Abstract
Background
One of the most prominent deficits in schizophrenia is impairment in executive function. This impairment is associated to aberrant function of the dorso-lateral prefrontal cortex (DLPFC)(Weinberger et al. 1986) and the fronto-parietal network (FPN) (Deserno et al. 2012). The FPN is involved in cognitive control (Seeley et al. 2007, Zanto & Gazzaley 2013). While correlations of activation of DLPFC and inferior parietal lobe (IPL) are well documented, fMRI based techniques cannot determine causal relationships of interactions between brain regions. We used Transcranial magnetic stimulation (TMS), which directly affects the stimulated brain region and connected brain areas (Valchev et al 2015) and therefore can be used to investigate causal interactions between brain regions. TMS stimulation to the DLPFC at 10 Hz may cause either putative increase or decrease of activation in the in the IPL, depending on whether connections are inhibitory or excitatory (Curtin et al 2019). We hypothesised that patients with schizophrenia would have slower reaction in IPL as a consequence of DLPFC stimulation.
Methods
Thirteen patients and fourteen healthy controls (HC) underwent transcranial magnetic stimulation (TMS) to the right DLPFC. TMS consisted of 20 trains of impulses at 10 Hz for 3 seconds, and 60 seconds waiting time. Simultaneously, we measured brain activation IPL using functional near infrared spectroscopy (fNIRS). Diagnostic category was confirmed using MINI plus interview. The severity of symptoms was assessed using the positive and negative syndrome scale (PANSS). We estimated levels of Oxygenised haemoglobin (HbO) using NIRSLab software. GLM was applied using both hemodynamic response function (HRF) and it’s derivative. T-test was used, with FDR correction, to compare time segments of HbO following TMS stimulation.
Results
There was no difference in age and gender between the groups. The two groups differed in education (t(2,25)= 2,584, p=0.016). GLM revealed decreased levels of HbO in HC in bilateral IPL following the TMS to the DLPFC (p_bonferroni=0.05). However, when patients were compared to HC higher levels of HbO were observed (p=0.05). However, no difference in derivative of HRF was observed. In addition, there was a significant difference in time courses between patients and HC following TMS stimulation. Namely, while there was an immediate decrease in parietal HbO levels in HC, in SZ first an increase, followed by a decrease was observed. This was significant (at a threshold level of pFDR=0.05) for several time segments and channels in both right and left IPL.
Discussion
We observed differences in activation of bilateral IPL as a consequence of DLPFC stimulation in patients with schizophrenia. Namely, there was an initial increase in HbO levels, as opposite to HC who had an immediate decrease in HbO level. This indicates opposite function of information processing from the frontal to parietal lobe in schizophrenia patients. This is in line with the idea of impaired fronto-parietal inhibition in schizophrenia which has been proposed to underlie impairments in schizophrenia such as lack of cognitive control.
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