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Background: Social amotivation is a core element of the negative symptoms of schizophrenia. However, it is still largely unknown which neural substrates underpin social amotivation in people with schizophrenia, though deficiencies in the mesocorticolimbic dopamine system have been proposed.Methods: We examined the association between social amotivation and substantia nigra/ventral tegmental area-seeded intrinsic connectivity in 84 people with schizophrenia using resting state functional magnetic resonance imaging.Results: Spontaneous fluctuations of midbrain dopaminergic regions were positively associated with striatal and prefrontal fluctuations in people with schizophrenia. Most importantly, social amotivation was negatively associated with functional connectivity between the midbrain's substantia nigra/ventral tegmental area and medial-and lateral prefrontal cortex, the temporoparietal junction, and dorsal and ventral striatum. These associations were observed independently of depressive and positive symptoms.Conclusions: Our findings suggest that social amotivation in people with schizophrenia is associated with altered intrinsic connectivity of mesocorticolimbic pathways linked to cognitive control and reward processing. Dysconnectivity of dopaminergic neuronal ensembles that are fundamental to approach behavior and motivation may help explain the lack of initiative social behavior in people with social amotivation. (C) 2019 Elsevier B.V. All rights reserved.

Apathy is a prominent and influential symptom in several neurological and psychiatric disorders, but it also occurs in the healthy population. It has considerable impact on daily life functioning, in clinical as well as healthy samples. Even though cognitive control is thought to be disrupted in people with apathy, the exact neural underpinnings of apathy remain unclear. Because flexible shifting between behaviors (set-shifting) is crucial for goal-directed behavior, disruptions in set-shifting may underlie apathy. In this study, the neural correlates of apathy during set-shifting were studied in 34 healthy participants with varying levels of apathy, measured by the Apathy Evaluation Scale. During functional MRI scanning participants performed a set-shifting task, distinguishing between behavioral switches (a change in response to different stimuli), cognitive switches (a change in response rule), and salience decoupling (detecting a change in relevant stimuli). Regression analysis was used to assess the relationship between apathy and brain activation. Results showed that higher apathy scores were related to reduced activation in the medial superior frontal gyrus and cerebellum (Crus I/II) during cognitive set-shifting, but not behavioral shifting and salience decoupling. No relationship between apathy and accuracy or response time was found. These results support the idea that alterations in the neural basis of cognitive control, especially cognitive set-shifting, may contribute to apathy. Hum Brain Mapp 38:2722-2733, 2017. © 2017 Wiley Periodicals, Inc.

Human behaviour can be externally driven, e.g. catching a falling glass, or self-initiated and goal-directed, e.g. drinking a cup of coffee when one deems it is time for a break. Apathy refers to a reduction of self-initiated goal-directed or motivated behaviour, frequently present in neurological and psychiatric disorders. The amount of undertaken goal-directed behaviour varies considerably in clinical as well as healthy populations. In the present study, we investigated behavioural and neural correlates of self-initiated action in a student sample (N = 39) with minimal to high levels of apathy. We replicated activation of fronto-parieto-striatal regions during self-initiation. The neural correlates of self-initiated action did not explain varying levels of apathy in our sample, neither when mass-univariate analysis was used, nor when multivariate patterns of brain activation were considered. Other hypotheses, e.g. regarding a putative role of deficits in reward anticipation, effort expenditure or executive difficulties, deserve investigation in future studies.

Apathy is a prominent and influential symptom in several neurological and psychiatric disorders, but it also occurs in the healthy population. It has considerable impact on daily life functioning, in clinical as well as healthy samples. Even though cognitive control is thought to be disrupted in people with apathy, the exact neural underpinnings of apathy remain unclear. Because flexible shifting between behaviors (set‐shifting) is crucial for goal‐directed behavior, disruptions in set‐shifting may underlie apathy. In this study, the neural correlates of apathy during set‐shifting were studied in 34 healthy participants with varying levels of apathy, measured by the Apathy Evaluation Scale. During functional MRI scanning participants performed a set‐shifting task, distinguishing between behavioral switches (a change in response to different stimuli), cognitive switches (a change in response rule), and salience decoupling (detecting a change in relevant stimuli). Regression analysis was used to assess the relationship between apathy and brain activation. Results showed that higher apathy scores were related to reduced activation in the medial superior frontal gyrus and cerebellum (Crus I/II) during cognitive set‐shifting, but not behavioral shifting and salience decoupling. No relationship between apathy and accuracy or response time was found. These results support the idea that alterations in the neural basis of cognitive control, especially cognitive set‐shifting, may contribute to apathy. Hum Brain Mapp 38:2722–2733, 2017. © 2017 Wiley Periodicals, Inc.

Background Apathy is a highly debilitating and frequently occurring behavioral characteristic, present in approximately half of the patients with schizophrenia. Apathy is considered a core negative symptom that relates strongest to lack of initiative and is the strongest predictor of poor functional outcome, poor medication compliance, and high caregiver burden. Notwithstanding, measuring apathy is still a challenge. Therefore, we aimed to investigate whether actigraphy, an objective and continuous measurement of activity levels, could yield an objective quantitative measure of apathy severity in schizophrenia patients. Moreover, we aimed to investigate whether actigraphy related to relevant functional neuroimaging underpinnings of apathy, i.e. self-initiated goal-directed behavior. Methods Quantity, variability, and initiation of motor behavior were studied in relation to apathy severity as measured with clinical measures, and in relation to neural correlates of self-initiated behavior using functional Magnetic Resonance Imaging (fMRI). All patients (N=58) suffered from clinical significant apathy, as measured with the Apathy Evaluation Scale and Scale for the Assessment of Negative Symptoms and wore an actigraph for 48 continuous hours. Physical activity was quantified as the total activity counts over the patients’ ten most active hours of each day, summed over two weekend days (Activity-total, i.e. 20 hours in total). Variability of motor behavior (Activity-variability) was calculated by taking the root of the Mean Squared Successive Difference of the activity counts. For 31 of these patients, fMRI data during a task tapping into self-initiative was available. Results Results showed that quantity, variability, and initiation of motor behavior were associated with negative symptoms, but not specifically with apathy. Motor behavior parameters were associated with brain activation during the self-initiative task in various brain regions including inferior parietal regions. The results were only observed during the condition wherein participants were asked to promptly reply to specific cues and not during the condition where more freedom in timing and selection of behavior was allowed. Discussion Actigraphy can be used to measure quantity as well as variability of motor behavior in patients with schizophrenia and with specific relevance for negative symptoms, and that it correlates with selective neural substrates of action selection and activation of motor programs. However, actigraphy may not capture higher-order motivational processes that contribute to apathy severity.