Resting fMRI measures are associated with cognitive deficits in schizophrenia assessed by the MATRICS consensus cognitive battery

The cognitive deficits of schizophrenia are largely resistant to current treatment, and are thus a life-long burden to patients. The MATRICS consensus cognitive battery (MCCB) provides a reliable and valid assessment of cognition across a comprehensive set of cognitive domains for schizophrenia. In resting-state fMRI, functional connectivity associated with MCCB has not yet been examined. In this paper, the interrelationships between MCCB and the abnormalities seen in two types of functional measures from resting-state fMRI—fractional amplitude of low frequency fluctuations (fALFF) and functional network connectivity (FNC) maps were investigated in data from 47 schizophrenia patients and 50 age-matched healthy controls. First, the fALFF maps were generated and decomposed by independent component analysis (ICA), and then the component showing the highest correlation with MCCB composite scores was selected. Second, the whole brain was separated into functional networks by group ICA, and the FNC maps were calculated. The FNC strengths with most significant correlations with MCCB were displayed and spatially overlapped with the fALFF component of interest. It demonstrated increased cognitive performance associated with higher fALFF values (intensity of regional spontaneous brain activity) in prefrontal regions, inferior parietal lobe (IPL) but lower ALFF values in thalamus, striatum, and superior temporal gyrus (STG). Interestingly, the FNC showing significant correlations with MCCB were in well agreement with the activated regions with highest z-values in fALFF component. Our results support the view that functional deficits in distributed cortico-striato-thalamic circuits and inferior parietal lobe may account for several aspects of cognitive impairment in schizophrenia.

[1]  L. Hazrati,et al.  Functional anatomy of the basal ganglia , 1995 .

[2]  V. Calhoun,et al.  Multisubject Independent Component Analysis of fMRI: A Decade of Intrinsic Networks, Default Mode, and Neurodiagnostic Discovery , 2012, IEEE Reviews in Biomedical Engineering.

[3]  Vince D. Calhoun,et al.  Altered Topological Properties of Functional Network Connectivity in Schizophrenia during Resting State: A Small-World Brain Network Study , 2011, PloS one.

[4]  Yong He,et al.  BrainNet Viewer: A Network Visualization Tool for Human Brain Connectomics , 2013, PloS one.

[5]  Karl J. Friston,et al.  Spatial registration and normalization of images , 1995 .

[6]  James M. Gold,et al.  The MATRICS Consensus Cognitive Battery (MCCB): Clinical and cognitive correlates , 2012, Schizophrenia Research.

[7]  Michael F. Green,et al.  Social cognition in schizophrenia, Part 1: performance across phase of illness. , 2012, Schizophrenia bulletin.

[8]  Chaozhe Zhu,et al.  An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: Fractional ALFF , 2008, Journal of Neuroscience Methods.

[9]  Jean-Francois Mangin,et al.  What is the best similarity measure for motion correction in fMRI time series? , 2002, IEEE Transactions on Medical Imaging.

[10]  Terrence J. Sejnowski,et al.  An Information-Maximization Approach to Blind Separation and Blind Deconvolution , 1995, Neural Computation.

[11]  V. D. Calhoun,et al.  Using joint ICA to link function and structure using MEG and DTI in schizophrenia , 2013, NeuroImage.

[12]  Vince D. Calhoun,et al.  An ICA-based method for the identification of optimal FMRI features and components using combined group-discriminative techniques , 2009, NeuroImage.

[13]  Rebecca Elliott,et al.  Executive functions and their disorders. , 2003, British medical bulletin.

[14]  V. Haughton,et al.  Mapping functionally related regions of brain with functional connectivity MR imaging. , 2000, AJNR. American journal of neuroradiology.

[15]  R. Freedman,et al.  Intrinsic hippocampal activity as a biomarker for cognition and symptoms in schizophrenia. , 2014, The American journal of psychiatry.

[16]  Jack C. Rogers,et al.  Combination of Resting State fMRI, DTI, and sMRI Data to Discriminate Schizophrenia by N-way MCCA + jICA , 2013, Front. Hum. Neurosci..

[17]  Mark Slifstein,et al.  Schizophrenia is associated with increased synaptic dopamine in associative rather than limbic regions of the striatum: Implications for mechanisms of action of antipsychotic drugs , 2006 .

[18]  D. Stuss,et al.  Neuropsychological studies of the frontal lobes. , 1984, Psychological bulletin.

[19]  V. Calhoun,et al.  Disrupted correlation between low frequency power and connectivity strength of resting state brain networks in schizophrenia , 2013, Schizophrenia Research.

[20]  Vince D. Calhoun,et al.  On network derivation, classification, and visualization: a response to Habeck and Moeller. , 2011, Brain connectivity.

[21]  Eleanor H. Simpson,et al.  A Possible Role for the Striatum in the Pathogenesis of the Cognitive Symptoms of Schizophrenia , 2010, Neuron.

[22]  Rex E. Jung,et al.  A Baseline for the Multivariate Comparison of Resting-State Networks , 2011, Front. Syst. Neurosci..

[23]  Tülay Adali,et al.  Comparison of multi‐subject ICA methods for analysis of fMRI data , 2010, Human brain mapping.

[24]  V. Calhoun,et al.  Altered Small-World Brain Networks in Schizophrenia Patients during Working Memory Performance , 2012, PloS one.

[25]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[26]  Michael F. Green,et al.  Approaching a consensus cognitive battery for clinical trials in schizophrenia: The NIMH-MATRICS conference to select cognitive domains and test criteria , 2004, Biological Psychiatry.

[27]  William W. Graves,et al.  Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. , 2009, Cerebral cortex.

[28]  Vince D Calhoun,et al.  Extracting Intrinsic Functional Networks with Feature-Based Group Independent Component Analysis , 2012, Psychometrika.

[29]  Anthony J. Rissling,et al.  Neurophysiologic Markers of Abnormal Brain Activity in Schizophrenia , 2010, Current psychiatry reports.

[30]  Michael F. Green,et al.  Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS , 2004, Schizophrenia Research.

[31]  R. Nathan Spreng,et al.  The Common Neural Basis of Autobiographical Memory, Prospection, Navigation, Theory of Mind, and the Default Mode: A Quantitative Meta-analysis , 2009, Journal of Cognitive Neuroscience.