Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined resting-state functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.
Growing evidence suggests that coordinated activity within specific functional brain networks supports cognitive ability, and that abnormalities in brain connectivity may underlie cognitive deficits observed in neuropsychiatric diseases, such as schizophrenia. Two functional networks, the fronto-parietal network (FPN) and cingulo-opercular network (CON), are hypothesized to support top-down control of executive functioning, and have therefore emerged as potential drivers of cognitive impairment in disease-states. Graph theoretic analyses of functional connectivity data can characterize network topology, allowing the relationships between cognitive ability and network integrity to be examined. In the current study we applied graph analysis to pseudo-resting state data in 54 healthy subjects and 46 schizophrenia patients, and measured overall cognitive ability as the shared variance in performance from tasks of episodic memory, verbal memory, processing speed, goal maintenance, and visual integration. We found that, across all participants, cognitive ability was significantly positively associated with the local and global efficiency of the whole brain, FPN, and CON, but not with the efficiency of a comparison network, the auditory network. Additionally, the participation coefficient of the right anterior insula, a major hub within the CON, significantly predicted cognition, and this relationship was independent of CON global efficiency. Surprisingly, we did not observe strong evidence for group differences in any of our network metrics. These data suggest that functionally efficient task control networks support better cognitive ability in both health and schizophrenia, and that the right anterior insula may be a particularly important hub for successful cognitive performance across both health and disease.
Previous work suggests that individuals with schizophrenia display accelerated aging of white matter integrity, however, it is still unknown whether functional brain networks also decline at an elevated rate in schizophrenia. Given the known degradation of functional connectivity and the normal decline in cognitive functioning throughout healthy aging, we aimed to test the hypothesis that efficiency of large-scale functional brain networks supporting overall cognition, as well as integrity of hub nodes within those networks, show evidence of accelerated aging in schizophrenia. Using pseudo-resting state data in 54 healthy controls and 46 schizophrenia patients, in which task-dependent signal from 3 tasks was regressed out to approximate resting-state data, we observed a significant diagnosis by age interaction in the prediction of both global and local efficiency of the cingulo-opercular network, and of the local efficiency of the fronto-parietal network, but no interaction when predicting both default mode network and whole brain efficiency. We also observed a significant diagnosis by age interaction for the node degree of the right anterior insula, left dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex. All interactions were driven by stronger negative associations between age and network metrics in the schizophrenia group than the healthy controls. These data provide evidence that is consistent with accelerated aging of large-scale functional brain networks in schizophrenia that support higher-order cognitive ability.
We compare the effects of two prominent organizational control mechanisms—social pressure and monetary incentive—on cognitive control. Cognitive control underlies the human ability to regulate thoughts and actions in the pursuit of behavioral goals. Previous studies show that monetary incentives can contribute to goal-oriented behavior by activating proactive control. There is, however, much less evidence of how social pressure affects cognitive control and task performance. In a within-subject experimental design, we tested 47 subjects performing the AX-CPT task to compare the activation of cognitive control modes under social pressure and monetary incentive beyond mere instructions to perform better. Our results indicate that instructing participants to improve their performance on its own leads to a signiﬁcant shift from a reactive to a proactive control mode and that both social pressure and monetary incentive further enhance performance.
Schizophrenia (SCZ) is a disabling neuropsychiatric disease associated with disruptions across distributed neural systems. Resting-state functional magnetic resonance imaging has identified extensive abnormalities in the blood-oxygen level-dependent signal in SCZ patients, including alterations in the average signal over the brain—i.e. the “global” signal (GS). It remains unknown, however, if these “global” alterations occur pervasively or follow a spatially preferential pattern. This study presents the first network-by-network quantification of GS topography in healthy subjects and SCZ patients. We observed a nonuniform GS contribution in healthy comparison subjects, whereby sensory areas exhibited the largest GS component. In SCZ patients, we identified preferential GS representation increases across association regions, while sensory regions showed preferential reductions. GS representation in sensory versus association cortices was strongly anti-correlated in healthy subjects. This anti-correlated relationship was markedly reduced in SCZ. Such shifts in GS topography may underlie profound alterations in neural information flow in SCZ, informing development of pharmacotherapies.