Cortical lamina-dependent blood volume changes in human brain at 7T

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8–1.6 mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans

Intrinsic Frontolimbic Connectivity and Mood Symptoms in Young Adult Cannabis Users.

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms. Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f 2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f 2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f 2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02). Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP: Research Network Neuroimaging Study.

Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N = 28), as well as group of age-matched healthy male controls (N = 27), had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing

Detaching from the negative by reappraisal: the role of right superior frontal gyrus (BA9/32)

The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself), i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and gray matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM) analysis to identify deficit related areas (ROI). Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM) analysis was run, in which healthy participant's REAPPself ability scores were correlated with gray matter intensities. Results showed that (1) regions in the right superior frontal gyrus (SFG), comprising the right dorsolateral prefrontal cortex (BA9) and the right dorsal anterior cingulate cortex (BA32), were associated with patient's impaired down-regulation of arousal, (2) a lesion in the depicted ROI occasioned significant REAPPself impairments, (3) REAPPself ability of controls was linked with increased gray matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32) might be indispensable for REAPPself. Implications for neurofeedback research are discussed.Fil: Falquez, Rosalux. University of Heidelberg; AlemaniaFil: Couto, Juan Blas Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Ibáñez Barassi, Agustín Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Freitag, Martin T.. German Cancer Research Center; AlemaniaFil: Berger, Moritz. German Cancer Research Center; AlemaniaFil: Arens, Elisabeth A.. University of Heidelberg; AlemaniaFil: Lang, Simone. University of Heidelberg; AlemaniaFil: Barnow, Sven. University of Heidelberg; Alemani

Evaluation of atlas-based segmentation of hippocampi in healthy humans

Introduction and aim: Region of interest (ROI)-based functional magnetic resonance imaging (fMRI) data analysis relies on extracting signals from a specific area which is presumed to be involved in the brain activity being studied. The hippocampus is of interest in many functional connectivity studies for example in epilepsy as it plays an important role in epileptogenesis. In this context, ROI may be defined using different techniques. Our study aims at evaluating the spatial correspondence of hippocampal ROIs obtained using three brain atlases with hippocampal ROI obtained using an automatic segmentation algorithm dedicated to the hippocampus. Material and methods: High-resolution volumetric T1-weighted MR images of 18 healthy volunteers (five females) were acquired on a 3T scanner. Individual ROIs for both hippocampi of each subject were segmented from the MR images using an automatic hippocampus and amygdala segmentation software called SACHA providing the gold standard ROI for comparison with the atlas-derived results. For each subject, hippocampal ROIs were also obtained using three brain atlases: PickAtlas available as a commonly used software toolbox; automated anatomical labeling (AAL) atlas included as a subset of ROI into PickAtlas toolbox and a frequency-based brain atlas by Hammers et al. The levels of agreement between the SACHA results and those obtained using the atlases were assessed based on quantitative indices measuring volume differences and spatial overlap. The comparison was performed in standard Montreal Neurological Institute space, the registration being obtained with SPM5 (http://www.fil.ion.ucl.ac.uk/spm/). Results: The mean volumetric error across all subjects was 73% for hippocampal ROIs derived from AAL atlas; 20% in case of ROIs derived from the Hammers atlas and 107% for ROIs derived from PickAtlas. The mean false-positive and false-negative classification rates were 60% and 10% respectively for the AAL atlas; 16% and 32% for the Hammers atlas and 6% and 72% for the PickAtlas. Conclusion: Though atlas-based ROI definition may be convenient, the resulting ROIs may be poor representations of the hippocampus in some studies critical to under- or oversampling. Performance of the AAL atlas was inferior to that of the Hammers atlas. Hippocampal ROIs derived from PickAtlas are highly significantly smaller, and this results in the worst performance out of three atlases. It is advisable that the defined ROIs should be verified with knowledge of neuroanatomy before using it for further data analysis

fMRI of Healthy Older Adults During Stroop Interference

The Stroop interference effect, caused by difficulty inhibiting overlearned word reading, is often more pronounced in older adults. This has been proposed to be due to declines in inhibitory control and frontal lobe functions with aging. Initial neuroimaging studies of inhibitory control show that older adults have enhanced activation in multiple frontal areas, particularly in inferior frontal gyrus, indicative of recruitment to aid with performance of the task. The current study compared 13 younger and 13 older adults, all healthy and well educated, who completed a Stroop test during functional magnetic resonance imaging. Younger adults were more accurate across conditions, and both groups were slower and less accurate during the interference condition. The groups exhibited comparable activation regions, but older adults exhibited greater activation in numerous frontal areas, including the left inferior frontal gyrus. The results support the recruitment construct and suggest, along with previous research, that the inferior frontal gyrus is important for successful inhibition

Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration.

OBJECTIVE: To quantify the regional and global cerebral atrophy rates and assess acceleration rates in healthy controls, subjects with mild cognitive impairment (MCI), and subjects with mild Alzheimer disease (AD). METHODS: Using 0-, 6-, 12-, 18-, 24-, and 36-month MRI scans of controls and subjects with MCI and AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we calculated volume change of whole brain, hippocampus, and ventricles between all pairs of scans using the boundary shift integral. RESULTS: We found no evidence of acceleration in whole-brain atrophy rates in any group. There was evidence that hippocampal atrophy rates in MCI subjects accelerate by 0.22%/year2 on average (p = 0.037). There was evidence of acceleration in rates of ventricular enlargement in subjects with MCI (p = 0.001) and AD (p < 0.001), with rates estimated to increase by 0.27 mL/year2 (95% confidence interval 0.12, 0.43) and 0.88 mL/year2 (95% confidence interval 0.47, 1.29), respectively. A post hoc analysis suggested that the acceleration of hippocampal loss in MCI subjects was mainly driven by the MCI subjects that were observed to progress to clinical AD within 3 years of baseline, with this group showing hippocampal atrophy rate acceleration of 0.50%/year2 (p = 0.003). CONCLUSIONS: The small acceleration rates suggest a long period of transition to the pathologic losses seen in clinical AD. The acceleration in hippocampal atrophy rates in MCI subjects in the ADNI seems to be driven by those MCI subjects who concurrently progressed to a clinical diagnosis of AD

Intersubject Regularity in the Intrinsic Shape of Human V1

Previous studies have reported considerable intersubject variability in the three-dimensional geometry of the human primary visual cortex (V1). Here we demonstrate that much of this variability is due to extrinsic geometric features of the cortical folds, and that the intrinsic shape of V1 is similar across individuals. V1 was imaged in ten ex vivo human hemispheres using high-resolution (200 μm) structural magnetic resonance imaging at high field strength (7 T). Manual tracings of the stria of Gennari were used to construct a surface representation, which was computationally flattened into the plane with minimal metric distortion. The instrinsic shape of V1 was determined from the boundary of the planar representation of the stria. An ellipse provided a simple parametric shape model that was a good approximation to the boundary of flattened V1. The aspect ration of the best-fitting ellipse was found to be consistent across subject, with a mean of 1.85 and standard deviation of 0.12. Optimal rigid alignment of size-normalized V1 produced greater overlap than that achieved by previous studies using different registration methods. A shape analysis of published macaque data indicated that the intrinsic shape of macaque V1 is also stereotyped, and similar to the human V1 shape. Previoud measurements of the functional boundary of V1 in human and macaque are in close agreement with these results

Changes in the Frontotemporal Cortex and Cognitive Correlates in First-Episode Psychosis

Background: Loss of cortical volume in frontotemporal regions has been reported in patients with schizophrenia and their relatives. Cortical area and thickness are determined by different genetic processes, and measuring these parameters separately may clarify disturbances in corticogenesis relevant to schizophrenia. Our study also explored clinical and cognitive correlates of these parameters.Methods: Thirty-seven patients with first-episode psychosis (34 schizophrenia, 3 schizoaffective disorder) and 38 healthy control subjects matched for age and sex took part in the study. Imaging was performed on an magnetic resonance imaging 1.5-T scanner. Area and thickness of the frontotemporal cortex were measured using a surface-based morphometry method (Freesurfer). All subjects underwent neuropsychologic testing that included measures of premorbid and current IQ, working and verbal memory, and executive function.Results: Reductions in cortical area, more marked in the temporal cortex, were present in patients. Overall frontotemporal cortical thickness did not differ between groups, although regional thinning of the right superior temporal region was observed in patients. There was a significant association of both premorbid IQ and IQ at disease onset with area, but not thickness, of the frontotemporal cortex, and working memory span was associated with area of the frontal cortex. These associations remained significant when only patients with schizophrenia were considered.Conclusions: Our results suggest an early disruption of corticogenesis in schizophrenia, although the effect of subsequent environmental factors cannot be excluded. In addition, cortical abnormalities are subject to regional variations and differ from those present in neurodegenerative diseases