Importantly, these dysfunctions are largely immune to current antipsychotic treatments and, as a result, constitute a major determinant

for psychosocial functioning and outcome (Green, 1996). The identification of the causes of dysfunctional cognition is, therefore, a prerequisite for the developmental of novel and more effective interventions. The search for the underlying pathophysiological processes has thus far focused on anatomical Antidiabetic Compound Library and functional abnormalities in circumscribed brain regions. This approach has yielded a large body of evidence implicating various brain areas in cognitive deficits, but the precise circuits and mechanisms underlying these dysfunctions have remained elusive. An alternative approach has been the focus on the role of impaired communication between regions in the pathophysiology of schizophrenia, which most likely involves a disconnection of functional networks (Friston, 1998). This hypothesis has received support through

findings from noninvasive studies using electro- and magneto-encephalography (EEG/MEG) that demonstrate impaired amplitude and synchrony of neural oscillations at low- and high-frequency ranges in patients with schizophrenia (Uhlhaas and Singer, 2010). This is of particular relevance because a large body of evidence suggests that the functional networks underlying perception, attention, and executive processes rely on dynamic coordination selleck screening library through the phase locking of synchronized oscillations (Varela et al., 2001). Accordingly, impairments in this mechanism could lead to a transient failure in the first establishment of functional interactions between brain regions, thereby affecting the associated cognitive processes. In this issue of Neuron, Parnaudeau et al. (2013) investigated the hypothesis that thalamocortical synchronization, in this case, between frontal

brain regions and the mediodorsal (MD) thalamus, might play an important role in WM and that disturbed synchrony in this circuit might be responsible for WM impairments in schizophrenia. Thalamic functions have recently received renewed interest in systems neuroscience because of their crucial role in gating communication between cortical areas through the synchronization of neuronal responses ( Saalmann et al., 2012). Because anatomical and functional abnormalities have been repeatedly demonstrated in the thalamus of patients with schizophrenia ( Ronenwett and Csernansky, 2010), abnormal synchronization in thalamocortical pathways could represent an intriguing pathophysiological mechanism for cognitive impairments. To test this hypothesis, the authors employed a novel pharmacogenetic approach (designer receptors exclusively activated by designer drugs [DREADD]) (Armbruster et al.