Reward-related Regions Research Articles

Associative memory in alcohol-related contexts: An fMRI study with young binge drinkers.

Alcohol-related cues are known to influence craving levels, a hallmark of alcohol misuse. Binge drinking (BD), a pattern of heavy alcohol use, has been associated with cognitive and neurofunctional alterations, including alcohol attentional bias, memory impairments, as well as disrupted activity in prefrontal- and reward-related regions. However, literature is yet to explore how memories associated with alcohol-related cues are processed by BDs, and how the recall of this information may influence their reward processing. The present functional magnetic resonance imaging (fMRI) study aimed to investigate the neurofunctional signatures of BD during an associative memory task. In all, 36 university students, 20 BDs and 16 alcohol abstainers, were asked to memorize neutral objects paired with either alcohol or non-alcohol-related contexts. Subsequently, neutral stimuli were presented, and participants were asked to classify them as being previously paired with alcohol- or non-alcohol-related contexts. While behavioral performance was similar in both groups, during the recall of alcohol-related cues, BDs showed increased brain activation in two clusters including the thalamus, globus pallidus and dorsal striatum, and cerebellum and occipital fusiform gyrus, respectively. These findings suggest that BDs display augmented brain activity in areas responsible for mental imagery and reward processing when trying to recall alcohol-related cues, which might ultimately contribute to alcohol craving, even without being directly exposed to an alcohol-related context. These results highlight the importance of considering how alcohol-related contexts may influence alcohol-seeking behavior and, consequently, the maintenance or increase in alcohol use.

Structural and functional correlates of olfactory reward processing in behavioral variant frontotemporal dementia

The behavioral variant of frontotemporal dementia (bvFTD) includes symptoms that reflect altered pursuit of rewards, including food, alcohol, and money. Little is known, however, about how these reward changes relate to atrophy and functional connectivity within reward-related regions. The goal of this study was to examine the structural and functional correlates of valence perception for olfactory rewards in 24 patients with bvFTD. Regression analysis of resting-state brain functional connectivity indicated that more positive valence ratings of olfactory stimuli were predicted by ventral pallidum connectivity to other reward circuit regions, particularly functional connectivity between ventral pallidum and bilateral anterior cingulate cortex/ventromedial prefrontal cortex. Structural analysis showed that atrophy of the anterior cingulate cortex was also significantly associated with perceiving stimuli as more rewarding. Finally, there was a significant interaction between ventral pallidum connectivity and atrophy of the anterior cingulate cortex. More specifically, the ventral pallidum connectivity had a greater effect on the positive perception of olfactory stimuli in the setting of low anterior cingulate cortex volume. These findings indicate that atrophy and functional connectivity within reward-relevant regions exert independent and interacting effects on the perception of pleasantness in bvFTD, potentially due to changes in hedonic “liking” signals.

Sex differences in glutamate transmission and plasticity in reward related regions.

Disruptions in glutamate homeostasis within the mesolimbic reward circuitry may play a role in the pathophysiology of various reward related disorders such as major depressive disorders, anxiety, and substance use disorders. Clear sex differences have emerged in the rates and symptom severity of these disorders which may result from differing underlying mechanisms of glutamatergic signaling. Indeed, preclinical models have begun to uncover baseline sex differences throughout the brain in glutamate transmission and synaptic plasticity. Glutamatergic synaptic strength can be assessed by looking at morphological features of glutamatergic neurons including spine size, spine density, and dendritic branching. Likewise, electrophysiology studies evaluate properties of glutamatergic neurons to provide information of their functional capacity. In combination with measures of glutamatergic transmission, synaptic plasticity can be evaluated using protocols that induce long-term potentiation or long-term depression. This review will consider preclinical rodent literature directly comparing glutamatergic transmission and plasticity in reward related regions of males and females. Additionally, we will suggest which regions are exhibiting evidence for sexually dimorphic mechanisms, convergent mechanisms, or no sex differences in glutamatergic transmission and plasticity and highlight gaps in the literature for future investigation.

Neighborhood Resources Associated With Psychological Trajectories and Neural Reactivity to Reward After Trauma

Research on resilience after trauma has often focused on individual-level factors (eg, ability to cope with adversity) and overlooked influential neighborhood-level factors that may help mitigate the development of posttraumatic stress disorder (PTSD). To investigate whether an interaction between residential greenspace and self-reported individual resources was associated with a resilient PTSD trajectory (ie, low/no symptoms) and to test if the association between greenspace and PTSD trajectory was mediated by neural reactivity to reward. As part of a longitudinal cohort study, trauma survivors were recruited from emergency departments across the US. Two weeks after trauma, a subset of participants underwent functional magnetic resonance imaging during a monetary reward task. Study data were analyzed from January to November 2023. Residential greenspace within a 100-m buffer of each participant's home address was derived from satellite imagery and quantified using the Normalized Difference Vegetation Index and perceived individual resources measured by the Connor-Davidson Resilience Scale (CD-RISC). PTSD symptom severity measured at 2 weeks, 8 weeks, 3 months, and 6 months after trauma. Neural responses to monetary reward in reward-related regions (ie, amygdala, nucleus accumbens, orbitofrontal cortex) was a secondary outcome. Covariates included both geocoded (eg, area deprivation index) and self-reported characteristics (eg, childhood maltreatment, income). In 2597 trauma survivors (mean [SD] age, 36.5 [13.4] years; 1637 female [63%]; 1304 non-Hispanic Black [50.2%], 289 Hispanic [11.1%], 901 non-Hispanic White [34.7%], 93 non-Hispanic other race [3.6%], and 10 missing/unreported [0.4%]), 6 PTSD trajectories (resilient, nonremitting high, nonremitting moderate, slow recovery, rapid recovery, delayed) were identified through latent-class mixed-effect modeling. Multinominal logistic regressions revealed that for individuals with higher CD-RISC scores, greenspace was associated with a greater likelihood of assignment in a resilient trajectory compared with nonremitting high (Wald z test = -3.92; P < .001), nonremitting moderate (Wald z test = -2.24; P = .03), or slow recovery (Wald z test = -2.27; P = .02) classes. Greenspace was also associated with greater neural reactivity to reward in the amygdala (n = 288; t277 = 2.83; adjusted P value = 0.02); however, reward reactivity did not differ by PTSD trajectory. In this cohort study, greenspace and self-reported individual resources were significantly associated with PTSD trajectories. These findings suggest that factors at multiple ecological levels may contribute to the likelihood of resiliency to PTSD after trauma.

Neural Responses to Auditory Food Stimuli Following Cognitive Behavioral Therapy for Binge-Eating Disorder.

Adults with binge-eating disorder (BED), compared with those without BED, demonstrate higher blood-oxygen-level-dependent (BOLD) response to food cues in reward-related regions of the brain. It is not known whether cognitive behavioral therapy (CBT) can reverse this reward system hyperactivation. This randomized controlled trial (RCT) assessed changes in BOLD response to binge-eating cues following CBT versus wait-list control (WLC). Females with BED (N = 40) were randomized to CBT or WLC. Participants completed assessments at baseline and 16 weeks including measures of eating and appetite and functional magnetic resonance imaging (fMRI) to measure BOLD response while listening to personalized scripts of binge-eating and neutral-relaxing cues. Data were analyzed using general linear models with mixed effects. Overall retention rate was 87.5%. CBT achieved significantly greater reductions in binge-eating episodes than WLC (mean ± standard error decline of 14.6 ± 2.7 vs. 5.7 ± 2.8 episodes in the past 28 days, respectively; p = 0.03). CBT and WLC did not differ significantly in changes in neural responses to binge-eating stimuli during the fMRI sessions. Compared with WLC, CBT had significantly greater improvements in reward-based eating drive, disinhibition, and hunger as assessed by questionnaires (ps < 0.05). CBT was effective in reducing binge eating, but, contrary to our hypothesis, CBT did not improve BOLD response to auditory binge-eating stimuli in reward regions of the brain. Further studies are needed to assess mechanisms underlying improvements with CBT for BED. ClinicalTrials.gov identifier: NCT03604172.

Altered neural anticipation of reward and loss but not receipt in adolescents with obsessive-compulsive disorder

BackgroundObsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD.MethodsUsing functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task.ResultsData revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group.ConclusionsThese findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward ‘wanting’ may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology).

Mindfulness Meditation Training Reduces Gaming Cravings by Reshaping the Functional Connectivity Between the Default Mode Network and Executive Control–Related Brain Regions

BackgroundInternet gaming disorder (IGD) can lead to psychological problems and cause behavioral problems in individuals. Traditional interventions have been ineffective in treating IGD. Meanwhile, mindfulness meditation (MM) is an emerging method that has proven to be effective for treating psychiatric disorders. In this study, MM was used to intervene in IGD and to explore its neural mechanism. MethodsEighty participants were recruited through advertisements. Eventually, 61 completed the 1-month training (MM group, n = 31; progressive muscle relaxation [PMR] group, n = 30), including a pretest, 8 training sessions, and a posttest. Regional homogeneity and degree centrality were calculated, and the tests (pre- and post-) and group (MM and PMR) analysis of variance was performed. The overlapping results were obtained as region of interest for functional connectivity (FC) analyses. Behavioral data and neurotransmitter availability maps were correlated with FC. ResultsCompared with PMR, MM decreased the severity of addiction and game craving in IGD. Brain imaging results showed that the FC between and within the executive control and default mode networks/reward-related regions were enhanced. Significant negative correlations were observed between FC and dopamine receptor D2, dopamine transporter, and vesicular acetylcholine transporter. Significant positive correlations were observed between FCs and serotonin and aminobutyric acid receptors. ConclusionsThis study confirmed the effectiveness of MM in treating IGD. MM altered the default mode and enhanced top-down control over game cravings. These findings were revealed by the correlations between brain regions and behavioral and biochemical effects. The results show the neural mechanism of MM in reducing IGD and lay the foundation for future research.

Reward-related regions play a role in natural story comprehension

The reward system was shown to be involved in a wide array of processes. Nevertheless, the exploration of the involvement of the reward system during language processing has not yet been directly tested. We investigated the role of reward-processing regions while listening to a natural story. We utilized a published dataset in which half of the participants listened to a natural story and the others listened to a scrambled version of it to compare the functional MRI signals in the reward system between these conditions and discovered a distinct pattern between conditions. This suggests that the reward system is activated during the comprehension of natural stories. We also show evidence that the fMRI signals in reward-related areas might potentially correlate with the predictability level of processed sentences. Further research is needed to determine the nature of the involvement and the way the activity interacts with various aspects of the sentences.

Relationship between functional connectivity and weight-gain risk of antipsychotics in schizophrenia

BackgroundThe mechanisms by which antipsychotic medications (APs) contribute to obesity in schizophrenia are not well understood. Because AP effects on functional brain connectivity may contribute to weight effects, the current study investigated how AP-associated weight-gain risk relates to functional connectivity in schizophrenia. MethodsFifty-five individuals with schizophrenia (final N = 54) were divided into groups based on previously reported AP weight-gain risk (no APs/low risk [N = 19]; moderate risk [N = 17]; high risk [N = 18]). Resting-state functional magnetic resonance imaging (fMRI) was completed after an overnight fast (“fasted”) and post-meal (“fed”). Correlations between AP weight-gain risk and functional connectivity were assessed at the whole-brain level and in reward- and eating-related brain regions (anterior insula, caudate, nucleus accumbens). ResultsWhen fasted, greater AP weight-gain risk was associated with increased connectivity between thalamus and sensorimotor cortex (pFDR = 0.021). When fed, greater AP weight-gain risk was associated with increased connectivity between left caudate and left precentral/postcentral gyri (pFDR = 0.048) and between right caudate and multiple regions, including the left precentral/postcentral gyri (pFDR = 0.001), intracalcarine/precuneal/cuneal cortices (pFDR < 0.001), and fusiform gyrus (pFDR = 0.008). When fed, greater AP weight-gain risk was also associated with decreased connectivity between right anterior insula and ventromedial prefrontal cortex (pFDR = 0.002). ConclusionsAPs with higher weight-gain risk were associated with greater connectivity between reward-related regions and sensorimotor regions when fasted, perhaps relating to motor anticipation for consumption. Higher weight-gain risk APs were also associated with increased connectivity between reward, salience, and visual regions when fed, potentially reflecting greater desire for consumption following satiety.

Distinct functional patterns in child and adolescent bipolar and unipolar depression during emotional processing.

Accumulating evidence from functional magnetic resonance imaging studies supported brain dysfunction during emotional processing in bipolar disorder (BD) and major depressive disorder (MDD). However, child and adolescent BD and MDD could display different activation patterns, which have not been fully understood. This study aimed to investigate common and distinct activation patterns of pediatric BD (PBD) and MDD (p-MDD) during emotion processing using meta-analytic approaches. Literature search identified 25 studies, contrasting 252 PBD patients, and 253 healthy controls (HCs) as well as 311 p-MDD patients and 263 HCs. A total of nine meta-analyses were conducted pulling PBD and p-MDD experiments together and separately. The results revealed that PBD and p-MDD showed distinct patterns during negative processing. PBD patients exhibited activity changes in bilateral precuneus, left inferior parietal gyrus, left angular gyrus, and right posterior cingulate cortex while p-MDD patients showed functional disruptions in the left rectus, left triangular part of the inferior frontal gyrus, left orbital frontal cortex, left insula, and left putamen. In conclusion, the activity changes in PBD patients were mainly in regions correlated with emotion perception while the dysfunction among p-MDD patients was in the fronto-limbic circuit and reward-related regions in charge of emotion appraisal and regulation.

Anhedonia and Delay Discounting: Differing Patterns of Brain-Behavior Relationships in Healthy Control Participants Versus Individuals With Posttraumatic Stress Disorder

BackgroundAnhedonia may contribute to individual differences in delay discounting (DD). In prior work, we found that higher anhedonia was associated with shallower DD in healthy control (HC) participants but steeper DD in individuals with posttraumatic stress disorder (PTSD). In this study, we aimed to directly compare the relationship between anhedonia and DD across groups and to identify functional brain correlates of this interaction. MethodsParticipants (HC group: n = 23, DSM-5 PTSD group: n = 23) completed a questionnaire assessing anhedonia (Snaith-Hamilton Pleasure Scale [SHAPS]), task-based functional magnetic resonance imaging of decision making including DD, and resting-state functional magnetic resonance imaging. Task-based activity and resting-state functional connectivity were evaluated in reward-related regions that have also been implicated in PTSD (nucleus accumbens [NAcc], right anterior insula). ResultsHigher SHAPS scores were associated with steeper DD in PTSD, but there was no relationship between DD and SHAPS in the HC group. There was a significant group-by-SHAPS interaction for NAcc activity, t31 = 2.92, p = .007: Greater NAcc activity when immediate rewards were chosen was associated with higher SHAPS in the PTSD group but lower SHAPS in the HC group. In resting-state functional connectivity, there was a group-by-SHAPS interaction between the NAcc seed and right parietal and frontal pole clusters. ConclusionsThese results extend prior findings that anhedonia is associated with steeper DD in PTSD and demonstrate that this behavioral finding occurs in the context of NAcc hyperactivity to immediate rewards and hyperconnectivity in anhedonic individuals with PTSD.

Large-scale brain correlates of sweet versus cocaine reward in rats.

Cocaine induces many supranormal changes in neuronal activity in the brain, notably in learning- and reward-related regions, in comparison with nondrug rewards-a difference that is thought to contribute to its relatively high addictive potential. However, when facing a choice between cocaine and a nondrug reward (e.g., water sweetened with saccharin), most rats do not choose cocaine, as one would expect from the extent and magnitude of its global activation of the brain, but instead choose the nondrug option. We recently showed that cocaine, though larger in magnitude, is also an inherently more delayed reward than sweet water, thereby explaining why it has less value during choice and why rats opt for the more immediate nondrug option. Here, we used a large-scale Fos brain mapping approach to measure brain responses to each option in saccharin-preferring rats, with the hope to identify brain regions whose activity may explain the preference for the nondrug option. In total, Fos expression was measured in 142 brain levels corresponding to 52 brain subregions and composing 5 brain macrosystems. Overall, our findings confirm in rats with a preference for saccharin that cocaine induces more global brain activation than the preferred nondrug option does. Only very few brain regions were uniquely activated by saccharin. They included regions involved in taste processing (i.e., anterior gustatory cortex) and also regions involved in processing reward delay and intertemporal choice (i.e., some components of the septohippocampal system and its connections with the lateral habenula).

Hypothalamic interaction with reward-related regions during subjective evaluation of foods

The reward system implemented in the midbrain, ventral striatum, orbitofrontal cortex, and ventromedial prefrontal cortex evaluates and compares various types of rewards given to the organisms. It has been suggested that autonomic factors influence reward-related processing via the hypothalamus, but how the hypothalamus modulates the reward system remains elusive. In this functional magnetic resonance imaging study, the hypothalamus was parcellated into individual hypothalamic nuclei performing different autonomic functions using boundary mapping parcellation analyses. The effective interaction during subjective evaluation of foods in a reward task was then investigated between the human hypothalamic nuclei and the reward-related regions. We found significant brain activity decrease in the paraventricular nucleus (PVH) and lateral nucleus in the hypothalamus in food evaluation compared with monetary evaluation. A psychophysiological interaction analysis revealed dual interactions between the PVH and (1) midbrain region and (2) ventromedial prefrontal cortex, with the former correlated with the stronger tendency of participants toward food-seeking. A dynamic causal modeling analysis further revealed unidirectional interactions from the PVH to the midbrain and ventromedial prefrontal cortex. These results suggest that the PVH in the human hypothalamus interacts with the reward-related regions in the cerebral cortex via multiple pathways (i.e., the midbrain pathway and ventromedial prefrontal pathway) to evaluate rewards for subsequent decision-making.

Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls

Chronic use of drugs may alter the brain’s reward system, though the extant literature concerning long-term cannabis use and neural correlates of reward processing has shown mixed results. Adolescents may be more vulnerable to the adverse effects of cannabis than adults; however, this has not been investigated for reward processing. As part of the ‘CannTeen’ study, in the largest functional magnetic resonance imaging study of reward processing and cannabis use to date, we investigated reward anticipation and feedback in 125 adult (26–29 years) and adolescent (16–17 years) cannabis users (1–7 days/week cannabis use) and gender- and age-matched controls, using the Monetary Incentive Delay task. Blood-oxygen-level-dependent responses were examined using region of interest (ROI) analyses in the bilateral ventral striatum for reward anticipation and right ventral striatum and left ventromedial prefrontal cortex for feedback, and exploratory whole-brain analyses. Results showed no User-Group or User-Group × Age-Group effects during reward anticipation or feedback in pre-defined ROIs. These null findings were supported by post hoc Bayesian analyses. However, in the whole-brain analysis, cannabis users had greater feedback activity in the prefrontal and inferior parietal cortex compared to controls. In conclusion, cannabis users and controls had similar neural responses during reward anticipation and in hypothesised reward-related regions during reward feedback. The whole-brain analysis revealed tentative evidence of greater fronto-parietal activity in cannabis users during feedback. Adolescents showed no increased vulnerability compared with adults. Overall, reward anticipation and feedback processing appear spared in adolescent and adult cannabis users, but future longitudinal studies are needed to corroborate this.

Neural heterogeneity underlying late adolescent motivational processing is linked to individual differences in behavioral sensation seeking.

Adolescent risk-taking, including sensation seeking (SS), is often attributed to developmental changes in connectivity among brain regions implicated in cognitive control and reward processing. Despite considerable scientific and popular interest in this neurodevelopmental framework, there are few empirical investigations of adolescent functional connectivity, let alone examinations of its links to SS behavior. The studies that have been done focus on mean-based approaches and leave unanswered questions about individual differences in neurodevelopment and behavior. The goal of this paper is to take a person-specific approach to the study of adolescent functional connectivity during a continuous motivational state, and to examine links between connectivity and self-reported SS behavior in 104 adolescents (MAge =19.3; SDAge =1.3). Using Group Iterative Multiple Model Estimation (GIMME), person-specific connectivity during two neuroimaging runs of a monetary incentive delay task was estimated among 12 a priori brain regions of interest representing reward, cognitive, and salience networks. Two data-driven subgroups were detected, a finding that was consistent between both neuroimaging runs, but associations with SS were only found in the first run, potentially reflecting neural habituation in the second run. Specifically, the subgroup that had unique connections between reward-related regions had greater SS and showed a distinctive relation between connectivity strength in the reward regions and SS. These findings provide novel evidence for heterogeneity in adolescent brain-behavior relations by showing that subsets of adolescents have unique associations between neural motivational processing and SS. Findings have broader implications for future work on reward processing, as they demonstrate that brain-behavior relations may attenuate across runs.

Risk-taking in humans and the medial orbitofrontal cortex reward system

Risk-taking differs between humans, and is associated with the personality measures of impulsivity and sensation-seeking. To analyse the brain systems involved, self-report risk-taking, resting state functional connectivity, and related behavioral measures were analyzed in 18,740 participants of both sexes from the UK Biobank. Functional connectivities of the medial orbitofrontal cortex, ventromedial prefrontal cortex (VMPFC), and the parahippocampal areas were significantly higher in the risk-taking group (p < 0.001, FDR corrected). The risk-taking measure was validated in that it was significantly associated with alcohol drinking amount (r = 0.08, p = 5.1×10−28), cannabis use (r = 0.12, p = 6.0×10−66), and anxious feelings (r = -0.12, p = 7.6×−98). The functional connectivity findings were cross-validated in two independent datasets. The higher functional connectivity of the medial orbitofrontal cortex and VMPFC included higher connectivity with the anterior cingulate cortex, which provides a route for these reward-related regions to have a greater influence on action in risk-taking individuals. In conclusion, the medial orbitofrontal cortex, which is involved in reward value and pleasure, was found to be related to risk-taking, which is associated with impulsivity. An implication is that risk-taking is driven by specific orbitofrontal cortex reward systems, and is different for different rewards which are represented differently in the brains of different individuals. This is an advance in understanding the bases and mechanisms of risk-taking in humans, given that the orbitofrontal cortex, VMPFC and anterior cingulate cortex are highly developed in humans, and that risk-taking can be reported in humans.

Dopamine D4 Receptor Is a Regulator of Morphine-Induced Plasticity in the Rat Dorsal Striatum.

Long-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D4 receptor (D4R) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the D4R agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of μ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K+ channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of D4R modulating morphine-induced plasticity in the dorsal striatum. Thus, D4R could represent a valuable pharmacological target for the safety use of morphine in pain management.

In(s) and out(s) of adolescent depression – Trajectories of development and recovery

While the role of biological markers in understanding major depressive disorder (MDD) in adults have been studied extensively, less has been done to identify the biomarkers of MDD development and recovery in adolescence. With the majority of mental health disorders starting in adolescence, identifying biomarkers of transition and recovery from MDD early in life is critical for developing effective prevention strategies. Considering most of the child and adolescent populations come from low-and-middle-income countries (LMICs), it is vital to focus on adolescent populations in these settings. With most studies coming from high-income countries (HICs), evidence suggests that elevated morning cortisol levels including cortisol awakening response (CAR), increased peripheral inflammation and brain abnormalities such as cortico-limbic dysregulation or blunted activity in reward related regions in response to positive information are associated with MDD and being at-risk for MDD development in adolescence. We also find that some of the biological mechanisms of recovery from MDD, mainly normalisation in the cortico-limbic dysregulation, are reported following psychological therapy, suggesting shared pathways leading to MDD vulnerability and recovery. Although, only a few studies include adolescent populations. Understanding molecular mechanisms through which psychological interventions are effective, as well as molecular markers of transition to depression in individuals at-risk, are important to inform effective prevention and intervention strategies.

Neural underpinnings of food choice and consumption in obesity.

Obesity is associated with unhealthy food choices. Food selection is driven by the subjective valuation of available options, and the perceived and actual rewards accompanying consumption. These cognitive operations are mediated by brain regions including the ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), and ventral striatum (vStr). This study investigated the relationship between body mass index (BMI) and functional activations in the vmPFC, dACC, and vStr during food selection and consumption. After overnight fasting, 26 individuals (BMI: 18-40 kg/m2) performed a food choice task while being scanned with functional magnetic resonance imaging (fMRI). Each trial involved selecting one beverage from a pair of presented options, followed by delivery of a 3 mL aliquot of the selected option using an MR-compatible gustometer. We also tracked subjective preference for each beverage throughout the experiment. During food choice, individuals with greater BMI had less activation in the dorsolateral prefrontal cortex when selecting a high-value option and less vmPFC activation upon its consumption. Independent of BMI, during food choice the dACC and anterior insula elicited higher activation when a less preferred beverage was selected. Activation of the dACC and a broader frontoparietal network was also observed when deciding between options more similar in value. During consumption, receipt of a more preferred beverage was associated with greater vmPFC response, and attenuation of the dACC. An individual's preference for a food option modulates the brain activity associated with choosing and consuming it. The relationship between food preference and underlying brain activity is altered in obesity, with reduced engagement of cognition-related regions when presented with a highly valued option, but a blunted response in reward-related regions upon consumption.

Electroacupuncture enhances resting-state functional connectivity between dorsal caudate and precuneus and decreases associated leptin levels in overweight/obese subjects.

Electroacupuncture (EA) is a safe and effective method for treating obesity. However, how it modulates reward-related brain activity/functional connectivity and gut hormones remains unclear. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and resting-state functional connectivity (RSFC) to investigate EA induced changes in resting-state activity and RSFC in reward-related regions and its association with gut hormones in overweight/obese subjects who received real (n = 20) and Sham (n = 15) stimulation. Results showed reduced leptin levels was positively correlated with reduced body mass index (BMI) and negatively correlated with increased cognitive-control as measured with Three-Factor-Eating-Questionnaire (TFEQ). Significant time effects on RSFC between dorsal caudate (DC) and precuneus were due to significant increased RSFC strength in both EA and Sham groups. In addition, increased RSFC of DC-precuneus was negatively correlated with reduced BMI and leptin levels in the EA group. Mediation analysis showed that the relationship between increased DC-precuneus RSFC strength and reduced BMI was mediated by reduced leptin levels. These findings reflect the association between EA-induced brain reward-related RSFC and leptin levels, and decreased leptin levels mediated altered DC-precuneus RSFC strength and consequent weight-loss, suggesting the potential role of EA in reducing weight and appetite.