The Effect of Dehydroepiandrosterone Administration during Rehabilitation on White Matter Integrity Among Individuals With Polysubstance Use Disorder.

OBJECTIVES: Individuals with polysubstance use disorder (pSUD) exhibit vulnerability to relapse even after prolonged abstinence, with rehabilitation efforts achieving limited success. Previous studies highlighted dehydroepiandrosterone (DHEA) as a putative therapeutic agent that may aid rehabilitation, potentially by impacting white matter (WM) properties. The current study tested, for the first time, the effect of DHEA administration during rehabilitation on WM integrity among pSUD individuals, while assessing its putative association with long-term relapse rates. METHODS: Immediately after admission to rehabilitation, 30 pSUD individuals were assigned to receive either placebo or DHEA (100 mg) daily for 3 months, via a randomized double-blind counterbalanced design. Participants also provided blood samples to assess circulating DHEA levels at treatment initiation and completed a diffusion tensor imaging (DTI) scan approximately 1 month after treatment initiation. Clinical status was evaluated 16 months after treatment initiation. Thirty matched healthy controls also underwent a DTI scan without any intervention. RESULTS: DHEA administration was not associated with reduced relapse rates compared with placebo. Nevertheless, exploratory analysis revealed that DHEA was associated with successful rehabilitation among pSUD individuals with low circulating DHEA levels at treatment initiation. White matter integrity in the splenium corpus callosum (CC) was reduced in pSUD individuals compared with healthy controls, yet pSUD individuals receiving DHEA exhibited recovery of splenium CC WM integrity. CONCLUSIONS: DHEA administration during rehabilitation may restore WM integrity in the CC among pSUD individuals. Although DHEA was not associated with reduced relapse rates in here, its therapeutic efficacy may depend on circulating DHEA levels at treatment initiation.

Self-evaluation of social-rank in socially anxious individuals associates with enhanced striatal reward function.

BACKGROUND: Negative self-views, especially in the domain of power (i.e. social-rank), characterize social anxiety (SA). Neuroimaging studies on self-evaluations in SA have mainly focused on subcortical threat processing systems. Yet, self-evaluation may concurrently invoke diverse affective processing, as motivational systems related to desired self-views may also be activated. To investigate the conflictual nature that may accompany self-evaluation of certain social domains in SA, we examined brain activity related to both threat and reward processing. METHODS: Participants (N = 74) differing in self-reported SA-severity underwent fMRI while completing a self-evaluation task, wherein they judged the self-descriptiveness of high- v. low-intensity traits in the domains of power and affiliation (i.e. social connectedness). Participants also completed two auxiliary fMRI tasks designated to evoke reward- and threat-related activations in the ventral striatum (VS) and amygdala, respectively. We hypothesized that self-evaluations in SA, particularly in the domain of power, involve aberrant brain activity related to both threat and reward processing. RESULTS: SA-severity was more negatively associated with power than with affiliation self-evaluations. During self-evaluative judgment of high-power (e.g. dominant), SA-severity associated with increased activity in the VS and ventromedial prefrontal cortex. Moreover, SA-severity correlated with higher similarity between brain activity patterns activated by high-power traits and patterns activated by incentive salience (i.e. reward anticipation) in the VS during the reward task. CONCLUSIONS: Our findings indicate that self-evaluation of high-power in SA involves excessive striatal reward-related activation, and pinpoint the downregulation of VS-VMPFC activity within such self-evaluative context as a potential neural outcome for therapeutic interventions.

The rediscovered motor-related area 55b emerges as a core hub of music perception.

Passive listening to music, without sound production or evident movement, is long known to activate motor control regions. Nevertheless, the exact neuroanatomical correlates of the auditory-motor association and its underlying neural mechanisms have not been fully determined. Here, based on a NeuroSynth meta-analysis and three original fMRI paradigms of music perception, we show that the long-ignored pre-motor region, area 55b, an anatomically unique and functionally intriguing region, is a core hub of music perception. Moreover, results of a brain-behavior correlation analysis implicate neural entrainment as the underlying mechanism of area 55b's contribution to music perception. In view of the current results and prior literature, area 55b is proposed as a keystone of sensorimotor integration, a fundamental brain machinery underlying simple to hierarchically complex behaviors. Refining the neuroanatomical and physiological understanding of sensorimotor integration is expected to have a major impact on various fields, from brain disorders to artificial general intelligence.

Neural Responsivity to Reward Versus Punishment Shortly After Trauma Predicts Long-Term Development of Posttraumatic Stress Symptoms.

BACKGROUND: Processing negatively and positively valenced stimuli involves multiple brain regions including the amygdala and ventral striatum (VS). Posttraumatic stress disorder (PTSD) is often associated with hyperresponsivity to negatively valenced stimuli, yet recent evidence also points to deficient positive valence functioning. It is yet unclear what the relative contribution is of such opposing valence processing shortly after trauma to the development of chronic PTSD. METHODS: Neurobehavioral indicators of motivational positive versus negative valence sensitivities were longitudinally assessed in 171 adults (87 females, age = 34.19 ± 11.47 years) at 1, 6, and 14 months following trauma exposure (time point 1 [TP1], TP2, and TP3, respectively). Using a gambling functional magnetic resonance imaging paradigm, amygdala and VS functionality (activity and functional connectivity with the prefrontal cortex) in response to rewards versus punishments were assessed with relation to PTSD severity at different time points. The effect of valence processing was depicted behaviorally by the amount of risk taken to maximize reward. RESULTS: PTSD severity at TP1 was associated with greater neural functionality in the amygdala (but not in the VS) toward punishments versus rewards, and with fewer risky choices. PTSD severity at TP3 was associated with decreased neural functionality in both the VS and the amygdala toward rewards versus punishments at TP1 (but not with risky behavior). Explainable machine learning revealed the primacy of VS-biased processing, over the amygdala, in predicting PTSD severity at TP3. CONCLUSIONS: These results highlight the importance of biased neural responsivity to positive relative to negative motivational outcomes in PTSD development. Novel therapeutic strategies early after trauma may thus target both valence fronts.

A corticostriatal pathway mediating self-efficacy enhancement.

Forming positive beliefs about one's ability to perform challenging tasks, often termed self-efficacy, is fundamental to motivation and emotional well-being. Self-efficacy crucially depends on positive social feedback, yet people differ in the degree to which they integrate such feedback into self-beliefs (i.e., positive bias). While diminished positive bias of this sort is linked to mood and anxiety, the neural processes by which positive feedback on public performance enhances self-efficacy remain unclear. To address this, we conducted a behavioral and fMRI study wherein participants delivered a public speech and received fictitious positive and neutral feedback on their performance in the MRI scanner. Before and after receiving feedback, participants evaluated their actual and expected performance. We found that reduced positive bias in updating self-efficacy based on positive social feedback associated with a psychopathological dimension reflecting symptoms of anxiety, depression, and low self-esteem. Analysis of brain encoding of social feedback showed that a positive self-efficacy update bias associated with a stronger reward-related response in the ventral striatum (VS) and stronger coupling of the VS with a temporoparietal region involved in self-processing. Together, our findings demarcate a corticostriatal circuit that promotes positive bias in self-efficacy updating based on social feedback, and highlight the centrality of such bias to emotional well-being.

Somatic engagement alters subsequent neurobehavioral correlates of affective mentalizing.

Socio-emotional encounters involve a resonance of others' affective states, known as affect sharing (AS); and attribution of mental states to others, known as theory-of-mind (ToM). Empathy necessitates the integration of both processes, yet their interaction during emotional episodes and subsequent generation of inferences on others' affective states has rarely been tested. To address this, we developed a novel experimental design, wherein we manipulated AS by presenting nonverbal emotionally negative movies twice-each time accompanied by one of two soundtracks that accentuated either somatic cues or externally generated sounds. Movies were followed by questions addressing affective-ToM (emotional inferences), cognitive-ToM (inferences on beliefs and knowledge), and non-ToM aspects. Results revealed a neural differentiation between AS, affective-ToM, and cognitive-ToM. AS movies activated regions that have been implicated in emotional (e.g., amygdala) and somatosensory processing, and synchronized brain activity between participants in the latter. Affective-ToM activated the middle insula, limbic regions, and both ventral and dorsal portions of the medial prefrontal cortex (ventral medial prefrontal cortex [VMPFC] and dorsal medial prefrontal cortex [DMPFC], respectively), whereas cognitive-ToM activated posteromedial and lateral-prefrontal and temporal cortices. Critically, AS movies specifically altered neural activation in AS and ToM-related regions during subsequent affective-ToM inferences, most notably in the DMPFC. Moreover, DMPFC-VMPFC connectivity correlated with affective-ToM accuracy, when such questions followed AS movies. Our results associate empathic processes with designated neural activations and shed light on how neuro-behavioral indices of affective ToM are shaped by preceding somatic engagement.

Is there a prediction network? Meta-analytic evidence for a cortical-subcortical network likely subserving prediction.

Predictive coding is an increasingly influential and ambitious concept in neuroscience viewing the brain as a 'hypothesis testing machine' that constantly strives to minimize prediction error, the gap between its predictions and the actual sensory input. Despite the invaluable contribution of this framework to the formulation of brain function, its neuroanatomical foundations have not been fully defined. To address this gap, we conducted activation likelihood estimation (ALE) meta-analysis of 39 neuroimaging studies of three functional domains (action perception, language and music) inherently involving prediction. The ALE analysis revealed a widely distributed brain network encompassing regions within the inferior and middle frontal gyri, anterior insula, premotor cortex, pre-supplementary motor area, temporoparietal junction, striatum, thalamus/subthalamus and the cerebellum. This network is proposed to subserve domain-general prediction and its relevance to motor control, attention, implicit learning and social cognition is discussed in light of the predictive coding scheme. Better understanding of the presented network may help advance treatments of neuropsychiatric conditions related to aberrant prediction processing and promote cognitive enhancement in healthy individuals.

Surprise-related activation in the nucleus accumbens interacts with music-induced pleasantness.

How can music-merely a stream of sounds-be enjoyable for so many people? Recent accounts of this phenomenon are inspired by predictive coding models, hypothesizing that both confirmation and violations of musical expectations associate with the hedonic response to music via recruitment of the mesolimbic system and its connections with the auditory cortex. Here we provide support for this model, by revealing associations of music-induced pleasantness with musical surprises in the activity and connectivity patterns of the nucleus accumbens (NAcc)-a central component of the mesolimbic system. We examined neurobehavioral responses to surprises in three naturalistic musical pieces using fMRI and subjective ratings of valence and arousal. Surprises were associated with changes in reported valence and arousal, as well as with enhanced activations in the auditory cortex, insula and ventral striatum, relative to unsurprising events. Importantly, we found that surprise-related activation in the NAcc was more pronounced among individuals who experienced greater music-induced pleasantness. These participants also exhibited stronger surprise-related NAcc-auditory cortex connectivity during the most pleasant piece, relative to participants who found the music less pleasant. These findings provide a novel demonstration of a direct link between musical surprises, NAcc activation and music-induced pleasantness.