Causal investigations of rhythmic electrophysiological mechanisms underlying healthy cognition and disease using transcranial alternating current stimulation
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Abstract
Learning from favorable feedback is fundamental for adaptive behavior. This learning is hypothesized to be facilitated by high beta-low gamma frequency (20-35 Hz) rhythmic activity, potentially originating from the orbitofrontal cortex (OFC), but no causal evidence currently exists. In Study 1, I tested this hypothesis using electroencephalography (EEG)-guided high-definition transcranial alternating current stimulation (HD-tACS) of OFC beta-gamma rhythms. In a randomized, double-blind, sham-controlled, between-subjects experiment with 60 healthy young adults (mean age 25.8, standard deviation [SD] 5.8 years), I showed that modulation of OFC beta-gamma rhythms selectively modulates reward-guided behavior without affecting punishment-guided behavior, supporting the hypothesis. Obsessive-compulsive (OC) behaviors involve abnormalities in reward processing and OFC activity. If OFC beta-gamma rhythms facilitate reward processing, then their modulation may be a strategy for improving OC symptoms. In Study 2, I investigated this hypothesis in 64 young adults (mean age 23.9, SD 3.8 years) using a randomized, double-blind, sham-controlled experiment. These participants did not have any neuropsychiatric diagnoses but exhibited a wide range of subclinical OC tendencies, as measured using the Obsessive-Compulsive Inventory – Revised (OCI-R; baseline scores: mean 20, SD 10.3; ≥16 indicates moderate OC symptoms). I found that repetitive entrainment of OFC beta-gamma rhythms in 30-minute sessions over five consecutive days rapidly reduced OCI-R scores. Improvements sustained for three months and were stronger for individuals with more severe symptoms at baseline. These findings set the foundation for novel rhythmic neurophysiological theories and therapeutics for OC behaviors. As tACS is an emerging technology, its overall efficacy remains a matter of debate. In Study 3, I examined whether tACS reliably modulates cognitive function by performing a statistical meta-analysis of 102 peer-reviewed studies. I found evidence for improvements in several cognitive domains (such as attention, working memory and long-term memory), with improvements also evident in subgroups of older adults (age > 60 years) and clinical populations. Using meta-regression analyses, I showed the importance of using current flow models and parameters such as modulation intensity and the timing of assessment of cognitive function. These findings suggest the promise of this tool for both causal investigational and translational purposes, and identify avenues for future improvement.
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2024