Functional Disconnectivity in Schizophrenia Patients with Auditory Hallucinations: a Dynamic Resting-State Functional MRI Study with a Multiband EPI Sequence
Wenjing Zhang1, Wei Deng2, Siyi Li1, John Sweeney3, Qiyong Gong1, and Su Lui1

1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, 2Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, 3Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, United States

Synopsis

A simultaneous multi-slice multiband EPI sequence, which could significantly increase temporal resolution for the fMRI scanning, was adopted to investigate the dynamic functional connectivity in the schizophrenia patients with auditory hallucinations. We found that, relative to traditional static functional connectivity calculation, dynamic analysis evaluated with multiband EPI provides much more information, including more widespread aberrant functional connectivity maps across different states and their temporal variability over time. The expanded information may help to give better insight into the pathological processes and subsequently reveal the spontaneous model of affected networks in schizophrenia.

Purpose

Auditory hallucinations (AH) are a core symptom of schizophrenia and may be the result from deficits of intrinsic functional networks involving auditory cortex in the superior temporal gyrus (STG). However, previous network studies using static functional connectivity (FC) averaged measures of brain activity over minutes and blurred the temporal changes of brain connectivity, while the neural process of AH has been considered dynamic and evolving over time.1 With a simultaneous multi-slice (SMS) multiband EPI sequence, the present study investigated the dynamic pattern of FC in schizophrenia patients with AH.

Materials and Methods

Structured interviews for the DSM-IV (SCID) Patient-Edition confirmed 14 schizophrenia patients with AH and an equal number of healthy controls were recruited in this study. The MRI examinations were performed on a 3 T scanner (MAGNETOM Trio, Siemens Healthcare, Germany) with a 32-channel head coil. The resting-state fMRI was acquired using a prototype SMS multiband GRE-EPI sequence (TR/TE=427/30 ms; flip angle=45°, multiband acceleration factor = 8, 48 slices with no gap, voxel size = 3 × 3 × 3 mm3). Each functional run contained 1000 volumes, and the first 23 (the volumes in the first 10s) were discarded for signal equilibrium and subjects' adaptation. The resting-state fMRI data were preprocessed using DPARSFA (http://www.restfmri.net). A seed-based voxel-wise correlation approach was used to estimate the FC using bilateral STG as seeds respectively to establish the FC network. The static FC were established with REST (http://www.restfmri.net), whereas the dynamic pattern of FC was calculated using DynamicBC (www.restfmri.net/forum/DynamicBC).2 Dynamic strategies and temporal variability were characterized with Flexible Least Squares (FSL), while the clustering analysis was used to window similar FC states in order to extract representative connectivity patterns.

Results

The temporal variability of dynamic FC showed that the FC map of left STG displayed significantly less dynamic variability with left middle frontal gyrus, left inferior frontal gyrus, and left middle temporal gyrus in schizophrenia patients when compared with that of healthy subjects. The connectivity between right STG and right inferior parietal gyrus, right supplementary motor area, left middle temporal gyrus, left inferior frontal gyrus (orbital part), and right postcentral gyrus was found to show significantly less temporal variability in schizophrenia patients (Figure 1). Clustering analysis showed that there are six main transient states, and the increased FC with bilateral medial frontal gyrus and right inferior parietal gyrus, as well as decreased connectivity with left middle temporal gyrus and right supplementary motor area, was the most replicated findings across different states (Figure 2). Traditional static FC analysis showed much less significant change of FC, including increased connectivity with bilateral superior frontal gyrus and decreased connectivity with bilateral middle temporal gyrus (p<0.05, Figure 3).

Discussion

This is the first study, to our best knowledge, to employ the SMS multiband EPI sequence to investigate the dynamics implicated in FC maps underlying the hallucinating schizophrenia. As suggested by previous study,3 different FC states across the time course were driven by the co-occurrence of FC states between specific regions. Therefore, our findings with clustering consistently verified that there likely different activity and connectivity states along the process of AH. Compared to traditional calculation of static FC, dynamic information in a function of time about the connectivity network abnormalities were spatiotemporally revealed in these patients. Furthermore, dynamic analysis revealed that the temporal variability of FC between temporal and prefrontal regions, as well as parietal areas, were more stable and showed a less time-varied feature in schizophrenia patients. While healthy subjects have been shown with a free-task- or situation-related FC switch, it could be implied that the connectivity pattern among these regions were constrained which may likely be attributed to the disorder.

Conclusion

Dynamic FC evaluated with SMS multiband EPI provides much more information beyond that revealed by static FC, including more widespread aberrant FC maps across different states and their temporal variability over time. The expanded information may help to give better insight into the pathological processes and subsequently reveal the spontaneous model of affected networks in schizophrenia.

Acknowledgements

This study was supported by National Natural Science Foundation (Grant Nos. 81222018, 81371527), National Key Technologies R&D Program (Program No. 2012BAI01B03) and Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, Grant No. IRT1272) of China.

References

1. Jones SR. Do we need multiple models of auditory verbal hallucinations? Examining the phenomenological fit of cognitive and neurological models. Schizophr Bull.2010. 36:566-575.

2. Liao W, Wu GR, Xu Q et al. DynamicBC: a MATLAB toolbox for dynamic brain connectome analysis. Brain connect. 2014. 4:780-790.

3. Allen EA, Damaraju E, Plis SM, et al. Tracking whole-brain connectivity dynamics in the resting state. Cereb Cortex. 2014 .24:663-676.

Figures

Fig 1. Regions with significant differences in temporal variability of functional connectivity between schizophrenia patients and healthy comparisons.

Fig 2. The significant differences of functional connectivity between discrete states in schizophrenia patients and healthy subjects.

Fig 3. The significant differences of functional connectivity between schizophrenia hallucinating patients and healthy subjects using static analysis.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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