Amphetamines modulate prefrontal γ oscillations during attention processing

Abstract

Amphetamine-based medications robustly suppress symptoms of attention-deficit/hyperactivity disorder (ADHD), but their exact mechanisms remain poorly understood. Recent hemodynamic imaging studies have suggested that amphetamines may modulate the prefrontal and anterior cingulate brain regions, although few studies have been published and the results have not been entirely consistent. Meanwhile, several electrophysiological studies have shown that abnormal fast oscillations (in the γ range) may be closely linked to inattention and other cardinal symptoms of ADHD. In this study, we utilized magnetoencephalography to examine how amphetamines modulate high-frequency brain activity in adults with ADHD. Participants performed an auditory attention task, which required sustained attention in one block and passive listening in a separate block. Participants completed the task twice in the on-medication and off-medication states. All data were analyzed using beamforming techniques to resolve cortical regions showing event-related synchronizations and desynchronizations. Our primary findings indicated that oral administration of amphetamine decreased γ-band event-related desynchronization activity significantly in the medial prefrontal area and decreased event-related synchronization in bilateral superior parietal areas, left inferior parietal, and the left inferior frontal gyrus. These results suggest that psychostimulants strongly modulate γ activity in frontal and parietal cortical areas, which are known to be central to the brain's core attentional networks.

Phenotypic profiling of mGlu7 knockout mice reveals new implications for neurodevelopmental disorders

“…Oscillations in the gamma range are regulated by a balance in glutamate and GABA function, 54,55 evolve throughout development 56 and are thought to contribute to cognitive functions. 57 Amphetamines have been shown to strongly modulate gamma activity in attention-associated regions in adults with ADHD, 58 and, interestingly, there have been reports that polymorphisms in GRM7 correlate with response to methylphenidate in ADHD patients. 30,31 We also observed a blunted effect of amphetamine on locomotor activity, which is consistent with the reported decrease in amphetamine-induced hyperlocomotion by the mGlu 7 NAM ADX71743.…”

Neuroimaging with magnetoencephalography: A dynamic view of brain pathophysiology

“…Related findings have emerged from MEG studies of attention in patients with ADHD. For example, one study of auditory attention found that stimulants modulate gamma activity in frontal and parietal areas, 48 whereas another found hyper-connectivity between prefrontal and auditory cortices in un-medicated adults with ADHD, which was significantly decreased following stimulant administration. 49 One other study focused on alpha differences during visual attention and found that decreased alpha lateralization correlated with impaired performance in patients with ADHD.…”

Trans-Synaptic Regulation of Metabotropic Glutamate Receptors by Elfn Proteins in Health and Disease

“…Furthermore, mGluR7-KO mice exhibit an attenuated response to amphetamine, with increased gamma oscillations (30-100 Hz) and lowered delta oscillations (1-3 Hz) in electroencephalography (Fisher et al, 2020). Amphetamines have been shown to strongly modulate gamma activity in attention-associated regions in adults with ADHD (Franzen and Wilson, 2012). As a possible link between Elfn1-mGluR7 trans-interaction and EEG wave control, SST-and PV-INs differentially correlate with beta (14-29 Hz) and gamma (30-100 Hz) oscillations, and they are thought to play different as well as cooperative roles in orchestrating specific cortical oscillations (Chen et al, 2017).…”