The effects of multi-day rTMS and cardiorespiratory fitness on working memory and local GABA concentration

Abstract

Working memory (WM) refers to the capacity to temporarily retain and manipulate finite amounts of information; a critical process in complex behaviours such as reasoning, comprehension, and learning. This cognitive function is supported by a parietal-prefrontal network and linked to the activity of key brain neurotransmitters, such as gamma-aminobutyric acid (GABA). Impairments in WM are seen in a range of psychiatric and neurological disorders, and there are currently no effective methods of remediating WM deficits. In this study, we analysed secondary outcome measures from a trial investigating the effects of multi-day rTMS on cognition. Participants received four days of 20 Hz rTMS to an individualised region of left parietal cortex in one week, and an individualised region of pre-supplementary motor area (pre-SMA) in a separate week. We assessed changes to WM function before and after each week of stimulation (N = 39), and changes to GABA concentration before and after stimulation in week one using MR spectroscopy (N = 18 per stimulation condition). We hypothesised that multi-day parietal rTMS would enhance WM and reduce GABA concentration, but this was not observed. Instead, we report some evidence of improved WM function and increased GABA concentration following pre-SMA rTMS, although this effect was variable across individuals. Additionally, we found that higher cardiorespiratory fitness was associated with greater WM improvement following pre-SMA stimulation. While there are a number of factors known to influence the response to rTMS, increasing cardiorespiratory fitness may provide a novel approach to enhance cognitive outcomes. Given the clinical utility of both exercise and rTMS, future studies are required to determine whether additive effects may be achieved when applied in tandem.

No evidence for changes in GABA concentration, functional connectivity, or working memory following continuous theta burst stimulation over dorsolateral prefrontal cortex

“…Considered in the context of the present study, these outcomes indicate that the effects of cTBS on GABA concentration may be regionally specific, with considerable variability observed across the distinct cortical regions targeted in past studies. This perspective is also supported by a recent study which reported differential effects of multi-day rTMS on GABA concentration between parietal cortex and pre-supplementary motor area targets (Hendrikse et al, 2020b). Overall, our findings challenge the consistency of cTBS-induced effects on GABA outside of the motor system.…”