From cortical excitation to cognition: the case of mathematics

Excitatory and inhibitory neurons have important roles in learning and skill acquisition in the brain. Glutamate and gamma-aminobutyric acid (GABA) are the brain’s major excitatory and inhibitory neurotransmitters in the brain, respectively. Until recently, the link between such neurochemicals and higher-order cognition could not be directly observed in the living human brain. With the advent of magnetic resonance spectroscopy (MRS), an MRI-based method to measure regional concentrations of a whole range of neurochemicals, it has become possible to link behavioral measures with glutamate and GABA. Here I investigated whether glutamate and GABA in a fronto-parietal mathematical brain network were associated with mathematical abilities in children, adults, and expert calculators, including an individual with prodigious calculation abilities. I found that the relationship differs as a function of the brain area (e.g. the hemisphere), age, gender, and ability.
Furthermore, regional levels of glutamate and GABA can be artificially modulated by transcranial electrical stimulation (tES), a non-invasive method to affect cortical excitability and increase the potential for plastic changes in the brain. As a possible neuro-enhancement tool, I investigated whether tES to frontal and parietal cortices during mathematical task execution can reliably improve complex arithmetic training effects, and whether such effects were accompanied by changes in regional concentrations in glutamate and GABA. In two double-blind, sham-controlled studies involving a five-day training paradigm, I could not replicate the exact results from a previous study. The previous study found beneficial effects of stimulation to bilateral dorsolateral prefrontal (DLPFCs), but not posterior parietal cortices (PPCs) on learning and transfer to novel task material using the same training paradigm. In a counter-balanced, sham-controlled, within-subjects design, I found that certain sub-tests improved when stimulating DLPFCs, while others improved when stimulating PPCs. In a subsequent between-subjects study, I found impairments in the group that received stimulation to PPCs. Moreover, I could not find changes in glutamate and GABA in the groups that received real, compared to sham stimulation. In a different paradigm, I also investigated whether an individual with exceptional calculation abilities, the 'lightning calculator' G.M., could benefit from tES. In a sham-controlled within-subject single-case study across six testing sessions on two separate days, I found no improvement of G.M.'s calculation abilities. In order to test whether other expert calculators would show the same lack of an effect, I tested six postgraduate students in mathematics fields in an adapted but similar tES paradigm. These experts showed impairment in calculation performance under tES compared to sham.
The failure to replicate previous results and the impairments observed in two different samples suggest that the effects of tES on cognition are currently relatively unpredictable. Therefore, positive outcomes of individual tES studies should be interpreted with caution. MRS can be a useful tool to investigate brain-behavior relationships at a neuro-biological level and ideally, further research will demonstrate whether glutamate and GABA can be used as neural markers for poor cognitive abilities. Ideally, MRS will aid the diagnosis of cognitive difficulties at the neurochemical level, such that neuro-intervention can be targeted to enhance cognitive plasticity accordingly.

Keywords: Arithmetic
Brain imaging
GABA
Magnetic resonance imaging (MRI)
Cognition
Magnetic resonance spectroscopy (MRS)
Glutamate
Brain stimulation
Advisor: Kadosh, R
Dowker, A