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.