Mohd Zulkifly, Mohd Faizal

Non-invasive brain stimulation (NIBS) dose-dependently influences ongoing brain activity either by electrical stimulation via electrodes attached to the scalp or by magnetic stimulation via coils. The latter then induces electric currents in the brain. The current state of knowledge suggests that a shift in membrane potential and changes in the neuronal firing rates underlie neuroplastic changes induced by NIBS. Neuroplastic changes lead to structural and functional reorganization that underlies amongst others learning and memory, due to the strengthening or weakening of the synaptic transmission. NIBS methods avoid the risks of invasive implantation associated with deep brain stimulation (DBS). However, when compared with DBS, long-lasting effects (i.e., aftereffects) induced by NIBS are necessary for therapeutic applications. Here response variability and the inconsistent reproducibility of the induced aftereffects remain challenges in the field. Efforts are underway to improve the efficacy of NIBS by optimizing the technical parameters, and others by exploring the intra- and inter-individual factors. In the present thesis, we investigated further confounding factors in plasticity studies at the sensorimotor cortex specifically focusing on modifiable factors. We used both transcranial electrical and magnetic stimulation methods to induce neuroplasticity in healthy human brains. As a readout, we measured the aftereffects using motor evoked potentials (MEPs).
The first experiment (chapter 2) explored the effects of caffeine on the plasticity aftereffects of 140 Hz transcranial alternating current stimulation (tACS) over the motor cortex. We recruited fourteen subjects who do not consume caffeine. Our results showed that the facilitatory aftereffects of tACS were reversed into inhibition after espresso with caffeine and no changes in the plasticity aftereffects after decaffeinated espresso.
Moving forward from the findings in chapter 2, we designed two randomized, placebo-controlled studies (chapter 3 and chapter 4) using a fixed dose of caffeine (200 mg). We measured sixty participants (study 1: caffeine naïve (n=30); study 2: caffeine consumers (n=30)). Our results in chapter 3 revealed three key findings; 1) caffeine strengthened and prolonged the plasticity aftereffects in caffeine naïve subjects, 2) an increase in alertness during tACS was associated with increases in MEP facilitation, 3) light-deprivation during tACS suppressed the MEP amplitudes in caffeine consumers. In chapter 4, we found that higher prestimulation caffeine concentrations were associated with higher baseline cortical excitability in caffeine consumers. In caffeine naïve, higher poststimulation caffeine concentrations were related with lower poststimulation MEPs after Sham. We showed that there were no relationships between poststimulation caffeine, poststimulation corticosteroids concentrations and plasticity aftereffects. Caffeine administration increases the salivary corticosteroid concentrations in both study groups. These corticosteroid concentrations vary significantly over the time of day and was not affected by stimulations. 
In summary, caffeine is a major confounding factor, which affects the cortical excitability. Alertness and ambient light joined caffeine as other potential confounders that reduce the efficacy of NIBS and plasticity-induction studies.2021-12-0

Modulation of plasticity aftereffects at the sensorimotor cortex by transcranial electrical and magnetic stimulation

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Georg-August-University Göttingen