Impairment of Neuroplasticity in the Dorsolateral Prefrontal Cortex by Alcohol

Abstract

Previous studies have demonstrated that alcohol consumption impairs neuroplasticity in the motor cortex. However, it is unknown whether alcohol produces a similar impairment of neuroplasticity in the dorsolateral prefrontal cortex (DLPFC), a brain region that plays an important role in cognitive functioning. The aim of the current study was to evaluate the effect of alcohol intoxication on neuroplasticity in the DLPFC. Paired associative stimulation (PAS) combined with electroencephalography (EEG) was used for the induction and measurement of associative LTP-like neuroplasticity in the DLPFC. Fifteen healthy subjects were administered PAS to the DLPFC following consumption of an alcohol (1.5 g/l of body water) or placebo beverage in a within-subject cross-over design. PAS induced neuroplasticity was indexed up to 60 minutes following PAS. Additionally, the effect of alcohol on PAS-induced potentiation of theta-gamma coupling (an index associated with learning and memory) was examined prior to and following PAS. Alcohol consumption resulted in a significant impairment of mean (t = 2.456, df = 13, p = 0.029) and maximum potentiation (t = −2.945, df = 13, p = 0.011) compared to the placebo beverage in the DLPFC and globally. Alcohol also suppressed the potentiation of theta-gamma coupling by PAS. Findings from the present study provide a potential neurophysiological mechanism for impairment of cognitive functioning by alcohol.

Impaired neuroplasticity in the prefrontal cortex in depression indexed through paired associative stimulation

“…PAS‐induced potentiation was evaluated by overall TEP power changes before and after PAS paradigm. As the timing point of maximum potentiation after PAS (post max TEP power) varies among participants, we selected the maximum time point of TEP powers for each participant in the offline analysis, following previously published methods (Loheswaran et al., ; Rajji et al., ).…”

“…These findings may represent a neurophysiological endophenotype, reflecting the neuroplasticity of DLPFC in healthy participants. Thus, PAS administered to the DLPFC (DLPFC‐PAS) may be a useful tool to evaluate functional neuroplasticity in the DLPFC in human participants (Loheswaran et al., ; Rajji et al., ).…”

Pharmacological Modulation of Long-Term Potentiation-Like Activity in the Dorsolateral Prefrontal Cortex

“…The RMT was then adjusted to a suprathreshold intensity to produce a mean peak-to-peak MEP amplitude of ~1 mV over 20 trials, which corresponded to approximately 120% of the RMT (Rajji et al, 2013 ). This intensity referred to as SI 1 mV was then used to deliver 100 single TMS pulses at 0.1 Hz to the scalp over the left DLPFC during pre-PAS while EEG was being recorded to determine baseline CEA then again for post-PAS 0, 17, 34 and 60 min to assess change in CEA (Figure 1 ; Rajji et al, 2013 ; Loheswaran et al, 2017 ). The left DLPFC determined by the participant’s MRI image was marked on the EEG cap with a marker to ensure identical placement throughout the experiment.…”

“…All electrodes (Ag/AgCl ring electrodes) impedance were ≤5 kΩ and referenced to an electrode positioned posterior to Cz electrode. In addition, EEG signals were recorded using DC and a low-pass anti-aliasing filter, of 200 Hz, at 20 kHz sampling rate, which has been shown to avoid saturation of amplifiers and minimize TMS-related artifact (Rajji et al, 2013 ; Loheswaran et al, 2017 ).…”

“…PAS simulates a spike-timing dependent plasticity protocol by combining single-pulse transcranial magnetic stimulation (TMS) to a cortical area with contralateral peripheral nerve stimulation (PNS) such as the two stimulations arrive contemporaneously at the targeted cortical area and in turn strengthen the cortical output in response to single-pulse TMS. Using well-established methods of combining TMS with electroencephalography (EEG), our group has shown that PAS results in LTP-like activity in the human DLPFC as captured by EEG as the potentiation of TMS-induced cortical evoked activity (CEA; Rajji et al, 2013 ; Kumar et al, 2017 ; Loheswaran et al, 2017 ). This PAS-induced LTP-like activity only simulates cellular LTP and will be referred to hereafter as PAS-induced LTP merely for simplicity.…”