Figure 4.

Characterizing connectivity alterations using pharmacological neuroimaging. While functional connectivity neuroimaging alone has been a powerful tool for characterizing neural system-level alterations in schizophrenia, it is ultimately a correlational tool. That is, we are examining alterations in the associations as a function of illness presence or absence. To move toward understanding the possible role of specific neurotransmitter mechanisms in schizophrenia, however, neuroimaging studies can be combined with pharmacological manipulations (47, 175). Such causal experimental manipulations can shed light on the role of specific neurotransmitter systems in schizophrenia (15). (A) Driesen and colleagues have shown that administration of ketamine profoundly altered the global connectivity of the brain. Specifically they demonstrated that the GBC measure increased following ketamine administration, possibly reflecting a hyper-glutamatergic state or a state of cortical disinhibition (54) consistent with animal models (111, 176). Formal computational models are needed in order to provide a deeper intuition for such pharmacological effects on large-scale neural systems. (B) Anticevic and colleagues have shown that administration of an NMDAR antagonist, ketamine, alters the connectivity of large-scale anti-correlated neural systems during performance of a working memory task (18). Although this connectivity study was performed during task performance rather than rest, it illustrates a proof of concept for how a pharmacological challenge can alter connectivity in a causal way. Note: figures adapted with permission from Driesen and colleagues (54) and Anticevic and colleagues (18).