Dynamic Functional Network Connectivity in Schizophrenia with Magnetoencephalography and Functional Magnetic Resonance Imaging: Do Different Timescales Tell a Different Story?

The importance of how brain networks function together to create brain states has become increasingly recognized. Therefore, an investigation of eyes-open resting-state dynamic functional network connectivity (dFNC) of healthy controls (HC) versus that of schizophrenia patients (SP) via both functional magnetic resonance imaging (fMRI) and a novel magnetoencephalography (MEG) pipeline was completed. The fMRI analysis used a spatial independent component analysis (ICA) to determine the networks on which the dFNC was based. The MEG analysis utilized a source space activity estimate (minimum norm estimate [MNE]/dynamic statistical parametric mapping [dSPM]) whose result was the input to a spatial ICA, on which the networks of the MEG dFNC were based. We found that dFNC measures reveal significant differences between HC and SP, which depended on the imaging modality. Consistent with previous findings, a dFNC analysis predicated on fMRI data revealed HC and SP remain in different overall brain states (defined by a k-means clustering of network correlations) for significantly different periods of time, with SP spending less time in a highly connected state. The MEG dFNC, in contrast, revealed group differences in more global statistics: SP changed between meta-states (k-means cluster states that are allowed to overlap in time) significantly more often and to states that were more different, relative to HC. MEG dFNC also revealed a highly connected state where a significant difference was observed in interindividual variability, with greater variability among SP. Overall, our results show that fMRI and MEG reveal between-group functional connectivity differences in distinct ways, highlighting the utility of using each of the modalities individually, or potentially a combination of modalities, to better inform our understanding of disorders such as schizophrenia.

Neuroimaging investigations of dorsal stream processing and effects of stimulus synchrony in schizophrenia.

Impairments in auditory and visual processing are common in schizophrenia (SP). In the unisensory realm visual deficits are primarily noted for the dorsal visual stream. In addition, insensitivity to timing offsets between stimuli are widely reported for SP. The aim of the present study was to test at the physiological level differences in dorsal/ventral stream visual processing and timing sensitivity between SP and healthy controls (HC) using MEG and a simple auditory/visual task utilizing a variety of multisensory conditions. The paradigm included all combinations of synchronous/asynchronous and central/peripheral stimuli, yielding 4 task conditions. Both HC and SP groups showed activation in parietal areas (dorsal visual stream) during all multisensory conditions, with parietal areas showing decreased activation for SP relative to HC, and a significantly delayed peak of activation for SP in intraparietal sulcus (IPS). We also observed a differential effect of stimulus synchrony on HC and SP parietal response. Furthermore, a (negative) correlation was found between SP positive symptoms and activity in IPS. Taken together, our results provide evidence of impairment of the dorsal visual stream in SP during a multisensory task, along with an altered response to timing offsets between presented multisensory stimuli.

Same task, different strategies: how brain networks can be influenced by memory strategy.

Previous functional neuroimaging studies demonstrated that different neural networks underlie different types of cognitive processing by engaging participants in particular tasks, such as verbal or spatial working memory (WM) tasks. However, we report here that even when a WM task is defined as verbal or spatial, different types of memory strategies may be used to complete it, with concomitant variations in brain activity. We developed a questionnaire to characterize the type of strategy used by individual members in a group of 28 young healthy participants (18-25 years) during a spatial WM task. A cluster analysis was performed to differentiate groups. We acquired functional magnetoencephalography and structural diffusion tensor imaging measures to characterize the brain networks associated with the use of different strategies. We found two types of strategies were used during the spatial WM task, a visuospatial and a verbal strategy, and brain regions and time courses of activation differed between participants who used each. Task performance also varied by type of strategy used with verbal strategies showing an advantage. In addition, performance on neuropsychological tests (indices from Wechsler Adult Intelligence Scale-IV, Rey Complex Figure Test) correlated significantly with fractional anisotropy measures for the visuospatial strategy group in white matter tracts implicated in other WM and attention studies. We conclude that differences in memory strategy can have a pronounced effect on the locations and timing of brain activation and that these differences need further investigation as a possible confounding factor for studies using group averaging as a means for summarizing results.