Maladaptive brain organization at 1 month into abstinence as an indicator for future relapse in patients with alcohol use disorder.

Abstinence is a lifelong endeavor, and the risk of a relapse is always present for patients with Alcohol Use Disorder (AUD). The aim of the study was to better understand specific characteristics of the intrinsic whole-brain-network architecture of 34 AUD patients that may support abstinence or relapse. We used Graph Theory Analysis (GTA) of resting-state fMRI data from treatment seekers at 1 month of abstinence and their follow-up data as abstainers or relapsers 3 months later, together with data from 30 light/non-drinking controls scanned at the same interval. We determined the group-specific intrinsic community configurations at both timepoints as well as the corresponding modularity Q, a GTA measure that quantifies how well individual network communities are separated from each other. Both AUD groups at both timepoints had community configurations significantly different from those of controls, but the three groups did not significantly differ in their Q values. However, relapsers showed a maladaptive community configuration at baseline, which became more similar to the controls' community organization after the relapsers had started consuming alcohol again during the study interval. Additionally, successful recovery from AUD was not associated with re-gaining the intrinsic brain organization found in light/non-drinkers, but with a re-configuration resulting in a new brain organization distinctly different from that of healthy controls. Resting-state fMRI provides useful measures reflecting neuroplastic adaptations related to AUD treatment outcome.

Hub distribution of the brain functional networks of newborns prenatally exposed to maternal depression and SSRI antidepressants.

BACKGROUND: Prenatal maternal depression (PMD) and selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with increased developmental risk in infants. Reports suggest that PMD is associated with hyperconnectivity of the insula and the amygdala, while SSRI exposure is associated with hyperconnectivity of the auditory network in the infant brain. However, associations between functional brain organization and PMD and/or SSRI exposure are not well understood. METHODS: We examined the relation between PMD or SSRI exposure and neonatal brain functional organization. Infants of control (n = 17), depressed SSRI-treated (n = 20) and depressed-only (HAM-D ≥ 8) (n = 16) women, underwent resting-state functional magnetic resonance imaging at postnatal Day 6. At 6 months, temperament was assessed using Infant Behavioral Questionnaire (IBQ). We applied GTA and partial least square regression (PLSR) to the resting-state time series to assess group differences in modularity, and connector and provincial hubs. RESULTS: Modularity was similar across all groups. The depressed-only group showed higher connector hub values in the left anterior cingulate, insula, and caudate as well as higher provincial hub values in the amygdala compared to the control group. The SSRI group showed higher provincial hub values in Heschl's gyrus relative to the depressed-only group. PLSR showed that newborns' hub values predicted 10% of the variability in infant temperament at 6 months, suggesting different developmental patterns between groups. CONCLUSIONS: Prenatal exposures to maternal depression and SSRIs have differential impacts on neonatal functional brain organization. Hub values at 6 days predict variance in temperament between infant groups at 6 months of age.

Older but still fluent? Insights from the intrinsically active baseline configuration of the aging brain using a data driven graph-theoretical approach.

A major part of our knowledge about the functioning of the aging brain comes from task-induced activation paradigms. However, the aging brain's intrinsic functional organization may be already a limiting factor for the outcome of an actual behavior. In order to get a better understanding of how this functional baseline configuration of the aging brain may affect cognitive performance, we analyzed task-free fMRI data of older 186 participants (mean age=70.4, 97 female) and their performance data in verbal fluency: First, we conducted an intrinsic connectivity contrast analysis (ICC) for the purpose of evaluating the brain regions whose degree of connectedness was significantly correlated with fluency performance. Secondly, using connectivity analyses we investigated how the clusters from the ICC functionally related to the other major resting-state networks. Apart from the importance of intact fronto-parietal long-range connections, the preserved capacity of the DMN for a finely attuned interaction with the executive-control network and the language network seems to be crucial for successful verbal fluency performance in older people. We provide further evidence that the right frontal regions might be more prominently affected by age-related decline.

Frontocerebellar gray matter plasticity in alcohol use disorder linked to abstinence.

Alcohol use disorder (AUD) is associated with brain-wide gray matter (GM) reduction, but the frontocerebellar circuit seems specifically affected by chronic alcohol consumption. T1 weighted MRI data from 38 AUD patients at one month of sobriety and three months later and from 25 controls were analyzed using voxel-based morphometry (VBM) and a graph theory approach (GTA). We investigated the degree to which the frontocerebellar circuit's integration within the brain's GM network architecture was altered by AUD-related GM volume loss. The VBM analyses did not reveal significant GM volume differences between relapsers and abstainers at either timepoint, but future relapsers at both timepoints had significantly less GM than controls in the frontocerebellar circuit. Abstainers, who at baseline also showed the most pronounced GM loss in the thalamus, showed a significant circuit-wide GM increase with inter-scan abstinence. The post-hoc GTAs revealed a persistent diffuse global atrophy in both AUD groups at follow-up relative to controls and different recovery patterns in the two AUD groups. Our findings suggest that future relapsers do not just present with a more severe expression of the same AUD consequences than abstainers, but that AUD affects the frontocerebellar circuit differently in relapsers and abstainers.

Substance-Specific and Shared Gray Matter Signatures in Alcohol, Opioid, and Polysubstance Use Disorder.

Substance use disorders (SUD) have been shown to be associated with gray matter (GM) loss, particularly in the frontal cortex. However, unclear is to what degree these regional GM alterations are substance-specific or shared across different substances, and if these regional GM alterations are independent of each other or the result of system-level processes at the intrinsic connectivity network level. The T1 weighted MRI data of 65 treated patients with alcohol use disorder (AUD), 27 patients with opioid use disorder (OUD) on maintenance therapy, 21 treated patients with stimulant use disorder comorbid with alcohol use disorder (polysubstance use disorder patients, PSU), and 21 healthy controls were examined via data-driven vertex-wise and voxel-wise GM analyses. Then, structural covariance analyses and open-access fMRI database analyses were used to map the cortical thinning patterns found in the three SUD groups onto intrinsic functional systems. Among AUD and OUD, we identified both common cortical thinning in right anterior brain regions as well as SUD-specific regional GM alterations that were not present in the PSU group. Furthermore, AUD patients had not only the most extended regional thinning but also significantly smaller subcortical structures and cerebellum relative to controls, OUD and PSU individuals. The system-level analyses revealed that AUD and OUD showed cortical thinning in several functional systems. In the AUD group the default mode network was clearly most affected, followed by the salience and executive control networks, whereas the salience and somatomotor network were highlighted as critical for understanding OUD. Structural brain alterations in groups with different SUDs are largely unique in their spatial extent and functional network correlates.

Longitudinal changes in brain parenchyma due to mild traumatic brain injury during the first year after injury.

Chronic gray matter (GM) atrophy is a known consequence of moderate and severe traumatic brain injuries but has not been consistently shown in mild traumatic brain injury (mTBI). The aim of this study was to investigate the longitudinal effect of uncomplicated mTBI on the brain's GM and white matter (WM) from 6 weeks to 12 months after injury. Voxel-based-morphometry (VBM) was computed with the T1-weighted images of 48 uncomplicated mTBI patients and 37 orthopedic controls. Over the period from 6 weeks to 12 months, only patients who experienced uncomplicated mTBI, but not control participants, showed significant GM decrease predominantly in the right hemisphere along the GM-CSF border in lateral and medial portions of the sensorimotor cortex extending into the rolandic operculum, middle frontal gyrus, insula, and temporal pole. Additionally, only mTBI patients, but not controls, experienced significant WM decrease predominantly in the right hemisphere in the superior fasciculus longitudinalis, arcuate fasciculus, and cortical-pontine tracts as well as a significant WM increase in left arcuate fasciculus and left capsula extrema. We did not observe any significant change in the controls for the same time interval or any significant group differences in GM and WM probability at each of the two timepoints. This suggests that the changes along the brain tissue borders observed in the mTBI group represent a reorganization associated with subtle microscopical changes in intracortical myelin and not a direct degenerative process as a result of mTBI.

Myelin water fraction decrease in individuals with chronic mild traumatic brain injury and persistent symptoms.

The diffuse and continually evolving secondary changes after mild traumatic brain injury (mTBI) make it challenging to assess alterations in brain-behaviour relationships. In this study we used myelin water imaging to evaluate changes in myelin water fraction (MWF) in individuals with chronic mTBI and persistent symptoms and measured their cognitive status using the NIH Toolbox Cognitive Battery. Fifteen adults with mTBI with persistent symptoms and twelve age, gender and education matched healthy controls took part in this study. We found a significant decrease in global white matter MWF in patients compared to the healthy controls. Significantly lower MWF was evident in most white matter region of interest (ROIs) examined including the corpus callosum (separated into genu, body and splenium), minor forceps, right anterior thalamic radiation, left inferior longitudinal fasciculus; and right and left superior longitudinal fasciculus and corticospinal tract. Although patients showed lower cognitive functioning, no significant correlations were found between MWF and cognitive measures. These results suggest that individuals with chronic mTBI who have persistent symptoms have reduced MWF.

Does an Over-Connected Visual Cortex Undermine Efforts to Stay Sober After Treatment for Alcohol Use Disorder?

A fine-tuned interplay of highly synchronized activity within and between the brain's communities is a crucial feature of the brain's functional organization. We wanted to investigate in individuals with alcohol use disorder (AUD) the degree to which the interplay of the brain's community-architecture and the extended brain reward system (eBRS) is affected by drinking status (relapse or abstinence). We used Graph Theory Analysis of resting-state fMRI data from treatment seekers at 1 month of abstinence to model the brain's intrinsic community configuration and their follow-up data as abstainers or relapsers 3 months later to quantify the degree of global across-community interaction between the eBRS and the intrinsic communities at both timepoints. After 1 month of abstinence, the ventromedial PFC in particular showed a significantly higher global across-community interaction in the 22 future relapsers when compared to 30 light/non-drinking controls. These differences were no longer present 3 months later when the relapsers had resumed drinking. We found no significant differences between abstainers and controls at either timepoint. Post hoc tests revealed that one eBRS region, the ventromedial PFC, showed a significant global across-community interaction with a community comprising the visual cortex in relapsers at baseline. In contrast, abstainers showed a significant negative association of the ventromedial PFC with the visual cortex. The increased across-community interaction of the ventromedial PFC and the visual cortex in relapsers at timepoint 1 may be an early indicator for treatment failure in a subgroup of AUD patients.

Stuck in a State of Inattention? Functional Hyperconnectivity as an Indicator of Disturbed Intrinsic Brain Dynamics in Adolescents With Concussion: A Pilot Study.

Sports-related concussion in youth is a major public health issue. Evaluating the diffuse and often subtle changes in structure and function that occur in the brain, particularly in this population, remains a significant challenge. The goal of this pilot study was to evaluate the relationship between the intrinsic dynamics of the brain using resting-state functional magnetic resonance imaging (rs-fMRI) and relate these findings to structural brain correlates from diffusion tensor imaging in a group of adolescents with sports-related concussions ( n = 6) and a group of healthy adolescent athletes ( n = 6). We analyzed rs-fMRI data using a sliding windows approach and related the functional findings to structural brain correlates by applying graph theory analysis to the diffusion tensor imaging data. Within the resting-state condition, we extracted three separate brain states in both groups. Our analysis revealed that the brain dynamics in healthy adolescents was characterized by a dynamic pattern, shifting equally between three brain states; however, in adolescents with concussion, the pattern was more static with a longer time spent in one brain state. Importantly, this lack of dynamic flexibility in the concussed group was associated with increased nodal strength in the left middle frontal gyrus, suggesting reorganization in a region related to attention. This preliminary report shows that both the intrinsic brain dynamics and structural organization are altered in networks related to attention in adolescents with concussion. This first report in adolescents will be used to inform future studies in a larger cohort.

Mesial temporal lobe epilepsy diminishes functional connectivity during emotion perception.

OBJECTIVES: Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with impaired recognition of emotional facial expressions. Correspondingly, imaging studies showed decreased activity of the amygdala and cortical face processing regions in response to emotional faces. However, functional connectivity among regions involved in emotion perception has not been studied so far. METHODS: To address this, we examined intrinsic functional connectivity (FC) modulated by the perception of dynamic fearful faces among the amygdala and limbic, frontal, temporal and brainstem regions. Regions of interest were identified in an activation analysis by presenting a block-design with dynamic fearful faces and dynamic landscapes to 15 healthy individuals. This led to 10 predominately right-hemispheric regions. Functional connectivity between these regions during the perception of fearful faces was examined in drug-refractory patients with left- (n=16) or right-sided (n=17) MTLE, epilepsy patients with extratemporal seizure onset (n=15) and a second group of 15 healthy controls. RESULTS: Healthy controls showed a widespread functional network modulated by the perception of fearful faces that encompassed bilateral amygdalae, limbic, cortical, subcortical and brainstem regions. In patients with left MTLE, a downsized network of frontal and temporal regions centered on the right amygdala was present. Patients with right MTLE showed almost no significant functional connectivity. A maintained network in the epilepsy control group indicates that findings in mesial temporal lobe epilepsy could not be explained by clinical factors such as seizures and antiepileptic medication. CONCLUSION: Functional networks underlying facial emotion perception are considerably changed in left and right MTLE. Alterations are present for both hemispheres in either MTLE group, but are more pronounced in right MTLE. Disruption of the functional network architecture possibly contributes to deficits in facial emotion recognition frequently reported in MTLE.

Small Changes, But Huge Impact? The Right Anterior Insula's Loss of Connection Strength during the Transition of Old to Very Old Age.

A major contribution to our understanding of the aging brain comes either from studies comparing young with older adults or from studies investigating pathological aging and using the healthy aging older adults as control group. In consequence, we know relatively well, what distinguishes young from old brains or pathological aging from healthy but that does not mean that we really understand the structural and functional transformations characterizing the healthy aging brain. By analyzing task-free fMRI data from a large cross-sectional sample of 186 older adults (mean age = 70.4, 97 female), we aimed to elucidate age-related changes in the intrinsically active functional architecture of the brain in our study group covering an age range from 65 to 85 years. First, we conducted an intrinsic connectivity contrast analysis (ICC) in order to detect the brain regions whose degree of connectedness was significantly correlated with increasing age. Secondly, using connectivity analyses we investigated how the clusters highlighted by the ICC analysis functionally related to the other major resting-state networks. The most important finding was the right anterior insula's loss of connectedness in the older participants of the study group because of the region's causal role in the switching from the task-negative to the task-positive state of the brain. Further, we found a higher functional dedifferentiation of two of the brain's major intrinsic connectivity networks, the DMN, and the cingulo-opercular network, caused by a reduction of functional connection strength, especially in the frontal regions. At last, we showed that all these age-related changes have the potential to impair older adult's performance of working memory tasks.

Language in the brain at rest: new insights from resting state data and graph theoretical analysis.

In humans, the most obvious functional lateralization is the specialization of the left hemisphere for language. Therefore, the involvement of the right hemisphere in language is one of the most remarkable findings during the last two decades of fMRI research. However, the importance of this finding continues to be underestimated. We examined the interaction between the two hemispheres and also the role of the right hemisphere in language. From two seeds representing Broca's area, we conducted a seed correlation analysis (SCA) of resting state fMRI data and could identify a resting state network (RSN) overlapping to significant extent with a language network that was generated by an automated meta-analysis tool. To elucidate the relationship between the clusters of this RSN, we then performed graph theoretical analyses (GTA) using the same resting state dataset. We show that the right hemisphere is clearly involved in language. A modularity analysis revealed that the interaction between the two hemispheres is mediated by three partitions: A bilateral frontal partition consists of nodes representing the classical left sided language regions as well as two right-sided homologs. The second bilateral partition consists of nodes from the right frontal, the left inferior parietal cortex as well as of two nodes within the posterior cerebellum. The third partition is also bilateral and comprises five regions from the posterior midline parts of the brain to the temporal and frontal cortex, two of the nodes are prominent default mode nodes. The involvement of this last partition in a language relevant function is a novel finding.