Functional Involvement of Human Periaqueductal Gray and Other Midbrain Nuclei in Cognitive Control.

Recent theoretical advances have motivated the hypothesis that the periaqueductal gray (PAG) participates in behaviors that involve changes in the autonomic control of visceromotor activity, including during cognitively demanding tasks. We used ultra-high-field (7 tesla) fMRI to measure human brain activity at 1.1 mm resolution while participants completed a working memory task. Consistent with prior work, participants were less accurate and responded more slowly with increasing memory load-signs of increasing task difficulty. Whole-brain fMRI analysis revealed increased activity in multiple cortical areas with increasing working memory load, including frontal and parietal cortex, dorsal cingulate, supplementary motor area, and anterior insula. Several dopamine-rich midbrain nuclei, such as the substantia nigra and ventral tegmental area, also exhibited load-dependent increases in activation. To investigate PAG involvement during cognitive engagement, we developed an automated method for segmenting and spatially normalizing the PAG. Analyses using cross-validated linear support vector machines showed that the PAG discriminated high versus low working memory load conditions with 95% accuracy in individual subjects based on activity increases in lateral and ventrolateral PAG. Effect sizes in the PAG were comparable in magnitude to those in many of the cortical areas. These findings suggest that cognitive control is not only associated with cortical activity in the frontal and parietal lobes, but also with increased activity in the subcortical PAG and other midbrain regions involved in the regulation of autonomic nervous system function.SIGNIFICANCE STATEMENT Functional neuroimaging in humans has shown that cognitive control engages multiple corticostriatal networks and brainstem nuclei, but theoretical advances suggest that the periaqueductal gray (PAG) should also be engaged during cognitively demanding tasks. Recent advances in ultra-high-field fMRI provided an opportunity to obtain the first evidence that increased activation of intermediate and rostral portions of lateral and ventrolateral PAG columns in humans is modulated by cognitive load. These findings suggest that cognitive control is not solely mediated by activity in the cortex, but that midbrain structures important for autonomic regulation also play a crucial role in higher-order cognition.

Cortical and subcortical mapping of the allostatic-interoceptive system in the human brain: replication and extension with 7 Tesla fMRI.

The brain continuously anticipates the energetic needs of the body and prepares to meet those needs before they arise, a process called allostasis. In support of allostasis, the brain continually models the internal state of the body, a process called interoception. Using published tract-tracing studies in non-human animals as a guide, we previously identified a large-scale system supporting allostasis and interoception in the human brain with functional magnetic resonance imaging (fMRI) at 3 Tesla. In the present study, we replicated and extended this system in humans using 7 Tesla fMRI (N = 91), improving the precision of subgenual and pregenual anterior cingulate topography as well as brainstem nuclei mapping. We verified over 90% of the anatomical connections in the hypothesized allostatic-interoceptive system observed in non-human animal research. We also identified functional connectivity hubs verified in tract-tracing studies but not previously detected using 3 Tesla fMRI. Finally, we demonstrated that individuals with stronger fMRI connectivity between system hubs self-reported greater interoceptive awareness, building on construct validity evidence from our earlier paper. Taken together, these results strengthen evidence for the existence of a whole-brain system supporting interoception in the service of allostasis and we consider the implications for mental and physical health.

The N400 indexes acquisition of novel emotion concepts via conceptual combination.

The ability to learn new emotion concepts is adaptive and socially valuable as it communicates culturally held understandings about values, goals, and experiences. Yet, little work has examined the underlying mechanisms that allow for new emotion concepts and words to be integrated into the conceptual system. One such mechanism may be conceptual combination, or the ability to form novel concepts by dynamically combining previously acquired conceptual knowledge. In this study, we used event-related potentials (ERPs) to investigate the electrophysiological correlates of novel emotion concept acquisition via conceptual combination. Participants were briefly trained on 30 novel emotion combinations, each consisting of two English emotion words (the components; e.g., "sadness + fatigue") and a pseudoword (the target; e.g., "despip"). Participants then completed a semantic congruency task while ERPs were recorded. On each trial, two components were presented serially, followed by a target; participants judged whether the target was a valid combination of the preceding components. Targets could be correct or incorrect trained pseudowords, or new untrained pseudowords. Furthermore, components could be presented in reversed order (e.g., "fatigue" then "sadness") or as synonyms (e.g., "exhaustion" for "fatigue"). Consistent with our main hypotheses, we found a main effect of target, such that the correct combinations showed reduced N400 amplitudes when compared to both incorrect and untrained pseudowords. Critically, this effect held regardless of how the preceding components were presented, suggesting deeper semantic learning. These results extend prior findings on conceptual combination and novel word learning, and are congruent with predictive processing accounts of brain function.