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Modulatory effects of modafinil on neural circuits regulating emotion and cognition.

ABSTRACT: Modafinil differs from other arousal-enhancing agents in chemical structure, neurochemical profile, and behavioral effects. Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition, but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior, too. We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions. Healthy volunteers were enrolled in this double-blinded placebo-controlled trial (100 mg/day for 7 days). They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks-a working memory (WM) task and a variable attentional control (VAC) task. A clinical assessment that included measurement of blood pressure, heart rate, the Hamilton anxiety scale, and the profile of mood state (POMS) questionnaire was also performed on each test day. BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition. During executive cognition tasks, a WM task and a VAC task, modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate. Although not statistically significant, there were trends for reduced anxiety, for decreased fatigue-inertia and increased vigor-activity, as well as decreased anger-hostility on modafinil. Modafinil in low doses has a unique physiologic profile compared with stimulant drugs: it enhances the efficiency of prefrontal cortical cognitive information processing, while dampening reactivity to threatening stimuli in the amygdala, a brain region implicated in anxiety.

SUBMITTER: Rasetti R

PROVIDER: S-EPMC3013347 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The human brain has the capacity to integrate various sources of information and continuously adapts our behavior according to situational needs in order to allow a healthy functioning. Emotion-cognition interactions are a key example for such integrative processing. However, the neuronal correlates investigating the effects of emotion on cognition remain to be explored and replication studies are needed. Previous neuroimaging studies have indicated an involvement of emotion and cognition related brain structures including parietal and prefrontal cortices and limbic brain regions. Here, we employed whole brain event-related functional magnetic resonance imaging (fMRI) during an affective number Stroop task and aimed at replicating previous findings using an adaptation of an existing task design in 30 healthy young adults. The Stroop task is an indicator of cognitive control and enables the quantification of interference in relation to variations in cognitive load. By the use of emotional primes (negative/neutral) prior to Stroop task performance, an emotional variation is added as well. Behavioral in-scanner data showed that negative primes delayed and disrupted cognitive processing. Trials with high cognitive demand furthermore negatively influenced cognitive control mechanisms. Neuronally, the emotional primes consistently activated emotion-related brain regions (e.g., amygdala, insula, and prefrontal brain regions) while Stroop task performance lead to activations in cognition networks of the brain (prefrontal cortices, superior temporal lobe, and insula). When assessing the effect of emotion on cognition, increased cognitive demand led to decreases in neural activation in response to emotional stimuli (negative > neutral) within prefrontal cortex, amygdala, and insular cortex. Overall, these results suggest that emotional primes significantly impact cognitive performance and increasing cognitive demand leads to reduced neuronal activation in emotion related brain regions, and therefore support previous findings investigating emotion-cognition interaction in healthy adults. Moreover, emotion and cognition seem to be tightly related to each other, as indicated by shared neural networks involved in both of these processes. Emotion processing, cognitive control, and their interaction are crucial for healthy functioning and a lack thereof is related to psychiatric disorders such as, disruptive behavior disorders. Future studies may investigate the neural characteristics of children and adolescents with disruptive behavior disorders.

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Modulatory effects of modafinil on neural circuits regulating emotion and cognition.

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