Smolker, H. R. | Search bioRxiv

bioRxiv2025

Multivariate Neural Markers of Individual Differences in Thought Control Difficulties

Difficulties in controlling thought, including pathological rumination, worry, and intrusive thoughts, occur in a range of mental health disorders. Here we identify specific patterns of brain activity distributed within and across canonical brain networks that are associated with self-reported difficulties in controlling ones thoughts. These activity patterns were derived using multivariate pattern analysis on fMRI data recorded while participants engaged in one of four operations on an item in working memory: maintaining it, replacing it with another, specifically suppressing it, or clearing the mind of all thought. Individuals who reported greater difficulties exhibited brain activation patterns that were more variable and less differentiated across the four operations in frontoparietal and default mode networks, and showed less distinct patterns of connectivity within the default mode network. These activity profiles were absent during rest but serve as promising task-based neural markers, explaining over 30% of the variance in thought control difficulties.

neuroscience↗

bioRxiv2018

Whole-Cortex Mapping of Common Genetic Influences on Depression and Social Deficits

BackgroundSocial processes are associated with depression, particularly understanding and responding to others, deficits in which can manifest as callousness/unemotionality (CU). Thus, CU may reflect some of the genetic risk to depression. Further, this vulnerability likely reflects the neurological substrates of depression, presenting biomarkers to capture genetic vulnerability of depression severity. However, heritability varies within brain regions, so a high-resolution genetic perspective is needed.\n\nMethod In a sample of 258 same-sex twin pairs from the Colorado Longitudinal Twin Study (LTS), we developed a toolbox that maps genetic and environmental associations between brain and behavior at high resolution. We used this toolbox to estimate brain areas that are genetically associated with both depressive symptoms and CU. We then overlapped the two maps to generate coordinates that allow for tests of downstream effects of genes influencing our clusters.\n\nResults Genetic variance influencing cortical thickness in the right dorsal lateral prefrontal cortex (DLFPC) sulci and gyri, ventral posterior cingulate cortex (PCC), pre-somatic motor cortex (PreSMA), medial precuneus, left occipital-temporal junction (OTJ), parietal-temporal junction (PTJ), ventral somatosensory cortex (vSMA), and medial and lateral precuneus were genetically associated with both depression and CU. Split-half replication found support for both DLPFC clusters. Meta-analytic term search identified \"theory of mind\", \"inhibit\", and \"pain\" as likely functions. Gene and transcript mapping/enrichment analyses implicated calcium channels.\n\nConclusionsCU reflects genetic vulnerability to depression that likely involves executive and social functioning in a distributed process across the cortex. This approach works to unify neuroimaging, neuroinformatics, and genetics to discover pathways to psychiatric vulnerability.

neuroscience↗