Neural predictors of cognitive-behavior therapy outcome in anxiety-related disorders: a meta-analysis of task-based fMRI studies

Background Cognitive-behavior therapy (CBT) is a well-established first-line intervention for anxiety-related disorders, including specific phobia, social anxiety disorder, panic disorder/agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. Several neural predictors of CBT outcome for anxiety-related disorders have been proposed, but previous results are inconsistent. Methods We conducted a systematic review and meta-analysis of task-based functional magnetic resonance imaging (fMRI) studies investigating whole-brain predictors of CBT outcome in anxiety-related disorders (17 studies, n = 442). Results Across different tasks, we observed that brain response in a network of regions involved in salience and interoception processing, encompassing fronto-insular (the right inferior frontal gyrus-anterior insular cortex) and fronto-limbic (the dorsomedial prefrontal cortex-dorsal anterior cingulate cortex) cortices was strongly associated with a positive CBT outcome. Conclusions Our results suggest that there are robust neural predictors of CBT outcome in anxiety-related disorders that may eventually lead (probably in combination with other data) to develop personalized approaches for the treatment of these mental disorders.

Anterior cingulate metabolite levels, memory, and inhibitory control in abstinent men and women with Alcohol Use Disorder

Aims: Alcohol use disorder (AUD), has been shown to have harmful cognitive and physiological effects, including altered brain chemistry. Further, although men and women may differ in vulnerability to the neurobiological effects of AUD, results of existing studies have been conflicting. Brain metabolite levels and cognitive functions were examined in a cross section of men with AUD (AUDm) and women with AUD (AUDw) to determine degree of abnormalities after extended periods of abstinence (mean, six years), and to evaluate gender differences in cognitive and metabolite measures. Methods: Participants were 40 abstinent individuals with AUD (22 AUDw, 18 AUDm) and 50 age-equivalent non-AUD comparison participants (26 NCw, 24 NCm). Proton magnetic resonance spectroscopy (MRS) was employed at 3 Tesla to acquire metabolite spectra from the dorsal anterior cingulate cortex (dACC). Brain metabolites N-acetylaspartate (NAA), choline (Cho), myo-Inositol (mI), and glutamate & glutamine (Glx) were examined relative to measures of memory and inhibitory control. Results: Metabolite levels in the AUD group showed no significant differences from the NC group. Memory and inhibitory-control impairments were observed in the AUD group. There also were significant group-specific associations between metabolite ratios and measures of inhibitory control. There were no Group-by-Gender interactions for the four metabolite ratios. Conclusions: These findings demonstrate that brain metabolite levels in men and women with AUD, following long-term abstinence, do not differ from individuals without AUD. The data also provide evidence of associations between metabolite levels and measures of inhibitory control, a functional domain important for curtailing harmful drinking.

The neural dynamics associated with computational complexity

Many everyday tasks require people to solve computationally complex problems. However, little is known about the effects of computational hardness on the neural processes associated with solving such problems. Here, we draw on computational complexity theory to address this issue. We performed an experiment in which participants solved several instances of the 0-1 knapsack problem, a combinatorial optimization problem, while undergoing ultra-high field (7T) functional magnetic resonance imaging (fMRI). Instances varied in two task-independent measures of intrinsic computational hardness: complexity and proof hardness. We characterise a network of brain regions whose activation was correlated with both measures but in distinct ways, including the anterior insula, dorsal anterior cingulate cortex and the intra-parietal sulcus/angular gyrus. Activation and connectivity changed dynamically as a function of complexity and proof hardness, in line with theoretical computational requirements. Overall, our results suggest that computational complexity theory provides a suitable framework to study the effects of computational hardness on the neural processes associated with solving complex cognitive tasks.

Importance of linear combination modeling for quantification of Glutathione and GABA levels using Hadamard-edited MRS

Purpose: Two main approaches are used for spectral analysis of edited data: simple peak fitting and linear combination modeling (LCM) with a simulated basis set. Recent consensus recommended LCM as the method of choice for the spectral analysis of edited data. The aim of this study is to compare the performance of simple peak fitting and LCM in a test-retest dataset, hypothesizing that the more sophisticated LCM approach will improve quantification of HERMES data compared with simple peak fitting. Methods: A test-retest dataset was re-analyzed using Gannet (simple peak fitting) and Osprey (LCM). These data were obtained from the dorsal anterior cingulate cortex of twelve healthy volunteers, with TE 80 ms for HERMES and TE 120 ms for MEGA-PRESS of glutathione (GSH). Within-subject coefficients of variance (CVs) were calculated to quantify between-scan reproducibility of each metabolite estimate. Results: The reproducibility of HERMES GSH estimates was substantially improved using LCM compared to simple peak fitting, from a CV of 19.0% to 9.9%. For MEGA-PRESS data, the GSH reproducibility was similar using LCM and simple peak fitting, with CVs of 7.3% and 8.8% respectively. Conclusion: Linear combination modeling with simulated basis functions substantially improves the reproducibility of GSH quantification for HERMES data.

Neuroimaging signature associated with symptom exacerbation in early-stage psychosis

Recent reports have indicated that the occurrence of symptom exacerbation in early-stage psychosis could result in brain changes, which are likely to underlie the poorer disease outcome. Thus, it is important to identify neuroimaging signature associated with symptom exacerbation in early-stage psychosis. We studied 85 patients with psychosis within two years after onset and 94 healthy controls (HC). The patient group was subdivided into two groups: 54 patients who did not experience major symptom exacerbation between the onset and study enrollment (P1), and 31 patients who experienced major symptom exacerbation (P2). We analyzed three brain imaging measures derived from resting-state functional MRI, such as global efficiency, nodal efficiency, and resting-state functional connectivity (rs-FC). After excluding some brain imaging measures that were potentially affected by clinical variables, we conducted a comparison between overall patient group and HC group as well as comparsions between HC, P1, and P2 groups for these three types of brain imaging measures, respectively. By integrating the information, we pinned down the dorsal anterior cingulate cortex and thalamus as key hubs in the context of several large-scale brain networks associated with symptom exacerbations in early-stage psychosis. Our study implies the importance of considering neural mechanism associated with symptom exacerbations in early stages of psychotic disorders.

Altered resting-state functional connectivity of the frontal-striatal circuit in elderly with apathy

Apathy is defined as reduction of goal-directed behaviors and a common nuisance syndrome of neurodegenerative and psychiatric disease. The underlying mechanism of apathy implicates changes of the front-striatal circuit, but its precise alteration is unclear for apathy in healthy aged people. The aim of our study is to investigate how the frontal-striatal circuit is changed in elderly with apathy using resting-state functional MRI. Eighteen subjects with apathy (7 female, 63.7 ± 3.0 years) and eighteen subjects without apathy (10 female, 64.8 ± 3.0 years) who underwent neuropsychological assessment and MRI measurement were recruited. We compared functional connectivity with/within the striatum between the apathy and non-apathy groups. The seed-to-voxel group analysis for functional connectivity between the striatum and other brain regions showed that the connectivity was decreased between the ventral rostral putamen and the right dorsal anterior cingulate cortex/supplementary motor area in the apathy group compared to the non-apathy group while the connectivity was increased between the dorsal caudate and the left sensorimotor area. Moreover, the ROI-to-ROI analysis within the striatum indicated reduction of functional connectivity between the ventral regions and dorsal regions of the striatum in the apathy group. Our findings suggest that the changes in functional connectivity balance among different frontal-striatum circuits contribute to apathy in elderly.

Community-level racial prejudice potentiates Whites’ neural responses to out-group faces: A spatial meta-analytic approach

A persistent question in social neuroscience is whether the amygdala underlies racial prejudice. Despite decades of research, evidence for a stronger amygdala response to racial out-group versus in-group members has been mixed. Here, we consider a potential explanation for these conflicting results: that neural responses to racial out-group members vary systematically based on the level of racial prejudice of the surrounding community. To test this contextual sensitivity hypothesis, we conducted a spatial meta-analysis that included a comprehensive set of studies (n=22) examining neural responses to Black vs. White faces in primarily White participants. We evaluated whether community-level racial prejudice moderated neural activation to Black (vs. White) faces by aggregating individual explicit racial attitudes, obtained from Project Implicit, to the county in which each study was conducted. Multi-level kernel density analysis demonstrated that neural activation to Black (vs. White) faces was significantly higher in the right amygdala, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex in communities with higher (vs. lower) levels of racial prejudice. This same pattern of neural activation was not observed for income inequality or for the percentage of the population who was Black or college-educated, indicating specificity to community-level prejudice. Our findings highlight the potential utility of spatial meta-analyses for reconciling conflicting results in the social neuroscience literature by identifying features of the broader social context that may moderate neural responses to socially relevant stimuli.

Distinct Patterns of Brain Metabolism in Patients at Risk of Sudden Unexpected Death in Epilepsy

Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (18FDG-PET).Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal 18FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS.Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cerebellar nuclei; uptake was decreased in the left planum temporale. These patterns were distinct from the effect of FBTCS frequency, where increasing frequency was associated with decreased uptake in bilateral medial superior frontal gyri, extending into the left dorsal anterior cingulate cortex.Significance: Regions critical to cardiorespiratory and somatomotor regulation and to recovery from vital challenges show altered interictal metabolic activity in patients with frequent FBTCS considered to be at relatively high-risk of SUDEP, and shed light on the processes that may predispose patients to SUDEP.