Structurally informed models of directed brain connectivity
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Latent circuit inference from heterogeneous neural responses during cognitive tasks
Higher cortical areas carry a wide range of sensory, cognitive and motor signals mixed in heterogeneous responses of single neurons tuned to multiple task variables. Dimensionality reduction methods that rely on correlations between neural activity and task variables leave unknown how heterogeneous responses arise from connectivity to drive behavior. We develop the latent circuit model, a dimensionality reduction approach in which task variables interact via low-dimensional recurrent connectivity to produce behavioral output. We apply the latent circuit inference to recurrent neural networks trained to perform a context-dependent decision-making task and find a suppression mechanism in which contextual representations inhibit irrelevant sensory responses. We validate this mechanism by confirming the behavioral effects of patterned connectivity perturbations predicted by the latent circuit model. We find similar suppression of irrelevant sensory responses in the prefrontal cortex of monkeys performing the same task. We show that incorporating causal interactions among task variables is critical for identifying behaviorally relevant computations from neural response data.
Dopaminergic modulation and dosage effects on brain state dynamics and working memory component processes in Parkinson’s disease
Parkinson’s disease (PD) is primarily diagnosed through its characteristic motor deficits, yet it also encompasses progressive cognitive impairments that profoundly affect quality of life. While dopaminergic medications are routinely prescribed to manage motor symptoms in PD, their influence extends to cognitive functions as well. Here we investigate how dopaminergic medication influences aberrant brain circuit dynamics associated with encoding, maintenance and retrieval working memory (WM) task-phases processes. PD participants, both on and off dopaminergic medication, and healthy controls, performed a Sternberg WM task during fMRI scanning. We employ a Bayesian state-space computational model to delineate brain state dynamics related to different task phases. Importantly, a within-subject design allows us to examine individual differences in the effects of dopaminergic medication on brain circuit dynamics and task performance. We find that dopaminergic medication alters connectivity within prefrontal-basal ganglia-thalamic circuits, with changes correlating with enhanced task performance. Dopaminergic medication also restores engagement of task-phase-specific brain states, enhancing task performance. Critically, we identify an “inverted-U-shaped” relationship between medication dosage, brain state dynamics, and task performance. Our study provides valuable insights into the dynamic neural mechanisms underlying individual differences in dopamine treatment response in PD, paving the way for more personalized therapeutic strategies.
Simultaneous tACS-fMRI reveals state- and frequency-specific modulation of hippocampal-cortical functional connectivity
Non-invasive indirect hippocampal-targeted stimulation is of broad scientific and clinical interest. Transcranial alternating current stimulation (tACS) is appealing because it allows oscillatory stimulation to study hippocampal theta (3–8 Hz) activity. We found that tACS administered during functional magnetic resonance imaging yielded a frequency-, mental state- and topologically-specific effect of theta stimulation (but not other frequencies) enhancing right (but not left) hippocampal-cortical connectivity during resting blocks but not during task blocks. Control analyses showed that this effect was not due to possible stimulation-induced changes in signal quality or head movement. Our findings are promising for targeted network modulations of deep brain structures for research and clinical intervention.
Prediction of alcohol intake patterns with olfactory and gustatory brain connectivity networks
Craving in alcohol drinkers is often triggered by chemosensory cues, such as taste and smell, which are linked to brain network connectivity. This study aimed to investigate whether these brain connectivity patterns could predict alcohol intake in young adults. Resting-state fMRI data were obtained from the Human Connectome Project (HCP) Young Adult cohort, comprising 1003 participants. Functional connectomes generated from 100 independent components were analyzed, identifying significant connections correlated with taste and odor scores after applying a false discovery rate (FDR) correction using the Benjamini-Hochberg (BH) method. These significant connections were then utilized as predictors in general linear models for various alcohol intake metrics. The models were validated in an independent sample to assess their accuracy. The training sample (n = 702) and the validation sample (n = 117) showed no significant demographic differences. Out of 742 possible connections, 41 related to odor and 25 related to taste passed the significance threshold (P < 0.05) after FDR-BH correction. Notable predictors included visual-visual connectivity (node32-node13: β = 0.028, P = 0.02) for wine consumption and connectivity between the ventral attention network (VAN) and the frontal parietal/caudate nucleus (FP/CN) (node27-node9: β = −0.31, P = 0.04) for total alcohol intake in the past-week and maximum number of drinks per day in the past-year. The predictive models demonstrated strong accuracy, with root mean square error (RMSE) values of 5.15 for odor-related models and 5.14 for taste-related models. The F1 scores were 0.74 for the odor model and 0.71 for the taste model, indicating reliable performance. These findings suggest that specific patterns of brain connectivity associated with taste and olfactory perception may serve as predictors of alcohol consumption behaviors in young adults. Our study highlight the need for longitudinal research to evaluate the potential of taste- and smell-related brain connectivity patterns for early screening and targeted interventions, as well as their role in personalized treatment strategies for individuals at risk of AUD.
Frontostriatal regulation of brain circuits contributes to flexible decision making
Deficits in behavioral or cognitive flexibility that are linked to altered activity in both cortical and subcortical brain regions, are often observed across multiple neuropsychiatric disorders. The medial prefrontal cortex (mPFC)-nucleus accumbens (NAc) pathway in rats plays a critical role in flexible control of behavior. However, the modulation of this pathway on activity and functional connectivity with the rest of the brain remains unclear. In this study, we first confirmed the role of the mPFC-NAc pathway in behavioral flexibility using a set-shifting task in rats and then evaluated the causal effects of mPFC-NAc activation induced by chemogenetic stimulation of the terminal axons of the NAc with DREADD expression on whole-brain activity and functional connectivity measured by functional MRI. mPFC-NAc activation improved performance on the set-shifting task by reducing perseverative errors. Additionally, stimulation of this pathway increased activity in a set of brain regions within the basal ganglia-thalamus-cortical loop network including NAc, thalamus, hypothalamus and various connected cortical regions, while also decreased functional connectivity strength of NAc-mPFC, NAc-secondary motor cortex (M2), and various cortical circuits. Moreover, performance on the set-shifting task was related to the functional connectivity strength of the above frontostriatal and cortical circuits. These findings provide insights into the link between specific frontostriatal circuits on decision making flexibility, which may inform potential future interventions for behavioral flexibility deficits.
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