Modafinil enhances cognitive, but not emotional conflict processing via enhanced inferior frontal gyrus activation and its communication with the dorsomedial prefrontal cortex.

Cognitive control regulates cognitive and emotional systems to facilitate goal-directed behavior in the context of task-irrelevant distractors. Cognitive control deficits contribute to residual functional impairments across psychiatric disorders and represent a promising novel treatment target. Translational evidence suggests that modafinil may enhance performance in executive functions; however, differential effects on regulatory control in cognitive and emotional domains have not been examined. The present pre-registered randomized-controlled pharmacological fMRI trial examined differential effects of modafinil (single-dose, 200 mg) on cognitive and emotional conflict processing. To further separate objective cognitive enhancing effects from subjective performance perception, a metacognitive paradigm was employed. Results indicated that modafinil specifically enhanced cognitive conflict performance and concomitantly increased activation in the inferior frontal gyrus and its functional communication with the dorsomedial prefrontal cortex. Exploratory analysis further revealed modafinil-enhanced basolateral amygdala reactivity to cognitive conflict, with stronger reactivity being associated with higher cognitive conflict performance. Whereas modafinil enhanced cognitive performance in the metacognitive paradigm, confidence indices remained unaffected. Overall, the present results suggest that modafinil has the potential to enhance cognitive conflict processing while leaving emotional conflict processing unaffected. On the neural level modafinil enhanced the recruitment of a network engaged in general conflict and regulatory control processes, whereas effects on the amygdala may reflect improved arousal-mediated attention processes for conflicting information. The pattern of cognitive enhancing effects in the absence of effects on affective processing suggests a promising potential to enhance cognitive control in clinical populations.

Relationship between subjective and objective cognitive function in the early and late prodrome.

BACKGROUND: Cognitive disturbances have been demonstrated in individuals with potentially prodromal symptoms in objective-neuropsychological as well as subjective-symptomatic studies. Yet, the relation between subjective and objective deficits and to different prodromal states is unclear. AIMS: To explore interactions between subjective and objective cognitive measures in different prodromal states. METHOD: In participants with an early (n=33) or late (n=69) initial prodromal state, cognitive subjective and objective deficits were assessed with the Schizophrenia Proneness Instrument and a comprehensive neuropsychological test battery. RESULTS: Participants with an early initial prodromal state were less impaired than those with a late initial state. Subjective and objective cognitive deficits were unrelated, except time-limited neurocognitive speed measures and subjectively reduced stress tolerance, especially in participants with an early initial prodromal state. CONCLUSIONS: Subjective and objective cognitive deficits are generally unrelated in the psychosis prodrome and as such they can add complementary information valuable for prediction. However, possible associations between the two levels might be better detectable in the less impaired early initial prodromal state.

The interaction of working memory and emotion in persons clinically at risk for psychosis: an fMRI pilot study.

Subtle emotional and cognitive dysfunctions may already be apparent in individuals at risk for psychosis. However, there is a paucity of research on the neural correlates of the interaction of both domains. It remains unclear whether those correlates are already dysfunctional before a transition to psychosis. We used functional magnetic resonance imaging to examine the interaction of working memory and emotion in 12 persons clinically at high risk for psychosis (CHR) and 12 healthy subjects individually matched for age, gender and parental education. Participants performed an n-back task while negative or neutral emotion was induced by olfactory stimulation. Although healthy and psychosis-prone subjects did not differ in their working memory performance or the evaluation of the induced emotion, decreased activations were found in CHR subjects in the superior parietal lobe and the precuneus during working memory and in the insula during emotion induction. Looking at the interaction, CHR subjects, showed decreased activation in the right superior temporal gyrus, which correlated negatively with psychopathological scores. Decreased activation was also found in the thalamus. However, an increase of activation emerged in several cerebellar regions. Dysfunctions in areas associated with controlling whether incoming information is linked to emotional content and in the integration of multimodal information might lead to compensatory activations of cerebellar regions known to be involved in olfactory and working memory processes. Our study underlines that cerebral dysfunctions related to cognitive and emotional processes, as well as their interaction, can emerge in persons with CHR, even in absence of behavioral differences.