VBM Analysis Research Articles

Resting-state functional connectivity associated with mild cognitive impairment in Parkinson’s disease

Cognitive impairment is common in PD, even in early stages. The construct of mild cognitive impairment has been used to identify clinically evident cognitive impairment without functional decline in PD patients (PD-MCI). The aim of the present study was to investigate brain connectivity associated with PD-MCI through RS-fMRI. RS-fMRI at 3T was collected in 42 PD patients and 20 matched healthy controls. Among PD patients, 21 were classified as having MCI (PD-MCI) and 21 as cognitively unimpaired (PD-nMCI) based on criteria for possible PD-MCI (level I category). Single-subject and group-level ICA was used to investigate the integrity of brain networks related to cognition in PD patients with and without MCI. Image data processing and statistical analysis were performed in BrainVoyager QX. In addition, we used VBM to test whether functional connectivity differences were related to structural abnormalities. PD-nMCI and PD-MCI patients compared with controls showed decreased DMN connectivity. PD-MCI patients, but not PD-nMCI, compared with controls, showed decreased functional connectivity of bilateral prefrontal cortex within the frontoparietal network. The decreased prefrontal cortex connectivity correlated with cognitive parameters but not with clinical variables. VBM analysis did not reveal any difference in local gray matter between patients and controls. Our findings suggest that an altered DMN connectivity characterizes PD patients, regardless of cognitive status, whereas a functional disconnection of the frontoparietal network could be associated with MCI in PD in the absence of detectable structural changes.

Dynamic cortical gray matter volume changes after botulinum toxin in cervical dystonia

Previous electrophysiological and functional imaging studies in focal dystonia have reported on cerebral reorganization after botulinum toxin (BoNT) injections. With the exception of microstructural changes, alterations in gray matter volume after BoNT have not been explored. In this study, we sought to determine whether BoNT influences gray matter volume in a group of cervical dystonia (CD) patients.We analyzed whole brain gray matter volume in a sample of CD patients with VBM analysis. In patients, scans were repeated immediately before and some weeks after BoNT injections; controls were only scanned once. We analyzed 1) BoNT-related gray matter volume changes within patients; 2) gray matter volume differences between patients and controls; and 3) correlations between gray matter volume and disease duration and disease severity.The pre- and post-BoNT treatment analysis revealed an increase of gray matter volume within the right precentral sulcus, at the lateral border of the premotor cortex. In comparison to healthy controls, CD patients had reduced gray matter volume in area 45 functionally corresponding to the left ventral premotor cortex. No gray matter volume increase was found for CD patients in comparison to controls. Gray matter volume of the left supramarginal gyrus and left premotor cortex correlated positively with disease duration, and that of the right inferior parietal lobule correlated negatively with disease severity.We have identified structural, yet dynamic gray matter volume changes in CD. There were specific gray matter volume changes related to BoNT injections, illustrating indirect central consequences of modified peripheral sensory input. As differences were exclusively seen in higher order motor areas relevant to motor planning and spatial cognition, these observations support the hypothesis that deficits in these cognitive processes are crucial in the pathophysiology of CD.

The relationship between finger gnosia and arithmetic: a VBM analysis

The relationship between finger gnosia and arithmetic: a VBM analysis

RESTING STATE-FMRI STUDY ON ELDERLY PEOPLE INGESTING FUNCTIONAL DIPEPTIDE FROM CHICKEN: FOR THE DEVELOPMENT OF PREVENTIVE INTERVENTIONS FOR ALZHEIMER'S DISEASE

RESTING STATE-FMRI STUDY ON ELDERLY PEOPLE INGESTING FUNCTIONAL DIPEPTIDE FROM CHICKEN: FOR THE DEVELOPMENT OF PREVENTIVE INTERVENTIONS FOR ALZHEIMER'S DISEASE

Logopenic and Nonfluent Variants of Primary Progressive Aphasia Are Differentiated by Acoustic Measures of Speech Production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r 2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA.

A visual MRI atrophy rating scale for the amyotrophic lateral sclerosis-frontotemporal dementia continuum

Our objective was to distinguish ALS, ALS-FTD and bvFTD via a novel visual MRI cortical atrophy scale that can be employed in a clinical setting. MRI images of 100 participants (33 ALS, 11 ALS-FTD, 22 bvFTD and 34 controls) were rated in four brain areas: orbitofrontal cortex, anterior temporal pole, anterior cingulate, and motor cortex. Areas were rated on a 5- point Likert scale by two raters blinded to the diagnosis. Results demonstrated that bvFTD patients showed the highest levels of atrophy across all regions, while ALS patients had the lowest atrophy scores. ALS-FTD patients have higher atrophy ratings compared to ALS patients for the motor cortex, anterior cingulate and anterior temporal lobe, with a statistical trend for the orbitofrontal cortex. ALS-FTD patients were not significantly different from bvFTD for any of the brain regions. These findings were confirmed in a post hoc VBM analysis of the same participants. Our study demonstrates that a simple visual MRI rating scale can reliably distinguish ALS, ALS-FTD and bvFTD atrophy patterns in a clinical setting. Motor cortex, anterior cingulate and anterior temporal atrophy emerged as good diagnostic markers for ALS-FTD. Employment of this MRI rating scale can complement clinical diagnostics of patients in the ALS-FTD continuum.

The social network-network: size is predicted by brain structure and function in the amygdala and paralimbic regions.

The social brain hypothesis proposes that the large size of the primate neocortex evolved to support complex and demanding social interactions. Accordingly, recent studies have reported correlations between the size of an individual's social network and the density of gray matter (GM) in regions of the brain implicated in social cognition. However, the reported relationships between GM density and social group size are somewhat inconsistent with studies reporting correlations in different brain regions. One factor that might account for these discrepancies is the use of different measures of social network size (SNS). This study used several measures of SNS to assess the relationships SNS and GM density. The second goal of this study was to test the relationship between social network measures and functional brain activity. Participants performed a social closeness task using photos of their friends and unknown people. Across the VBM and functional magnetic resonance imaging analyses, individual differences in SNS were consistently related to structural and functional differences in three regions: the left amygdala, right amygdala and the right entorhinal/ventral anterior temporal cortex.

EPA-1043 – The eye of the self: precuneus and depression

To review the role of the precuneus in major depression We will review the literature involving the precuneus in the pathophysiology of depression. We will also report a recent study of our group using structural MRI and VBM analyses to assess the role of precuneus in Autobiographical Memory (AM). Visual perspective during AM retrieval was assessed in two independent datasets of 45 and 20 healthy young adults with two different AM retrieval tasks. Precuneus, a medial part of the parietal cortex, is a central component of the default mode network. Results from our VBM study show that the precuneus volume in healthy subjects is correlated with the ability to retrieve autobiographical memories with a first-person perspective. Consistent with its role in integration of self-relevant mental simulations with past experiences and visuo-spatial processes during AM retrieval, the precuneus may subserve emotion regulation processes in healthy subjects and depressed patients. The precuneus and the default mode network show abnormal connectivity in depressed patients that may indicate abnormal self-processing in depression. Abnormal activity and connectivity of the precuneus within the default mode network is associated with impairment in self-processing in depression and may be related to the tendency of depressed patients to retrieve AM using third-person perspective. Further studies are needed to evaluate if impaired function or structure of the precuneus may predict the clinical response to antidepressant treatment.

Toward Defining the Neural Substrates of ADHD

Objective: We assessed the neural correlates of adult ADHD in treatment-naïve participants, an approach necessary for identifying neural substrates unconfounded by medication effects. Method: The sample consisted of 24 medication-naïve adults with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnosed ADHD and 24 healthy controls, comparable on age, sex, handedness, reading achievement, IQ, and psychiatric comorbidity. All participants were assessed with structured diagnostic interviews. Magnetic resonance imaging (MRI)-based regional voxel-based morphometry (r-VBM) was used to assess volumetric differences in a priori defined brain regions of interest. Results: VBM analysis revealed group differences in the hypothesized cortical and subcortical areas; however, only cerebellar volume reductions in ADHD retained significance (p < .05) after corrections for multiple comparisons. Conclusion: These results support the notion that medication-naïve ADHD as expressed in adulthood, manifests subtle brain volume reductions from normal in the cerebellum, and possibly in other syndrome-congruent gray-matter structures. Larger samples are required to confirm these findings.

THE EVOLUTION OF FRONTOTEMPORAL DEMENTIA DUE TO THE MAPT MUTATION: A SEVENTEEN YEAR NATURAL HISTORY STUDY

IntroductionFrontotemporal Dementia (FTD) is a common cause of early–onset dementia. A high proportion of cases are due to autosomal dominant mutations. Understanding the natural history of these disorders will be...

Adaptive Modulation of Adult Brain Gray and White Matter to High Altitude: Structural MRI Studies

The aim of this study was to investigate brain structural alterations in adult immigrants who adapted to high altitude (HA). Voxel-based morphometry analysis of gray matter (GM) volumes, surface-based analysis of cortical thickness, and Tract-Based Spatial Statistics analysis of white matter fractional anisotropy (FA) based on MRI images were conducted on 16 adults (20–22 years) who immigrated to the Qinghai-Tibet Plateau (2300–4400 m) for 2 years. They had no chronic mountain sickness. Control group consisted of 16 matched sea level subjects. A battery of neuropsychological tests was also conducted. HA immigrants showed significantly decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, and increased GM volumes in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1. While there was some divergence in the left hemisphere, surface-based patterns of GM changes in the right hemisphere resembled those seen for VBM analysis. FA changes were observed in multiple WM tracts. HA immigrants showed significant impairment in pulmonary function, increase in reaction time, and deficit in mental rotation. Parahippocampal and middle frontal GM volumes correlated with vital capacity. Superior frontal GM volume correlated with mental rotation and postcentral GM correlated with reaction time. Paracentral lobule and frontal FA correlated with mental rotation reaction time. There might be structural modifications occurred in the adult immigrants during adaptation to HA. The changes in GM may be related to impaired respiratory function and psychological deficits.

Grapheme-color synesthetes show peculiarities in their emotional brain: cortical and subcortical evidence from VBM analysis of 3D-T1 and DTI data

Grapheme-color synesthesia is a neurological phenomenon in which viewing achromatic letters/numbers leads to automatic and involuntary color experiences. In this study, voxel-based morphometry analyses were performed on T1 images and fractional anisotropy measures to examine the whole brain in associator grapheme-color synesthetes. These analyses provide new evidence of variations in emotional areas (both at the cortical and subcortical levels), findings that help understand the emotional component as a relevant aspect of the synesthetic experience. Additionally, this study replicates previous findings in the left intraparietal sulcus and, for the first time, reports the existence of anatomical differences in subcortical gray nuclei of developmental grapheme-color synesthetes, providing a link between acquired and developmental synesthesia. This empirical evidence, which goes beyond modality-specific areas, could lead to a better understanding of grapheme-color synesthesia as well as of other modalities of the phenomenon.

Secondary Degeneration Detected by Combining Voxel-Based Morphometry and Tract-Based Spatial Statistics in Subcortical Strokes with Different Outcomes in Hand Function

Secondary degeneration of the pyramidal tract after focal motor pathway stroke has been observed by diffusion tensor imaging. However, the relationships between outcomes in hand function and secondary degeneration in widespread regions are not well understood. For the first time, we investigated the differences of secondary degeneration across the whole brain between subgroups of patients with stroke. We selected 23 patients who had a subcortical stroke in the left motor pathway and displayed only motor deficits. The patients were divided into 2 subgroups: CPH (11 patients) and PPH (12 patients). Twelve healthy controls matched for age and handedness were also recruited. We used both optimized VBM and TBSS to explore differences of FA across the whole brain between CPH and PPH. Furthermore, ROI analysis was carried out in the identified regions detected by VBM analysis to further quantify the degree of secondary degeneration in the CPH and PPH and compare these with healthy controls. Compared with PPH, FA was significantly decreased in the CPH in widespread regions of the motor system remote from the primary lesion, including the ipsilesional brain stem, medial frontal gyrus, precentral gyrus, superior temporal gyrus, supplementary motor area, and contralesional postcentral gyrus. In addition, FA within these identified regions correlated with Fugl-Meyer Assessment scores (hand+wrist). This study suggests a potential biomarker for outcome differences in hand function after subcortical stroke.

Intratumoral Haemorrhage Causing an Unusual Clinical Presentation of a Vestibular Schwannoma

We present a case of an elderly woman with no history of audiological disease with sudden onset of visual and hearing deficits associated with systemic clinical signs. On examination she had impairment of right CNs from V to X. CT and MR imaging demonstrated a cystic vestibular schwannoma with a rare intralesional fluid-fluid level correlated to a recent bleed. We include high quality MR images to show the acute impairment of the cranial nerves next to the tumour after acute bleeding. Our case report includes a voxel-based morphometry (VMB) analysis of the tumour that, as far as we know, has never been done before for such a tumour. VBM analysis was performed to calculate the hypothesized volume changes after the acute bleed which likely resulted in a sudden increase in the overall size of the tumour resulting in atypical clinical signs and symptoms due to the establishment of a mechanical conflict with the adjacent cranial nerves.

Morphometric Correlation of Impulsivity in Medial Prefrontal Cortex

Impulsivity is a complex behaviour composed of different domains encompassing behavioural dis-inhibition, risky decision-making and delay discounting abnormalities. To investigate regional brain correlates between levels of individual impulsivity and grey matter volume, we performed voxel-based morphometric correlation analysis in 34 young, healthy subjects using impulsivity scores measured with Barratt Impulsivity Scale-11 and computerized Kirby's delay discounting task. The VBM analysis showed that impulsivity appears to be reliant on a network of cortical (medial prefrontal cortex and dorsolateral prefrontal cortex) and subcortical (ventral striatum) structures emphasizing the importance of brain networks associated with reward related decision-making in daily life as morphological biomarkers for impulsivity in a normal healthy population. While our results in healthy volunteers may not directly extend to pathological conditions, they provide an insight into the mechanisms of impulsive behaviour in patients with abnormalities in prefrontal/frontal-striatal connections, such as in drug abuse, pathological gambling, ADHD and Parkinson's disease.

Structural Brain MR Imaging Changes Associated with Obsessive-Compulsive Disorder in Patients with Multiple Sclerosis

Psychiatric symptoms occur in approximately 30% of patients with MS. Such symptoms include OCD, which may interfere heavily with the patient's daily life. We hypothesized that the widespread involvement of both GM and WM, which characterizes MS, may be responsible for the occurrence of OCD when specific brain structures are affected. The aim of this study was to evaluate the relationship between GM and WM tissue damage and OCD in patients with MS. We evaluated 16 patients with relapsing-remitting MS who had been diagnosed with OCD on the basis of the Diagnostic and Statistical Manual of Mental Disorders (4th edition) and 15 age- and sex-matched patients with relapsing-remitting MS with no psychiatric disorders as a CG. The MR study (1.5T) included 3D T1-weighted fast-field echo sequences, DTI (32 directions), and conventional MRI. Images were processed using SPM5, FSL, and Jim 5.0 software to evaluate VBM, TBSS, and global and regional LV, respectively. The VBM analysis revealed a set of clusters of reduced GM volume in the OCD group, compared with the CG, located in the right inferior and middle temporal gyri and in the inferior frontal gyrus. TBSS did not detect any differences in the FA values between the 2 groups; global and regional LV values also did not differ significantly between the 2 groups. Our study suggests that OCD in MS may be caused by damage in the right frontotemporal cortex.

Identifying the Neural Correlates of Executive Functions in Early Cerebral Microangiopathy: A Combined VBM and DTI Study

Cerebral microangiopathy (CMA) has been associated with executive dysfunction and fronto-parietal neural network disruption. Advances in magnetic resonance imaging allow more detailed analyses of gray (e.g., voxel-based morphometry—VBM) and white matter (e.g., diffusion tensor imaging—DTI) than traditional visual rating scales. The current study investigated patients with early CMA and healthy control subjects with all three approaches. Neuropsychological assessment focused on executive functions, the cognitive domain most discussed in CMA. The DTI and age-related white matter changes rating scales revealed convergent results showing widespread white matter changes in early CMA. Correlations were found in frontal and parietal areas exclusively with speeded, but not with speed-corrected executive measures. The VBM analyses showed reduced gray matter in frontal areas. All three approaches confirmed the hypothesized fronto-parietal network disruption in early CMA. Innovative methods (DTI) converged with results from conventional methods (visual rating) while allowing greater spatial and tissue accuracy. They are thus valid additions to the analysis of neural correlates of cognitive dysfunction. We found a clear distinction between speeded and nonspeeded executive measures in relationship to imaging parameters. Cognitive slowing is related to disease severity in early CMA and therefore important for early diagnostics.

Spatial Normalization and Regional Assessment of Cord Atrophy: Voxel-Based Analysis of Cervical Cord 3D T1-Weighted Images

VBM is widely applied to characterize regional differences in brain volume among groups of subjects. The aim of this study was to develop and validate a method for voxelwise statistical analysis of cord volume and to test, with this method, the correlation between cord tissue loss and aging. 3D T1-weighted scans of the spinal cord were acquired from 90 healthy subjects spanning several decades of life. Using an AS method, we outlined the cord surface and created output images reformatted with image planes perpendicular to the estimated cord centerline. Unfolded cervical cord images were coregistered into a common standard space, and smoothed cord binary masks, produced by using the cord outlines estimated by the AS approach, were used as input images for spatial statistics. High spatial correlation between normalized images was observed. Averaging of the normalized scans allowed the creation of a cervical cord template and of a standardized region-of-interest atlas. VBM analysis showed some significant associations between a decreased probability of cord tissue and aging. Results were robust across different smoothing levels, but the use of an anisotropic Gaussian kernel gave the optimal trade-off between spatial resolution and the requirements of the Gaussian random field theory. VBM analysis of the cervical cord was feasible and holds great promise for accurate localization of regional cord atrophy in several neurologic conditions.

Regional Gray Matter Atrophy in Patients with Parkinson Disease and Freezing of Gait

FOG is a troublesome symptom of PD. Despite growing evidence suggesting that FOG in PD may be associated with cognitive dysfunction, the relationship between regional brain atrophy and FOG has been poorly investigated. Optimized VBM was applied to 3T brain MR images of 24 patients with PD and 12 HC. Patients were classified as either FOG- or FOG+ (n = 12) based on their responses to a validated FOG Questionnaire and clinical observation. All patients with PD also underwent a detailed neuropsychological evaluation. The VBM analysis in patients with FOG+ showed a reduced GM volume in the left cuneus, precuneus, lingual gyrus, and posterior cingulate cortex compared with both patients with FOG- and HC. We did not detect any significant change of GM volume when comparing HC versus all patients with PD (FOG- and FOG+). FOG clinical severity was significantly correlated with GM loss in posterior cortical regions. Finally, patients with FOG+ scored lower on tests of frontal lobe function. Our findings provide the first evidence that the development of FOG in patients with PD is associated with posterior GM atrophy, which may play a role in the complex pathophysiology of this disabling symptom.

Cystatin C Predicts Changes in Brain Structure and Cognition in the Elderly (P02.063)

Objective: This study examined the relationships between renal function, measured by cystatin C, and brain small vessel disease (SVD), gray matter (GM) volume and cognition, in cognitively normal elderly subjects. Background Kidney dysfunction is related to neurological disorders, including cerebrovascular and cognitive syndromes. Cystatin C is a measure of kidney function that is considered to be more sensitive than creatinine in the elderly. Previous studies have linked higher cystatin C levels to subclinical brain infarcts and white matter lesions and to a higher incidence of cognitive impairment. Design/Methods: We analyzed demographic, medical, biochemical, neuropsychological, and brain imaging data from 735 cognitively normal subjects from the Cardiovascular Health Cognition Study. The GM volumes were analyzed using Voxel-Based Morphometry. Visual ratings of white matter lesions are used to determine the severity of brain SVD. Results: Elevated cystatin C levels were associated with lower neuropsychological test scores, greater prevalence of brain infarcts, higher white matter grade (WMG), and GM atrophy. Brain SVD was independently associated with higher serum cystatin C concentrations. In adjusted models, cystatin C levels also were significantly associated with GM volume only until body mass index (BMI) and WMG were added to the model. This finding suggests that the statistical effect of cystatin C on GM volume is mediated by these two variables. The VBM analysis found that higher cystatin C levels were associated with lower GM volume. Conclusions: Cystatin C levels are associated with structural brain changes, especially brain SVD and GM volume loss. These findings are consistent with the hypothesis that age-related vascular disease creates a vulnerability state for cognitive decline and dementia, possibly due to a decrease in brain reserve. Disclosure: Dr. Riverol has nothing to disclose. Dr. Becker has nothing to disclose. Dr. Lopez has received personal compensation for activities with Lundbeck and Johnson & Johnson as a consultant. Dr. Raji has nothing to disclose. Dr. Thompson has nothing to disclose. Dr. Carmichael has nothing to disclose. Dr. Gach has nothing to disclose. Dr. Longstreth has nothing to disclose. Dr. Fried has received personal compensation for activities with Pfizer Inc and Bayer Pharmaceuticals as a consultant. Dr. Fried has received personal compensation in an editorial capacity for ACP. Dr. Fried has received research support from Merck & Co., Inc. and Roche Diagnostics. Dr. Tracy has nothing to disclose. Dr. Kuller has nothing to disclose.