Ventral Anterior Cingulate Cortex Research Articles

Appetitive conditioning with pornographic stimuli elicits stronger activation in reward regions than monetary and gaming-related stimuli.

Appetitive conditioning plays an important role in the development and maintenance of pornography-use and gaming disorders. It is assumed that primary and secondary reinforcers are involved in these processes. Despite the common use of pornography and gaming in the general population appetitive conditioning processes in this context are still not well studied. This study aims to compare appetitive conditioning processes using primary (pornographic) and secondary (monetary and gaming-related) rewards as unconditioned stimuli (UCS) in the general population. Additionally, it investigates the conditioning processes with gaming-related stimuli as this type of UCS was not used in previous studies. Thirty-one subjects participated in a differential conditioning procedure in which four geometric symbols were paired with either pornographic, monetary, or gaming-related rewards or with nothing to become conditioned stimuli (CS + porn, CS + game, CS + money, and CS-) in an functional magnetic resonance imaging study. We observed elevated arousal and valence ratings as well as skin conductance responses for each CS+ condition compared to the CS-. On the neural level, we found activations during the presentation of the CS + porn in the bilateral nucleus accumbens, right medial orbitofrontal cortex, and the right ventral anterior cingulate cortex compared to the CS-, but no significant activations during CS + money and CS + game compared to the CS-. These results indicate that different processes emerge depending on whether primary and secondary rewards are presented separately or together in the same experimental paradigm. Additionally, monetary and gaming-related stimuli seem to have a lower appetitive value than pornographic rewards.

Neuroanatomical substrates of circuit specific cholinergic modulation across the primate anterior cingulate cortex.

Acetylcholine is a robust neuromodulator of the limbic system and a critical regulator of arousal, emotions, and stress. The anterior cingulate cortex (ACC) and the amygdala (AMY) are key limbic structures that are both densely innervated by cholinergic afferents and interact with each other for emotional regulation. The ACC is comprised of functionally-distinct dorsal (A24), rostral (A32), and ventral (A25) areas that differ in their connections with the AMY. The structural substrates of cholinergic modulation of distinct ACC microcircuits and outputs to AMY are thought to depend on the laminar and subcellular localization of cholinergic receptors. The present study examines the distribution of muscarinic acetylcholine receptors, m1 and m2, on distinct excitatory and inhibitory neuronal classes and on AMY-targeting projection neurons within ACC areas, via immunohistochemistry and in vivo injections of neural tracers into the basolateral AMY in adult rhesus monkeys of both sexes. We found that laminar densities of m1+ and m2+ expressing excitatory and inhibitory neurons depended on area and cell-type. Among the ACC areas, ventral subgenual ACC A25 exhibited greater m2+ localization on presynaptic inhibitory axon terminals and greater density of m1+ and m2+ expressing AMY-targeting (tracer+) pyramidal neurons. These patterns suggest robust cholinergic dis-inhibition and potentiation of amygdalar outputs from the limbic ventral ACC, which may be linked to the hyperexcitability of this subgenual ACC area in depression. These findings reveal the anatomical substrate of diverse cholinergic modulation of specific ACC microcircuits and amygdalar outputs that mediate cognitive-emotional integration and dysfunctions underlying stress and affective disorders.Significance Statement Cholinergic neuromodulation of anterior cingulate (ACC) cortico-limbic networks are consequential for cognitive-emotional integration. This study explored muscarinic acetylcholine receptor (m1 and m2) expression on distinct excitatory and inhibitory neurons across functionally-distinct ACC subregions and their outputs to the amygdala, a key limbic structure for emotional regulation. Our findings reveal that muscarinic receptor expression is most robust in ventral subgenual ACC area 25, in patterns that suggest cholinergic dis-inhibition and potentiation of area 25 outputs to the amygdala. These neuromodulatory interactions may be linked to the hyperexcitability of subgenual ACC found in depression. Our findings yield novel insight on how cholinergic modulation of specific ACC microcircuits and amygdalar outputs can contribute to cognitive-emotional processing and dysfunction in stress and affective disorders.

Reduced functional connectivity of the right dorsolateral prefrontal cortex at rest in obsessive-compulsive disorder.

Neuroimaging studies have revealed the role of the right dorsolateral prefrontal cortex (DLPFC) in the neurobiological mechanism of obsessive-compulsive disorder (OCD). However, only a few studies have examined the functional connectivity (FC) pattern of the right DLPFC at rest in OCD. The aim of this research is to examine the FC patterns of the right DLPFC at rest in OCD. Twenty-eight medication-free patients with OCD and 20 healthy controls underwent resting-state functional magnetic resonance imaging. Seed-based FC and support vector machine (SVM) were used to analyze the imaging data. The patients with OCD showed reduced FC values in the right middle temporal gyrus (MTG), right superior temporal gyrus, right ventral anterior cingulate cortex (vACC), and left Crus II. No brain regions showed a remarkable difference in FC values in patients with OCD after 8 weeks of medication treatment. The reduced right DLPFC-right MTG and right DLPFC-right vACC connectivities were correlated with the clinical symptoms of OCD. SVM results showed that reduced right DLPFC-right MTG connectivity at rest could predict the therapeutic response to OCD medication. The findings highlight the important role of the right DLPFC in the pathophysiological mechanism of OCD.

Ventral Anterior Cingulate Atrophy as a Predisposing Factor for Transient Global Amnesia.

This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether the brains of TGA patients have pre-existing structural abnormalities. We evaluated the brain MRI data from 87 TGA patients and 20 age- and sex-matched control subjects. We included brain MRIs obtained from TGA patients within 72 hours of symptom onset to verify the pre-existence of structural change. For voxel-based morphometric analyses, statistical parametric mapping was employed to analyze the structural differences between patients with TGA and control subjects. TGA patients exhibited significant volume reductions in the bilateral ventral anterior cingulate cortices (corrected p<0.05). TGA patients might have pre-existing structural changes in bilateral ventral anterior cingulate cortices prior to TGA attacks.

Hypo- and hyper-activation in frontotemporal lobe during humor processing in patients with first episode schizophrenia

BackgroundPatients with schizophrenia present difficulties in humor recognition and appreciation, but the neural mechanism of these deficits remains unclear. This study aimed to elucidate neural substrates underlying humor processing in patients with first episode schizophrenia (FES). MethodsThis study recruited 40 patients with FES (illness duration ≤ 4 years) and 31 healthy controls matching for age, gender and education level. Participants completed a fMRI verbal humor processing paradigm comprising 96 stories, half for funny punch-line condition and the other half for unfunny condition. Participants were required to judge whether the story was funny or not. Signal detection theory (SDT) analysis was used to calculate d' and β values which represented sensitivity and inner criteria for humor signals respectively. The funny-unfunny contrast was analyzed to identify the brain regions related with humor processing. d' and β values were put into the imaging regression analysis. ResultsPatients with FES showed significantly lower hit rate and sensitivity of humor signals (d'). At the neural level, patients with FES hypo-activated in ventral medial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) while hyper-activated in middle temporal gyrus (MTG) and superior temporal gyrus (STG) compared to controls. In addition, activity in vmPFC and ACC was positively associated with d’ and β values, while activity in STG was positively associated with β values in the clinical group. ConclusionsPatients with FES exhibited decreased sensitivity to humor signals. Hypo-activation in frontal regions and hyper-activation in temporal regions were associated with the humor processing deficits.

Abnormal white and gray matter functional connectivity is associated with cognitive dysfunction in presbycusis.

Presbycusis is characterized by high-frequency hearing loss and is closely associated with cognitive decline. Previous studies have observed functional reorganization of gray matter in presbycusis, but the information transmission between gray matter and white matter remains ill-defined. Using resting-state functional magnetic resonance imaging, we investigated differences in functional connectivity (GM-GM, WM-WM, and GM-WM) between 60 patients with presbycusis and 57 healthy controls. Subsequently, we examined the correlation between these connectivity differences with high-frequency hearing loss as well as cognitive impairment. Our results revealed significant alterations in functional connectivity involving the body of the corpus callosum, posterior limbs of the internal capsule, retrolenticular region of the internal capsule, and the gray matter regions in presbycusis. Notably, disrupted functional connectivity was observed between the body of the corpus callosum and ventral anterior cingulate cortex in presbycusis, which was associated with impaired attention. Additionally, enhanced functional connectivity was found in presbycusis between the internal capsule and the ventral auditory processing stream, which was related to impaired cognition in multiple domains. These two patterns of altered functional connectivity between gray matter and white matter may involve both bottom-up and top-down regulation of cognitive function. These findings provide novel insights into understanding cognitive compensation and resource redistribution mechanisms in presbycusis.

Joint contributions from brain activity and activity-independent functional connectivity to working memory aging.

Working memory (WM) impairment has been well characterized in normal aging. Various studies have explored changes in either the regional activity or the interregional connectivity underlying the aging process of WM. We proposed that brain activity and connectivity would independently alter with aging and affect WM performance. WM was assessed with a classical N-back task during functional magnetic resonance imaging in a community-based sample comprising 168 elderly subjects (aged 55-86 years old). Following the rationale of background functional connectivity, we assessed age-related alterations in brain activity and seed-based interregional connectivity independently. Analyses revealed age-related decrease in positive activity of the inferior parietal lobule (IPL) and an increase in the negative activity of the ventral anterior cingulate cortex (ACC), and the local functional dysfunctions were accompanied by alterations in their connectivity to other cortical regions. Importantly, regional activity impairments in the IPL and ACC could mediate age-related effects on accuracy rate and reaction time, respectively, and those effects were further counterbalanced by enhancement of their background functional connectivity. We thus claimed that age-induced alterations in regional activity and interregional connectivity occurred independently and contributed to WM changes in aging. Our findings presented the way brain activity and functional connectivity interact in the late adulthood, thus providing a new perspective for understanding WM and cognitive aging.

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

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. 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. 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). 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.

When the brain turns on with sexual desire: fMRI findings, issues, and future directions.

More than 2 decades of neuroimaging research has sought to uncover the neurologic basis of sexual desire. However, the lack of a clear conceptual distinction between sexual desire and sexual arousal or even a broadly accepted definition of sexual desire has led to confusion in the literature regarding brain areas uniquely associated with sexual desire. (1) To critically review the neuroimaging literature that seeks to identify brain areas and networks involved in sexual desire; (2) to identify and discuss those brain areas and potential networks that are most promising for providing insights to sexual desire; and (3) to offer recommendations for future studies. Existing meta-analyses were used as a starting point to identify relevant neuroimaging studies on sexual desire, arousal, and love. This base was then expanded via Google Scholar and forward citation tracking of already identified studies. Brain areas that are commonly associated with sexual desire and arousal include the amygdala, hypothalamus, dorsal and ventral striatum, anterior cingulate, insula, and prefrontal and orbitofrontal cortex. However, because the same basic paradigm has been used to study sexual desire and arousal, unambiguous conclusions regarding areas uniquely involved in sexual desire cannot be drawn. Moreover, the lack of connectivity analyses and a failure to acknowledge negative BOLD (blood-oxygen level dependent) significantly limit conclusions on the neural basis of sexual desire. Five recommendations are made. First, stimulus types (ie, erotic vs sexually explicit) should be selected by the meaningful theoretical conceptualization of the constructs of interest. Second, participants should be provided with definitions of sexual desire, mental sexual arousal, and perceived genital sexual arousal, so they can choose which terms best describe their experience. Third, event-related designs should be used with caution when investigating sexual desire. Fourth, time series analyses should be used to identify both positive and negative BOLD. Fifth, connectivity analyses should be performed to identify brain networks.

Relationship Between Interoception and Autistic Traits: A Resting-State Functional Connectivity Study.

Interoception, the sense of the physiological condition of our body, is impaired in individuals with autism spectrum disorders. Evidence suggests that subclinical autistic traits are mild manifestations of autistic symptoms, present in the general population. We examined the resting-state functional connectivity (rsFC) associating with interoception and autistic traits in 62 healthy young adults. Autistic traits correlated negatively with the rsFC between the lateral ventral anterior insula and anterior cingulate cortex. Interoceptive accuracy and sensibility correlated positively with the rsFC between interoceptive brain networks and the cerebellum, supplementary motor area, and visual regions. The results suggest that a negative relationship between interoception and autistic traits is largely accounted for by both self-report measures and decreased rsFC amongst the interoceptive brain network.

Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression

Intravenous ketamine is posited to rapidly reverse depression by rapidly enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. In this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 to a single infusion of intravenous ketamine (0.5 mg/kg) or vehicle (saline) and completed diffusion tensor imaging (DTI) assessments at pre-infusion baseline and 24-h post-infusion. DTI mean diffusivity (DTI-MD), a putative marker of microstructural neuroplasticity in gray matter, was calculated for 7 regions of interest (left and right BA10, amygdala, and hippocampus; and ventral Anterior Cingulate Cortex) and compared to clinical response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR). Individual differences in DTI-MD change (greater decrease from baseline to 24-h post-infusion, indicative of more neuroplasticity enhancement) were associated with larger improvements in depression scores across several regions. In the left BA10 and left amygdala, these relationships were driven primarily by the ketamine group (group * DTI-MD interaction effects: p = 0.016–0.082). In the right BA10, these associations generalized to both infusion arms (p = 0.007). In the left and right hippocampus, on the MADRS only, interaction effects were observed in the opposite direction, such that DTI-MD change was inversely associated with depression change in the ketamine arm specifically (group * DTI-MD interaction effects: p = 0.032–0.06). The acute effects of ketamine on depression may be mediated, in part, by acute changes in neuroplasticity quantifiable with DTI.

Cognitive Stress Regulation in Schizophrenia Patients and Healthy Individuals: Brain and Behavior.

Stress is an important factor in the development, triggering, and maintenance of psychotic symptoms. Still, little is known about the neural correlates of cognitively regulating stressful events in schizophrenia. The current study aimed at investigating the cognitive down-regulation of negative, stressful reactions during a neuroimaging psychosocial stress paradigm (non-regulated stress versus cognitively regulated stress). In a randomized, repeated-measures within-subject design, we assessed subjective reactions and neural activation in schizophrenia patients (SZP) and matched healthy controls in a neuroimaging psychosocial stress paradigm. In general, SZP exhibited an increased anticipation of stress compared to controls (p = 0.020). During non-regulated stress, SZP showed increased negative affect (p = 0.033) and stronger activation of the left parietal operculum/posterior insula (p < 0.001) and right inferior frontal gyrus/anterior insula (p = 0.005) than controls. Contrarily, stress regulation compared to non-regulated stress led to increased subjective reactions in controls (p = 0.003) but less deactivation in SZP in the ventral anterior cingulate cortex (p = 0.027). Our data demonstrate stronger reactions to and anticipation of stress in patients and difficulties with cognitive stress regulation in both groups. Considering the strong association between mental health and stress, the investigation of cognitive regulation in individuals vulnerable to stress, including SZP, has crucial implications for improving stress intervention trainings.

Revisiting reward impairments in schizophrenia spectrum disorders: a systematic review and meta-analysis for neuroimaging findings.

Abnormal reward functioning is central to anhedonia and amotivation symptoms of schizophrenia (SCZ). Reward processing encompasses a series of psychological components. This systematic review and meta-analysis examined the brain dysfunction related to reward processing of individuals with SCZ spectrum disorders and risks, covering multiple reward components. After a systematic literature search, 37 neuroimaging studies were identified and divided into four groups based on their target psychology components (i.e. reward anticipation, reward consumption, reward learning, effort computation). Whole-brain Seed-based d Mapping (SDM) meta-analyses were conducted for all included studies and each component. The meta-analysis for all reward-related studies revealed reduced functional activation across the SCZ spectrum in the striatum, orbital frontal cortex, cingulate cortex, and cerebellar areas. Meanwhile, distinct abnormal patterns were found for reward anticipation (decreased activation of the cingulate cortex and striatum), reward consumption (decreased activation of cerebellum IV/V areas, insula and inferior frontal gyri), and reward learning processing (decreased activation of the striatum, thalamus, cerebellar Crus I, cingulate cortex, orbitofrontal cortex, and parietal and occipital areas). Lastly, our qualitative review suggested that decreased activation of the ventral striatum and anterior cingulate cortex was also involved in effort computation. These results provide deep insights on the component-based neuro-psychopathological mechanisms for anhedonia and amotivation symptoms of the SCZ spectrum.

Predictive neuromodulation of cingulo-frontal neural dynamics in major depressive disorder using a brain-computer interface system: A simulation study.

Deep brain stimulation (DBS) is a promising therapy for treatment-resistant major depressive disorder (MDD). MDD involves the dysfunction of a brain network that can exhibit complex nonlinear neural dynamics in multiple frequency bands. However, current open-loop and responsive DBS methods cannot track the complex multiband neural dynamics in MDD, leading to imprecise regulation of symptoms, variable treatment effects among patients, and high battery power consumption. Here, we develop a closed-loop brain-computer interface (BCI) system of predictive neuromodulation for treating MDD. We first use a biophysically plausible ventral anterior cingulate cortex (vACC)-dorsolateral prefrontal cortex (dlPFC) neural mass model of MDD to simulate nonlinear and multiband neural dynamics in response to DBS. We then use offline system identification to build a dynamic model that predicts the DBS effect on neural activity. We next use the offline identified model to design an online BCI system of predictive neuromodulation. The online BCI system consists of a dynamic brain state estimator and a model predictive controller. The brain state estimator estimates the MDD brain state from the history of neural activity and previously delivered DBS patterns. The predictive controller takes the estimated MDD brain state as the feedback signal and optimally adjusts DBS to regulate the MDD neural dynamics to therapeutic targets. We use the vACC-dlPFC neural mass model as a simulation testbed to test the BCI system and compare it with state-of-the-art open-loop and responsive DBS treatments of MDD. We demonstrate that our dynamic model accurately predicts nonlinear and multiband neural activity. Consequently, the predictive neuromodulation system accurately regulates the neural dynamics in MDD, resulting in significantly smaller control errors and lower DBS battery power consumption than open-loop and responsive DBS. Our results have implications for developing future precisely-tailored clinical closed-loop DBS treatments for MDD.

Differential Modulation of Dorsal Raphe Serotonergic Activity in Rat Brain by the Infralimbic and Prelimbic Cortices

The reciprocal connectivity between the medial prefrontal cortex (mPFC) and the dorsal raphe nucleus (DR) is involved in mood control and resilience to stress. The infralimbic subdivision (IL) of the mPFC is the rodent equivalent of the ventral anterior cingulate cortex, which is intimately related to the pathophysiology/treatment of major depressive disorder (MDD). Boosting excitatory neurotransmission in the IL-but not in the prelimbic cortex, PrL-evokes depressive-like or antidepressant-like behaviors in rodents, which are associated with changes in serotonergic (5-HT) neurotransmission. We therefore examined the control of 5-HT activity by both of the mPFC subdivisions in anesthetized rats. The electrical stimulation of IL and PrL at 0.9 Hz comparably inhibited 5-HT neurons (53% vs. 48%, respectively). However, stimulation at higher frequencies (10-20 Hz) revealed a greater proportion of 5-HT neurons sensitive to IL than to PrL stimulation (86% vs. 59%, at 20 Hz, respectively), together with a differential involvement of GABAA (but not 5-HT1A) receptors. Likewise, electrical and optogenetic stimulation of IL and PrL enhanced 5-HT release in DR in a frequency-dependent manner, with greater elevations after IL stimulation at 20 Hz. Hence, IL and PrL differentially control serotonergic activity, with an apparent superior role of IL, an observation that may help to clarify the brain circuits involved in MDD.

Stressor-Specific Sex Differences in Amygdala-Frontal Cortex Networks.

Females and males differ in stress reactivity, coping, and the prevalence rates of stress-related disorders. According to a neurocognitive framework of stress coping, the functional connectivity between the amygdala and frontal regions (including the dorsolateral prefrontal cortex (dlPFC), ventral anterior cingulate cortex (vACC), and medial prefrontal cortex (mPFC)) plays a key role in how people deal with stress. In the current study, we investigated the effects of sex and stressor type in a within-subject counterbalanced design on the resting-state functional connectivity (rsFC) of the amygdala and these frontal regions in 77 healthy participants (40 females). Both stressor types led to changes in subjective ratings, with decreasing positive affect and increasing negative affect and anger. Females showed higher amygdala-vACC and amygdala-mPFC rsFC for social exclusion than for achievement stress, and compared to males. Whereas a higher amygdala-vACC rsFC indicates the activation of emotion processing and coping, a higher amygdala-mPFC rsFC indicates feelings of reward and social gain, highlighting the positive effects of social affiliation. Thus, for females, feeling socially affiliated might be more fundamental than for males. Our data indicate interactions of sex and stressor in amygdala-frontal coupling, which translationally contributes to a better understanding of the sex differences in prevalence rates and stress coping.

Voxel-wise Mapping of Functional Magnetic Resonance Imaging in Impression Formation

Social interactions often involve encountering inconsistent information about social others. We conducted a functional magnetic resonance imaging (fMRI) study to comprehensively investigate voxel-wise temporal dynamics showing how impressions are anchored and/or adjusted in response to inconsistent social information. The participants performed a social impression task inside an fMRI scanner in which they were shown a male face, together with a series of four adjectives that described the depicted person''s personality traits, successively presented beneath the image of the face. Participants were asked to rate their impressions of the person at the end of each trial on a scale of 1 to 8 (where 1 is most negative and 8 is most positive). We established two hypothetical models that represented two temporal patterns of voxel activity: Model 1 featured decreasing patterns of activity towards the end of each trial, anchoring impressions to initially presented information, and Model 2 showed increasing patterns of activity toward the end of each trial, where impressions were being adjusted using new and inconsistent information. Our data-driven model fitting analyses showed that the temporal activity patterns of voxels within the ventral anterior cingulate cortex, medial orbitofrontal cortex, posterior cingulate cortex, amygdala, and fusiform gyrus fit Model 1 (i.e., they were more involved in anchoring first impressions) better than they did Model 2 (i.e., showing impression adjustment). Conversely, voxel-wise neural activity within dorsal ACC and lateral OFC fit Model 2 better than it did Model 1, as it was more likely to be involved in processing new, inconsistent information and adjusting impressions in response. Our novel approach to model fitting analysis replicated previous impression-related neuroscientific findings, furthering the understanding of neural and temporal dynamics of impression processing, particularly with reference to functionally segmenting each region of interest based on relative involvement in impression anchoring as opposed to adjustment.

Persistent Ventral Anterior Cingulate Cortex and Resolved Amygdala Hyper-responses to Negative Outcomes After Depression Remission: A Combined Cross-sectional and Longitudinal Study

BackgroundMajor depressive disorder (MDD) is a highly prevalent mood disorder affecting more than 300 million people worldwide. Biased processing of negative information and neural hyper-responses to negative events are hallmarks of depression. This study combined cross-sectional and longitudinal experiments to explore both persistent and resolved neural hyper-responses to negative outcomes from risky decision making in patients with current MDD (cMDD) and remitted MDD (rMDD). MethodsA total of 264 subjects participated in the cross-sectional study, including 117 patients with medication-naïve, first-episode current depression; 45 patients with rMDD with only 1 episode of depression; and 102 healthy control subjects. Participants completed a modified balloon analog risk task during functional magnetic resonance imaging. In the longitudinal arm of the study, 42 patients with cMDD were followed and 26 patients with rMDD were studied again after 8 weeks of antidepressant treatment. ResultsPatients with cMDD showed hyper-responses to loss outcomes in multiple limbic regions including the amygdala and ventral anterior cingulate cortex (vACC). Amygdala but not vACC hyperactivity correlated with depression scores in patients with cMDD. Furthermore, amygdala hyperactivity resolved while vACC hyperactivity persisted in patients with rMDD in both cross-sectional and longitudinal studies. ConclusionsThese findings provide consistent evidence supporting differential patterns of amygdala and vACC hyper-responses to negative outcomes during depression remission. Amygdala hyperactivity may be a symptomatic and state-dependent marker of depressive neural responses, while vACC hyperactivity may reflect a persistent and state-independent effect of depression on brain function. These findings offer new insights into the neural underpinnings of depression remission and prevention of depression recurrence.

Methylation of genes and regulation of inflammatory processes on emotional response in young adults with alcoholic parents

Many Americans are adult children of an alcoholic parent (ACoA), which can confer an increased risk of trauma and hazardous alcohol use, as well as heritable and environmental genetic influence. Psychological health and related neural activity can be influenced by inflammation responses, but it is not clear how these factors interact regarding risk or resilience to hazardous alcohol use. The goals of this study were to better understand the relationships between current alcohol use and inflammation, how these are modified by single nucleotide polymorphisms (SNPs) and/or epigenetic modifications of inflammation-associated genes; and how these alter neural reactivity to emotionally-salient stimuli. To do so, ACoA participants were dichotomized as resilient (not engaged in hazardous alcohol use) or vulnerable (currently engaged in hazardous alcohol use). Measures of blood-oxygen-level-dependent (BOLD) activity within regions of interest (ROIs), SNPs and DNA methylation of specific inflammation regulatory genes, and biological markers of inflammation were compared between these groups. Vulnerable ACoAs exhibited higher plasma C-reactive protein (CRP) and greater BOLD activity in the right hippocampus and ventral anterior cingulate cortex in response to emotional cues as well as reduced methylation of CRP and glucocorticoid-related genes. Path analysis revealed significant relationships between alcohol use, SNPs, DNA methylation of inflammatory-related genes, CRP levels, and BOLD activity to emotional stimuli. Taken together, these findings suggest a complex association related to hazardous alcohol use in ACoAs that may predict current inflammation and neural reactivity to emotional stimuli. A better understanding of these associations could direct the future of individual treatment options.

Resting-state neural signal variability in women with depressive disorders

Aberrant activity and connectivity in default mode (DMN), frontoparietal (FPN), and salience (SN) network regions is well-documented in depression. Recent neuroimaging research suggests that altered variability in the blood oxygen level-dependent (BOLD) signal may disrupt normal network integration and be an important novel predictor of psychopathology. However, no studies have yet determined the relationship between resting-state BOLD signal variability and depressive disorders nor applied BOLD signal variability features to the classification of depression history using machine learning (ML). We collected resting-state fMRI data for 79 women with different depression histories: no history, past history, and current depressive disorder. We tested voxelwise differences in BOLD signal variability related to depression group and severity. We also investigated whether BOLD signal variability of DMN, FPN, and SN regions could predict depression history group using a supervised random forest ML model. Results indicated that individuals with any history of depression had significantly decreased BOLD signal variability in the left and right cerebellum and right parietal cortex (pFWE <0.05). Furthermore, greater depression severity was also associated with reduced BOLD signal variability in the cerebellum. A random forest model classified participant depression history with 74% accuracy, with the ventral anterior cingulate cortex of the DMN as the most important variable in the model. These findings provide novel support for resting-state BOLD signal variability as a marker of neural dysfunction in depression and implicate decreased neural signal variability in the pathophysiology of depression.