Using concurrent EEG and fMRI to probe the state of the brain in schizophrenia

Judith M Ford, Brian J Roach, Vanessa A Palzes, Daniel H Mathalon, Judith M Ford, Brian J Roach, Vanessa A Palzes, Daniel H Mathalon

Abstract

Perceptional abnormalities in schizophrenia are associated with hallucinations and delusions, but also with negative symptoms and poor functional outcome. Perception can be studied using EEG-derived event related potentials (ERPs). Because of their excellent temporal resolution, ERPs have been used to ask when perception is affected by schizophrenia. Because of its excellent spatial resolution, functional magnetic resonance imaging (fMRI) has been used to ask where in the brain these effects are seen. We acquired EEG and fMRI data simultaneously to explore when and where auditory perception is affected by schizophrenia. Thirty schizophrenia (SZ) patients and 23 healthy comparison subjects (HC) listened to 1000 Hz tones occurring about every second. We used joint independent components analysis (jICA) to combine EEG-based event-related potential (ERP) and fMRI responses to tones. Five ERP-fMRI joint independent components (JIC) were extracted. The "N100" JIC had temporal weights during N100 (peaking at 100 ms post-tone onset) and fMRI spatial weights in superior and middle temporal gyri (STG/MTG); however, it did not differ between groups. The "P200" JIC had temporal weights during P200 and positive fMRI spatial weights in STG/MTG and frontal areas, and negative spatial weights in the nodes of the default mode network (DMN) and visual cortex. Groups differed on the "P200" JIC: SZ had smaller "P200" JIC, especially those with more severe avolition/apathy. This is consistent with negative symptoms being related to perceptual deficits, and suggests patients with avolition/apathy may allocate too few resources to processing external auditory events and too many to processing internal events.

Keywords: Avolition/apathy; Concurrent EEG + fMRI; N100; P200; Perception; Schizophrenia.

Figures

Fig. A1
Fig. A1
The spatial loadings and time courses for joint independent component 1 (jIC1). The flat line blue waveform shows the ERP loading for the patients, and the red waveform shows the ERP loading for the controls.
Fig. A2
Fig. A2
The spatial loadings and time courses for joint independent component 3 (jIC3). The relatively flat line blue waveform shows the ERP loading for the schizophrenia patients (SZ), and the red waveform shows the ERP loading for the controls (HC), which is slightly positive in the 0–100 ms interval.
Fig. A3
Fig. A3
The spatial loadings and time courses for joint independent component 4 (jIC4). The ERP loading waveforms for the schizophrenia patients (SZ, blue) and the controls (HC, red) track one another closely, with a positive peak around 92 milliseconds (ms) and negative peak around 156 ms.
Fig. 1
Fig. 1
Results from the fMRI/ERP jICA analysis at electrode Fz, showing the “N100” JIC. On the left are shown average ERP waveforms for HC (black solid line) and SZ (black dotted line) overlaid onto the temporal aspect of the “N100” JIC for HC (red) and SZ (blue). On the right, regions depicted in red reflect areas where the “N100” JIC is positively correlated with BOLD activation. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 2
Fig. 2
Results from the fMRI/ERP jICA analysis at electrode Fz, showing the “P200” JIC. On the left are shown average ERP waveforms for HC (black solid line) and SZ (black dotted line) overlaid onto the temporal aspect of the “P200” joint independent component (JIC) for HC (red) and SZ (blue). On the right, regions depicted in red reflect areas where the “P200” JIC is positively correlated with BOLD activation, and those in cyan reflect areas where there is negative covariation between P200 amplitude and BOLD activation. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 3
Fig. 3
“N100” and “P200” JICs are overlaid, in yellow and red, respectively, to illustrate their overlap and dissociability. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 4
Fig. 4
The scatterplot showing a significant relationship between SANS global score on avolition/apathy and the “P200” linked component mixing matrix coefficients (arbitrary units), shown in Fig. 2. SZ with more severe avolition/apathy had smaller “P200” JIC magnitude. This also illustrates the point that while SZ have an overall smaller “P200” linked component than HC, some have positive values.

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