Voxel-based morphometry in narcolepsy

BACKGROUND AND PURPOSE: Voxel-based morphometry (VBM) is a magnetic resonance imaging (MRI)-based indirect volumetry, which allows the investigation of the entire brain without restriction of predefined regions-of-interest. Recent studies using this technique reported controversial results in patients with narcolepsy. PATIENTS AND METHODS: In this study, 12 patients with narcolepsy according to the criteria of the International Classification of Sleep Disorders were compared to 12 age-matched controls with normal MR images using VBM. Sex and global differences in voxel intensities were used as confounding covariates. RESULTS: Significant gray matter loss was found in the right prefrontal and frontomesial cortex of patients with narcolepsy. White matter comparison revealed no significant changes in patients or controls. The comparison of cerebrospinal fluid partition detected an enlargement of subarachnoidal space of controls close to the prefrontal cortex. CONCLUSIONS: The volume reduction of gray matter in narcoleptic patients could indicate a disease-related atrophy pattern. However, the results of VBM studies in narcolepsy are contradictory. A possible systematic bias due to inhomogeneous patient groups, stimulant medication history or pre-statistical image processing must be considered. We suggest that studies with drug-naive patients and/or region-of-interest-based volumetric studies should be performed in areas defined by VBM.     

Voxel-based morphometry in Alzheimer's disease

Recent morphometric MRI studies have investigated brain volume abnormalities associated with the diagnosis of Alzheimer's disease (AD) using voxel-based morphometry (VBM). This technique allows the assessment of gray matter volumes in subjects with AD or related conditions compared with healthy controls in an automated fashion, across the whole brain. This article reviews VBM findings related to different AD stages and its prodrome, mild cognitive impairment. These findings include not only gray matter deficits in medial temporal structures as seen in former MRI studies of AD conducted using manual region-of-interest measurements, but also volume changes in several other brain regions not assessed in previous MRI studies. We also discuss potential applications of VBM to improve AD diagnostic accuracy in routine clinical practice. Finally, we highlight future research directions in this field, including: investigations on the relationship between VBM findings of multifocal gray matter deficits and changes in white matter tracts that interconnect such regions; the need for population-based VBM studies using large AD samples; and the potential of studies combining VBM measurements with other potential biological markers (such as brain imaging indices of amyloid-beta deposition and cerebrospinal fluid AD markers) to further advance our knowledge about the physiopathology of AD.     

Voxel-based morphometry of disgust sensitivity

Background: Difficulties with the regulation of negative affect have been extensively studied in neuroimaging research. However, dysregulation of a specific emotion, disgust, has hardly been investigated. In the present study, we used voxel-based morphometry to identify whether gray matter volume (GMV) of frontal regions is correlated with personality traits associated with general and disgust-specific emotion regulation difficulties.

Method: We analyzed T1-weighted images of 49 females (mean age = 22.8 years, SD = 3.2). The women rated their disgust sensitivity (DS) (temporally stable tendency to experience disgust as uncontrollable and extremely aversive) as well as general difficulties with emotion regulation.

Results: DS and general emotion regulation deficits were positively associated with a heightened GMV of the orbitofrontal cortex. DS additionally showed a negative association with GMV of the medial prefrontal cortex.

Conclusion: The present study revealed shared and distinct contributions of frontal brain regions to disgust-specific and general emotion regulation difficulties.     

Voxel-based morphometry indicates relative preservation of the limbic prefrontal cortex in early Huntington disease

Summary. In Huntington disease (HD), both the genetic defect and mutant gene product huntington are known but the exact mechanisms that lead to neuronal loss are poorly understood. Until now, the distribution of tissue loss throughout the brain has been investigated intensively. Here we searched for areas that, antipodal to the striatum, display grey-matter (GM) preservation. We performed high resolution T1-weighted magnetic resonance imaging and voxel-based morphometry in 46 patients in early HD and 46 healthy controls. We applied an analysis of covariance (ANCOVA) model with the total GM volume of each participant as covariate. In accordance with earlier reports, group comparisons revealed GM decrease in the striatum, insula, and thalamus as well as in dorsolateral frontal and occipital areas. In contrast, the limbic prefrontal cortex displayed GM preservation. Our findings support hypotheses that postulate differential involvement of frontosubcortical circuits in the pathophysiology of HD.     

Voxel-based morphometry and its application to movement disorders

Voxel-based morphometry (VBM) is an automated technique that assesses patterns of regional grey and white matter atrophy on MRI between two groups of subjects. VBM has been used to assess patterns of regional atrophy in subjects with movement disorders. These studies have demonstrated specific patterns of regional loss in each disorder, compared different movement disorders to look for differences that could be diagnostically useful, and have correlated regions of loss to cognitive and motor deficits in these subjects. This article will review the findings of these studies and discuss the role of VBM in movement disorders.     

Voxel-based morphometry in unmedicated patients with restless legs syndrome

BACKGROUND: The pathophysiology of restless legs syndrome (RLS) is not yet understood. A prior voxel-based morphometry (VBM) study reported gray matter increase in the pulvinar of the thalamus in a group of patients, most of whom were on medical treatment. Since there is evidence that medication can change the volume of cerebral structures, the question arises as to whether the reported morphometric alterations are caused by the RLS itself or, alternatively, are a consequence of drug treatment. To address this issue, we performed VBM in unmedicated RLS patients. METHODS: Fourteen patients with idiopathic RLS with no (n=11) or only minimal (n=3) treatment exposure in the past and 14 age- and sex-matched healthy subjects were investigated. All subjects were free of psychotropic drugs for at least 4 months. Morphological data were analyzed by using optimized VBM. RESULTS: We did not detect any structural changes except for slightly increased gray matter density in the ventral hippocampus (p=0.046 on the left and p=0.055 on the right side) and in the middle orbitofrontal gyrus (p=0.046 on the right and p=0.097 on the left side). CONCLUSION: Our study could not confirm the findings of a prior study. A possible explanation for the divergent findings is the difference between the populations examined. Since, in our study, essentially treatment-na?ve patients were investigated, it is possible that the prior findings reflect treatment-induced effects on cerebral morphology in RLS.     

Voxel-based morphometry in unmedicated patients with restless legs syndrome

BackgroundThe pathophysiology of restless legs syndrome (RLS) is not yet understood. A prior voxel-based morphometry (VBM) study reported gray matter increase in the pulvinar of the thalamus in a group of patients, most of whom were on medical treatment. Since there is evidence that medication can change the volume of cerebral structures, the question arises as to whether the reported morphometric alterations are caused by the RLS itself or, alternatively, are a consequence of drug treatment. To address this issue, we performed VBM in unmedicated RLS patients.MethodsFourteen patients with idiopathic RLS with no (n = 11) or only minimal (n = 3) treatment exposure in the past and 14 age- and sex-matched healthy subjects were investigated. All subjects were free of psychotropic drugs for at least 4 months. Morphological data were analyzed by using optimized VBM.ResultsWe did not detect any structural changes except for slightly increased gray matter density in the ventral hippocampus (p = 0.046 on the left and p = 0.055 on the right side) and in the middle orbitofrontal gyrus (p = 0.046 on the right and p = 0.097 on the left side).ConclusionOur study could not confirm the findings of a prior study. A possible explanation for the divergent findings is the difference between the populations examined. Since, in our study, essentially treatment-naïve patients were investigated, it is possible that the prior findings reflect treatment-induced effects on cerebral morphology in RLS.     

Voxel-based morphometry in adolescents with bipolar disorder: first results

Bipolar disorder is an increasingly recognized cause of significant morbidity in the pediatric age group. However, there is still a large degree of uncertainty regarding the underlying neurobiological deficits. In this preliminary study, we performed automated volumetric studies and whole-brain voxel-based morphometry (VBM) on gray matter. Imaging data from 10 adolescents with bipolar disorder were compared with data from 52 age- and gender-matched healthy controls. Previously defined brain parcellations and optimized VBM protocols were used, based on custom-made pediatric reference data. An additional, exploratory whole-brain comparison was also implemented. The volumetric region-of-interest study revealed significantly greater gray matter volume in central gray matter structures bilaterally (including the basal ganglia and the thalamus) and the left temporal lobe in the bipolar group. VBM confirmed bilaterally larger basal ganglia. Localized gray matter deficits in bipolar subjects were found in the medial temporal lobe, orbito-frontal cortex, and the anterior cingulate, confirming and extending earlier studies.     

Voxel-based morphometry elucidates structural neuroanatomy of high-functioning autism and Asperger syndrome

Efforts to examine the structural neuroanatomy of autism by using traditional methods of imaging analysis have led to variable findings, often based on methodological differences in image acquisition and analysis. A voxel-based computational method of whole-brain anatomy allows examination of small patterns of tissue differences between groups. High-resolution structural magnetic resonance images were acquired for nine males with high-functioning autism (HFA; mean age 14y [SD3y 4mo]), 11 with Asperger syndrome (ASP; mean age 13y 6mo [SD2y 5mo]), and 13 comparison (COM) participants (mean age 13y 7mo [SD 3y 1mo]). Using statistical parametric mapping, we examined contrasts of gray matter differences between the groups. Males with HFA and ASP had a pattern of decreased gray matter density in the ventromedial regions of the temporal cortex in comparison with males from an age-matched comparison group. Examining contrasts revealed that the COM group had increased gray matter density compared with the ASP or combined HFA and ASP group in the right inferior temporal gyrus, entorhinal cortex, and rostral fusiform gyrus. The ASP group had less gray matter density in the body of the cingulate gyrus in comparison with either the COM or HFA group. The findings of decreased gray matter density in ventromedial aspects of the temporal cortex in individuals with HFA and ASP lends support to theories suggesting an involvement of these areas in the pathophysiology of autism, particularly in the integration of visual stimuli and affective information.     

Voxel-based morphometry and intellectual assessment in patients with congenital bilateral perisylvian syndrome

Congenital bilateral perisylvian syndrome (CBPS) presents with heterogeneous clinical manifestations such as pseudobulbar palsy, language disorder, variable cognitive deficits, epilepsy, and perisylvian abnormalities (most frequently polymicrogyria) on imaging studies. We investigated the relationship between seizures and extent of gray matter (GM) and white matter (WM) abnormalities using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI) as well the association between seizures, structural abnormalities and cognitive ability. In this cross-sectional study, we evaluated 51 healthy volunteers and 18 patients with CBPS with epilepsy (seizure group, n = 7) and without (non-seizure group, n = 11). We used VBM (SPM8/DARTEL) to investigate areas with excess and atrophy of both gray and white matter, comparing groups of patients with controls. Intellectual ability of patients was assessed by the WISC-III or WAIS-III. Both groups with CBPS and the control group were homogeneous with respect to gender (p = 0.07) and age (p = 0.065). Besides perisylvian polymicrogyria, the seizure group exhibited areas with GM and WM reduction including temporal, frontal, parietal and occipital lobes. In contrast, we identified fewer areas with GM and WM reduction in the non-seizure group. The seizure group presented worse intellectual performance (performance IQ and global IQ) than the non-seizure group. The seizure group presented with a more widespread pattern of cortical and sub-cortical abnormalities, as well as worse cognition. Our results suggest that patients with CBPS and epilepsy appear to have widespread neuronal damage that goes beyond the areas with MRI-visible perisylvian polymicrogyria.     

Voxel-based morphometry evaluation of patients with photosensitive juvenile myoclonic epilepsy

We aim to investigate structural brain abnormalities in juvenile myoclonic epilepsy (JME) patients with photosensitivity (PS). Sixty JME patients, 19 (32%) of whom were photosensitive, were submitted to 1.5 T magnetic resonance voxel-based morphometry (VBM). The control group (CTL) consisted of 30 sex-matched healthy volunteers. JME patients with (JME-PS) and without (JME-NPS) PS did not differ in their duration of disease, treatment or seizure control. VBM revealed significantly reduced bilateral gray matter volume (GMV) in thalami, insula cortices and cerebellar hemispheres; while significantly increased GMV was observed in the right superior frontal, orbitofrontal and medial frontal gyri of the JME group compared to CTL. JME-PS had reduced bilateral GMV of visual cortices when compared with CTL; while it was not seen among JME-NPS patients. Reduced left hippocampus and left inferior frontal gyrus volume was observed among JME-PS compared with JME-NPS. This study demonstrates structural abnormalities beyond the limits of the frontal lobes and provides evidence for the role of the occipital cortex in human PS, reinforcing the existence of functional-anatomic ictogenic networks in JME and the concept of ‘system epilepsies’.     

Voxel-based morphometry study on brain structure in children with high-functioning autism

Earlier studies have suggested abnormal brain volumes in autism, but inconsistencies exist. Using voxel-based morphometry, we compared global and regional brain volumes in 17 high-functioning autistic children with 15 matched controls. We identified significant reduction in left white matter volume and white/gray matter ratio in autism. Regional brain volume reductions were detected for right anterior cingulate, left superior parietal lobule white matter volumes, and right parahippocampal gyrus gray matter volume, whereas enlargements in bilateral supramarginal gyrus, right postcentral gyrus, right medial frontal gyrus, and right posterior lobe of cerebellum gray matter in autism. Our findings showed global and regional brain volumes abnormality in high-functioning autism.     

帕金森病患者脑灰质变化的VBM-MRI研究

目的应用核磁共振的基于体素形态学(voxel-based morphometry method of magnetic resonanceimaging,VBM-MRI)技术,研究帕金森病(Parkinson disease,PD)患者大脑灰质变化的状况。方法 28例PD组与年龄、受教育年限相匹配32例健康对照组的VBM-MRI图像数据进行比较,PD组中,早期PD组(early Parkinson disease,EPD,n=14)与晚期PD组((late Parkinson disease,LPD,n=14)的VBM-MRI图像数据进行比较。结果与健康对照组比较,VBM-MRI显示PD组患者存在下列脑区灰质体积减少:额叶(双侧额上回、左额下回)、双侧颞叶(颞上回、颞中回)、右侧扣带回、右侧丘脑、双侧尾状核及左顶下小叶。与EPD比较,VBM-MRI显示LPD在下列脑区存在灰质体积减少:额叶(双侧额上回、右侧额下回、右侧额叶眶部、双侧内侧前额叶),颞叶(右侧颞上回、左侧颞中回),右侧海马旁回、右侧尾状核、右侧下丘脑,差异均有显著统计学意义。结论本组PD患者的脑灰质改变,主要集中在额叶、颞叶、右侧扣带回及皮质下的灰质。随着PD病程进展,这些部位的灰质减少加剧,并在边缘叶有进展的趋势。     

Voxel-based morphometry of grey matter densities in subjects at high risk of schizophrenia

The grey matter (GM) segments from T1 structural magnetic resonance (MR) images of the brain in subjects at high risk of schizophrenia (n=146) were compared with normal control subjects (n=36) and first episode schizophrenic subjects (n=34) using automated voxel-based morphometry (VBM). The subjects were recruited for the Edinburgh High Risk Study (EHRS) and regional brain volumes had previously been measured using a semi-automated volumetric region of interest (ROI) method of analysis. For the current report, the images were processed using a study specific template and statistically analysed using the SPM99 program. The small volume correction tool in SPM was also used to restrict the analyses to specific voxels. Reductions in the probability of grey matter (GM) density were seen bilaterally in the anterior cingulate, and as a trend in the left parahippocampal gyrus for the high-risk vs. control subjects. In contrast, first episode schizophrenia subjects had less GM than high-risk subjects in several frontal and temporal regions. These results are compatible with the findings of our previous volumetric ROI analysis.     

Voxel-based morphometry in frontotemporal lobar degeneration with ubiquitin-positive inclusions with and without progranulin mutations

BACKGROUND: Mutations in the progranulin gene (PGRN) have recently been identified as a cause of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) in some families. OBJECTIVE: To determine whether there is a difference in the patterns of atrophy in FTLD-U cases with and without PGRN mutations. DESIGN: Case-control study. SETTING: Brain bank of a tertiary care medical center. Patients Eight subjects who had screened positive for PGRN mutations (PGRN-positive) and who underwent volumetric magnetic resonance imaging were identified. Subjects were then matched by clinical diagnosis to a group of 8 subjects with a pathological diagnosis of FTLD-U who had screened negative for PGRN mutations (PGRN-negative). All subjects were then age-matched and sex-matched to a control subject. MAIN OUTCOME MEASURES: Voxel-based morphometry was used to assess the patterns of gray matter atrophy in the PGRN-positive group compared with the PGRN-negative group and compared with controls. RESULTS: The PGRN-positive group showed a widespread and severe pattern of gray matter loss predominantly affecting the frontal, temporal, and parietal lobes. The PGRN-negative group showed a less severe pattern of gray matter loss restricted mainly to the temporal and frontal lobes. On direct comparison, the PGRN-positive group showed greater gray matter loss in the frontal and parietal lobes compared with the PGRN-negative group. CONCLUSION: Findings from this study suggest that PGRN mutations may be associated with a specific and severe pattern of cerebral atrophy in subjects with FTLD-U.