RESUMO
BACKGROUND: Deficits in cognitive control are implicated in numerous neuropsychiatric disorders. However, relevant pharmacological treatments are limited, likely due to weak translational validity of applicable preclinical models used. Neural indices derived from electroencephalography (EEG) may prove useful in comparing and translating the effects of cognition-enhancing drugs between species. In the current study, we aimed to extend our previous cross-species results by examining if methylphenidate (MPH) modulates behavioral and neural indices of cognitive control in independent cohorts of humans and rats. METHODS: We measured continuous EEG data from healthy adults (n=25; 14 female) and Long Evans rats (n=22; 8 female) and compared both stimulus- and response-locked event-related potentials (ERPs) and spectral power measures across species, and their MPH-related moderation following treatment with vehicle (placebo) or one of two doses of MPH. RESULTS: Across both species, linear mixed effects modeling confirmed the expected Flanker interference effect on behavior (e.g., accuracy) and response-related ERPs. Unexpectedly, in contrast to past work, we did not observe any task-related effects on the spectral power of rodents. Moreover, MPH generally did not modulate cognitive control of either species, although some species-specific patterns offer insight for future research. CONCLUSIONS: Collectively, these findings in independent human and rodent subjects replicate some of our previously reported behavioral and neurophysiological patterns partly consistent with the notion that similar neural mechanisms may regulate cognitive control in both species. Nonetheless, these results showcase an approach to accelerate translation using a coordinated between-species platform to evaluate pro-cognitive treatments.
RESUMO
BACKGROUND: Neurocognitive factors including aberrant reward learning, blunted GABA (gamma-aminobutyric acid), and potentiated stress sensitivity have been linked to anhedonia, a hallmark depressive symptom, possibly in a sex-dependent manner. However, previous research has not investigated the putative associations among these factors or the extent to which they represent trait- or state-based vulnerabilities for depression. METHODS: Young adults with current major depressive disorder (MDD) (n = 44), remitted MDD (n = 42), and healthy control participants (HCs) (n = 44), stratified by sex assigned at birth, underwent magnetic resonance spectroscopy to assess macromolecular contaminated GABA (GABA+) and then a reward learning task before and after acute stress. We assessed changes in reward learning after stress and associations with GABA+. RESULTS: Results revealed blunted baseline reward learning in participants with remitted MDD versus participants with current MDD and HCs but, surprisingly, no differences between participants with current MDD and HCs. Reward learning was reduced following acute stress regardless of depressive history. GABA+ in the rostral anterior cingulate cortex, but not the dorsolateral prefrontal cortex, was associated with reduced baseline reward learning only in female participants. GABA+ did not predict stress-related changes in reward learning. CONCLUSIONS: To our knowledge, this is the first study to investigate associations among GABA, reward learning, and stress reactivity in current versus past depression. Hypothesized depression-related differences in reward learning did not emerge, precluding claims about state versus trait vulnerabilities. However, our finding that blunted GABA was associated with greater reward learning in female participants provides novel insights into sex-selective associations between the frontal GABAergic inhibitory system and reward processing.