Tracking spatial dynamics of functional connectivity during a task.

Functional connectivity (FC) measured from functional magnetic resonance imaging (fMRI) provides a powerful tool to explore brain organization. Studies of the temporal dynamics of brain organization have shown a large temporal variability of the functional connectome, which may be associated with mental status transitions and/or adaptive process. Most dynamic studies, e.g. functional connectome and functional network connectivity (FNC), have focused on the macroscopic FC changes, i.e. the changes of temporal coherence across various brain network sources, nodes and/or regions of interest, where it is assumed within the network or node that the FC is static. In this paper, we develop a novel method to examine the spatial dynamics of FC, without the assumption of its intra-network stationarity. We applied our approach to fMRI data during an auditory oddball task (AOD) from twenty-two subjects, in an attempt to capture/validate the approach by evaluating whether spatial connectivity varies with task condition. The results showed that connectivity networks exhibit spatial variability over time, in addition to participating in conventional temporal dynamics, i.e. cross-network variability or dynamic functional network connectivity (dFNC). Furthermore, we studied the relationship of spatial dynamic in FC to cognitive processes, by performing a cluster analysis to evaluate an individual's functional correspondence towards the 'target' (oddball) detection from AOD task, and extracting cognitive task correspondence states as well as their dynamic FC spatial maps segregated by such states. We found a clear trend in different task-guided states, particularly, a prominent reduction of task stimulus synchrony state along with strong anticorrelation between default mode network (DMN) and cognitive attentional networks. We also observed an increasing occurrence of the task desynchrony state which showed an absence of DMN anticorrelation. The results highlight the impact of a well-studied cognitive task on the observed spatial dynamic structure. We also showed that the FC spatial dynamic pattern from our method largely corresponds to macroscopic dFNC patterns, but with more details and specifications over space, meanwhile the connectivity within the source itself provides novel information and varies over time. Overall, we demonstrate clear evidence of the presence of the (usually ignored) spatial dynamics of connectivity, its links to the task and implications of cognition/mental status.

In search of multimodal brain alterations in Alzheimer's and Binswanger's disease.

Structural and functional brain abnormalities have been widely identified in dementia, but with variable replicability and significant overlap. Alzheimer's disease (AD) and Binswanger's disease (BD) share similar symptoms and common brain changes that can confound diagnosis. In this study, we aimed to investigate correlated structural and functional brain changes in AD and BD by combining resting-state functional magnetic resonance imaging (fMRI) and diffusion MRI. A group independent component analysis was first performed on the fMRI data to extract 49 intrinsic connectivity networks (ICNs). Then we conducted a multi-set canonical correlation analysis on three features, functional network connectivity (FNC) between ICNs, fractional anisotropy (FA) and mean diffusivity (MD). Two inter-correlated components show significant group differences. The first component demonstrates distinct brain changes between AD and BD. AD shows increased cerebellar FNC but decreased thalamic and hippocampal FNC. Such FNC alterations are linked to the decreased corpus callosum FA. AD also has increased MD in the frontal and temporal cortex, but BD shows opposite alterations. The second component demonstrates specific brain changes in BD. Increased FNC is mainly between default mode and sensory regions, while decreased FNC is mainly within the default mode domain and related to auditory regions. The FNC changes are associated with FA changes in posterior/middle cingulum cortex and visual cortex and increased MD in thalamus and hippocampus. Our findings provide evidence of linked functional and structural deficits in dementia and suggest that AD and BD have both common and distinct changes in white matter integrity and functional connectivity.

Reduced white matter integrity in the cingulum and anterior corona radiata in posttraumatic stress disorder in male combat veterans: a diffusion tensor imaging study.

Posttraumatic stress (PTSD) and alcohol use (AUD) disorders are associated with abnormal anterior cingulate cortex/ventromedial prefrontal cortex, thalamus, and amygdala function, yet microstructural white matter (WM) differences in executive-limbic tracts are likely also involved. Investigating WM in limbic-thalamo-cortical tracts, this study hypothesized (1) fractional anisotropy (FA) in dorsal cingulum, parahippocampal cingulum, and anterior corona radiata (ACR) would be lower in individuals with comorbid PTSD/AUD compared to in individuals with AUD-only and (2) that FA would be related to both AUD and PTSD severity. 22 combat veterans with comorbid PTSD/AUD or AUD-only completed DTI scans. ANCOVAs indicated lower FA in right (F(df=1,19)=9.091, P=0.0071) and left (F(df=1,19)=10.375, P=0.0045) dorsal cingulum and right ACR (F(df=1,19)=18.914, P=0.0003) for individuals with comorbid PTSD/AUD vs. individuals with AUD-only, even controlling for alcohol use. Multiple linear regressions revealed that FA in the right ACR was inversely related to PTSD severity (r=-0.683, P=0.004). FA was not significantly related to alcohol severity. Reduced WM integrity in limbic-thalamo-cortical tracts is implicated in PTSD, even in the presence of comorbid AUD. These findings suggest that diminished WM integrity in tracts important for top-down control may be an important anomaly in PTSD and/or comorbid PTSD/AUD.

Diffusion tensor imaging of white matter networks in individuals with current and remitted alcohol use disorders and comorbid conditions.

Individuals with alcohol use disorders show white matter abnormality relative to normal samples, but differences in white matter profiles have not yet been investigated as a function of abstinence. Individuals with current alcohol use disorders (AUD-C; n = 10), individuals with alcohol use disorders in remission for at least 1 year (AUD-R; n = 9), and healthy control participants (HC; n = 15) matched to alcohol groups on age and smoking status underwent MRI. Diffusion tensor imaging (DTI) data were analyzed using tract-based spatial statistics (TBSS). Compared with HC, AUD-C showed reduced axial diffusivity in bilateral frontal and temporal white matter. In AUD-R, lower fractional anisotropy relative to HC was widespread in bilateral parietal regions. A combined AUD-C and AUD-R group had decreased fractional anisotropy primarily in the fornix and thalamus. In conclusion, AUD-R manifested damage in parietal regions integral to processing of visuospatial information and self-awareness whereas AUD-C showed abnormal diffusivity in fronto-temporal regions that regulate impulsivity, attention, and memory. As a combined group, AUD individuals exhibited abnormality in subcortical areas associated with sensory processing and memory. White matter differences in individuals with AUD may be attributable to premorbid vulnerability or persisting effects of alcohol abuse, but the pattern of abnormality across groups suggests that these abnormalities may be secondary to alcohol use.

Spatial characteristics of white matter abnormalities in schizophrenia.

There is considerable evidence implicating brain white matter (WM) abnormalities in the pathophysiology of schizophrenia; however, the spatial localization of WM abnormalities reported in the existing studies is heterogeneous. Thus, the goal of this study was to quantify the spatial characteristics of WM abnormalities in schizophrenia. One hundred and fourteen patients with schizophrenia and 138 matched controls participated in this multisite study involving the Universities of Iowa, Minnesota, and New Mexico, and the Massachusetts General Hospital. We measured fractional anisotropy (FA) in brain WM regions extracted using 3 different image-processing algorithms: regions of interest, tract-based spatial statistics, and the pothole approach. We found that FA was significantly lower in patients using each of the 3 image-processing algorithms. The region-of-interest approach showed multiple regions with lower FA in patients with schizophrenia, with overlap at all 4 sites in the corpus callosum and posterior thalamic radiation. The tract-based spatial statistic approach showed (1) global differences in 3 of the 4 cohorts and (2) lower frontal FA at the Iowa site. Finally, the pothole approach showed a significantly greater number of WM potholes in patients compared to controls at each of the 4 sites. In conclusion, the spatial characteristics of WM abnormalities in schizophrenia reflect a combination of a global low-level decrease in FA, suggesting a diffuse process, coupled with widely dispersed focal reductions in FA that vary spatially among individuals (ie, potholes).

Delays in auditory processing identified in preschool children with FASD.

BACKGROUND: Both sensory and cognitive deficits have been associated with prenatal exposure to alcohol; however, very few studies have focused on sensory deficits in preschool-aged children. As sensory skills develop early, characterization of sensory deficits using novel imaging methods may reveal important neural markers of prenatal alcohol exposure. METHODS: Participants in this study were 10 children with a fetal alcohol spectrum disorder (FASD) and 15 healthy control (HC) children aged 3 to 6 years. All participants had normal hearing as determined by clinical screens. We measured their neurophysiological responses to auditory stimuli (1,000 Hz, 72 dB tone) using magnetoencephalography (MEG). We used a multidipole spatio-temporal modeling technique to identify the location and timecourse of cortical activity in response to the auditory tones. The timing and amplitude of the left and right superior temporal gyrus sources associated with activation of left and right primary/secondary auditory cortices were compared across groups. RESULTS: There was a significant delay in M100 and M200 latencies for the FASD children relative to the HC children (p = 0.01), when including age as a covariate. The within-subjects effect of hemisphere was not significant. A comparable delay in M100 and M200 latencies was observed in children across the FASD subtypes. CONCLUSIONS: Auditory delay revealed by MEG in children with FASDs may prove to be a useful neural marker of information processing difficulties in young children with prenatal alcohol exposure. The fact that delayed auditory responses were observed across the FASD spectrum suggests that it may be a sensitive measure of alcohol-induced brain damage. Therefore, this measure in conjunction with other clinical tools may prove useful for early identification of alcohol affected children, particularly those without dysmorphia.

Anterior cingulate and frontal lobe white matter spectroscopy in early childhood of former very LBW premature infants.

Neurometabolic sequelae of children born at very LBW (VLBW) are not well characterized in early childhood. Proton magnetic resonance spectroscopy (1H-MRS) and developmental assessments were acquired from children age 18-22 mo (16 VLBW/7 term) and 3-4 y (12 VLBW/8 term) from the anterior cingulate and left frontal periventricular white matter. Metabolites obtained included combined N-acetylaspartylglutamate and N-acetylaspartate (NAA), total choline-containing compounds (Cho), combined glutamate and glutamine (Glx), combined creatine and phosphocreatine (Cr), myoinositol (mI), and the following ratios: NAA/Cr, Cho/Cr, Glx/Cr, mI/Cr, and NAA/Cho. Significant differences were present only in white matter: at 18-22 mo, NAA was decreased in VLBW children (p < 0.04), and at 3-4 y, VLBW children showed lower Cr (p < 0.01), lower NAA/Cho (p < 0.005), higher Glx/Cr (p < 0.02), and higher Cho/Cr (p < 0.005). On developmental testing, VLBW children scored lower on language expression (p < 0.05) and on the A-not-B test of early executive function (p < 0.01) at 18-22 mo and had lower verbal intelligence quotient (IQ) (p < 0.005), performance IQ (p < 0.04), and several measures of early executive function including the bear-dragon test (p < 0.004), gift delay (p < 0.07), and summary categorization score (p < 0.03) at 3-4 y. VLBW children may have neurometabolic and developmental abnormalities that persist at least through early childhood.

White matter integrity, creativity, and psychopathology: disentangling constructs with diffusion tensor imaging.

That creativity and psychopathology are somehow linked remains a popular but controversial idea in neuroscience research. Brain regions implicated in both psychosis-proneness and creative cognition include frontal projection zones and association fibers. In normal subjects, we have previously demonstrated that a composite measure of divergent thinking (DT) ability exhibited significant inverse relationships in frontal lobe areas with both cortical thickness and metabolite concentration of N-acetyl-aspartate (NAA). These findings support the idea that creativity may reside upon a continuum with psychopathology. Here we examine whether white matter integrity, assessed by Fractional Anisotropy (FA), is related to two measures of creativity (Divergent Thinking and Openness to Experience). Based on previous findings, we hypothesize inverse correlations within fronto-striatal circuits. Seventy-two healthy, young adult (18-29 years) subjects were scanned on a 3 Tesla scanner with Diffusion Tensor Imaging. DT measures were scored by four raters (alpha = .81) using the Consensual Assessment Technique, from which a composite creativity index (CCI) was derived. We found that the CCI was significantly inversely related to FA within the left inferior frontal white matter (t = 5.36, p = .01), and Openness was inversely related to FA within the right inferior frontal white matter (t = 4.61, p = .04). These findings demonstrate an apparent overlap in specific white matter architecture underlying the normal variance of divergent thinking, openness, and psychotic-spectrum traits, consistent with the idea of a continuum.

Failure of Rhodiola rosea to alter skeletal muscle phosphate kinetics in trained men.

Rhodiola rosea is an herbal supplement purported to improve resistance to stressors and to enhance physical performance, potentially by improving adenosine triphosphate (ATP) turnover. Phosphocreatine (PCr) kinetics serves as a reflection of ATP turnover. The purpose of this investigation was to examine the effect of R rosea ingestion on human skeletal muscle PCr recovery after exhaustive exercise. Twelve resistance-trained men, aged 19 to 39 years, completed incremental forearm wrist flexion exercise to volitional fatigue, once after ingesting 1500 mg R rosea per day for 4 days, and once after ingesting an equivalent placebo dose. During exercise and recovery from exercise, muscle phosphates were examined using phosphorus 31 nuclear magnetic resonance spectroscopy. [PCr] during recovery was fit with a monoexponential function, and the resulting rate constants (k) were compared between groups. Rating of perceived exertion per stage and time to exhaustion were also compared between groups. For R rosea, k=0.3744+/-0.1532, whereas for placebo, k=0.3956+/-0.2238. Although rating of perceived exertion significantly increased within groups as workload increased, it did not differ between conditions, nor did time to exhaustion (R rosea, 10.71+/-0.54 minutes; placebo, 10.48+/-0.68 minutes). Estimates of [PCr] at time 0, 5, 10, 15, and 20 minutes of recovery were nearly identical between groups. In summary, there were no significant differences between groups for any of theparameters measured. Based on these results, we conclude that R rosea ingestion does not improve ATP turnover during or immediately after exercise.

Reproducibility of quantitative tractography methods applied to cerebral white matter.

Tractography based on diffusion tensor imaging (DTI) allows visualization of white matter tracts. In this study, protocols to reconstruct eleven major white matter tracts are described. The protocols were refined by several iterations of intra- and inter-rater measurements and identification of sources of variability. Reproducibility of the established protocols was then tested by raters who did not have previous experience in tractography. The protocols were applied to a DTI database of adult normal subjects to study size, fractional anisotropy (FA), and T2 of individual white matter tracts. Distinctive features in FA and T2 were found for the corticospinal tract and callosal fibers. Hemispheric asymmetry was observed for the size of white matter tracts projecting to the temporal lobe. This protocol provides guidelines for reproducible DTI-based tract-specific quantification.