correlations between fractional anisotropy alterations in the putamen and other PD‐affected regions were also found in the context of PD subtypes index analysis. Our data suggest that microstructural alterations detected with diffusion tensor might serve as a potential biomarker for PD. © 2011 Movement Disorder Society     

Deep Brain Stimulation of the Subthalamic and Pedunculopontine Nucleus in a Patient with Parkinson's Disease

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel therapy developed to treat Parkinson''s disease. We report a patient who underwent bilateral DBS of the PPN and subthalamic nucleus (STN). He suffered from freezing of gait (FOG), bradykinesia, rigidity and mild tremors. The patient underwent bilateral DBS of the PPN and STN. We compared the benefits of PPN-DBS and STN-DBS using motor and gait subscores. The PPN-DBS provided modest improvements in the gait disorder and freezing episodes, while the STN-DBS failed to improve the dominant problems. This special case suggests that PPN-DBS may have a unique role in ameliorating the locomotor symptoms and has the potential to provide improvement in FOG.     

Altered corticomotor‐cerebellar integrity in young ataxia telangiectasia patients

Magnetic resonance imaging (MRI) research in identifying altered brain structure and function in ataxia‐telangiectasia, an autosomal recessive neurodegenerative disorder, is limited. Diffusion‐weighted MRI were obtained from 11 ataxia telangiectasia patients (age range, 7‐22 years; mean, 12 years) and 11 typically developing age‐matched participants (age range, 8‐23 years; mean, 13 years). Gray matter volume alterations in patients were compared with those of healthy controls using voxel‐based morphometry, whereas tract‐based spatial statistics was employed to elucidate white matter microstructure differences between groups. White matter microstructure was probed using quantitative fractional anisotropy and mean diffusivity measures. Reduced gray matter volume in both cerebellar hemispheres and in the precentral‐postcentral gyrus in the left cerebral hemisphere was observed in ataxia telangiectasia patients compared with controls (P < 0.05, corrected for multiple comparisons). A significant reduction in fractional anisotropy in the cerebellar hemispheres, anterior/posterior horns of the medulla, cerebral peduncles, and internal capsule white matter, particularly in the left posterior limb of the internal capsule and corona radiata in the left cerebral hemisphere, was observed in patients compared with controls (P < 0.05). Mean diffusivity differences were observed within the left cerebellar hemisphere and the white matter of the superior lobule of the right cerebellar hemisphere (P < 0.05). Cerebellum‐localized gray matter changes are seen in young ataxia telangiectasia patients along with white matter tract degeneration projecting from the cerebellum into corticomotor regions. The lack of cortical involvement may reflect early‐stage white matter motor pathway degeneration within young patients. © 2014 International Parkinson and Movement Disorder Society     

Apathy in Parkinson's disease is associated with nucleus accumbens atrophy: A magnetic resonance imaging shape analysis

Apathy is characterized by lack of interest, loss of initiative, and flattening of affect. It is a frequent, very disabling nonmotor complication of Parkinson's disease (PD). The condition may notably occur when dopaminergic medications are tapered after the initiation of subthalamic stimulation and thus can be referred to as “dopaminergic apathy.” Even in the absence of tapering, some patients may develop a form of apathy as PD progresses. This form is often related to cognitive decline and does not respond to dopaminergic medications (dopa‐resistant apathy). We aimed at determining whether dopa‐resistant apathy in PD is related to striatofrontal morphological changes. We compared the shape of the striatum (using spherical harmonic parameterization and sampling in a three‐dimensional point distribution model [SPHARM‐PDM]), cortical thickness, and fractional anisotropy (using tract‐based spatial statistics) in 10 consecutive patients with dopamine‐refractory apathy, 10 matched nonapathetic PD patients and 10 healthy controls. Apathy in PD was associated with atrophy of the left nucleus accumbens. The SPHARM‐PDM analysis highlighted (1) a positive correlation between the severity of apathy and atrophy of the left nucleus accumbens, (2) greater atrophy of the dorsolateral head of the left caudate in apathetic patients than in nonapathetic patients, and (3) greater atrophy in the bilateral nucleus accumbens in apathetic patients than in controls. There were no significant intergroup differences in cortical thickness or fractional anisotropy. Dopa‐resistant apathy in PD was associated with atrophy of the left nucleus accumbens and the dorsolateral head of the left caudate. © 2014 International Parkinson and Movement Disorder Society     

White matter abnormalities in gene‐positive myoclonus‐dystonia

Myoclonus‐dystonia is an autosomal dominantly inherited movement disorder clinically characterized by myoclonic jerks and dystonic movements of the upper body. Functional imaging and structural gray matter imaging studies in M‐D suggest defective sensorimotor integration and an association between putaminal volume and severity of dystonia, possibly because of neuronal plasticity. As we expect changes in the connections between the cortical and subcortical regions, we performed a combination of white matter voxel‐based morphometry (wVBM) and diffusion tensor imaging (DTI) to detect macro‐ and microstructural white matter changes, respectively, in DYT‐11 mutations carriers (M‐D). Sixteen clinically affected DYT‐11 mutation carriers and 18 control subjects were scanned with 3‐Tesla MRI to compare white matter volume, fractional anisotropy, and mean diffusivity between groups. In DYT11 mutation carriers, increased white matter volume and FA and decreased mean diffusivity werefound in the subthalamic area of the brain stem, including the red nucleus. Furthermore, decreased mean diffusivity was found in the subgyral cortical sensorimotor areas. The white matter changes found in the subthalamic area of the brain stem, connecting the cerebellum with the thalamus, are compatible with the hypothesis that abnormal function in M‐D involves a network that includes the cerebellum, brain stem, and basal ganglia. Whether these changes are causative or an effect of M‐D requires further study. © 2012 Movement Disorder Society     

White matter abnormalities in Parkinson's disease patients with glucocerebrosidase gene mutations

Glucocerebrosidase gene mutations represent a genetic risk factor for the development of Parkinson's disease. This study investigated brain alterations in Parkinson's disease patients carrying heterozygous glucocerebrosidase gene mutations using structural and diffusion tensor magnetic resonance imaging. Among 360 Parkinson's disease patients screened for glucocerebrosidase gene mutations, 19 heterozygous mutation carriers (5.3%) were identified. Of these, 15 patients underwent a neuropsychological evaluation and a magnetic resonance imaging scan. Sixteen age‐ and sex‐matched healthy controls and 14 idiopathic Parkinson's disease patients without glucocerebrosidase gene mutations were also studied. Tract‐based spatial statistics was used to perform a white matter voxel‐wise analysis of diffusion tensor magnetic resonance imaging metrics. Mean fractional anisotropy values were obtained from white matter tracts of interest. Voxel‐based morphometry was used to assess gray‐matter atrophy. Cognitive deficits were found in 9 mutation carrier patients (60%). Compared with controls, Parkinson's disease patients carrying glucocerebrosidase gene mutations showed decreased fractional anisotropy in the olfactory tracts, corpus callosum, and anterior limb of the internal capsule bilaterally, as well as in the right anterior external capsule, and left cingulum, parahippocampal tract, parietal portion of the superior longitudinal fasciculus, and occipital white matter. Mutation carrier patients also had decreased fractional anisotropy of the majority of white matter tracts compared with Parkinson's disease patients with no mutations. No white matter abnormalities were found in Parkinson's disease patients without glucocerebrosidase gene mutations. No gray matter difference was found between patients and controls. In Parkinson's disease patients, verbal fluency scores correlated with white matter abnormalities. Parkinson's disease patients carrying glucocerebrosidase gene mutations experience a distributed pattern of white matter abnormalities involving the interhemispheric, frontal corticocortical, and parahippocampal tracts. White matter pathology in these patients may have an impact on the clinical manifestations of the disease, including cognitive impairment. © 2013 Movement Disorder Society     

Diffusion tensor imaging in male premutation carriers of the fragile X mental retardation gene

Older male premutation carriers of the FMR1 gene are associated with the risk of developing a late‐onset neurodegenerative disorder, fragile X–associated tremor/ataxia syndrome. Although previous postmortem and in vivo magnetic resonance imaging studies have indicated white matter pathology, the regional selectivity of abnormalities, as well as their relationship with molecular variables of the FMR1 gene, has not been investigated. In this study, we used diffusion tensor imaging to study male premutation carriers with and without fragile X–associated tremor/ataxia syndrome and healthy sex‐matched controls. We performed a tract of interest analysis for fractional anisotropy and axial and radial diffusivities of major white matter tracts in the cerebellar–brain stem and limbic systems. Compared with healthy controls, patients with fragile X–associated tremor/ataxia syndrome showed significant reductions of fractional anisotropy in multiple white matter tracts, including the middle cerebellar peduncle, superior cerebellar peduncle, cerebral peduncle, and the fornix and stria terminalis. Significant reduction of fractional anisotropy in these tracts was confirmed by voxel‐wise analysis using tract‐based spatial statistics. Analysis of axial and radial diffusivities showed significant elevation of these measures in middle cerebellar peduncle, even among premutation carriers without fragile X–associated tremor/ataxia syndrome. Furthermore, regression analyses demonstrated a clear inverted U‐shaped relationship between CGG‐repeat size and axial and radial diffusivities in middle cerebellar peduncle. These results provide new evidence from diffusion tensor imaging for white matter abnormalities in the cerebellar–brain stem and limbic systems among individuals with the fragile X premutation and suggest the involvement of molecular mechanisms related to the FMR1 gene in their white matter pathology. © 2011 Movement Disorder Society     

Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review

Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20‐80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. © 2017 International Parkinson and Movement Disorder Society     

Longitudinal white matter changes in frontotemporal dementia subtypes

Frontotemporal dementia is a degenerative brain condition characterized by focal atrophy affecting the frontal and temporal lobes predominantly. Changes in white matter with disease progression and their relationship to grey matter atrophy remain unknown in FTD. This study aimed to establish longitudinal white matter changes and compare these changes to regional grey matter atrophy in the main FTD subtypes. Diffusion and T₁‐weighted images were collected from behavioral‐variant FTD (bvFTD: 12), progressive non‐fluent aphasia (PNFA: 10), semantic dementia (SD: 11), and 15 controls at baseline and 12 months apart. Changes in white matter integrity were established by fractional anisotropy, mean, axial and radial diffusivity measurements using tract‐based spatial statistics. Patterns of cortical grey matter atrophy were measured using voxel‐based morphometry. At baseline, bvFTD showed severe cross‐sectional changes in orbitofrontal and anterior temporal tracts, which progressed to involve posterior temporal and occipital white matter over the 12‐month. In PNFA, cross‐sectional changes occurred bilaterally in frontotemporal white matter (left > right), with longitudinal changes more prominent on the right. Initial white matter changes in SD were circumscribed to the left temporal lobe, with longitudinal changes extending to bilateral frontotemporal tracts. In contrast, progression of grey matter change over time was less pronounced in all FTD subtypes. Mean diffusivity was most sensitive in detecting baseline changes while fractional anisotropy and radial diffusivity revealed greatest changes over time, possibly reflecting different underlying pathological processes with disease progression. Our results indicate that investigations of white matter changes reveal important differences across FTD syndromes with disease progression. Hum Brain Mapp 35:3547–3557, 2014. © 2013 Wiley Periodicals, Inc .     

Effect of high‐frequency subthalamic neurostimulation on gait and freezing of gait in Parkinson's disease: a systematic review and meta‐analysis

The aim of this meta‐analysis was to summarize the short‐ and long‐term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN‐DBS) on gait and freezing of gait (FOG) in Parkinson's disease and to detect predictors of post‐stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN‐DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinson's Disease Rating Scale (UPDRS) and six studies with the FOG item (no. 14) were included. Data were summarized for the following follow‐up periods: 6–15, 24–48 and >48 months. For the medication (Med)‐Off/stimulation(Stim)‐On condition compared with baseline Med‐Off, STN‐DBS significantly improved gait on average from 2.43 to 0.96, 2.53 to 1.31 and 2.56 to 1.40 points at 6–15, 24–48 and >48 months, respectively (P < 0.05). Pre‐operative levodopa responsiveness of UPDRS‐III and Med‐Off severity of gait were the predictors of this beneficial effect. STN‐DBS significantly improved FOG for the Med‐Off/Stim‐On condition compared with baseline on average from 2.26 to 0.82, 2.43 to 1.13 and 2.48 to 1.38 points at 6–15, 24–48 and >48 months, respectively (P < 0.05). There was no significant effect in the Med‐On/Stim‐On condition. This meta‐analysis showed a robust improvement of gait and FOG by STN‐DBS for more than 4 years in the Med‐Off/Stim‐On condition. No beneficial effect was found for the On state of medication. Pre‐operative levodopa responsiveness of global motor performance (UPDRS‐III) is the strongest predictor of the effect of deep brain stimulation on gait.     

High‐frequency oscillations in Parkinson's disease: Spatial distribution and clinical relevance

The pathophysiology of Parkinson's disease (PD) has been related to excessive beta band oscillations in the basal ganglia. Recent recordings from the subthalamic nucleus of PD patients showed that beta oscillations show strong cross‐frequency coupling with high‐frequency oscillations (>200 Hz). However, little is known about the characteristics and functional properties of these oscillations. We studied the spatial distribution of high‐frequency oscillations and their relation to PD motor symptoms. We included 10 PD patients in medication OFF who underwent implantation of deep brain stimulation (DBS) electrodes. Intraoperative five‐channel microelectrode recordings were performed at 9 to 10 recording sites within the subthalamic nucleus and its immediate surroundings. We found a focal spatial distribution of high‐frequency oscillations with highest power 2 mm below the dorsolateral border of the subthalamic nucleus. Within the subthalamic nucleus, power peaked slightly anterior to the DBS target site. In addition, contralateral akinesia/rigidity scores were negatively correlated with high‐frequency oscillation power. Our results demonstrate a focal origin of high‐frequency oscillations within the subthalamic nucleus and provide further evidence for their functional association with motor state. © 2014 International Parkinson and Movement Disorder Society     

The structural correlates of functional deficits in early huntington's disease

Neuropathological studies in Huntington disease (HD) have demonstrated neuronal loss in the striatum, as well as in other brain regions including the cortex. With diffusion tensor MRI we evaluated the hypothesis that the clinical dysfunction in HD is related to regionally specific lesions of circuit‐specific cortico–basal ganglia networks rather than to the striatum only. We included 27 HD and 24 controls from the TRACK‐HD Paris cohort. The following assessments were used: self‐paced tapping tasks, trail B making test (TMT), University of Pennsylvania smell identification test (UPSIT), and apathy scores from the problem behaviors assessment. Group comparisons of fractional anisotropy and mean diffusivity and correlations were performed using voxel‐based analysis. In the cortex, HD patients showed significant correlations between: (i) self paced tapping and mean diffusivity in the parietal lobe at 1.8 Hz and prefrontal areas at 3 Hz, (ii) UPSIT and mean diffusivity in the parietal, and median temporal lobes, the cingulum and the insula, and fractional anisotropy in the insula and the external capsule, (iii) TMT B and mean diffusivity in the white matter of the superior frontal, orbital, temporal, superior parietal and post central areas, and (iv) apathy and fractional anisotropy in the white matter of the rectus gyrus. In the basal ganglia, we found correlations between the self paced tapping, UPSIT, TMT tests, and mean diffusivity in the anterior part of the putamen and the caudate nucleus. In conclusion, disruption of motor, associative and limbic cortico‐striatal circuits differentially contribute to the clinical signs of the disease. Hum Brain Mapp 34:2141–2153, 2013. © 2012 Wiley Periodicals, Inc.     

Subthalamic Nucleus Activity during Cognitive Load and Gait Dysfunction in Parkinson's Disease

Background

Gait freezing is a common, disabling symptom of Parkinson's disease characterized by sudden motor arrest during walking. Adaptive deep brain stimulation devices that detect freezing and deliver real-time, symptom-specific stimulation are a potential treatment strategy. Real-time alterations in subthalamic nucleus firing patterns have been demonstrated with lower limb freezing, however, whether similar abnormal signatures occur with freezing provoked by cognitive load, is unknown.

Methods

We obtained subthalamic nucleus microelectrode recordings from eight Parkinson's disease patients performing a validated virtual reality gait task, requiring responses to on-screen cognitive cues while maintaining motor output.

Results

Signal analysis during 15 trials containing freezing or significant motor output slowing precipitated by dual-tasking demonstrated reduced θ frequency (3–8 Hz) firing compared to 18 unaffected trials.

Conclusions

These preliminary results reveal a potential neurobiological basis for the interplay between cognitive factors and gait disturbances including freezing in Parkinson's disease, informing development of adaptive deep brain stimulation protocols. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Reduced after-effects following podokinetic adaptation in people with Parkinson's disease and freezing of gait

IntroductionGait dysfunction is common in people with Parkinson's disease (PD). Freezing of gait (FOG) is one such gait disturbance that significantly impacts mobility and quality of life in PD. Recent evidence suggests that cerebellar connectivity may differ in people with PD and FOG (PD+FOG) relative to those without FOG (PD-FOG). Investigation of gait adaptation, or the ability to change gait patterns in response to external perturbations, is cerebellum-dependent, is a practical means of probing cerebellar integrity and may provide additional insights regarding the FOG phenomenon.MethodsIn this study, we investigated gait adaptation in PD and FOG by measuring after-effects, namely whole-body rotation, following stepping on a rotating disc in PD+FOG compared to PD-FOG and older healthy adults. We refer to the period of stepping on the rotating disc as the podokinetic (PK) stimulation and after-effects as podokinetic after-rotation (PKAR). Our primary measure of adaptation was the magnitude and rate of decay of the after-effects.ResultsWe noted that PKAR was diminished in PD+FOG compared to the other groups, indicating reduced storage of the adapted gait pattern in PD+FOG. In the PD groups, FOG explained about 20% of the variability in peak velocity. Furthermore, these differences were independent of stepping cadence or motor sign severity.ConclusionOur results show that gait adaptation is impaired in PD+FOG, suggesting the cerebellum may be differentially impacted in PD+FOG compared to PD-FOG. This supports previous neuroimaging evidence of cerebellar dysfunction in PD+FOG. Overall, these data further our understanding of gait deficits in PD+FOG.     

Disrupted white matter connectivity underlying developmental dyslexia: A machine learning approach

Developmental dyslexia has been hypothesized to result from multiple causes and exhibit multiple manifestations, implying a distributed multidimensional effect on human brain. The disruption of specific white‐matter (WM) tracts/regions has been observed in dyslexic children. However, it remains unknown if developmental dyslexia affects the human brain WM in a multidimensional manner. Being a natural tool for evaluating this hypothesis, the multivariate machine learning approach was applied in this study to compare 28 school‐aged dyslexic children with 33 age‐matched controls. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging were acquired to extract five multitype WM features at a regional level: white matter volume, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) classifier achieved an accuracy of 83.61% using these MRI features to distinguish dyslexic children from controls. Notably, the most discriminative features that contributed to the classification were primarily associated with WM regions within the putative reading network/system (e.g., the superior longitudinal fasciculus, inferior fronto‐occipital fasciculus, thalamocortical projections, and corpus callosum), the limbic system (e.g., the cingulum and fornix), and the motor system (e.g., the cerebellar peduncle, corona radiata, and corticospinal tract). These results were well replicated using a logistic regression classifier. These findings provided direct evidence supporting a multidimensional effect of developmental dyslexia on WM connectivity of human brain, and highlighted the involvement of WM tracts/regions beyond the well‐recognized reading system in dyslexia. Finally, the discriminating results demonstrated a potential of WM neuroimaging features as imaging markers for identifying dyslexic individuals. Hum Brain Mapp 37:1443‐1458, 2016. © 2016 Wiley Periodicals, Inc.     

Diffusion tensor imaging reveals widespread white matter abnormalities in children and adolescents with myotonic dystrophy type 1

Diffusion tensor imaging was used to evaluate cerebral white matter in 16 patients (ages 9–18) with myotonic dystrophy type 1 compared to 15 matched controls. Patients with myotonic dystrophy showed abnormalities in mean diffusivity compared to controls in frontal, temporal, parietal, and occipital white matter and in all individual tracts examined. Whole cerebrum mean diffusivity was 8.6 % higher overall in patients with myotonic dystrophy compared to controls. Whole cerebrum fractional anisotropy was also abnormal (10.8 % low overall) in all regions and tracts except corticospinal tracts. Follow-up analysis of parallel and perpendicular diffusivity suggests possible relative preservation of myelin in corticospinal tracts. Correlations between Wechsler working memory performance and mean diffusivity were strong for all regions. Frontal and temporal fractional anisotropy were correlated with working memory as well. Results are consistent with earlier studies demonstrating that significant white matter disturbances are characteristic in young patients with myotonic dystrophy and that these abnormalities are associated with the degree of working memory impairment seen in this disease.     

Magnetic resonance imaging correlates of first-episode psychosis in young adult male patients: combined analysis of grey and white matter

Background: Several patterns of grey and white matter changes have been separately described in young adults with first-episode psychosis. Concomitant investigation of grey and white matter densities in patients with first-episode psychosis without other psychiatric comorbidities that include all relevant imaging markers could provide clues to the neurodevelopmental hypothesis in schizophrenia. Methods: We recruited patients with first-episode psychosis diagnosed according to the DSM-IV-TR and matched controls. All participants underwent magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis and mean diffusivity voxel-based analysis (VBA) were used for grey matter data. Fractional anisotropy and axial, radial and mean diffusivity were analyzed using tract-based spatial statistics (TBSS) for white matter data. Results: We included 15 patients and 16 controls. The mean diffusivity VBA showed significantly greater mean diffusivity in the first-episode psychosis than in the control group in the lingual gyrus bilaterally, the occipital fusiform gyrus bilaterally, the right lateral occipital gyrus and the right inferior temporal gyrus. Moreover, the TBSS analysis revealed a lower fractional anisotropy in the first-episode psychosis than in the control group in the genu of the corpus callosum, minor forceps, corticospinal tract, right superior longitudinal fasciculus, left middle cerebellar peduncle, left inferior longitudinal fasciculus and the posterior part of the fronto-occipital fasciculus. This analysis also revealed greater radial diffusivity in the first-episode psychosis than in the control group in the right corticospinal tract, right superior longitudinal fasciculus and left middle cerebellar peduncle. Limitations: The modest sample size and the absence of women in our series could limit the impact of our results. Conclusion: Our results highlight the structural vulnerability of grey matter in posterior areas of the brain among young adult male patients with first-episode psychosis. Moreover, the concomitant greater radial diffusivity within several regions already revealed by the fractional anisotropy analysis supports the idea of a late myelination in patients with first-episode psychosis.     

The dimensionality of between‐person differences in white matter microstructure in old age

Between‐person differences in white matter microstructure may partly generalize across the brain and partly play out differently for distinct tracts. We used diffusion‐tensor imaging and structural equation modeling to investigate this issue in a sample of 260 adults aged 60–87 years. Mean fractional anisotropy and mean diffusivity of seven white matter tracts in each hemisphere were quantified. Results showed good fit of a model positing that individual differences in white matter microstructure are structured according to tracts. A general factor, although accounting for variance in the measures, did not adequately represent the individual differences. This indicates the presence of a substantial amount of tract‐specific individual differences in white matter microstructure. In addition, individual differences are to a varying degree shared between tracts, indicating that general factors also affect white matter microstructure. Age‐related differences in white matter microstructure were present for all tracts. Correlations among tract factors did not generally increase as a function of age, suggesting that aging is not a process with homogenous effects on white matter microstructure across the brain. These findings highlight the need for future research to examine whether relations between white matter microstructure and diverse outcomes are specific or general. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.