Disconnection Between Amygdala and Medial Prefrontal Cortex in Psychotic Disorders

Abstract

Distracting emotional information impairs attention more in schizophrenia (SCZ) than in never-psychotic individuals. However, it is unclear whether this impairment and its neural circuitry is indicative generally of psychosis, or specifically of SCZ, and whether it is even more specific to certain SCZ symptoms (eg, deficit syndrome). It is also unclear if this abnormality contributes to impaired behavioral performance and real-world functioning. Functional imaging data were recorded while individuals with SCZ, bipolar disorder with psychosis (BDP) and no history of psychotic disorders (CON) attended to identity of faces while ignoring their emotional expressions. We examined group differences in functional connectivity between amygdala, involved in emotional evaluation, and sub-regions of medial prefrontal cortex (MPFC), involved in emotion regulation and cognitive control. Additionally, we examined correlation of this connectivity with deficit syndrome and real-world functioning. Behaviorally, SCZ showed the worst accuracy when matching the identity of emotional vs neutral faces. Neurally, SCZ showed lower amygdala-MPFC connectivity than BDP and CON. BPD did not differ from CON, neurally or behaviorally. In patients, reduced amygdala-MPFC connectivity during emotional distractors was related to worse emotional vs neutral accuracy, greater deficit syndrome severity, and unemployment. Thus, reduced amygdala-MPFC functional connectivity during emotional distractors reflects a deficit that is specific to SCZ. This reduction in connectivity is associated with worse clinical and real-world functioning. Overall, these findings provide support for the specificity and clinical utility of amygdala-MPFC functional connectivity as a potential neural marker of SCZ.

Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia

“…But neurophysiological evidence of impaired temporal coordination of neural activity in the brains of patients has more recently given the theory a neurophysiological basis (Friston, 1999; Friston and Frith, 1995; Lawrie et al, 2002; Scariati et al, 2016; Stephan et al, 2009). Consistent with this hypothesis, functional imaging studies in patients have repeatedly shown that schizophrenia weakens functional coupling in prefrontal networks based on reduced temporal correlations in BOLD signal across brain areas (Kang et al, 2011; Kubota et al, 2013; Lawrie et al, 2002; Mitelman et al, 2005; Mukherjee et al, 2016; Scariati et al, 2016; Tu et al, 2012, 2013). Measurements of brain activity at higher temporal resolution using electroencephalograms (EEG) and magnetoencephalography (MEG) have shown reduced synchrony in gamma band during task performance (Dale et al, 2016; Uhlhaas and Singer, 2015).…”

Modulating functional connectivity between medial frontopolar cortex and amygdala by inhibitory and excitatory transcranial magnetic stimulation

“…Although there is strong anatomical and functional connectivity between the vmPFC and OFC, on the one hand, and the amygdala, on the other (see above), and this connectivity is highly relevant for psychiatric disorders (Downar & Daskalakis, ; Kamphausen et al, ; Likhtik & Paz, ; Mukherjee et al, ; Myers‐Schulz & Koenigs, ; Park et al, ; A. K. Roy et al, ), the mFP was selected for TMS instead. The mFP is located both proximal to the scalp, which ensures effective stimulation with a conventional TMS coil (Downar & Daskalakis, ), and atop a medial brain circuit that includes pathways between vmPFC, OFC and amygdala (Forbes & Grafman, ).…”

“…Although there is strong anatomical and functional connectivity between the vmPFC and OFC, on the one hand, and the amygdala, on the other (see above), and this connectivity is highly relevant for psychiatric disorders (Downar & Daskalakis, 2013;Kamphausen et al, 2013;Likhtik & Paz, 2015;Mukherjee et al, 2016;Myers-Schulz & Koenigs, 2012;Park et al, 2018;A. K. Roy et al, 2013), the mFP was selected for TMS instead.…”

“…Furthermore, participants completed a set of mood and anxiety questionnaires (Q&A). Fifty-five participants were included in the statistical analysis Kamphausen et al, 2013;Mukherjee et al, 2016;Shin & Liberzon, 2010).…”

Involvement of amygdala–prefrontal dysfunction in the influence of negative emotion on the resolution of cognitive conflict in patients with schizophrenia

“…Amygdala–prefrontal connectivity is reduced in patients with schizophrenia during emotion perception (Bjorkquist, Olsen, Nelson, & Herbener, 2016) or emotional distractors (Mukherjee et al., 2016), and during bottom–up emotional processes (Comte et al., 2017). However, the tasks used in previous studies have involved emotional rather than cognitive conflict.…”