Transcranial direct current stimulation effects on auditory event-related potentials in schizophrenia

by Lilly Knechtel

Institution: University of Newcastle
Degree: PhD
Year: 2015
Keywords: schizophrenia; tDCS; ERP
Record ID: 1069337
Full text PDF: http://hdl.handle.net/1959.13/1059906


Research Doctorate - Doctor of Philosophy (PhD) Transcranial direct current stimulation (tDCS) is considered a non-invasive and well-tolerated brain stimulation technique with very few adverse side effects. Importantly, tDCS does not directly evoke neuronal firing (as induced by electroconvulsive or transcranial magnetic stimulation), but instead alters the resting membrane potential of pre- and post-synaptic neurons dependent on the current polarity in the stimulated brain region. Animal studies suggest that changes in long-term potentiation occur via glutamate release in response to anodal tDCS, thereby affecting learning and memory. In clinical studies, a current not exceeding 2 mA/cm2 is applied for 10–30 min via electrodes placed above the target brain region. To date, a number of clinical studies have reported some promising effects when treating patients with depression, chronic pain, schizophrenia, dementia, Parkinson’s disease and cerebral stroke. However, appropriately designed randomized controlled clinical trials are scarce and reported intervention effect sizes only vary from small to moderate, with little evidence for sustained long-term effects. Particularly the effects of tDCS on human cognition are poorly understood, including the underlying neurophysiological mechanisms. Hence, the current thesis investigated the effects of anodal tDCS over the prefrontal cortex on auditory event-related potentials (ERPs) and related changes in the neurochemistry of the stimulated brain tissue with high-field proton magnetic resonance spectroscopy (MRS) in healthy volunteers. The effects of a single session of 20 min of 2 mA left-prefrontal anodal versus sham stimulation on auditory ERPs was investigated by employing a randomized single-blind crossover design. Stimulation effects on cortical glutamate (Glu) and glutamine (Glx) levels were subsequently measured in a 3 Tesla MRS scan. tDCS was associated with a significant increase of N1 amplitudes while smaller P3b amplitudes correlated with higher cortical Glu and Glx levels in the stimulated brain area when performing an auditory go/no-go discrimination task. tDCS did not change mismatch negativity, nor task performance or cortical Glu/Glx levels. Cortical Glu/Glx levels and N1 amplitudes were both depended on stimulation order (“sham” vs “active”). Notwithstanding, increased N1 amplitudes with anodal tDCS support the notion of increased cortical excitability, thereby potentially supporting impaired cognitive processes in neuropsychiatric conditions. Hence, the effects of tDCS on ERPs were also investigated in schizophrenia. Schizophrenia patients usually present with significantly smaller N1, MMN and P3 amplitudes when compared to their healthy counterparts. This was also confirmed in the current study. However, anodal tDCS had no effect on any ERPs in schizophrenia patients and did not affect the performance in the go/no go task. In fact, both groups, healthy controls and schizophrenia patients, performed equally well on this task. Taken together, these…