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GABAergic modulation of visual gamma and alpha oscillations and its consequences for working memory performance

Elsevier Inc.
DOI: 10.1016/j.cub.2014.10.017
  • Biology
  • Computer Science
  • Pharmacology


Summary Background Impressive in vitro research in rodents and computational modeling have uncovered the core mechanisms responsible for generating neuronal oscillations. In particular GABAergic interneurons play a crucial role for synchronizing neural populations. Do these mechanistic principles apply to human oscillations associated with function? To address this we recorded ongoing brain activity using magnetoencephalography (MEG) in healthy human subjects participating in a double blind pharmacological study receiving placebo, 0.5 mg and 1.5 mg of lorazepam (LZP; a benzodiazepine upregulating GABAergic conductance). Participants performed a demanding visuo-spatial working memory (WM) task. Results We found that occipital gamma power associated with WM recognition increased with LZP dosage. Importantly, the frequency of the gamma activity decreased with dosage as predicted by models derived from the rat hippocampus. A regionally specific gamma increase correlated with the drug related performance decrease. Despite the system-wide pharmacological intervention, gamma power drug-modulations were specific to visual cortex: sensorimotor gamma power and frequency during button-presses remained unaffected. In contrast, occipital alpha power modulations during the delay interval decreased parametrically with drug dosage, predicting performance impairment. Consistent with alpha oscillations reflecting functional inhibition, LZP affected alpha power strongly in early visual regions not required for the task demonstrating a regional specific occipital impairment. Conclusion GABAergic interneurons are strongly implicated in the generation of gamma and alpha oscillations in human occipital cortex where drug-induced power modulations predicted WM performance. Our findings bring us an important step closer to linking neuronal dynamics to behavior by embracing established animal models.

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