Subtypes of exercise are differentially associated with baseline eating disorder pathology and treatment outcome among individuals with bulimia nervosa.

OBJECTIVE: Individuals with bulimia nervosa (BN) engage in both maladaptive (i.e., compulsive and/or compensatory) and adaptive exercise (e.g., for enjoyment). No research has examined whether those who engage in adaptive, compulsive, and/or compensatory exercise exhibit differences in BN pathology or treatment outcome compared to those not engaging in exercise, limiting intervention efficacy. METHOD: We examined associations of baseline exercise engagement with baseline and posttreatment BN pathology among 106 treatment-seeking adults (Mage = 37.4, SDage = 12.95, 87.74% female, 68.87% White) enrolled across four clinical trials of outpatient enhanced cognitive behavioral therapy for BN (range: 12-16 sessions). Analysis of covariances examined associations between baseline exercise type and baseline/posttreatment global eating pathology, dietary restraint, loss-of-control (LOC) eating, and purging frequency. RESULTS: Those engaging in only adaptive exercise reported lower global eating pathology compared to those engaging in compulsive-only exercise (Est = -1.493, p = .014, Mdiff = -.97) while those engaging in baseline compulsive exercise reported less LOC eating compared to those not engaging in exercise (Est = -22.42, p = .012, Mdiff = -12.50). Baseline engagement in compulsive-only exercise was associated with lower posttreatment global eating pathology compared to baseline engagement in no exercise (Est = -.856, p = .023, Mdiff = -.64) and both compulsive and compensatory exercise (Est = .895, p = .026, Mdiff = -1.08). DISCUSSION: Those engaging in compulsive, compensatory, adaptive, and no exercise exhibit different patterns and severity of BN pathology. Future research is needed to position treatments to intervene on maladaptive, while still promoting adaptive, exercise. PUBLIC SIGNIFICANCE STATEMENT: No research to date has examined whether those who engage in adaptive, compulsive, and/or compensatory exercise exhibit differences in BN pathology or treatment outcome compared to those not engaging in exercise, limiting targeted intervention efforts. We found that those engaging in compulsive, compensatory, and adaptive exercise exhibit different patterns of BN pathology and that adaptive exercise engagement was related to lower cognitive eating disorder symptoms at baseline.

Low frequency repetitive transcranial magnetic stimulation to the right dorsolateral prefrontal cortex engages thalamus, striatum, and the default mode network.

The positive treatment outcomes of low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) when applied over the right dorsolateral prefrontal cortex (DLPFC) in treatment-refractory depression has been verified. However, the mechanism of action behind these results have not been well-explored. In this work we used simultaneous functional magnetic resonance imaging (fMRI) during TMS to explore the effect of LF rTMS on brain activity when applied to the right [RDLPFC1 (MNI: 50, 30, 36)] and left DLPFC sites [LDLPFC1 (MNI: -50, 30, 36), LDLPFC2 (MNI: -41, 16, 54)]. Seventeen healthy adult volunteers participated in this study. To identify brain areas affected by rTMS, an independent component analysis and a general linear model were used. Our results showed an important laterality effect when contrasting rTMS over the left and right sites. Specifically, LF rTMS increased brain activity at the striatum, thalamus, and areas of the default mode network when applied to the right, but not to the contralateral left DLPFC. In contrast, no site differences were observed when evaluating the effect of LF rTMS over the two left sites. These findings demonstrate that LF rTMS to the right DLPFC was able to stimulate the cortico-striato-thalamo-cortical pathway, which is dysregulated in patients with major depressive disorder; therefore, possibly providing some neurobiological justification for the successful outcomes found thus far for LF rTMS in the treatment of depression.

High-Frequency Transcranial Magnetic Stimulation Combined With Functional Magnetic Resonance Imaging Reveals Distinct Activation Patterns Associated With Different Dorsolateral Prefrontal Cortex Stimulation Sites.

OBJECTIVES: Transcranial magnetic stimulation (TMS) has been extensively used for the treatment of depression, obsessive-compulsive disorder, and certain neurologic disorders. Despite having promising treatment efficacy, the fundamental neural mechanisms of TMS remain understudied. MATERIALS AND METHODS: In this study, 15 healthy adult participants received simultaneous TMS and functional magnetic resonance imaging to map the modulatory effect of TMS when it was applied over three different sites in the dorsolateral prefrontal cortex. Independent component analysis (ICA) was used to identify the networks affected by TMS when applied over the different sites. The standard general linear model (GLM) analysis was used for comparison. RESULTS: ICA showed that TMS affected the stimulation sites as well as remote brain areas, some areas/networks common across all TMS sites, and other areas/networks specific to each TMS site. In particular, TMS site and laterality differences were observed at the left executive control network. In addition, laterality differences also were observed at the dorsal anterior cingulate cortex and dorsolateral/dorsomedial prefrontal cortex. In contrast with the ICA findings, the GLM-based results mainly showed activation of auditory cortices regardless of the TMS sites. CONCLUSIONS: Our findings support the notion that TMS could act through a top-down mechanism, indirectly modulating deep subcortical nodes by directly stimulating cortical regions. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03394066.

Short-term nicotine deprivation alters dorsal anterior cingulate glutamate concentration and concomitant cingulate-cortical functional connectivity.

Most cigarette smokers who wish to quit too often relapse within the first few days of abstinence, primarily due to the aversive aspects of the nicotine withdrawal syndrome (NWS), which remains poorly understood. Considerable research has suggested that the dorsal anterior cingulate cortex (dACC) plays a key role in nicotine dependence, with its functional connections between other brain regions altered as a function of trait addiction and state withdrawal. The flow of information between dACC and fronto-striatal regions is secured through different pathways, the vast majority of which are glutamatergic. As such, we investigated dACC activity using resting state functional connectivity (rsFC) with functional magnetic resonance imaging (fMRI) and glutamate (Glu) concentration with magnetic resonance spectroscopy (MRS). We also investigated the changes in adenosine levels in plasma during withdrawal as a surrogate for brain adenosine, which plays a role in fine-tuning synaptic glutamate transmission. Using a double-blind, placebo-controlled, randomized crossover design, nontreatment seeking smoking participants (N = 30) completed two imaging sessions, one while nicotine sated and another after 36 h nicotine abstinence. We observed reduced dACC Glu (P = 0.029) along with a significant reduction in plasma adenosine (P = 0.03) and adenosine monophosphate (AMP; P < 0.0001) concentrations during nicotine withdrawal in comparison with nicotine sated state. This withdrawal state manipulation also led to an increase in rsFC strength (P < 0.05) between dACC and several frontal cortical regions, including left superior frontal gyrus (LSFG), and right middle frontal gyrus (RMFG). Moreover, the state-trait changes in dACC Glu and rsFC strength between the dACC and both SFG and MFG were positively correlated (P = 0.012, and P = 0.007, respectively). Finally, the change in circuit strength between dACC and LSFG was negatively correlated with the change in withdrawal symptom manifestations as measured by the Wisconsin Smoking Withdrawal Scale (P = 0.04) and Tobacco Craving Questionnaire (P = 0.014). These multimodal imaging-behavioral findings reveal the complex cascade of changes induced by acute nicotine deprivation and call for further investigation into the potential utility of adenosine- and glutamate-signaling as novel therapeutic targets to treat the NWS.

Sex difference in the progression of manic symptoms during acute hospitalization: A prospective pilot study.

OBJECTIVES: Acute mania is a serious medical condition that impacts men and women equally. Longtime presentation of manic symptoms is sex-dependent; however, little is known about acute symptoms of mania. The objective of this study is to track and compare acute manic symptoms for sex differences during inpatient hospitalization. METHODS: All patients with bipolar mania admitted to a large university hospital between January and October 2017 were invited to participate in this longitudinal naturalistic follow-up study. Manic (YMRS), depressive (MADRS), and psychotic (PAS) symptoms were tracked daily from admission to discharge. RESULTS: The total YMRS scores decreased significantly overtime (p < .0001) in both male (n = 34) and female (n = 23) patients (p = .7). However, male patients scored significantly higher in sexual interest (p = .01), disruptive and aggressive behavior (p = .01), and appearance (p < .001) while females had better insight into their illness (p = .01). Males and females received similar doses of lithium (p = .1), but males received significantly higher doses of valproic acid (VPA) in comparison with females (p = .003). However, plasma lithium and VPA concentrations at discharge were not significantly different between sexes. CONCLUSION: Our results show sex differences in the progression of certain domains of manic symptoms in a cohort of 23 female and 34 male patients admitted to a large academic center in Turkey. Males, in this sample, exhibited more sexual interest, disruptive and aggressive behaviors, better grooming, and less insight compared to females. While these results are concordant with our preclinical findings and with anecdotal clinical observations, replication in larger samples is needed.