Causal connectivity from right DLPFC to IPL in schizophrenia patients: a pilot study

Abstract

Abnormal function and connectivity of the fronto-parietal network (FPN) have been documented in patients with schizophrenia, but studies are correlational. We applied repetitive transcranial magnetic stimulation (rTMS) to the dorso-lateral prefrontal cortex (DLPFC) and observed causal connectivity to the inferior parietal lobe (IPL). We hypothesized that patients with schizophrenia would have lower activation and slower reaction in the IPL following DLPFC stimulation. Thirteen patients with schizophrenia (SZ) and fourteen healthy controls subjects (HC) underwent rTMS at 10 Hz to the right DLPFC. Simultaneously, we measured brain activation in the IPL, represented as oxygenized hemoglobin (HbO) levels, using functional near-infrared spectroscopy (fNIRS). rTMS consisted of 20 trains of impulses at 10 Hz for 3 seconds, and 60 seconds waiting time. Using NIRSLab software, GLM was applied to estimate both hemodynamic response function (HRF) and its derivative. Following TMS to the DLPFC, SZ showed a smaller decrease in HbO levels in the bilateral IPL than HC (p = 0.05). Timecourse analysis revealed an immediate decrease in parietal HbO levels in HC, but not in SZ. This difference was significant (at a threshold level of p ≤ 0.05, with Bonferroni correction) for several time segments and channels in both rights and left IPL. Our findings suggest abnormal fronto-temporal connectivity in patients with schizophrenia, beyond a mere decrease or slowing of information processing. This is in line with the hypothesis of reduced fronto-parietal inhibition in schizophrenia.

Fig. 1. GLM results of group activation measured by HbO changes in ipsilateral and contralateral IPL as a consequence of 10 Hz rTMS delivered to the DLPFC.

The red dots (sources) and yellow dots (detectors), same as in a, illustrate coverage by fNIRS. a GLM of HRF in HC threshold set at p_bonferroni ≤ 0.05 (or p ≤ 0.002). There was a significant decrease of activation in both hemispheres. b GLM of HRF in schizophrenia patients. The decrease of activation is significant at the threshold of p_uncorrected ≤ 0.05 only in the left hemisphere. There was no significant change of activation in the right hemisphere. c GLM of HRF of HC vs schizophrenia patients. The difference in activation was significant at threshold of p_uncorrected ≤ 0.05. After correction for multiple comparisons only significant in the right hemisphere. There was no significant difference in activation in the left hemisphere.

Fig. 2. Timecourses of the HbO levels across the ipsilateral IPL after the 10 Hz rTMS delivered to the DLPFC.

Top incision: Right brain hemisphere with distributed optodes (red and yellow dots are sources and detectors, respectively) and the channels depicted in the panels below. Black numbers correspond to the channel numbers, blue lines illustrate the path over which the channel data was collected. Panels middle and below: Solid lines represent grand averages of time courses and shaded areas represent standard error of mean (S.E.M.): red—healthy controls, blue—patients with schizophrenia. Here we depicted representative channels from ipsilateral hemisphere: Ch 2 posterior part of IPL, Ch 5—inferior part of IPL, Ch 10—superior part of IPL and 12 central part of IPL.

Fig. 3. Timecourses of the HbO levels across the contralateral IPL after the 10 Hz rTMS delivered to the DLPFC.

Top incision: Left brain hemisphere with distributed optodes (red and yellow dots are sources and detectors, respectively) and the channels depicted in the panels below. Black numbers correspond to the channel numbers, blue lines illustrate the path over which the channel data were collected. Panels middle and below: Solid lines are grand average and shaded areas present standard error of mean (SEM)): red—healthy controls, blue—patients with schizophrenia. Here we depicted representative channels from contralateral hemisphere: Ch 16—central part of IPL, Ch 19—inferior part of IPL, Ch 25—posterior part of IPL and 26 superior part of IPL.

Fig. 4. Optodes (S—sources, D—detectors) and channel placement.

a Distribution of sources (red dots) and detectors (yellow dots) projected on the brain surface. b Illustration of the TMS coil orientation. c Placement of the sources and detectors on the cap. d Measured channels: right—in the ipsilateral hemisphere (channels 1–15); and left in the contralateral hemisphere (channels 16–26).