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 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 treatments. 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 parietal rTMS would enhance WM and alter GABA concentration at the site of stimulation, but this was not observed. Instead, we report some evidence of improved WM function following the first week of pre-SMA rTMS stimulation, and a generalised increase in GABA concentration across both parietal and pre-SMA voxels following pre-SMA rTMS. Additionally, we found that higher cardiorespiratory fitness was associated with greater WM improvement following pre-SMA stimulation. This study does not support the use of parietal multi-day rTMS for the enhancement of working memory. In contrast, the results suggest that increasing cardiorespiratory fitness may provide a novel approach to enhance the effects of pre-SMA rTMS on cognition.