Brain structural signatures of negative symptoms in depression and schizophrenia.

Negative symptoms occur in several major mental health disorders with undetermined mechanisms and unsatisfactory treatments; identification of their neural correlates might unveil the underlying pathophysiological basis and pinpoint the therapeutic targets. In this study, participants with major depressive disorder (n = 24), schizophrenia (n = 22), and healthy controls (n = 20) were assessed with 10 frequently used negative symptom scales followed by principal component analysis (PCA) of the scores. A linear model with the prominent components identified by PCA was then regressed on gray and white-matter volumes estimated from T1-weighted magnetic resonance imaging. In depressed patients, negative symptoms such as blunted affect, alogia, withdrawal, and cognitive impairment, assessed mostly via clinician-rated scales were inversely associated with gray matter volume in the bilateral cerebellum. In patients with schizophrenia, anhedonia, and avolition evaluated via self-rated scales inversely related to white-matter volume in the left anterior limb of internal capsule/anterior thalamic radiation and positively in the left superior longitudinal fasiculus. The pathophysiological mechanisms underlying negative symptoms might differ between depression and schizophrenia. These results also point to future negative symptom scale development primarily focused on detecting and monitoring the corresponding changes to brain structure or function.This work was supported by Brain and Behavior Research Foundation (NARSAD) and Medical Research Council (MRC) awards to GKM, and by the Wellcome Trust/MRC Behavioural and Clinical Neuroscience Institute, University of Cambridge. We thank Dr. Zheng Ye for her help with image analysis and technical support, Niels Reinders and staff at the Wolfson Brain Imaging Centre for help with data collection, and staff at IAPT, CAMEO and the Rehabilitation and Recovery Service in the Cambridgeshire and Peterborough NHS Foundation Trust for help with recruitment. The study was supported by infrastructure provided by the Wellcome Trust/MRC Behavioural and Clinical Neuroscience Institute at the University of Cambridge.This is the final version published by Frontiers here: http://journal.frontiersin.org/Journal/10.3389/fpsyt.2014.00116/abstract

The meditative mind: a comprehensive meta-analysis of MRI studies

Over the past decade mind and body practices, such as yoga and meditation, have raised interest in different scientific fields; in particular, the physiological mechanisms underlying the beneficial effects observed in meditators have been investigated. Neuroimaging studies have studied the effects of meditation on brain structure and function and findings have helped clarify the biological underpinnings of the positive effects of meditation practice and the possible integration of this technique in standard therapy. The large amount of data collected thus far allows drawing some conclusions about the neural effects of meditation practice. In the present study we used activation likelihood estimation (ALE) analysis to make a coordinate-based meta-analysis of neuroimaging data on the effects of meditation on brain structure and function. Results indicate that meditation leads to activation in brain areas involved in processing self-relevant information, self-regulation, focused problem-solving, adaptive behavior, and interoception. Results also show that meditation practice induces functional and structural brain modifications in expert meditators, especially in areas involved in self-referential processes such as self-awareness and self-regulation. These results demonstrate that a biological substrate underlies the positive pervasive effect of meditation practice and suggest that meditation techniques could be adopted in clinical populations and to prevent disease

Substantia nigra activity level predicts trial-to-trial adjustments in cognitive control

Effective adaptation to the demands of a changing environment requires flexible cognitive control. The medial and the lateral frontal cortices are involved in such control processes, putatively in close interplay with the BG. In particular, dopaminergic projections from the midbrain (i.e., from the substantia nigra [SN] and the ventral tegmental area) have been proposed to play a pivotal role in modulating the activity in these areas for cognitive control purposes. In that dopaminergic involvement has been strongly implicated in reinforcement learning, these ideas suggest functional links between reinforcement learning, where the outcome of actions shapes behavior over time, and cognitive control in a more general context, where no direct reward is involved. Here, we provide evidence from functional MRI in humans that activity in the SN predicts systematic subsequent trial-to-trial RT prolongations that are thought to reflect cognitive control in a stop-signal paradigm. In particular, variations in the activity level of the SN in one trial predicted the degree of RT prolongation on the subsequent trial, consistent with a modulating output signal from the SN being involved in enhancing cognitive control. This link between SN activity and subsequent behavioral adjustments lends support to theoretical accounts that propose dopaminergic control signals that shape behavior both in the presence and in the absence of direct reward. This SN-based modulatory mechanism is presumably mediated via a wider network that determines response speed in this task, including frontal and parietal control regions, along with the BG and the associated subthalamic nucleus

Neurophysiological Profile of Antismoking Campaigns

Over the past few decades, antismoking public service announcements (PSAs) have been used by governments to promote healthy behaviours in citizens, for instance, against drinking before the drive and against smoke. Effectiveness of such PSAs has been suggested especially for young persons. By now, PSAs efficacy is still mainly assessed through traditional methods (questionnaires and metrics) and could be performed only after the PSAs broadcasting, leading to waste of economic resources and time in the case of Ineffective PSAs. One possible countermeasure to such ineffective use of PSAs could be promoted by the evaluation of the cerebral reaction to the PSA of particular segments of population (e.g., old, young, and heavy smokers). In addition, it is crucial to gather such cerebral activity in front of PSAs that have been assessed to be effective against smoke (Effective PSAs), comparing results to the cerebral reactions to PSAs that have been certified to be not effective (Ineffective PSAs). &e eventual differences between the cerebral responses toward the two PSA groups will provide crucial information about the possible outcome of new PSAs before to its broadcasting. &is study focused on adult population, by investigating the cerebral reaction to the vision of different PSA images, which have already been shown to be Effective and Ineffective for the promotion of an antismoking behaviour. Results showed how variables as gender and smoking habits can influence the perception of PSA images, and how different communication styles of the antismoking campaigns could facilitate the comprehension of PSA’s message and then enhance the related impac

Development during adolescence of the neural processing of social emotion

In this fMRI study, we investigated the development between adolescence and adulthood of the neural processing of social emotions. Unlike basic emotions (such as disgust and fear), social emotions (such as guilt and embarrassment) require the representation of another's mental states. Nineteen adolescents (10–18 years) and 10 adults (22–32 years) were scanned while thinking about scenarios featuring either social or basic emotions. In both age groups, the anterior rostral medial prefrontal cortex (MPFC) was activated during social versus basic emotion. However, adolescents activated a lateral part of the MPFC for social versus basic emotions, whereas adults did not. Relative to adolescents, adults showed higher activity in the left temporal pole for social versus basic emotions. These results show that, although the MPFC is activated during social emotion in both adults and adolescents, adolescents recruit anterior (MPFC) regions more than do adults, and adults recruit posterior (temporal) regions more than do adolescents

Frontostriatal Maturation Predicts Cognitive Control Failure to Appetitive Cues in Adolescents

Adolescent risk-taking is a public health issue that increases the odds of poor lifetime outcomes. One factor thought to influence adolescents' propensity for risk-taking is an enhanced sensitivity to appetitive cues, relative to an immature capacity to exert sufficient cognitive control. We tested this hypothesis by characterizing interactions among ventral striatal, dorsal striatal, and prefrontal cortical regions with varying appetitive load using fMRI scanning. Child, teen, and adult participants performed a go/no-go task with appetitive (happy faces) and neutral cues (calm faces). Impulse control to neutral cues showed linear improvement with age, whereas teens showed a nonlinear reduction in impulse control to appetitive cues. This performance decrement in teens was paralleled by enhanced activity in the ventral striatum. Prefrontal cortical recruitment correlated with overall accuracy and showed a linear response with age for no-go versus go trials. Connectivity analyses identified a ventral frontostriatal circuit including the inferior frontal gyrus and dorsal striatum during no-go versus go trials. Examining recruitment developmentally showed that teens had greater between-subject ventral-dorsal striatal coactivation relative to children and adults for happy no-go versus go trials. These findings implicate exaggerated ventral striatal representation of appetitive cues in adolescents relative to an intermediary cognitive control response. Connectivity and coactivity data suggest these systems communicate at the level of the dorsal striatum differentially across development. Biased responding in this system is one possible mechanism underlying heightened risk-taking during adolescence

The role of anterior cingulate cortex in the affective evaluation of conflict

An influential theory of anterior cingulate cortex (ACC) function argues that this brain region plays a crucial role in the affective evaluation of performance monitoring and control demands. Specifically, control-demanding processes such as response conflict are thought to be registered as aversive signals by ACC, which in turn triggers processing adjustments to support avoidance learning. In support of conflict being treated as an aversive event, recent behavioral studies demonstrated that incongruent (i.e., conflict inducing), relative to congruent, stimuli can speed up subsequent negative, relative to positive, affective picture processing. Here, we used fMRI to investigate directly whether ACC activity in response to negative versus positive pictures is modulated by preceding control demands, consisting of conflict and task-switching conditions. The results show that negative, relative to positive, pictures elicited higher ACC activation after congruent, relative to incongruent, trials, suggesting that ACC's response to negative (positive) pictures was indeed affectively primed by incongruent (congruent) trials. Interestingly, this pattern of results was observed on task repetitions but disappeared on task alternations. This study supports the proposal that conflict induces negative affect and is the first to show that this affective signal is reflected in ACC activation

Physiological, behavioral and subjective sadness reactivity in frontotemporal dementia subtypes.

Frontotemporal dementia (FTD), a neurodegenerative disease broadly characterized by socioemotional impairments, includes three clinical subtypes: behavioral variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and non-fluent variant primary progressive aphasia (nfvPPA). Emerging evidence has shown emotional reactivity impairments in bvFTD and svPPA, whereas emotional reactivity in nfvPPA is far less studied. In 105 patients with FTD (49 bvFTD, 31 svPPA and 25 nfvPPA) and 27 healthy controls, we examined three aspects of emotional reactivity (physiology, facial behavior and subjective experience) in response to a sad film. In a subset of the sample, we also examined the neural correlates of diminished aspects of reactivity using voxel-based morphometry. Results indicated that all three subtypes of FTD showed diminished physiological responding in respiration rate and diastolic blood pressure; patients with bvFTD and svPPA also showed diminished subjective experience, and no subtypes showed diminished facial behavior. Moreover, there were differences among the clinical subtypes in brain regions where smaller volumes were associated with diminished sadness reactivity. These results show that emotion impairments extend to sadness reactivity in FTD and underscore the importance of considering different aspects of sadness reactivity in multiple clinical subtypes for characterizing emotional deficits and associated neurodegeneration in FTD

The role of the lateral prefrontal cortex and anterior cingulate in stimulus–response association reversals

Many complex tasks require us to flexibly switch between behavioral rules, associations, and strategies. The prefrontal cerebral cortex is thought to be critical to the performance of such behaviors, although the relative contribution of different components of this structure and associated subcortical regions are not fully understood. We used functional magnetic resonance imaging to measure brain activity during a simple task which required repeated reversals of a rule linking a colored cue and a left/right motor response. Each trial comprised three discrete events separated by variable delay periods. A colored cue instructed which response was to be executed, followed by a go signal which told the subject to execute the response and a feedback instruction which indicated whether to ‘‘hold’’ or ‘‘f lip’’ the rule linking the colored cue and response. The design allowed us to determine which brain regions were recruited by the specific demands of preparing a rule contingent motor response, executing such a response, evaluating the significance of the feedback, and reconfiguring stimulus–response (SR) associations. The results indicate that an increase in neural activity occurs within the anterior cingulate gyrus under conditions in which SR associations are labile. In contrast, lateral frontal regions are activated by unlikely/unexpected perceptual events regardless of their significance for behavior. A network of subcortical structures, including the mediodorsal nucleus of the thalamus and striatum were the only regions showing activity that was exclusively correlated with the neurocognitive demands of reversing SR associations. We conclude that lateral frontal regions act to evaluate the behavioral significance of perceptual events, whereas medial frontal–thalamic circuits are involved in monitoring and reconfiguring SR associations when necessary