Over the last decade, there has been an increasing number of studies combining transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS). MRS provides a manner to non-invasively investigate molecular concentrations in the living brain and thus identify metabolites involved in physiological and pathological processes. Particularly the MRS-detectable metabolites glutamate, the major excitatory neurotransmitter, and gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter, are of interest when combining TMS and MRS. TMS is a non-invasive brain stimulation technique that can be applied either as a neuromodulation or neurostimulation tool, specifically targeting glutamatergic and GABAergic mechanisms. The combination of TMS and MRS can be used to evaluate alterations in brain metabolite levels following an interventional TMS protocol such as repetitive TMS (rTMS) or paired associative stimulation (PAS). MRS can also be combined with a variety of non-interventional TMS protocols to identify the interplay between brain metabolite levels and measures of excitability or receptor-mediated inhibition and facilitation. In this review, we provide an overview of studies performed in healthy and patient populations combining MRS and TMS, both as a measurement tool and as an intervention. TMS and MRS may reveal complementary and comprehensive information on glutamatergic and GABAergic neurotransmission. Potentially, connectivity changes and dedicated network interactions can be probed using the combined TMS-MRS approach. Considering the ongoing technical developments in both fields, combined studies hold future promise for investigations of brain network interactions and neurotransmission.

Establishing the associations between magnetic resonance spectroscopy (MRS)-assessed gamma-aminobutyric acid (GABA) levels and transcranial magnetic stimulation (TMS)-derived 'task-related' modulations in GABA_A receptor-mediated inhibition and how these associations change with advancing age is a topic of interest in the field of human neuroscience. In this study, we identified the relationship between GABA levels and task-related modulations in GABA_A receptor-mediated inhibition in the dominant (left) and non-dominant (right) sensorimotor (SM) cortices. GABA levels were measured using edited MRS and task-related GABA_A receptor-mediated inhibition was measured using a short-interval intracortical inhibition (SICI) TMS protocol during the preparation and premotor period of a choice reaction time (CRT) task in 25 young (aged 18-33 years) and 25 older (aged 60-74 years) adults. Our results demonstrated that GABA levels in both SM voxels were lower in older adults as compared to younger adults; and higher SM GABA levels in the dominant as compared to the non-dominant SM voxel pointed to a lateralization effect, irrespective of age group. Furthermore, older adults showed decreased GABA_A receptor-mediated inhibition in the preparation phase of the CRT task within the dominant primary motor cortex (M1), as compared to young adults. Finally, results from an exploratory correlation analysis pointed towards positive relationships between MRS-assessed GABA levels and TMS-derived task-related SICI measures. However, after correction for multiple comparisons none of the correlations remained significant.

The Compensation Related Utilization of Neural Circuits Hypothesis (CRUNCH) proposes a framework for understanding task-related brain activity changes as a function of healthy aging and task complexity. Specifically, it affords the following predictions: (i) all adult age groups display more brain activation with increases in task complexity, (ii) older adults show more brain activation compared with younger adults at low task complexity levels, and (iii) disproportionately increase brain activation with increased task complexity, but (iv) show smaller (or no) increases in brain activation at the highest complexity levels. To test these hypotheses, performance on a bimanual tracking task at 4 complexity levels and associated brain activation were assessed in 3 age groups (20–40, 40–60, and 60–80 years, n = 99). All age groups showed decreased tracking accuracy and increased brain activation with increased task complexity, with larger performance decrements and activation increases in the older age groups. Older adults exhibited increased brain activation at a lower complexity level, but not the predicted failure to further increase brain activity at the highest complexity level. We conclude that older adults show more brain activation than younger adults and preserve the capacity to deploy increased neural resources as a function of task demand.

In a multisite study of brain MR spectroscopy performed at 26 sites, interindividual differences were found as the main contributor to variability, demonstrating that appropriately analyzed MR spec... Background The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better und...