Treating new-onset cognitive complaints after risk-reducing salpingo-oophorectomy: A randomized controlled crossover trial of lisdexamfetamine.

OBJECTIVE: To determine whether the psychostimulant lisdexamfetamine improves subjective and objective measures of cognitive functioning among women genetically at-risk for cancer who have undergone risk-reducing salpingo-oophorectomy and report new-onset executive functioning difficulties. METHODS: 69 participants were assigned to a randomized controlled crossover trial with 6-week trials of active medication (lisdexamfetamine) and placebo, separated by a minimum 2-week washout in an intent-to-treat framework (clinical trial registration number: NCT03187353). At trial baseline, midpoint, and endpoint, participants completed a self-report measure of executive functioning (Brown Attention Deficit Disorder Scale). At study baseline and trial endpoint, participants completed sustained attention, attention/working memory, and verbal learning/memory cognitive tasks. Side effects were assessed at 2, 3, 4, and 6 weeks for each trial. RESULTS: From trial baseline to trial endpoint, lisdexamfetamine - relative to placebo - significantly improved total scores on the self-report Brown Attention Deficit Disorder Scale (and scores on four of five subdomains) as well as attention and working memory performance. Significantly more participants endorsed side effects across the lisdexamfetamine trial versus placebo; however, trial completion rates were similar, indicating that lisdexamfetamine was nonetheless well-tolerated. CONCLUSIONS: Lisdexamfetamine improved both subjective and objective measures of attention and working memory and could offer women experiencing cognitive difficulties post-risk-reducing salpingo-oophorectomy an alternative therapeutic option.

Randomized Controlled Trial of Effects of Behavioral Weight Loss Treatment on Food Cue Reactivity.

BACKGROUND: It is not known whether behavioral weight loss can attenuate blood oxygen level-dependent responses to food stimuli. OBJECTIVES: This randomized controlled trial assessed the effects of a commercially available behavioral weight loss program (WW, WeightWatchers) compared to a wait-list control on blood oxygen level-dependent response to food cues. METHODS: Females with obesity ( N = 61) were randomized to behavioral weight loss or wait-list control. At baseline and follow-up, participants completed assessments that included functional magnetic resonance imaging scans to assess response to images of high-calorie foods (HCF) or low-calorie foods (LCF), and neutral objects. RESULTS: There were no significant between-group differences in change from baseline to follow-up in any regions of the brain in response to viewing HCF or LCF. From baseline to follow-up, participants in behavioral weight loss, compared with wait-list control, reported significantly greater increases in desire for LCF. Changes in liking and palatability of LCF and liking, palatability, and desire for HCF did not differ between groups. DISCUSSION: Behavioral weight loss was associated with increased desire for LCF without changes in neural reactivity to food cues. These results suggest that alteration of neurological processes underlying responsiveness to food is difficult to achieve through behavioral weight management alone.

Addicted to green: priming effect of menthol cigarette packaging on brain response to smoking cues.

INTRODUCTION: Mentholated tobacco cigarettes are believed to be more addictive than non-menthol ones. Packaging of most menthol cigarette brands includes distinctive green hues, which may act as conditioned stimuli (ie, cues) and promote menthol smoking. To examine the cue properties of menthol cigarette packaging, we used a priming paradigm to assess the effect of packaging on the neural substrates of smoking cue reactivity. We hypothesised that menthol packaging will exert a specific priming effect potentiating smoking cue reactivity in menthol compared with non-menthol smokers. METHODS: Forty-two menthol and 33 non-menthol smokers underwent functional MRI while viewing smoking and neutral cues. The cues were preceded (ie, primed) by briefly presented images of menthol or non-menthol cigarette packages. Participants reported craving for cigarettes in response to each cue. RESULTS: Menthol packaging induced greater frontostriatal and occipital smoking cue reactivity in menthol smokers than in non-menthol smokers. Menthol packaging also enhanced the mediation by neural activity of the relationship between cue exposure and cigarette craving in menthol but not non-menthol smokers. Dynamic causal modelling showed stronger frontostriatal-occipital connectivity in response to menthol packaging in menthol compared with non-menthol smokers. The effects of non-menthol packaging did not differ between categories of smokers. CONCLUSIONS: Our findings demonstrate heightened motivational and perceptual salience of the green-hued menthol cigarette packaging that may exacerbate menthol smokers' susceptibility to smoking cues. These effects could contribute to the greater addiction severity among menthol smokers and could be considered in the development of science-based regulation and legal review of tobacco product marketing practices.

Brain and cortisol responses to smoking cues are linked in tobacco-smoking individuals.

Cues associated with smoking can induce relapse, which is likely driven by cue-induced neurobiological and physiological mechanisms. For instance, greater relapse vulnerability is associated with increases in cue-induced insula activation and heightened cortisol concentrations. Determining if there is a link between such cue-induced responses is critical given the need for biomarkers that can be easily measured in clinical settings and used to drive targeted treatment. Further, comprehensively characterising biological reactions to cues promises to aid in the development of therapies that address this specific relapse risk factor. To determine whether brain and cortisol responses to smoking cues are linked, this study recruited 27 nicotine-dependent tobacco-smoking individuals and acquired whole-brain functional activation during a cue reactivity task; salivary cortisol was measured before and after scanning. The results showed that increases in blood-oxygen-level-dependent activation in the right anterior insula and right dorsolateral prefrontal cortex (DLPFC) when viewing smoking versus neutral cues were positively correlated with a post-scan rise in salivary cortisol concentrations. These brain regions have been previously implicated in substance use disorders for their role in salience, interoception and executive processes. These findings show that those who have a rise in cortisol following smoking cue exposure also have a related rise in cue-induced brain reactivity, in brain regions previously linked with heightened relapse vulnerability. This is clinically relevant as measuring cue-induced cortisol responses is a more accessible proxy for assessing the engagement of cue-induced neurobiological processes associated with the maintenance of nicotine dependence.

Effects of current smoking severity on brain gray matter volume in opioid use disorder - a voxel-based morphometry study.

Background: Cigarette smoking (CS) and opioid use disorder (OUD) significantly alter brain structure. Although OUD and cigarette smoking are highly comorbid, most prior neuroimaging research in OUD did not control for smoking severity. Specifically, the combined effect of smoking and OUD on the brain gray matter volume (GMV) remains unknown.Objectives: We used structural magnetic resonance imaging (sMRI) to examine: (1) the GMV differences between OUD and non-OUD individuals with comparable smoking severity; and (2) the differential effect of smoking severity on the brain GMV between individuals with and without OUD.Methods: We performed a secondary analysis of existing sMRI datasets of 116 individuals who smoked cigarettes daily, among whom 60 had OUD (CS-OUD; 37 male, 23 female) and 56 did not (CS; 31 male, 25 female). Brain GMV was estimated by voxel-based morphometry analysis.Results: Compared to the CS group, the CS-OUD group had a higher GMV in the occipital cortex and lower GMV in the prefrontal and temporal cortex, striatum, and pre/postcentral gyrus (whole-brain corrected-p < .05). There was a significant interaction between group and smoking severity on GMV in the medial orbitofrontal cortex (whole-brain corrected-p < .05), such that heavier smoking was associated with lower medial orbitofrontal GMV in the CS-OUD but not CS participants (r=-0.32 vs. 0.12).Conclusions: Our findings suggest a combination of independent and interactive effects of cigarette smoking and OUD on the brain gray matter. Elucidating the neuroanatomical correlates of comorbid opioid and tobacco use may shed the light on the development of novel interventions for affected individuals.

Progesterone Increases Nicotine Withdrawal and Anxiety in Male but Not Female Smokers During Brief Abstinence.

INTRODUCTION: Although exogenous progesterone may hold promise as a treatment for nicotine use disorders, it is unclear whether it is similarly effective in males and females. This study examined the effects of progesterone on nicotine use disorder comprehensively using behavioral, psychological, and neural measures in male and female smokers exposed to brief abstinence. AIMS AND METHODS: Thirty-three male and 33 female non-treatment-seeking smokers participated in a double-blind, randomized, placebo-controlled crossover study of 200 mg of progesterone or placebo daily over a four-day abstinence period. Smoking behavior and subjective effects of nicotine were assessed at baseline and after final drug administration. Nicotine withdrawal, smoking urges, mood states, and neural response to smoking cues were measured at baseline, after the first drug administration, and after the final drug administration. RESULTS: No main effect of drug (progesterone vs. placebo) emerged for any outcome. Significant sex by drug interactions emerged for nicotine withdrawal (p = .020), perceived strength of nicotine (p = .040), and perceived bad effects of nicotine (p = .029). Males receiving progesterone reported worse nicotine withdrawal (p = .046) and a trend towards decreased bad effects of nicotine (p = .070). Males on progesterone also reported greater tension and anxiety relative to placebo (p = .021). Females on progesterone perceived nicotine's effects as being stronger relative to placebo (p = .046). CONCLUSIONS: Progesterone causes sex-dependent effects on smoking-related outcomes during brief abstinence. Specifically, progesterone in males may increase rather than decrease nicotine withdrawal and negative affect during abstinence, potentially hindering efforts to quit smoking. IMPLICATIONS: In male and female smokers undergoing a brief period of abstinence, we examined the effects of progesterone on smoking outcomes. While progesterone had limited effects in female smokers, in males, it worsened nicotine withdrawal and negative affect. Our findings emphasize the importance of analyzing sex differences in future studies examining progesterone as a potential treatment and suggest that progesterone in males could potentially exacerbate aspects of nicotine dependence. CLINICALTRIALS.GOV REGISTRATION: NCT01954966. https://clinicaltrials.gov/ct2/show/NCT01954966.

Brain Marker Links Stress and Nicotine Abstinence.

BACKGROUND: Subjective stress is a well-documented predictor of early smoking relapse, yet our understanding of stress and tobacco use is limited by reliance on self-reported measures of stress. We utilized a validated functional neuroimaging paradigm to examine whether stress exposure during early abstinence alters objective measures of brain function. METHODS: Seventy-five participants underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) during the Montreal Imaging Stress Task (MIST) on two occasions: once during smoking satiety and once following biochemically confirmed 24-hour abstinence (order counterbalanced). The primary outcome measure was brain response during stress (vs. control) blocks of the MIST, assessed using whole-brain analysis corrected for multiple comparisons using clusters determined by Z ≥ 3.1. RESULTS: Abstinence (vs. satiety) was associated with significantly increased activation in the left inferior frontal gyrus, a brain region associated with inhibitory control. Abstinence-induced change in brain response to stress was positively associated with change in self-reported stress. CONCLUSIONS: This study provides objective evidence that the brain response to stress is altered during the first 24 hours of a quit attempt compared to smoking satiety. IMPLICATIONS: These results point to the potential value of inoculating smokers with stress management training prior to a quit attempt.

Neural cue reactivity during acute abstinence predicts short-term smoking relapse.

In smokers, neural responses to smoking cues can be sensitive to acute abstinence, but the degree to which abstinence-related cue reactivity contributes to relapse is not fully understood. This study addressed this question in a sample of 75 smokers who were motivated to quit smoking. Participants underwent blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during presentation of visual smoking cues and neutral stimuli on two occasions: once during smoking satiety and once following 24-hour abstinence (order counterbalanced). Following the imaging sessions, participants received brief smoking cessation counseling prior to a short-term (7-day) quit attempt. The primary smoking cessation outcome was biochemically confirmed 7-day relapse. The secondary smoking cessation outcome measure was total number of self-reported days of abstinence. During abstinence (vs satiety), smoking cue reactivity was significantly increased only in the anterior cingulate cortex (ACC); other regions showing a cue (vs neutral) response did not exhibit an abstinence effect in the stringent whole-brain analysis. Participants who showed greater smoking cue reactivity in the ACC during acute abstinence (compared with smoking satiety) were more likely to relapse (OR = 2.10 per standard deviation increase in percent signal change [abstinence minus smoking satiety], 95% CI: 1.05 to 4.20, P = 0.036). Greater abstinence-induced change in ACC activation also predicted fewer total days abstinent (ß = -0.63, 95% CI = 0.43 to 0.66, P < 0.0001). This study provides the first evidence that changes in smoking cue reactivity in the ACC during acute abstinence predict smoking relapse, thereby improving our understanding of the neurobiology of smoking cessation.

Got chocolate? Bilateral prefrontal cortex stimulation augments chocolate consumption.

BACKGROUND: Understanding the mechanisms behind exerting self-control may reveal why health behaviors are resistant to change. Activity in the right inferior frontal gyrus (rIFG) plays a role in self-control processes and may be modulated using transcranial direct current stimulation (tDCS). OBJECTIVE: In this early phase behavioral research study, we investigated whether anodal stimulation over the rIFG with cathodal stimulation over the left IFG (versus sham) reduced chocolate consumption. METHODS: Twenty-three healthy females (ages 18-35) completed two tDCS sessions (2.0 mA vs. sham; order counterbalanced) in a within-subject, double-blind, randomized design with a 4-week washout. Participants were self-reported "chocolate cravers" and restrained eaters. Self-report assessments on disinhibited eating were completed at intake. Delay discounting and inhibitory control were assessed at the remaining visits. During stimulation, participants completed an inhibitory control training task (chocolate go/no-go task) and were randomized to the chocolate no-go condition (inhibit all responses to chocolate cues) or the control condition (inhibit responses to chocolate cues on half the trials). Following stimulation, participants completed a 15-min chocolate "taste test" with chocolate rating forms. Afterwards, staff measured the remaining chocolate to determine total consumption. RESULTS: Contrary to our hypotheses, active tDCS significantly increased chocolate consumption vs. sham (mean = 43.2 vs. 32.2, p=0.005) in both task conditions, but had no effect on chocolate ratings (ps > 0.05). Higher delay discounting and self-reported disinhibited eating predicted greater consumption (ps < 0.05). CONCLUSIONS: The results suggest widespread activation of the prefrontal cortex may reduce the ability to resist chocolate. Our data highlights important methodological considerations for conducting tDCS studies to target health behaviors.

Content matters: neuroimaging investigation of brain and behavioral impact of televised anti-tobacco public service announcements.

Televised public service announcements are video ads that are a key component of public health campaigns against smoking. Understanding the neurophysiological correlates of anti-tobacco ads is an important step toward novel objective methods of their evaluation and design. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the brain and behavioral effects of the interaction between content ("argument strength," AS) and format ("message sensation value," MSV) of anti-smoking ads in humans. Seventy-one nontreatment-seeking smokers viewed a sequence of 16 high or 16 low AS ads during an fMRI scan. Dependent variables were brain fMRI signal, the immediate recall of the ads, the immediate change in intentions to quit smoking, and the urine levels of a major nicotine metabolite cotinine at a 1 month follow-up. Whole-brain ANOVA revealed that AS and MSV interacted in the inferior frontal, inferior parietal, and fusiform gyri; the precuneus; and the dorsomedial prefrontal cortex (dMPFC). Regression analysis showed that the activation in the dMPFC predicted the urine cotinine levels 1 month later. These results characterize the key brain regions engaged in the processing of persuasive communications and suggest that brain fMRI response to anti-smoking ads could predict subsequent smoking severity in nontreatment-seeking smokers. Our findings demonstrate the importance of the quality of content for objective ad outcomes and suggest that fMRI investigation may aid the prerelease evaluation of televised public health ads.

Functional maturation of the executive system during adolescence.

Adolescence is characterized by rapid development of executive function. Working memory (WM) is a key element of executive function, but it is not known what brain changes during adolescence allow improved WM performance. Using a fractal n-back fMRI paradigm, we investigated brain responses to WM load in 951 human youths aged 8-22 years. Compared with more limited associations with age, WM performance was robustly associated with both executive network activation and deactivation of the default mode network. Multivariate patterns of brain activation predicted task performance with a high degree of accuracy, and also mediated the observed age-related improvements in WM performance. These results delineate a process of functional maturation of the executive system, and suggest that this process allows for the improvement of cognitive capability seen during adolescence.

Neuroimaging of the Philadelphia neurodevelopmental cohort.

The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale, NIMH funded initiative to understand how brain maturation mediates cognitive development and vulnerability to psychiatric illness, and understand how genetics impacts this process. As part of this study, 1445 adolescents ages 8-21 at enrollment underwent multimodal neuroimaging. Here, we highlight the conceptual basis for the effort, the study design, and the measures available in the dataset. We focus on neuroimaging measures obtained, including T1-weighted structural neuroimaging, diffusion tensor imaging, perfusion neuroimaging using arterial spin labeling, functional imaging tasks of working memory and emotion identification, and resting state imaging of functional connectivity. Furthermore, we provide characteristics regarding the final sample acquired. Finally, we describe mechanisms in place for data sharing that will allow the PNC to become a freely available public resource to advance our understanding of normal and pathological brain development.

Age-related differences in working memory deficits during nicotine withdrawal.

Nicotine withdrawal is associated with subtle working memory deficits that predict subsequent relapse. We examined the neural substrates underlying these processes in treatment-seeking smokers, and explored the moderating influence of age on abstinence-induced alterations in brain activity and performance. Sixty-three smokers participated in two blood oxygen level-dependent (BOLD) functional magnetic resonance imaging scans while performing a visual N-back task on two separate occasions: smoking as usual and after 24 hours of biochemically confirmed abstinence (order counterbalanced). Abstinence (versus smoking) led to reduced accuracy, slower median correct response time and reduced BOLD signal change in the three a priori regions of interest: medial frontal/cingulate gyrus and right and left dorsolateral prefrontal cortex. Significant age × session effects were found for BOLD signal change in all three regions, as well as for withdrawal and craving; for all measures, abstinence effects were attenuated in smokers aged ≥50 years compared with those <50 years old. These results suggest that abstinence effects on neurocognitive function may be more pronounced for younger smokers, and may indicate a new avenue for research exploring mechanisms underlying age differences in smoking cessation success.

Extended-release naltrexone modulates brain response to drug cues in abstinent heroin-dependent patients.

Drug cues play an important role in relapse to drug use. Naltrexone is an opioid antagonist that is used to prevent relapse in opioid dependence. Central opioidergic pathways may be implicated in the heightened drug cue-reactivity, but the effects of the opioid receptors' blockade on the brain responses to drug cues in opioid dependence are unknown. To pursue this question, we studied 17 abstinent i.v. heroin users with brain functional magnetic resonance imaging (fMRI) during exposure to visual heroin-related cues and matched neutral images before and 10-14 days after an injection of extended-release naltrexone (XRNTX). Whole brain analysis of variance of fMRI data showed main effect of XRNTX in the medial frontal gyrus, precentral gyrus, cuneus, precuneus, caudate and the amygdala. fMRI response was decreased in the amygdala, cuneus, caudate and the precentral gyrus and increased in the medial frontal gyrus and the precuneus. Higher plasma levels of naltrexone's major metabolite, 6-beta-naltrexol, were associated with larger reduction in the fMRI response to drug cues after XRNTX in the precentral, caudate and amygdala clusters. The present data suggest that XRNTX pharmacotherapy of opioid-dependent patients may, respectively, decrease and potentiate prefrontal and limbic cortical responses to drug cues and that this effect might be related to the XRNTX metabolism. Our findings call for further evaluation of the brain fMRI response to drug-related cues and of the 6-beta-naltrexol levels as potential biomarkers of XRNTX therapeutic effects in patients with opioid dependence.

Human Mu Opioid Receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers.

Evidence points to the endogenous opioid system, and the mu-opioid receptor (MOR) in particular, in mediating the rewarding effects of drugs of abuse, including nicotine. A single nucleotide polymorphism (SNP) in the human MOR gene (OPRM1 A118G) has been shown to alter receptor protein level in preclinical models and smoking behavior in humans. To clarify the underlying mechanisms for these associations, we conducted an in vivo investigation of the effects of OPRM1 A118G genotype on MOR binding potential (BP(ND) or receptor availability). Twenty-two smokers prescreened for genotype (12 A/A, 10 */G) completed two [(11)C]carfentanil positron emission tomography (PET) imaging sessions following overnight abstinence and exposure to a nicotine-containing cigarette and a denicotinized cigarette. Independent of session, smokers homozygous for the wild-type OPRM1 A allele exhibited significantly higher levels of MOR BP(ND) than smokers carrying the G allele in bilateral amygdala, left thalamus, and left anterior cingulate cortex. Among G allele carriers, the extent of subjective reward difference (denicotinized versus nicotine cigarette) was associated significantly with MOR BP(ND) difference in right amygdala, caudate, anterior cingulate cortex, and thalamus. Future translational investigations can elucidate the role of MORs in nicotine addiction, which may lead to development of novel therapeutics.

Medial prefrontal neuroplasticity during extended-release naltrexone treatment of opioid use disorder - a longitudinal structural magnetic resonance imaging study.

Opioid use disorder (OUD) has been linked to macroscopic structural alterations in the brain. The monthly injectable, extended-release formulation of µ-opioid antagonist naltrexone (XR-NTX) is highly effective in reducing opioid craving and preventing opioid relapse. Here, we investigated the neuroanatomical effects of XR-NTX by examining changes in cortical thickness during treatment for OUD. Forty-seven OUD patients underwent structural magnetic resonance imaging and subjectively rated their opioid craving ≤1 day before (pre-treatment) and 11 ± 3 days after (on-treatment) the first XR-NTX injection. A sample of fifty-six non-OUD individuals completed a single imaging session and served as the comparison group. A publicly available [¹¹C]carfentanil positron emission tomography dataset was used to assess the relationship between changes in cortical thickness and µ-opioid receptor (MOR) binding potential across brain regions. We found that the thickness of the medial prefrontal and anterior cingulate cortices (mPFC/aCC; regions with high MOR binding potential) was comparable between the non-OUD individuals and the OUD patients at pre-treatment. However, among the OUD patients, mPFC/aCC thickness significantly decreased from pre-treatment to on-treatment. A greater reduction in mPFC/aCC thickness was associated with a greater reduction in opioid craving. Taken together, our study suggests XR-NTX-induced cortical thickness reduction in the mPFC/aCC regions in OUD patients. The reduction in thickness does not appear to indicate a restoration to the non-OUD level but rather reflects XR-NTX's distinct therapeutic impact on an MOR-rich brain structure. Our findings highlight the neuroplastic effects of XR-NTX that may inform the development of novel OUD interventions.

Delayed effects of cigarette graphic warning labels on smoking behavior.

Introduction: Graphic warning labels (GWLs) are widely employed to communicate smoking-related health risks; however, their implementation in the US has been held back by concerns about their efficacy. Most GWLs elicit a high level of emotional reaction (ER). The extent to which ER contributes to GWLs efficacy in improving smoking outcomes is a subject of debate. Our recent study showed poorer efficacy of the high-ER GWLs versus the low-ER ones during a month-long naturalistic exposure. Whether GWL effects persist after discontinuing the exposure remains unclear. Methods: We conducted a secondary analysis to investigate the delayed effects of GWLs on smoking severity in adult smokers. The number of cigarettes smoked per day (CPD) was measured immediately as well as 4 weeks after the end of a month-long exposure to high-ER versus low-ER GWLs. Participants indicated their subjective feeling of being relieved from having to see the GWLs. Results: We found a significant reduction in CPD from the immediate to the 4-week post-exposure timepoint. There was no difference in CPD reduction between the high-ER and low-ER groups.Subjective sense of relief from GWL exposure was associated with greater CPD reduction in the high-ER group, but not the low-ER group. Conclusions: Our study suggests lasting impact of GWLs on smoking behavior. The findings may be particularly important to high-arousal GWLs, which appear less effective in reducing smoking during active exposure. Implications: Whether GWLs that evoke higher ER are more effective remains inconclusive. We recently showed that high-ER GWLs are less effective than low-ER ones in reducing smoking during continuous exposure. Here, we found evidence of delayed GWL effects such that smoking decreased from immediately to four weeks after the end of GWL exposure. Feeling of relief from GWL exposure was associated greater smoking reduction in the high-ER group. We suggest that continuously exposing smokers to high-ER GWLs that have been well remembered may be unnecessary and counterproductive.

Natural vs. Surgical Postmenopause and Psychological Symptoms Confound the Effect of Menopause on Executive Functioning Domains of Cognitive Experience.

Objective: The menopause transition is associated with difficulties in executive function. However, it is unclear whether these difficulties persist past perimenopause. This study investigated whether potential confounders, including natural vs. surgical postmenopause and menopause-related psychological symptoms, influence whether executive dysfunction persists into postmenopause. Study Design: A cross-sectional sample of women aged 35-65 years (N = 1971) in one of four groups, premenopause, perimenopause, natural postmenopause, and surgical postmenopause, were surveyed. Participants self-reported executive functioning with the Brown Attention Deficit Disorder Scale (BADDS), anxiety symptom severity with the Generalized Anxiety Disorder Questionnaire (GAD-7), and depression symptom severity with the Center for Epidemiologic Studies Depression Scale (CES-D). Main Outcome Measures: We analyzed the association between group and BADDS scores using linear regression models - first, by controlling for age, education, and self-reported attention deficit hyperactivity disorder (ADHD) diagnosis (Model #1) and, second, by further controlling for current difficulty sleeping, anxiety, and depression (Model #2). Results: In both models, BADDS scores were significantly elevated (indicating more difficulties in executive function) among women in the perimenopausal and surgical postmenopausal groups compared with those in the premenopausal group. Likewise, the perimenopausal and surgical postmenopausal groups had the highest proportions of participants who reported difficulty sleeping and clinical levels of anxiety and depression. BADDS scores were significantly higher in natural postmenopausal vs. premenopausal women without controlling for difficulty sleeping, anxiety, and depression (Model #1), but not when adjusting for these variables (Model #2). Conclusions: The type of menopause and psychological symptoms are important confounders of the relationship between the menopause transition and executive dysfunction, and help explain whether executive dysfunction persists or recovers in postmenopause.Reprinted from Maturitas 2023; 170:64-73, with permission from Elsevier. Copyright © 2023.

Application of glutamate weighted CEST in brain imaging of nicotine dependent participants in vivo at 7T.

INTRODUCTION: With nicotine dependence being a significant healthcare issue worldwide there is a growing interest in developing novel therapies and diagnostic aids to assist in treating nicotine addiction. Glutamate (Glu) plays an important role in cognitive function regulation in a wide range of conditions including traumatic brain injury, aging, and addiction. Chemical exchange saturation transfer (CEST) imaging via ultra-high field MRI can image the exchange of certain saturated labile protons with the surrounding bulk water pool, making the technique a novel tool to investigate glutamate in the context of addiction. The aim of this work was to apply glutamate weighted CEST (GluCEST) imaging to study the dorsal anterior cingulate cortex (dACC) in a small population of smokers and non-smokers to determine its effectiveness as a biomarker of nicotine use. METHODS: 2D GluCEST images were acquired on 20 healthy participants: 10 smokers (ages 29-50) and 10 non-smokers (ages 25-69), using a 7T MRI system. T1-weighted images were used to segment the GluCEST images into white and gray matter tissue and further into seven gray matter regions. Wilcoxon rank-sum tests were performed, comparing mean GluCEST contrast between smokers and non-smokers across brain regions. RESULTS: GluCEST levels were similar between smokers and non-smokers; however, there was a moderate negative age dependence (R2 = 0.531) in smokers within the cingulate gyrus. CONCLUSION: Feasibility of GluCEST imaging was demonstrated for in vivo investigation of smokers and non-smokers to assess glutamate contrast differences as a potential biomarker with a moderate negative age correlation in the cingulate gyrus suggesting reward network involvement.

An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data.

Several recent reports in large, independent samples have demonstrated the influence of motion artifact on resting-state functional connectivity MRI (rsfc-MRI). Standard rsfc-MRI preprocessing typically includes regression of confounding signals and band-pass filtering. However, substantial heterogeneity exists in how these techniques are implemented across studies, and no prior study has examined the effect of differing approaches for the control of motion-induced artifacts. To better understand how in-scanner head motion affects rsfc-MRI data, we describe the spatial, temporal, and spectral characteristics of motion artifacts in a sample of 348 adolescents. Analyses utilize a novel approach for describing head motion on a voxelwise basis. Next, we systematically evaluate the efficacy of a range of confound regression and filtering techniques for the control of motion-induced artifacts. Results reveal that the effectiveness of preprocessing procedures on the control of motion is heterogeneous, and that improved preprocessing provides a substantial benefit beyond typical procedures. These results demonstrate that the effect of motion on rsfc-MRI can be substantially attenuated through improved preprocessing procedures, but not completely removed.