Neural signal variability relates to maladaptive rumination in depression.

Rumination is a common feature of depression and predicts the onset and maintenance of depressive episodes. Maladaptive and adaptive subtypes of rumination contribute to distinct outcomes, with brooding worsening negative mood and reflection related to fewer depression symptoms in healthy populations. Neuroimaging studies have implicated several cortical midline and lateral prefrontal brain regions in rumination. Recent research indicates that blood oxygen level-dependent (BOLD) signal variability may be a novel predictor of cognitive flexibility. However, no prior studies have investigated whether brooding and reflection are associated with distinct patterns of BOLD signal variability in depression. We collected resting-state fMRI data for 79 women with different depression histories: no history, past history, and current depression. We examined differences in BOLD signal variability (BOLDSD) related to rumination subtypes for the following regions of interest previously implicated in rumination: amygdala, medial prefrontal, anterior cingulate, posterior cingulate, and dorsolateral prefrontal cortices (dlPFC). Rumination subtype was associated with BOLDSD in the dlPFC, with greater levels of brooding associated with lower BOLDSD in the dlPFC, even after controlling for depression severity. Depression history was related to BOLDSD in the dlPFC, with reduced BOLDSD in those with current depression versus no history of depression. These findings provide a novel demonstration of the neural circuitry associated with maladaptive rumination in depression and implicate decreased prefrontal neural signal variability in the pathophysiology of depression.

Comparing resting-state connectivity of working memory networks in U.S. Service members with mild traumatic brain injury and posttraumatic stress disorder.

Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are prevalent among military populations, and both have been associated with working memory (WM) impairments. Previous resting-state functional connectivity (rsFC) research conducted separately in PTSD and mTBI populations suggests that there may be similar and distinct abnormalities in WM-related networks. However, no studies have compared rsFC of WM brain regions in participants with mTBI versus PTSD. We used resting-state fMRI to investigate rsFC of WM networks in U.S. Service Members (n = 127; ages 18-59) with mTBI only (n = 46), PTSD only (n = 24), and an orthopedically injured (OI) control group (n = 57). We conducted voxelwise rsFC analyses with WM brain regions to test for differences in WM network connectivity in mTBI versus PTSD. Results revealed reduced rsFC between ventrolateral prefrontal cortex (vlPFC), lateral premotor cortex, and dorsolateral prefrontal cortex (dlPFC) WM regions and brain regions in the dorsal attention and somatomotor networks in both mTBI and PTSD groups versus controls. When compared to those with mTBI, individuals with PTSD had lower rsFC between both the lateral premotor WM seed region and middle occipital gyrus as well as between the dlPFC WM seed region and paracentral lobule. Interestingly, only vlPFC connectivity was significantly associated with WM performance across the samples. In conclusion, we found primarily overlapping patterns of reduced rsFC in WM brain regions in both mTBI and PTSD groups. Our finding of decreased vlPFC connectivity associated with WM is consistent with previous clinical and neuroimaging studies. Overall, these results provide support for shared neural substrates of WM in individuals with either mTBI or PTSD.

Resting-state neural signal variability in women with depressive disorders.

Aberrant activity and connectivity in default mode (DMN), frontoparietal (FPN), and salience (SN) network regions is well-documented in depression. Recent neuroimaging research suggests that altered variability in the blood oxygen level-dependent (BOLD) signal may disrupt normal network integration and be an important novel predictor of psychopathology. However, no studies have yet determined the relationship between resting-state BOLD signal variability and depressive disorders nor applied BOLD signal variability features to the classification of depression history using machine learning (ML). We collected resting-state fMRI data for 79 women with different depression histories: no history, past history, and current depressive disorder. We tested voxelwise differences in BOLD signal variability related to depression group and severity. We also investigated whether BOLD signal variability of DMN, FPN, and SN regions could predict depression history group using a supervised random forest ML model. Results indicated that individuals with any history of depression had significantly decreased BOLD signal variability in the left and right cerebellum and right parietal cortex (pFWE <0.05). Furthermore, greater depression severity was also associated with reduced BOLD signal variability in the cerebellum. A random forest model classified participant depression history with 74% accuracy, with the ventral anterior cingulate cortex of the DMN as the most important variable in the model. These findings provide novel support for resting-state BOLD signal variability as a marker of neural dysfunction in depression and implicate decreased neural signal variability in the pathophysiology of depression.

Influence of anhedonic symptom severity on reward circuit connectivity in PTSD.

Anhedonia, marked by deficits in reward processing, is a prominent symptom of several psychiatric conditions and has been shown to influence functional connectivity between reward-related regions. However, the unique influence of anhedonia severity on reward circuit connectivity in posttraumatic stress disorder (PTSD) remains unclear. To address this, we examined resting-state functional connectivity (rsFC) of the ventral striatum as a function of anhedonia for individuals with PTSD. Resting-state functional MRI scans and behavioral assessments were collected for 71 women diagnosed with PTSD. Seed-based voxelwise rsFC analyses for left and right nucleus accumbens (NAcc) seed regions of interest were performed. Voxelwise regression analyses were conducted to examine the relationship between anhedonia severity and rsFC of left and right NAcc. Results indicated that greater anhedonia severity was associated with reduced rsFC between the left NAcc and a cluster in the left caudate extending to the thalamus. This relationship between anhedonia and rsFC remained significant after controlling for PTSD symptom severity or depression severity. Our findings suggest that reward circuit dysfunction at rest is associated with anhedonia in PTSD. These results further contribute to our understanding of the neural correlates of anhedonia in psychiatric conditions.

Cortical midline structures associated with rumination in women with PTSD.

Elevated rumination, characterized by repetitive, negative self-focused cognition, is common in posttraumatic stress disorder (PTSD) and has been shown to predict the onset and maintenance of the disorder. Neuroimaging research has implicated cortical midline brain structures, including the rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), and isthmus cingulate (IsthCing), in rumination in healthy and depressed populations. While past research has revealed dysfunction in cortical midline regions in PTSD, no studies have yet investigated the structural and functional neural mechanisms underlying rumination in women with PTSD. In the current study, we used structural MRI and resting-state fMRI to examine relationships between rumination and brain volume, as well as resting-state functional connectivity (rsFC) of cortical midline structures in women with PTSD due to interpersonal trauma (N = 71). We performed multiple linear regression analyses to relate brain volume in rACC, PCC, and IsthCing regions to self-reported rumination, after controlling for age and total intracranial volume. We also conducted standard seed-based voxelwise rsFC analyses for significant regions identified in the structural analysis. We found a significant relationship between greater rumination and volume in the left IsthCing (p = .025). Results from the rsFC analyses revealed a significant relationship between greater rumination and diminished rsFC between the left IsthCing and left precuneus (pFWE < .05). These findings provide novel support for alterations in the neural substrates of ruminative thought in women with PTSD. More broadly, we discuss clinical implications for targeted interventions to reduce rumination through psychotherapy or non-invasive brain stimulation.