Estradiol Replacement as a Potential Enhancer of Working Memory and Neuroplasticity in Hypogonadal Trans Women.

INTRODUCTION: The cognitive effects of cross-sex hormone therapy (CSHT) are not well understood. In cisgender individuals, sex hormone therapy can impact neurotransmitter levels and structural anatomy. Similarly, in gender-diverse persons, CSHT has been associated with neural adaptations, such as growth in brain structures resembling those observed in cisgender individuals of the same sex. Hormone-related changes in learning and memory, as seen in menopause, are associated with physiological hypogonadism or a decline in hormones, such as estradiol. The present study examined the effect of estradiol administration in humans on glutamate concentration in brain regions involved in semantic and working memory (i.e., the dorsolateral prefrontal cortex [DLPFC], the posterior hippocampus, and the pregenual anterior cingulate cortex) and its relationship with memory. METHODS: Eighteen trans women (male biological sex assigned at birth) ceased CSHT for 30 days for a washout phase (t1) upon study enrollment to reach a hypogonadal state. Working and semantic memory, cognition, hormonal assays, and brain imaging were assessed. Participants resumed CSHT for 60 days for a replacement phase (t2), after which the same evaluations from t1 were repeated. RESULTS: Estradiol increased among trans women after 60 days of resumed CSHT with significant improvements in semantic memory compared to the hypogonadal phase. Working memory recall was significantly and positively correlated to glutamate in the DLPFC during the reinstatement phase, although the relationship was not moderated by levels of estradiol. DISCUSSION: These results may have clinical implications for the therapeutic effects of estradiol replacement, serving as a protective factor against cognitive decline and impairment for trans women post-gonadectomy.

A DSM-5-based tool to monitor concurrent mood and premenstrual symptoms: the McMaster Premenstrual and Mood Symptom Scale (MAC-PMSS).

BACKGROUND: Despite high co-morbidity between premenstrual dysphoric disorder and mood disorders, there is a gap of research-based tools to monitor concurrent premenstrual and mood symptoms. In this study, we developed a new DSM-5-based questionnaire to prospectively monitor concurrent premenstrual and mood symptoms. METHODS: Fifty-two females with bipolar or major depressive disorder, ages 16-45, were enrolled in the study. Participants completed two months of prospective symptom charting including the McMaster Premenstrual and Mood Symptom Scale (MAC-PMSS) and the Daily Record of Severity of Problems (DRSP). At the end of the prospective charting, participants also completed the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). The MAC-PMSS was correlated with the DRSP, MADRS, HDRS and YMRS. RESULTS: All individual items of the MAC-PMSS correlated strongly with the individual DRSP scores (all p < 0.001). The mood section of the MAC-PMSS also significantly correlated with MADRS (r = 0.572; p < 0.01), HDRS (r = 0.555; p < 0.01) and YMRS scores (r = 0.456; p < 0.01). CONCLUSIONS: The MAC-PMSS is a reliable to tool to measure concurrent mood and premenstrual symptoms in women with mood disorders.

Investigating biological rhythms disruptions across the menstrual cycle in women with comorbid bipolar disorder and premenstrual dysphoric disorder.

We investigated whether women diagnosed with comorbid bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD) experience higher disruptions in biological rhythms in two independent study samples. The first study has a population-based sample of 727 women, including 104 women with PMDD only, 43 women with BD only, 24 women with comorbid PMDD and BD, and 556 women without BD or PMDD (controls). Biological rhythm disruptions were cross-sectionally evaluated using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). The second study enrolled 77 outpatient women who completed prospective assessments at two timepoints: during the mid-follicular and the late-luteal phases of their menstrual cycles, using the BRIAN, and included 19 women with PMDD, 16 with BD, 17 with comorbid PMDD and BD, and 25 controls. In the population-based sample, all the diagnostic groups (BD, PMDD, BDPMDD) presented greater biological rhythm disruption than controls. In addition, women with BD presented greater overall biological rhythms disruption, and greater disruption in sleep, activity, and eating patterns, than women with PMDD. In the outpatient sample study, women with BDPMDD showed greater disruption in the social domain than women with PMDD. In the outpatient sample, women with BDPMDD reported significantly higher disruptions in biological rhythms across both the follicular and the luteal phases of the menstrual cycle. The comorbidity between BD and PMDD may affect biological rhythms beyond the luteal phase of the menstrual cycle. These results support previous literature on the increased illness burden of women diagnosed with comorbid BD and PMDD.

Delayed Reward Discounting as a Prognostic Factor for Smoking Cessation Treatment Outcome: A Systematic Review.

INTRODUCTION: While large proportions of smokers attempt to quit, rates of relapse remain high and identification of valid prognostic markers is of high priority. Delayed reward discounting (DRD) is a behavioral economic index of impulsivity that has been associated with smoking cessation, albeit inconsistently. This systematic review sought to synthesize the empirical findings on DRD as a predictor of smoking cessation treatment outcome, to critically appraise the quality of the literature, and to propose directions for future research. AIMS AND METHODS: A total of 734 articles were identified, yielding k = 14 studies that met the eligibility criteria. The Quality in Prognosis Studies (QUIPS) tool was used to assess methodological quality of the included studies. RESULTS: Individual study methods were highly heterogeneous, including substantial variation in research design, DRD task, clinical subpopulation, and treatment format. The predominant finding was that steeper DRD (higher impulsivity) was associated with significantly worse smoking cessation outcomes (10/14 studies). Negative results tended to be in pregnant and adolescent subpopulations. The QUIPS results suggested low risk of bias across studies; 11/14 studies were rated as low risk of bias for 5/6 QUIPS domains. CONCLUSIONS: This review revealed consistent low-bias evidence for impulsive DRD as a negative prognostic predictor of smoking cessation treatment outcome in adults. However, methodological heterogeneity was high, precluding meta-analysis and formal tests of small study bias. The prospects of targeting impulsive DRD as a potentially modifiable risk factor or providing targeted treatment for smokers exhibiting high levels of discounting are discussed. IMPLICATIONS: These findings indicate consistent evidence for DRD as a negative prognostic factor for smoking cessation outcome in adults. As such, DRD may be a useful as a novel treatment target or for identifying high-risk populations requiring more intensive treatment.

Associations Between Drinking and Cortical Thickness in Younger Adult Drinkers: Findings From the Human Connectome Project.

BACKGROUND: Previous neuroimaging studies examining relations between alcohol misuse and cortical thickness have revealed that increased drinking quantity and alcohol-related problems are associated with thinner cortex. Although conflicting regional effects are often observed, associations are generally localized to frontal regions (e.g., dorsolateral prefrontal cortex [DLPFC], inferior frontal gyrus [IFG], and anterior cingulate cortex). Inconsistent findings may be attributed to methodological differences, modest sample sizes, and limited consideration of sex differences. METHODS: This study examined neuroanatomical correlates of drinking quantity and heavy episodic drinking in a large sample of younger adults (N = 706; Mage  = 28.8; 51% female) using magnetic resonance imaging data from the Human Connectome Project. Exploratory analyses examined neuroanatomical correlates of executive function (flanker task) and working memory (list sorting). RESULTS: Hierarchical linear regression models (controlling for age, sex, education, income, smoking, drug use, twin status, and intracranial volume) revealed significant inverse associations between drinks in past week and frequency of heavy drinking and cortical thickness in a majority of regions examined. The largest effect sizes were found for frontal regions (DLPFC, IFG, and the precentral gyrus). Follow-up regression models revealed that the left DLPFC was uniquely associated with both drinking variables. Sex differences were also observed, with significant effects largely specific to men. CONCLUSIONS: This study adds to the understanding of brain correlates of alcohol use in a large, gender-balanced sample of younger adults. Although the cross-sectional methodology precludes causal inferences, these findings provide a foundation for rigorous hypothesis testing in future longitudinal investigations.

Cannabidiol as a Novel Candidate Alcohol Use Disorder Pharmacotherapy: A Systematic Review.

There is substantial interest in the therapeutic potential of cannabidiol (CBD), a nonpsychoactive cannabinoid found in plants of the genus Cannabis. The goal of the current systematic review was to characterize the existing literature on this topic and to evaluate the credibility of CBD as a candidate pharmacotherapy for alcohol use disorder (AUD). Using a comprehensive search strategy, 303 unique potential articles were identified and 12 ultimately met criteria for inclusion (8 using rodent models, 3 using healthy adult volunteers, and 1 using cell culture). In both rodent and cell culture models, CBD was found to exert a neuroprotective effect against adverse alcohol consequences on the hippocampus. In rodent models, CBD was found to attenuate alcohol-induced hepatotoxicity, specifically, alcohol-induced steatosis. Finally, findings from preclinical rodent models also indicate that CBD attenuates cue-elicited and stress-elicited alcohol seeking, alcohol self-administration, withdrawal-induced convulsions, and impulsive discounting of delayed rewards. In human studies, CBD was well tolerated and did not interact with the subjective effects of alcohol. Collectively, given its favorable effects on alcohol-related harms and addiction phenotypes in preclinical models, CBD appears to have promise as a candidate AUD pharmacotherapy. This is further bolstered by the absence of abuse liability and its general tolerability. A clear limitation to the literature is the paucity of human investigations. Human preclinical and clinical studies are needed to determine whether these positive effects in model systems substantively translate into clinically relevant outcomes.

Resting-state functional connectivity in individuals with bipolar disorder during clinical remission: a systematic review.

BACKGROUND: Bipolar disorder is chronic and debilitating. Studies investigating resting-state functional connectivity in individuals with bipolar disorder may help to inform neurobiological models of illness. METHODS: We conducted a systematic review with the following goals: to summarize the literature on resting-state functional connectivity in bipolar disorder during clinical remission (euthymia) compared with healthy controls; to critically appraise the literature and research gaps; and to propose directions for future research. We searched PubMed/MEDLINE, Embase, PsycINFO, CINAHL and grey literature up to April 2017. RESULTS: Twenty-three studies were included. The most consistent finding was the absence of differences in resting-state functional connectivity of the default mode network (DMN), frontoparietal network (FPN) and salience network (SN) between people with bipolar disorder and controls, using independent component analysis. However, 2 studies in people with bipolar disorder who were positive for psychosis history reported DMN hypoconnectivity. Studies using seed-based analysis largely reported aberrant resting-state functional connectivity with the amygdala, ventrolateral prefrontal cortex, cingulate cortex and medial prefrontal cortex in people with bipolar disorder compared with controls. Few studies used regional homogeneity or amplitude of low-frequency fluctuations. LIMITATIONS: We found heterogeneity in the analysis methods used. CONCLUSION: Stability of the DMN, FPN and SN may reflect a state of remission. Further, DMN hypoconnectivity may reflect a positive history of psychosis in patients with bipolar disorder compared with controls, highlighting a potentially different neural phenotype of psychosis in people with bipolar disorder. Resting-state functional connectivity changes between the amygdala, prefrontal cortex and cingulate cortex may reflect a neural correlate of subthreshold symptoms experienced in bipolar disorder euthymia, the trait-based pathophysiology of bipolar disorder and/or a compensatory mechanism to maintain a state of euthymia.

Structural and functional changes in the somatosensory cortex in euthymic females with bipolar disorder.

OBJECTIVE: Current evidence from neuroimaging data suggests possible dysfunction of the fronto-striatal-limbic circuits in individuals with bipolar disorder. Somatosensory cortical function has been implicated in emotional recognition, risk-taking and affective responses through sensory modalities. This study investigates anatomy and function of the somatosensory cortex in euthymic bipolar women. METHODS: In total, 68 right-handed euthymic women (bipolar disorder = 32 and healthy controls = 36) between 16 and 45 years of age underwent high-resolution anatomical and functional magnetic resonance imaging during the mid-follicular menstrual phase. The somatosensory cortex was used as a seed region for resting-state functional connectivity analysis. Voxel-based morphometry was used to evaluate somatosensory cortical gray matter volume between groups. RESULTS: We found increased resting-state functional connectivity between the somatosensory cortex and insular cortex, inferior prefrontal gyrus and frontal orbital cortex in euthymic bipolar disorder subjects compared to healthy controls. Voxel-based morphometry analysis showed decreased gray matter in the left somatosensory cortex in the bipolar disorder group. Whole-brain voxel-based morphometry analysis controlled by age did not reveal any additional significant difference between groups. CONCLUSION: This study is the first to date to evaluate anatomy and function of the somatosensory cortex in a well-characterized sample of euthymic bipolar disorder females. Anatomical and functional changes in the somatosensory cortex in this population might contribute to the pathophysiology of bipolar disorder.

Resting state functional connectivity in women with bipolar disorder during clinical remission.

OBJECTIVES: Periods of euthymia in bipolar disorder (BD) serve as a valuable time to study trait-based pathophysiology. The use of resting state functional connectivity (Rs-FC) can aid in the understanding of BD pathophysiology free of task or mood state biases. The present study investigated two unexplored areas of Rs-FC research in bipolar remission: (i) Rs-FC in women, controlling for the potential influence of premenstrual symptoms, and (ii) the use of both independent component analysis (ICA) and seed-based analysis (SBA) to investigate Rs-FC. METHODS: We investigated Rs-FC of the default mode network, meso-paralimbic network and fronto-parietal network in a sample of 32 euthymic women with BD and 36 age-matched controls during the mid-follicular phase of their menstrual cycle. Rs-FC was assessed with ICA and SBA using the posterior cingulate cortex (PCC), amygdala and dorsolateral prefrontal cortex (dlPFC) as seed points for their respective resting state networks. RESULTS: In BD, compared to controls, SBAs revealed increased coupling between the PCC and the angular gyrus (P=.002, false discovery rate [FDR]-corrected) and between the right dlPFC and the brainstem (P=.03, FDR-corrected). In BD only, PCC-angular gyrus coupling was correlated with anxiety symptoms. Group differences in Rs-FC using ICA did not survive multiple comparisons. CONCLUSIONS: Negative findings from whole-brain ICA Rs-FC may reflect a state of clinical remission in BD. Heightened activation between the PCC and the angular gyrus and between the dlPFC and the brainstem may reflect (i) an abnormal trait integration of affective information during clinical remission and/or (ii) an adaptive compensatory mechanism required for clinical stabilization.

High-resolution examination of changes in drinking during the COVID-19 pandemic: Nine-wave findings from a longitudinal observational cohort study of community adults.

Few multi-wave longitudinal studies have examined changes in drinking across extended periods of the coronavirus 2019 (COVID-19) pandemic. Using multiple indicators over three years, the current study examined: a) overall drinking changes; b) sex, income, age, and pre-COVID drinking level as moderators of changes; and c) the clinical significance of the observed changes. Using a longitudinal observational cohort design with nonclinical adults from the general community (N = 1395), assessments were collected over nine waves, two pre-COVID (April 2019 and October 2019) and seven intra-COVID (April 2020-April 2022). Drinking was measured as percent drinking days, percent heavy drinking days, and the Alcohol Use Disorders Identification Test (AUDIT) score. Clinically significant changes were defined based on the World Health Organization risk levels. All indicators exhibited significant changes from pre-pandemic to intra-pandemic periods, with drinking changes comprising early pandemic increases followed by subsequent decreases and AUDIT scores consistently declining. Pre-pandemic drinking level substantially moderated all changes. Heavier drinkers exhibited larger decreases compared to other drinking groups. In terms of clinically important changes, ∼10% of pre-pandemic abstinent or low-risk drinkers transitioned to medium- or high-risk status during the pandemic. In contrast, 37.1% of medium-risk drinkers and 44.6% of high-risk drinkers exhibited clinically significant decreases during the intra-pandemic period. Collectively, these findings highlight the multifarious impacts of the pandemic on drinking over time, comprising both increases and decreases in drinking behaviour.

Resting state functional connectivity as a predictor of brief intervention response in adults with alcohol use disorder: A preliminary study.

BACKGROUND: Brief interventions for alcohol use disorder (AUD) are generally efficacious, albeit with variability in response. Resting state functional connectivity (rsFC) may characterize neurobiological indicators that predict the response to brief interventions and is the focus of the current investigation. MATERIALS AND METHODS: Forty-six individuals with AUD (65.2% female) completed a resting state functional magnetic resonance imaging (fMRI) scan immediately followed by a brief intervention aimed at reducing alcohol consumption. Positive clinical response was defined as a reduction in alcohol consumption by at least one World Health Organization (WHO) risk drinking level at 3-month follow-up. rsFC was analyzed using seed-to-voxel analysis with seed regions from four networks: salience network, reward network, frontoparietal network, and default mode network. RESULTS: At baseline, responders had greater rsFC between the following seed regions in relation to voxel-based clusters than non-responders: (i) anterior cingulate cortex (ACC) in relation to left postcentral gyrus and right supramarginal gyrus (salience network); (ii) right posterior parietal cortex in relation to right ventral ACC (salience network); (iii) right interior frontal gyrus (IFG) pars opercularis in relation to right cerebellum and right occipital fusiform gyrus (frontoparietal); and (iv) right primary motor cortex in relation to left thalamus (default mode). Lower rsFC in responders vs. nonresponders was seen between the (i) right rostral prefrontal cortex in relation to left IFG pars triangularis (frontoparietal); (ii) right IFG pars triangularis in relation to right cerebellum (frontoparietal); (iii) right IFG pars triangularis in relation to right frontal eye fields and right angular gyrus (frontoparietal); and (iv) right nucleus accumbens in relation to right orbital frontal cortex and right insula (reward). CONCLUSIONS: Resting state functional connectivity in the frontoparietal, salience, and reward networks predicts the response to a brief intervention in individuals with AUD and could reflect greater receptivity or motivation for behavior change.

Resting state functional connectivity in alcohol users and co-users of other substances.

Polysubstance use (PSU) is the use of more than one psychoactive substance simultaneously or independently, and occurs in roughly half of individuals who seek treatment for substance use. The current study sought to use resting state functional connectivity (rs-FC) to examine functional connectivity in participants who report using multiple or single substances. Participants were drawn from a larger neuroimaging study. From there, participants were placed into one of three groups based on their frequency of alcohol, tobacco, cannabis, and illicit drug use. The final sample consisted of 82 participants. We observed three clusters that differed significantly between the three groups; one within the salience network and two within the temporal network. Tri+ users were found to have a lesser amount of rs-FC in these regions (compared to the other two groups) and dual users were found to have a greater amount of rs-FC within these regions. Findings indicate that use of three or more substances may significantly impact rs-FC within the salience and temporal networks, and that those who use alcohol+cannabis have significantly greater rs-FC than those who use alcohol+tobacco. Research is needed to examine larger samples of PSU for comparisons across specific substance combinations.

Public health guideline compliance and perceived government effectiveness during the COVID-19 pandemic in Canada: Findings from a longitudinal cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has imposed enormous adversity worldwide. Public health guidelines have been a first line of defense but rely on compliance with evolving recommendations and restrictions. This study sought to characterize adherence to and perceptions of public health guidelines over a one-year timeframe during the pandemic. METHODS: Participants were 1435 community adults in Ontario who completed assessments at five time points (April 2020, July 2020, October 2020, January 2021, and April 2021; 92% retention). Participants were assessed for self-reported adherence to government protocols and perceptions of government response (importance, compliance, and effectiveness). Analyses used general linear mixed-effects modelling of overall changes by time and examined differences based on age and sex. FINDINGS: Over time, participants reported high or increasing behavioural engagement in public health guidelines, including physical distancing, restricting activity, and masking. In contrast, participants exhibited significant reductions in perceived importance and compliance, with evidence of more negative changes in younger participants. The largest changes were a substantial reduction in perceived government effectiveness, from predominantly positive perceptions to predominantly negative perceptions. INTERPRETATION: These results illuminate evolving trends in public health compliance and perceptions over the course of the pandemic in Canada, revealing the malleability of public perceptions of public health recommendations and government effectiveness. FUNDING: This research was funded by a grant from the Canadian Institutes of Health Research (CIHR). CIHR had no role in study design, data collection, data analysis, interpretation, or writing of the report.

Dysregulated resting state functional connectivity and obesity: A systematic review.

Obesity has been variously linked to differences in brain functional connectivity in regions associated with reward, emotional regulation and cognition, potentially revealing neural mechanisms contributing to its development and maintenance. This systematic review summarizes and critically appraises the existing literature on differences in resting state functional connectivity (Rs-FC) between overweight and individuals with obesity in relation healthy-BMI controls. Twenty-nine studies were identified and the results consistently support the hypothesis that obesity is associated with differences in Rs-FC. Specifically, obesity/overweight was consistently associated with (i) DMN hypoconnectivity and salience network hyperconnectivity; (ii) increased Rs-FC between the hypothalamus and reward, limbic and salience networks, and decreased Rs-FC between the hypothalamus and cognitive regions; (iii) increased power within regions associated with inhibition/emotional reasoning; (iv) decreased nodal efficiency, degree centrality, and global efficiency. Collectively, the results suggest obesity is associated with disrupted connectivity of brain networks responsible for cognition, reward, self-referential processing and emotional regulation.

COVID-19 Vaccine Perceptions and Differences by Sex, Age, and Education in 1,367 Community Adults in Ontario.

Background: COVID-19 is a global pandemic and vaccination efforts may be impeded by vaccine hesitancy. The present study examined willingness to receive a COVID-19 vaccine, the associated reasons for willingness/unwillingness, and vaccine safety perceptions in a cross-sectional assessment of community adults in Ontario. Methods: One thousand three hundred sixty seven individuals (60.6% female, mean age = 37.5%) participated in this study between January 15, 2021 and February 15, 2021. Perceptions of vaccine safety and reasons for willingness/unwillingness to receive the COVID-19 vaccine were investigated using an online assessment. Perceptions were investigated in general and by age, sex and education using analysis of variance. Results: Overall, 82.8% of the sample reported they were willing to receive a COVID-19 vaccine and 17.2% reported they were unwilling. The three most common reasons for unwillingness were long-term side effects (65.5%), immediate side effects (60.5%), and lack of trust in the vaccine (55.2%). Vaccine willingness significantly differed by sex and education level, with female participants and those with less than a bachelor's degree being more likely to report unwillingness. Perception of COVID-19 vaccine safety was significantly lower (-10.3%) than vaccines in general and differed by age, sex and education, with females, older adults, and individuals with less than a bachelor's degree reporting lower perceived COVID-19 vaccine safety. Conclusion: In this sample of community adults, the COVID-19 vaccine hesitancy rate was less than one in five individuals, but with higher rates in population subgroups. Targeting public health messaging to females and individuals with less than bachelor's degree, and addressing concerns about long-term and immediate side effects may increase vaccine uptake.

Predictors of premature treatment termination in a large residential addiction medicine program.

BACKGROUND: While inpatient programs are a common setting for addiction treatment, patients' premature termination is a major concern. Predicting premature treatment termination has the potential to substantially improve patient outcomes by identifying high-risk profiles and suggesting care paths that might reduce dropout. The current study examined the predictors of premature termination from an inpatient addiction medicine service. METHODS: In 1082 patients admitted to a large inpatient addiction medicine service, we used intake assessments of severity of alcohol use disorder, illicit drug use disorder, post-traumatic stress disorder (PTSD), anxiety disorders, and major depressive disorder to predict planned termination (n = 922) or premature termination (n = 160). We used two complementary analytic approaches-traditional binary logistic regression and a data-driven latent profile analysis (LPA). RESULTS: Binary logistic regression revealed that alcohol use severity, illicit drug use severity, and PTSD severity significantly predicted termination status, although alcohol use severity notably exhibited an inverse relationship. The LPA revealed four distinct profiles, with one profile exhibiting a significantly higher rate of premature termination and another exhibiting a significantly lower rate of premature termination. The high-risk profile was characterized by high drug severity, high comorbid psychopathology (PTSD, depression, and anxiety symptoms), but low alcohol severity. The low-risk profile was characterized by high alcohol severity, but low drug use and low comorbid psychopathology. CONCLUSIONS: These results provide converging evidence that illicit drug severity and psychiatric severity, and particularly PTSD, were associated with premature termination. Moreover, the LPA revealed distinct latent subgroups of patients with meaningfully higher and lower risk of premature termination, suggesting that addiction services should develop strategies for identifying high-risk individuals or develop care paths for high-risk symptom clusters. Approaches that are trauma-informed or otherwise focus on the management of comorbid psychiatric conditions may be particularly appropriate for reducing premature termination.

From anatomy to function: the role of the somatosensory cortex in emotional regulation.

Since the pioneering work of Penfield and his colleagues in the 1930s, the somatosensory cortex, which is located on the postcentral gyrus, has been known for its central role in processing sensory information from various parts of the body. More recently, a converging body of literature has shown that the somatosensory cortex also plays an important role in each stage of emotional processing, including identification of emotional significance in a stimulus, generation of emotional states, and regulation of emotion. Importantly, studies conducted in individuals suffering from mental disorders associated with abnormal emotional regulation, such as major depression, bipolar disorder, schizophrenia, post-traumatic stress disorder, anxiety and panic disorders, specific phobia, obesity, and obsessive-compulsive disorder, have found structural and functional changes in the somatosensory cortex. Common observations in the somatosensory cortices of individuals with mood disorders include alterations in gray matter volume, cortical thickness, abnormal functional connectivity with other brain regions, and changes in metabolic rates. These findings support the hypothesis that the somatosensory cortex may be a treatment target for certain mental disorders. In this review, we discuss the anatomy, connectivity, and functions of the somatosensory cortex, with a focus on its role in emotional regulation.

Deficits in executive function and suppression of default mode network in obesity.

BACKGROUND: Although nutritional and metabolic factors are well established in obesity, neurocognitive determinants are less understood. Using data from the Human Connectome Project, this study concurrently investigated neurocognitive performance, neural activation during a working memory task, and cortical brain morphometry in relation to obesity in a group of young adults, 22-35 years old. METHODS: Using a case-control design, obese individuals (n = 243, body mass index [BMI] ≥ 30 kg/m2) were compared to a control group of lean BMI individuals (n = 469, BMI = 18-24.9 kg/m2). Performance tests comprised a battery of behavioral neurocognitive assessments. Neural activity was measured as blood-oxygenation-level-dependent (BOLD) activity during an N-Back task using functional magnetic resonance imaging (fMRI). Cortical morphometry included indices of volume, thickness, and surface area. RESULTS: Relative to the control group, the obese group exhibited significantly worse performance in terms of the National Institutes of Health Toolkit (NIH) 9-Hole Peg Board, Penn Working Memory Test, Delay Discounting, Penn Progressive Matrices, NIH Picture Vocabulary Test, Dimensional Change Card Sort Test and the in-scanner N-Back working memory test (FDR-corrected ps<0.05; ds = 0.231-0.405). The obese group also exhibited significantly greater BOLD activation in N-Back task-negative regions, including the ventromedial prefrontal cortex, posterior cingulate, and right precentral gyrus (FDR-corrected ps<0.05). Supplemental functional connectivity analyses provided evidence that the implicated regions were part of the default mode network. Significant differences in morphometry were present in the medial orbitofrontal cortex, rostral anterior cingulate cortex, inferior and superior parietal gyri, and temporal pole (FDR-corrected p<0.001). A data-driven integrative model classified 73.8% of participants correctly. CONCLUSIONS AND RELEVANCE: This multimodal investigation suggests diverse aspects of neurocognition are associated with obesity, particularly implicating deficits in executive function and ineffective suppression of the default mode network.

Functional and structural neuroimaging studies of delayed reward discounting in addiction: A systematic review.

Given the robust behavioral association between delayed reward discounting (DRD) and addictive behavior, there is an expanding literature investigating the neural correlates of this relationship. The objective of this systematic review was to characterize and critically appraise the existing literature examining the neural correlates of DRD in individuals exhibiting addictive behavior using functional and structural MRI (fMRI/MRI) and to do so through the lens of the neural networks implicated in addiction. Using a systematic search strategy, 20 studies were identified, with 12 focusing on task fMRI, 4 focusing on functional connectivity fMRI, and 4 focusing on structural MRI. Behaviorally, significantly steeper DRD was present in individuals with addictive disorders across studies, reproducing earlier findings. Among individuals with addictive disorders, there was substantial evidence of greater neural activity in the executive control network during choices for larger-delayed rewards (delayed gratification) relative to choices for smaller-immediate rewards (immediate gratification), particularly in dorsolateral prefrontal cortex, as well as moderate evidence of greater recruitment of the default mode, salience, and reward valuation networks during larger-delayed choices. In functional connectivity fMRI studies, there was moderate evidence for greater connectivity between the executive control, salience, and default mode networks in individuals exhibiting addictive behavior. Structural MRI studies reported highly heterogeneous findings and no consistent conclusions could be drawn. As a whole, this review suggests consistent differences in neural activation and connectivity relating to DRD in individuals with addictive disorders. It also reveals heterogeneity of methods and findings in this line of inquiry. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Effects of Estradiol Therapy on Resting-State Functional Connectivity of Transgender Women After Gender-Affirming Related Gonadectomy.

An extreme incongruence between sex and gender identity leads individuals with gender dysphoria (GD) to seek cross-sex hormone therapy (CSHT), and gender-affirming surgery (GAS). Although few studies have investigated the effects of CSHT on the brain prior to GAS, no studies in the extant literature have evaluated its impact during hypogonadism in post-GAS individuals. Here, we aimed to evaluate the effects of estradiol on resting-state functional connectivity (rs-FC) of the sensorimotor cortex (SMC) and basal ganglia following surgical hypogonadism. Eighteen post-GAS (male-to-female) participants underwent functional magnetic resonance imaging (fMRI) and neuropsychiatric and hormonal assessment at two time points (t1, hormonal washout; t2, CSHT reintroduction). Based on the literature, the thalamus was selected as a seed, while the SMC and the dorsolateral striatum were targets for seed-based functional connectivity (sbFC). A second sbFC investigation consisted of a whole-brain voxel exploratory analysis again using the thalamus as a seed. A final complementary data-driven approach using multivoxel pattern analysis (MVPA) was conducted to identify a potential seed for further sbFC analyses. An increase in the rs-FC between the left thalamus and the left SCM/putamen followed CSHT. MVPA identified a cluster within the subcallosal cortex (SubCalC) representing the highest variation in peak activation between time points. Setting the SubCalC as a seed, whole-brain analysis showed a decoupling between the SubCalC and the medial frontal cortex during CSHT. These results indicate that CSHT with estradiol post-GAS, modulates rs-FC in regions engaged in cognitive, emotional, and sensorimotor processes.