Cortical and Subcortical Signatures of Incentive Salience Attribution in Tobacco Use Disorder

FIGURE 1. Changes in cortical thickness provide one measure of brain maturation. A large longitudinal study found that for most areas of cortex, children with attention deficit hyperactivity disorder (ADHD) reach peak cortical thickness several years later than typically developing children, supporting presence of developmental delay. The rate of cortical thinning also differed between the group who continued to meet diagnostic criteria into adulthood (persistent ADHD) and those who did not (remitted ADHD). Areas of cortex in which the rate of thinning correlated with adult symptom level (green, more symptoms associated with more thinning) are approximated on medial and lateral simplified representations of cortex. An earlier study also identified multiple areas in which cortex was thinner in adults with persistent ADHD compared with controls (orange). In addition, this study noted some areas of thicker cortex in remitted ADHD when compared with persistent ADHD (blue).

We studied the neural activation associated with the expectancy of emotional stimuli using whole brain fMRI. Fifteen healthy subjects underwent fMRI scanning during which they performed a warned reaction task using emotional pictures carrying pleasant, unpleasant, or neutral content. The task involved an expected or unexpected condition. Data were analyzed by comparing the images acquired under the different conditions. In the expected condition, compared with the unexpected condition, significant activation was observed in the medial, inferior and dorsolateral prefrontal cortex. Whereas the expectancy of pleasant stimuli produced activation in the left dorsolateral and left medial prefrontal cortex as well as in the right cerebellum, the expectancy of unpleasant stimuli produced activation in the right inferior and right medial prefrontal cortex, the right amygdala, the left anterior cingulate cortex, and bilaterally in the visual cortex. These results suggest that the expectancy of emotional stimuli is mediated by the prefrontal area including the medial, inferior, and dorsolateral prefrontal cortex. Furthermore, our data suggest that left frontal activation is associated with the expectancy of pleasant stimuli and that right frontal activation is associated with the expectancy of unpleasant stimuli. Finally, our findings suggest that the amygdala and anterior cingulate cortex may play an important role in the expectancy of unpleasant stimuli and that the input of this negative information is modulated by these specific brain areas.

Background:The neural mechanisms of chronic migraine remain largely unknown but linked to the decreased connectivity to intrinsic brain networks.Objective:To characterize the intranetwork functional connectivity within the Central Executive Network (CEN) and Default Mode Network (DMN) in chronic migraine (CM), with and without medication overuse headache (MOH).Methods:Using functional magnetic resonance imaging, we performed post-hoc analysis of a total of 136 pairs of nodes to node functional connectivity (NTNC) within the CEN and 6 pairs of NTNC within the DMN in CM (n=13) and CMMOH (n=16) as compared to controls, and between these two subgroups.Results:Connectivity between right ventrolateral prefrontal cortex (PFC) to contralateral anterior thalamus and connectivity between left dorsal PFC/frontal eye field (FEF) to dorsomedial PFC were decreased within the CEN in both CM and CMMOH subgroups. In the CEN, there was more widespread disruption in the CMMOH (n=16) versus CM (n=13), when compared to healthy controls. Within the subgroups, connectivity between right inferior frontal gyrus to left dorsolateral PFC was decreased in CMMOH compared to CM. In the DMN, only one NTNC (left lateral parietal to precuneus/PCC) was disrupted in the CMMOH group when compared to controls.Conclusion:There are similar patterns of NTNC dysfunction within CEN in CM regardless of MOH status. We observed more extensive intranetwork disruption in CMMOH than CM. The decreased coherence between the right inferior frontal gyrus and the left dorsolateral PFC in CMMOH is likely associated with a significant disruption in the inhibitory control and a maladaptive response in risk aversion and reward; whereas the decreased coherence between right dorsolateral and ventrolateral PFC to contralateral dorsal PFC/FEF may be related to lack of cognitive control and top-down regulation of pain in both CM and CMMOH.

Transcranial direct current stimulation (tDCS) over prefrontal cortex (PFC) regions is currently proposed as therapeutic intervention for major depression and other psychiatric disorders. The in-depth mechanistic understanding of this bipolar and non-focal stimulation technique is still incomplete. In a pilot study, we investigated the effects of bifrontal stimulation on brain metabolite levels and resting state connectivity under the cathode using multiparametric MRI techniques and computational tDCS modeling. Within a double-blind cross-over design, 20 subjects (12 women, 23.7 ± 2 years) were randomized to active tDCS with standard bifrontal montage with the anode over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the right DLPFC. Magnetic resonance spectroscopy (MRS) was acquired before, during, and after prefrontal tDCS to quantify glutamate (Glu), Glu + glutamine (Glx) and gamma aminobutyric acid (GABA) concentration in these areas. Resting-state functional connectivity MRI (rsfcMRI) was acquired before and after the stimulation. The individual distribution of tDCS induced electric fields (efields) within the MRS voxel was computationally modelled using SimNIBS 2.0. There were no significant changes of Glu, Glx and GABA levels across conditions but marked differences in the course of Glu levels between female and male participants were observed. Further investigation yielded a significantly stronger Glu reduction after active compared to sham stimulation in female participants, but not in male participants. For rsfcMRI neither significant changes nor correlations with MRS data were observed. Exploratory analyses of the effect of efield intensity distribution on Glu changes showed distinct effects in different efield groups. Our findings are limited by the small sample size, but correspond to previously published results of cathodal tDCS. Future studies should address gender and efield intensity as moderators of tDCS induced effects.

Neural coupling between contralesional motor and frontoparietal networks correlates with motor ability in individuals with chronic stroke

IntroductionAbout 31 million people worldwide suffer from substance use disorders (SUDs), causing significant health and economic burdens.SUDs are linked to reduced dopamine activity in the mesolimbic region of the brain, as well as dysfunction in the dorsolateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC), which are responsible for decision-making and self-control. Additionally, the ventral prefrontal cortex (PFC), including the orbitofrontal cortex (OFC) and ventral anterior cingulate cortex (vACC), play a role in emotional processing and limbic arousal.A promising approach to treating SUDs involves non-invasive neuromodulation techniques (NIBS), specifically repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS).ObjectivesTo better understand the role of non-invasive neuromodulation techniques in substance use disorders.MethodsA search was conducted in various databases, including PubMed.ResultsMany studies using rTMS to treat SUDs have targeted the DLPFC. When the left DLPFC is stimulated, the effects are generally positive, and the treatment produces clinically significant results for tobacco, stimulant, and opioid use disorders.It has been found that the medial PFC (mPFC) could be a potential target for therapy, especially when using deep TMS, as demonstrated by studies involving alcohol and cocaine. Both the DLPFC and mPFC are promising targets for rTMS.Regarding tDCS, it seems that right anodal DLPFC stimulation is the most effective method across all types of substances.ConclusionsMuch remains unknown regarding the mechanisms by which rTMS or tDCS induce therapeutic effects in SUDs. Further research is necessary to determine the clinical safety and efficacy of these treatments.Disclosure of InterestNone Declared

The mechanisms underlying the effects of antidepressant treatment in patients with Parkinson's disease (PD) are unclear. The neural changes after successful therapy investigated by neuroimaging methods can give insights into the mechanisms of action related to a specific treatment choice. To study the mechanisms of neural modulation of repetitive transcranial magnetic stimulation (rTMS) and fluoxetine, 21 PD depressed patients were randomized into only two active treatment groups for 4 wk: active rTMS over left dorsolateral prefrontal cortex (DLPFC) (5 Hz rTMS; 120% motor threshold) with placebo pill and sham rTMS with fluoxetine 20 mg/d. Event-related functional magnetic resonance imaging (fMRI) with emotional stimuli was performed before and after treatment - in two sessions (test and re-test) at each time-point. The two groups of treatment had a significant, similar mood improvement. After rTMS treatment, there were brain activity decreases in left fusiform gyrus, cerebellum and right DLPFC and brain activity increases in left DLPFC and anterior cingulate gyrus compared to baseline. In contrast, after fluoxetine treatment, there were brain activity increases in right premotor and right medial prefrontal cortex. There was a significant interaction effect between groups vs. time in the left medial prefrontal cortex, suggesting that the activity in this area changed differently in the two treatment groups. Our findings show that antidepressant effects of rTMS and fluoxetine in PD are associated with changes in different areas of the depression-related neural network.

Adolescent substance use is associated with disrupted communication among brain regions underlying reward-driven behaviors (e.g., nucleus accumbens (NAcc)) and cognitive/emotional control (e.g., prefrontal cortex (PFC); medial temporal lobe), which may be linked to poor future outcomes (e.g., substance use disorder). However, the relationship functional brain connectivity has with trajectories of adolescent alcohol, tobacco, and cannabis use has received limited attention. Investigate relationships between adolescent substance use trajectories and young adult whole-brain NAcc resting-state functional connectivity (rsFC). Substance use was assessed at ages 11, 13, 16, and 19. Subsequently (age 20), a subset of participants (N = 299) completed a single neuroimaging session. Latent growth curve models estimated substance use trajectories that included the intercept (age 14 use), linear slope (progression), and quadratic slope (acceleration), which served as predictors in neuroimaging analyses. Substance use trajectories representing greater age 14 usage, faster progression of use, and acceleration of use across adolescence would show stronger NAcc rsFC with regions implicated in cognitive/emotional control. Age 14 use (alcohol, tobacco, and cannabis) was associated with NAcc rsFC with dorsolateral PFC, dorsomedial PFC, parahippocampal gyrus (PHG), hippocampus, and amygdala. Progression of use was associated with NAcc rsFC with dorsolateral PFC, dorsomedial PFC, ventrolateral PFC, PHG, and amygdala. Finally, acceleration of use was linked with NAcc rsFC with dorsolateral PFC, ventromedial PFC, PHG, and hippocampus. NAcc rsFC with several brain regions (e.g., PFC subregions) varied with adolescent substance use, which may represent common neural mechanisms linking adolescent substance use with common psychological outcomes.

In this study, the authors systematically reviewed structural and functional neuroimaging studies of cannabis use. Structural abnormalities generally have not been identified with chronic use. Regular users demonstrate reciprocal changes in brain activity globally and in cerebellar and frontal regions. Abstinence results in decreases, and administration results in increases correlating with subjective intoxication. Chronic use and cannabis administration result in attenuated brain activity in task-activated regions or activation of compensatory regions. Findings correlate partially with neuropsychological data, but generalization is limited by the lack of use of diagnostic criteria, appropriately paired neuropsychological testing or means to better quantify cannabis use and abstinence.

Understanding Emotion Regulation in Borderline Personality Disorder: Contributions of Neuroimaging

Cerebral blood flow ratio of the dorsolateral prefrontal cortex to the ventromedial prefrontal cortex as a potential predictor of treatment response to transcranial magnetic stimulation in depression

Around one-third of people develop depression following ischaemic stroke, yet the underlying mechanisms are poorly understood. Post-stroke depression has been linked to frontal infarcts, mainly lesions in the left dorsolateral prefrontal cortex (DLPFC). But depression is a network disorder that cannot be fully characterised through lesion-symptom mapping. Researchers of depression in non-stroke populations have successfully tapped into the cognitive control network (CCN) using the bilateral DLPFC as a seed, and found that CCN resting-state connectivity is reduced in even mildly depressed subjects, compared to healthy controls. Hence, we aimed to investigate the association between post-stroke depressive features and the CCN resting-state connectivity in a stroke population. We analysed DLPFC resting-state connectivity in 64 stroke participants, 20 of whom showed depressive features assessed with the Patient Health Questionnaire (PHQ-9) at 3 months after stroke. We directly compared groups showing symptoms of depression with those who did not, and performed a regression with PHQ-9 scores in all participants, controlling for age, gender, lesion volume and stroke severity. Post-stroke depression was associated with lower connectivity between the left DLPFC and the right supramarginal gyrus (SMG) in both group and regression analyses. Neither the seed nor the results overlapped with stroke lesions. These findings confirm an important role of the left DLPFC in post-stroke depression, but now show that large-scale network disruptions following stroke associated with depressive features occur without lesions in the DLPFC.

Background and Aims: Substance and tobacco use is associated with poor maternal and child health outcomes. Although these have each been linked to lower breastfeeding rates when examined separately, studies have yet to examine how the combination of tobacco and other substance use influences breastfeeding initiation and continuation. The aim of this study was to examine how the combination of smoking tobacco and use of illicit substances influences the odds of breastfeeding initiation and continuation. Materials and Methods: This retrospective cohort study (n = 15,634) used survey data from the 2016-2018 Centers for Disease Control and Prevention (CDC) Pregnancy Risk Assessment Monitoring System from eight US states to examine the association of tobacco and illicit substance use with breastfeeding initiation and continuation (≥6 weeks). The odds of breastfeeding initiation and continuation for individuals with and without prenatal tobacco and illicit substance use, adjusting for maternal and infant characteristics, were estimated using weighted, multivariable logistic regression models. Results: The combination of prenatal tobacco and illicit substance use was associated with a 42% reduction in the odds of initiating breastfeeding (adjusted odds ratio [aOR] 0.58 [95% confidence interval, CI 0.39-0.87]) and a 39% reduction in the odds of breastfeeding for at least 6 weeks (aOR 0.61 [95% CI 0.41-0.92]) when compared with those without tobacco and substance use. Conclusion: The odds of breastfeeding initiation and continuation are significantly lower among individuals with both prenatal tobacco and illicit substance use. Future studies are needed to identify barriers to breastfeeding within this population, to inform patient-centered interventions aimed at overcoming these barriers.

Changes in Regional Cerebral Blood Flow After Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex in Treatment-Resistant Depression

Working memory (WM) impairment, a core feature of schizophrenia, is often associated with aberrant dorsolateral prefrontal cortex (dlPFC) activation. Reduced resting-state connectivity within the frontoparietal control network (FPCN) has also been reported in schizophrenia. However, interpretation of WM-related dlPFC dysfunction has been limited by performance differences between patients and controls, and by uncertainty over the relevance of resting-state connectivity to network engagement during task. We contrasted brain activation in 40 schizophrenia patients and 40 controls during verbal WM performance, and evaluated underlying functional connectivity during rest and task. During correct trials, patients demonstrated normal FPCN activation, despite an inverse relationship between positive symptoms and activation. FPCN activation differed between the groups only during error trials (controls>patients). In contrast, controls demonstrated stronger deactivation of the ventromedial prefrontal cortex (vmPFC) during correct and error trials. Functional connectivity analysis indicated impaired resting-state FPCN connectivity in patients, but normal connectivity during task. However, patients showed abnormal connectivity among regions such as vmPFC, lateral orbitofrontal cortex, and parahippocampal gyrus (PHG) during both rest and task. During task, patients also exhibited altered thalamic connectivity to PHG and FPCN. Activation and connectivity patterns that were more characteristic of controls generally correlated with better performance. In summary, patients demonstrated normal FPCN activation when they remained on-task, and exhibited normal FPCN connectivity during WM, whereas vmPFC deactivation differences persisted regardless of WM performance. Our findings suggest that altered FPCN activation in patients reflects performance difference, and that limbic and thalamic dysfunction is critically involved in WM deficits in schizophrenia.