The Virtual Brain links transcranial magnetic stimulation evoked potentials and inhibitory neurotransmitter changes in major depressive disorder
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Background
Transcranial magnetic stimulation evoked potentials (TEPs) show promise as a biomarker in major depressive disorder (MDD), but the origin of the increased TEP amplitude in these patients remains unclear. Gamma aminobutyric acid (GABA) may be involved, as TEP peak amplitude is known to increase with GABAergic activity, but paradoxically MDD patients exhibit reduced GABA levels. We employed a computational modeling approach to investigate this contradiction.
Methods
Whole-brain simulations in ‘The Virtual Brain’ ( thevirtualbrain.org ), employing the Jansen and Rit neural mass model, were optimized to simulate TEPs of healthy individuals ( N subs =20, 14 females, 24.5±4.9 years). To mimic MDD, a GABAergic deficit was introduced to the simulations by altering one of two selected inhibitory parameters, the inhibitory synaptic time constant b or the number of inhibitory synapses C 4 . The TEP amplitude was quantified and compared for all simulations.
Results
Both parameters, the inhibitory synaptic time constant (r=-0.6, p<0.001) and the number of inhibitory synapses (r=-0.79, p<0.001), showed a significant negative linear correlation to the TEP amplitude. Thus, under local parameter changes, we were able to alter the TEP amplitude towards pathological levels, i.e. creating an MDD-like increase of the global mean field amplitude in line with empirical results.
Conclusions
Our model suggests specific GABAergic deficits as the cause of increased TEP amplitude in MDD patients, which may serve as therapeutic targets. This work highlights the potential of whole-brain simulations in the investigation of neuropsychiatric diseases.
