ABSTRACT
BACKGROUND: Disorders with psychotic features, including schizophrenia and some bipolar disorders, are associated with impairments in regulation of goal-directed behavior, termed cognitive control. Cognitive control-related neural alterations have been studied in psychosis. However, studies are typically unimodal, and relationships across modalities of brain function and structure remain unclear. Thus, we performed transdiagnostic multimodal analyses to examine cognitive control-related neural variation in psychosis. METHODS: Structural, resting, and working memory task imaging for 31 control participants, 27 participants with bipolar disorder, and 23 participants with schizophrenia were collected and processed identically to the Human Connectome Project, enabling identification of relationships with prior multimodal work. Two cognitive control-related independent components (ICs) derived from the Human Connectome Project using multiset canonical correlation analysis with joint IC analysis were used to predict performance in psychosis. De novo multiset canonical correlation analysis with joint IC analysis was performed, and the results were correlated with cognitive control. RESULTS: A priori working memory and cortical thickness maps significantly predicted cognitive control in psychosis. De novo multiset canonical correlation analysis with joint IC analysis identified an IC correlated with cognitive control that also discriminated groups. Structural contributions included insular and cingulate regions; task contributions included precentral, posterior parietal, cingulate, and visual regions; and resting-state contributions highlighted canonical network organization. Follow-up analyses suggested that correlations with cognitive control were primarily influenced by participants with schizophrenia. CONCLUSIONS: A priori and de novo imaging replicably identified a set of interrelated patterns across modalities and the healthy-to-psychosis spectrum, suggesting robustness of these features. Relationships between imaging and cognitive control performance suggest that shared symptomatology may be key to identifying transdiagnostic relationships in psychosis.
Subject(s)
Bipolar Disorder/physiopathology , Cognition/physiology , Neuroimaging , Psychotic Disorders/physiopathology , Schizophrenia/physiopathology , Adult , Bipolar Disorder/complications , Connectome/methods , Female , Gyrus Cinguli/pathology , Gyrus Cinguli/physiopathology , Humans , Male , Memory, Short-Term/physiology , Neuroimaging/methods , Neuropsychological Tests , Psychotic Disorders/complications , Schizophrenia/complicationsABSTRACT
In primary cultures of mesencephalon small-conductance calcium-activated potassium channels (SK) are expressed in dopaminergic neurons. We characterized SK-mediated currents (I(SK)) in this system and evaluated their role on homeostasis against excitotoxicity. I(SK) amplitude was reduced by the glutamatergic agonist AMPA through a reduction in SK channel number in the membrane. Blockade of I(SK) for 12 h with apamin or NS8593 reduced the number of dopaminergic neurons in a concentration-dependent manner. The effect of apamin was not additive to AMPA toxicity. On the other hand, two I(SK) agonists, 1-EBIO and CyPPA, caused a significant reduction of spontaneous loss of dopaminergic neurons. 1-EBIO reversed the effects of both AMPA and apamin as well. Thus, I(SK) influences survival and differentiation of dopaminergic neurons in vitro, and is part of protective homeostatic responses, participating in a rapidly acting negative feedback loop coupling calcium levels, neuron excitability and cellular defenses. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.