fMRI Paradigm Research Articles

Identifying the neural correlates of anticipatory postural control: A novel fMRI paradigm.

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the thigh remains supported. For the unsupported leg raise (ULR) the leg is raised from the hip, requiring postural muscle activation in the abdominal/hip extensor musculature. Significant brain activation during the SLR task occurred predominantly in the right primary and secondary sensorimotor cortical regions. Brain activation during the ULR task occurred bilaterally in the primary and secondary sensorimotor cortical regions, as well as cerebellum and putamen. In comparison with the SLR, the ULR was associated with significantly greater activation in the right premotor/SMA, left primary motor and cingulate cortices, primary somatosensory cortex, supramarginal gyrus/parietal operculum, superior parietal lobule, cerebellar vermis, and cerebellar hemispheres. Cortical and subcortical regions activated during the ULR, but not during the SLR, were consistent with the planning, and execution of a task involving multisegmental, bilateral postural control. Future studies using this paradigm will determine mechanisms underlying impaired postural control in patients with neurological and musculoskeletal dysfunction.

The Scanner as the Stimulus: Deficient Gamma-BOLD Coupling in Schizophrenia at Rest.

Functional magnetic resonance imaging (fMRI) scanners are unavoidably loud and uncomfortable experimental tools that are necessary for schizophrenia (SZ) neuroscience research. The validity of fMRI paradigms might be undermined by well-known sensory processing abnormalities in SZ that could exert distinct effects on neural activity in the presence of scanner background sound. Given the ubiquity of resting-state fMRI (rs-fMRI) paradigms in SZ research, elucidating the relationship between neural, hemodynamic, and sensory processing deficits during scanning is necessary to refine the construct validity of the MR neuroimaging environment. We recorded simultaneous electroencephalography (EEG)-fMRI at rest in people with SZ (n = 57) and healthy control participants without a psychiatric diagnosis (n = 46) and identified gamma EEG activity in the same frequency range as the background sounds emitted from our scanner during a resting-state sequence. In participants with SZ, gamma coupling to the hemodynamic signal was reduced in bilateral auditory regions of the superior temporal gyri. Impaired gamma-hemodynamic coupling was associated with sensory gating deficits and worse symptom severity. Fundamental sensory-neural processing deficits in SZ are present at rest when considering scanner background sound as a "stimulus." This finding may impact the interpretation of rs-fMRI activity in studies of people with SZ. Future neuroimaging research in SZ might consider background sound as a confounding variable, potentially related to fluctuations in neural excitability and arousal.

368. The Effect of OCD-Symptom Provocation on Neurometabolites in the Lateral Occipital Cortex and Their Relation to the BOLD Response, a Combined fMRS and fMRI Paradigm

368. The Effect of OCD-Symptom Provocation on Neurometabolites in the Lateral Occipital Cortex and Their Relation to the BOLD Response, a Combined fMRS and fMRI Paradigm

Power spectral analysis can determine language laterality from resting-state functional MRI data in healthy controls.

Resting-state functional magnetic resonance imaging (rsfMRI) has been proposed as an alternative to task-based fMRI including clinical situations such as preoperative brain tumor planning, due to advantages including ease of performance and time savings. However, one of its drawbacks is the limited ability to accurately lateralize language function. Using the rsfMRI data of healthy controls, we carried out a power spectra analysis on three regions of interest (ROIs): Broca's area (BA) in the frontal cortex for language, hand motor (HM) area in the primary motor cortex, and the primary visual cortex (V1). Spike removal, motion correction, linear trend removal, and spatial smoothing were applied. Spontaneous low-frequency fluctuations (0.01-0.1Hz) were filtered to enable functional integration. BA showed greater power on the left hemisphere relative to the right (p=.0055), while HM (p=.1563) and V1 (p=.4681) were not statistically significant. A novel index, termed the power laterality index (PLI), computed to estimate the degree of power lateralization for each brain region, revealed a statistically significant difference between BA and V1 (p<.00001), where V1 was used as a control since the primary visual cortex does not lateralize. Validation studies used to compare PLI to a laterality index computed using phonemic fluency, a task-based, language fMRI paradigm, demonstrated good correlation. The power spectra for BA revealed left language lateralization, which was not replicated in HM or V1. This work demonstrates the feasibility and validity of an ROI-based power spectra analysis on rsfMRI data for language lateralization.

Functional network interactions in patients with schizophrenia with persistent auditory verbal hallucinations: A multimodal MRI fusion approach using three-way pICA

Over the last decade, there have been an increasing number of functional magnetic resonance imaging (fMRI) studies examining brain activity in schizophrenia (SZ) patients with persistent auditory verbal hallucinations (AVH) using either task-based or resting-state fMRI (rs-fMRI) paradigms. Such data have been conventionally collected and analyzed as distinct modalities, disregarding putative crossmodal interactions. Recently, it has become possible to incorporate two or more modalities in one comprehensive analysis to uncover hidden patterns of neural dysfunction not sufficiently captured by separate analysis. A novel multivariate fusion approach to multimodal data analysis, i.e., parallel independent component analysis (pICA), has been previously shown to be a powerful tool in this regard. We utilized three-way pICA to study covarying components among fractional amplitude of low-frequency fluctuations (fALFF) for rs-MRI and task-based activation computed from an alertness and a working memory (WM) paradigm of 15 SZ patients with AVH, 16 non-hallucinating SZ patients (nAVH), and 19 healthy controls (HC). The strongest connected triplet (false discovery rate (FDR)-corrected pairwise correlations) comprised a frontostriatal/temporal network (fALFF), a temporal/sensorimotor network (alertness task), and a frontoparietal network (WM task). Frontoparietal and frontostriatal/temporal network strength significantly differed between AVH patients and HC. Phenomenological features such as omnipotence and malevolence of AVH were associated with temporal/sensorimotor and frontoparietal network strength. The transmodal data confirm a complex interplay of neural systems subserving attentional processes and cognitive control interacting with speech and language processing networks. In addition, the data emphasize the importance of sensorimotor regions modulating specific symptom dimensions of AVH.

PD22-09 CENTRAL BLADDER PROPRIOCEPTION: ROBUST FINDINGS FROM SENSATION-DRIVEN FUNCTIONAL MRI STUDY

You have accessJournal of UrologyCME1 Apr 2023PD22-09 CENTRAL BLADDER PROPRIOCEPTION: ROBUST FINDINGS FROM SENSATION-DRIVEN FUNCTIONAL MRI STUDY Anugrah Santoso, Stefan Sunaert, and Dirk De Ridder Anugrah SantosoAnugrah Santoso More articles by this author , Stefan SunaertStefan Sunaert More articles by this author , and Dirk De RidderDirk De Ridder More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003295.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Despite being long utilized to study the central control of bladder perception in response to repetitive bladder filling, the reliability and repeatability of functional MRI (fMRI) studies remain problematic. To our knowledge, most of the studies used a block design consisting of discrete epochs of on-off tasks. As proprioception of the bladder filling is immensely subjective, a desire to void event can only be indicated by the participant. In this pilot study, we aim to evaluate the brain response to even-related bladder filling fMRI paradigm. METHODS: Seven healthy female subjects with mean age 30.1 years were included. Ethical approval was obtained. All subjects underwent a baseline urodynamic study and the catheters were maintained for the subsequent MRI session. We used a 3 Tesla scanner with an in-bore screen and response buttons. Each fMRI session lasted 8.5 minutes and was repeated 2-4 times, depending on the subjects’ coping ability with the task. The paradigm consisted of repetitive bladder filling (60ml/minute) until first desire (FD) and strong desire (SD) was indicated, followed by a plateau (5 seconds) and withdrawal of 30 seconds (30ml). To prevent constant engagement of the viscerosensory cortex, a diversion visuomotor task was presented to which the subjects had to respond with the button press. All responses were recorded with Psychopy and further incorporated in data analysis. MRI preprocessing was done with fMRIPrep pipeline (version 20.2.6). SPM12 was used to smooth the data with a 6mm Gaussian filter and to analyse them. A General Linear Model was used to model the FD, SD and distraction tasks as events. Second-level mixed effect analysis was then performed for the 3 event-contrasts and significance was set to cluster level p<0.05 false discovery rate correction. RESULTS: On average subjects indicated FD 3.75 times and SD 4.71 times. The distraction task occurred on average 23.47 times. Figure 1 depicts the brain regions that show stronger mean activation during FD and SD from 7 subjects, including insula, thalamus, cerebellum, pontine micturition center, supplementary motor area and anterior cingulate cortex. CONCLUSIONS: Here we designed a sensation-driven fMRI paradigm that enables evaluation of bladder proprioception during FD and SD. The results were robust despite small number of subjects. Source of Funding: Departmental Funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e667 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anugrah Santoso More articles by this author Stefan Sunaert More articles by this author Dirk De Ridder More articles by this author Expand All Advertisement PDF downloadLoading ...

Deep brain stimulation normalizes amygdala responsivity in treatment-resistant depression.

Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is a promising intervention for treatment-resistant depression (TRD). However, the working mechanisms of vALIC DBS in TRD remain largely unexplored. As major depressive disorder has been associated with aberrant amygdala functioning, we investigated whether vALIC DBS affects amygdala responsivity and functional connectivity. To investigate the long-term effects of DBS, eleven patients with TRD performed an implicit emotional face-viewing paradigm during functional magnetic resonance imaging (fMRI) before DBS surgery and after DBS parameter optimization. Sixteen matched healthy controls performed the fMRI paradigm at two-time points to control for test-retest effects. To investigate the short-term effects of DBS de-activation after parameter optimization, thirteen patients additionally performed the fMRI paradigm after double-blind periods of active and sham stimulation. Results showed that TRD patients had decreased right amygdala responsivity compared to healthy controls at baseline. Long-term vALIC DBS normalized right amygdala responsivity, which was associated with faster reaction times. This effect was not dependent on emotional valence. Furthermore, active compared to sham DBS increased amygdala connectivity with sensorimotor and cingulate cortices, which was not significantly different between responders and non-responders. These results suggest that vALIC DBS restores amygdala responsivity and behavioral vigilance in TRD, which may contribute to the DBS-induced antidepressant effect.

Elucidating medial temporal and frontal lobe contributions to approach-avoidance conflict decision-making using functional MRI and the hierarchical drift diffusion model.

The prefrontal cortex (PFC) has long been associated with arbitrating between approach and avoidance in the face of conflicting and uncertain motivational information, but recent work has also highlighted medial temporal lobe (MTL) involvement. It remains unclear, however, how the contributions of these regions differ in their resolution of conflict information and uncertainty. We designed an fMRI paradigm in which participants approached or avoided object pairs that differed by motivational conflict and outcome uncertainty (complete certainty vs. complete uncertainty). Behavioral data and decision-making parameters estimated using the hierarchical drift diffusion model revealed that participants' responding was driven by conflict rather than uncertainty. Our neural data suggest that PFC areas contribute to cognitive control during approach-avoidance conflict by potentially adjusting response caution and the strength of evidence generated towards either choice, with differential involvement of anterior cingulate cortex and dorsolateral prefrontal cortex. The MTL, on the other hand, appears to contribute to evidence generation, with the hippocampus linked to evidence accumulation for stimuli. Although findings within perirhinal cortex were comparatively equivocal, some evidence suggests contributions to perceptual representations, particularly under conditions of threat. Our findings provide evidence that MTL and PFC regions may contribute uniquely to arbitrating approach-avoidance conflict.

Evaluation of visual food stimuli paradigms on healthy adolescents for future use in fMRI studies in anorexia nervosa

BackgroundMostly, visual food stimuli paradigms for functional Magnetic Resonance Imaging are used in studies of eating disorders. However, the optimal contrasts and presentation modes are still under discussion. Therefore, we aimed to create and analyse a visual stimulation paradigm with defined contrast.MethodsIn this prospective study, a block-design fMRI paradigm with conditions of randomly altering blocks of high- and low-calorie food images and images of fixation cross was established. Food pictures were rated in advance by a group of patients diagnosed with anorexia nervosa to address the dedicated perception of patients with eating disorders. To optimize the scanning procedure and fMRI contrasts we have analysed neural activity differences between high-calorie stimuli versus baseline (H vs. X), low-calorie stimuli versus baseline (L vs. X) and high- versus low-calorie stimuli (H vs. L).ResultsBy employing the developed paradigm, we were able to obtain results comparable to other studies and analysed them with different contrasts. Implementation of the contrast H versus X led to increased blood-oxygen-level-dependent signal (BOLD) mainly in unspecific areas, such as the visual cortex, the Broca´s area, bilaterally in the premotor cortex and the supplementary motor area, but also in thalami, insulae, the right dorsolateral prefrontal cortex, the left amygdala, the left putamen (p < .05). When applying the contrast L versus X, an enhancement of the BOLD signal was detected similarly within the visual area, the right temporal pole, the right precentral gyrus, Broca´s area, left insula, left hippocampus, the left parahippocampal gyrus, bilaterally premotor cortex and thalami (p < .05). Comparison of brain reactions regarding visual stimuli (high- versus low-calorie food), assumed to be more relevant in eating disorders, resulted in bilateral enhancement of the BOLD signal in primary, secondary and associative visual cortex (including fusiform gyri), as well as angular gyri (p < .05).ConclusionsA carefully designed paradigm, based on the subject’s characteristics, can increase the reliability of the fMRI study, and may reveal specific brain activations elicited by this custom-built stimuli. However, a putative disadvantage of implementing the contrast of high- versus low-calorie stimuli might be the omission of some interesting outcomes due to lower statistical power.Trial registration NCT02980120.

Task fMRI paradigms may capture more behaviorally relevant information than resting-state functional connectivity

Characterizing the optimal fMRI paradigms for detecting behaviorally relevant functional connectivity (FC) patterns is a critical step to furthering our knowledge of the neural basis of behavior. Previous studies suggested that FC patterns derived from task fMRI paradigms, which we refer to as task-based FC, are better correlated with individual differences in behavior than resting-state FC, but the consistency and generalizability of this advantage across task conditions was not fully explored. Using data from resting-state fMRI and three fMRI tasks from the Adolescent Brain Cognitive Development Study ® (ABCD), we tested whether the observed improvement in behavioral prediction power of task-based FC can be attributed to changes in brain activity induced by the task design. We decomposed the task fMRI time course of each task into the task model fit (the fitted time course of the task condition regressors from the single-subject general linear model) and the task model residuals, calculated their respective FC, and compared the behavioral prediction performance of these FC estimates to resting-state FC and the original task-based FC. The FC of the task model fit was better than the FC of the task model residual and resting-state FC at predicting a measure of general cognitive ability or two measures of performance on the fMRI tasks. The superior behavioral prediction performance of the FC of the task model fit was content-specific insofar as it was only observed for fMRI tasks that probed similar cognitive constructs to the predicted behavior of interest. To our surprise, the task model parameters, the beta estimates of the task condition regressors, were equally if not more predictive of behavioral differences than all FC measures. These results showed that the observed improvement of behavioral prediction afforded by task-based FC was largely driven by the FC patterns associated with the task design. Together with previous studies, our findings highlighted the importance of task design in eliciting behaviorally meaningful brain activation and FC patterns.

Multimodal assessment of the spatial correspondence between fNIRS and fMRI hemodynamic responses in motor tasks

Functional near-infrared spectroscopy (fNIRS) provides a cost-efficient and portable alternative to functional magnetic resonance imaging (fMRI) for assessing cortical activity changes based on hemodynamic signals. The spatial and temporal underpinnings of the fMRI blood-oxygen-level-dependent (BOLD) signal and corresponding fNIRS concentration of oxygenated (HbO), deoxygenated (HbR), and total hemoglobin (HbT) measurements are still not completely clear. We aim to analyze the spatial correspondence between these hemodynamic signals, in motor-network regions. To this end, we acquired asynchronous fMRI and fNIRS recordings from 9 healthy participants while performing motor imagery and execution. Using this multimodal approach, we investigated the ability to identify motor-related activation clusters in fMRI data using subject-specific fNIRS-based cortical signals as predictors of interest. Group-level activation was found in fMRI data modeled from corresponding fNIRS measurements, with significant peak activation found overlapping the individually-defined primary and premotor motor cortices, for all chromophores. No statistically significant differences were observed in multimodal spatial correspondence between HbO, HbR, and HbT, for both tasks. This suggests the possibility of translating neuronal information from fMRI into an fNIRS motor-coverage setup with high spatial correspondence using both oxy and deoxyhemoglobin data, with the inherent benefits of translating fMRI paradigms to fNIRS in cognitive and clinical neuroscience.

Changing role of the amygdala in affective and cognitive traits between early and late adulthood.

Healthy aging is typically associated with cognitive decline and lower negative affect. Previous studies have reported a significant and opposite role of the amygdala in relation to cognitive and affective processing in early adulthood. However, it remains unclear how aging impacts such relationships. Seventy-seven healthy participants including 40 young (mean age = 26.1 years) and 37 older (mean age = 61.8 years) adults completed a functional MRI Affective Stroop (AS) paradigm, a cognitive battery, and the state-trait anxiety inventory. The AS fMRI paradigm included "task trials," where participants saw a positively, negatively or neutrally valenced distractor image, followed by a numerical display, followed by another distractor image. We extracted signal in both amygdalas during the AS Task and compared it across all conditions and age group. We further conducted moderation analyses to investigate the impact of aging on the relationship between amygdala activation and anxiety or cognitive variables, respectively. At the behavioral level, older participants showed lower trait anxiety than the younger adults (p = 0.002). While overall slower during the AS task, older adults achieved comparable accuracy during the AS task, relative to the younger adults. At the brain level, we revealed a significant interaction between age group and trial types in amygdala activation (F = 4.9, p = 0.03), with the older group showing stronger activation during the most complex trials compared to the passive view trials. We further found that age significantly modulated the relationship between anxiety and the left amygdala activation during negative stimuli, where the younger adults showed a positive association while the older adults showed a negative association. Age also significantly modulated the relationship between verbal fluency and left amygdala activation during incongruent versus view trials, with the younger adults showing a negative association and the older adults showing a positive association. The current study suggests that the role of the amygdala on both emotional processing and cognitive traits changes between early and late adulthood.

Transcranial direct current stimulation with functional magnetic resonance imaging: a detailed validation and operational guide.

Introduction: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used to modulate human brain and behavioural function in both research and clinical interventions. The combination of functional magnetic resonance imaging (fMRI) with tDCS enables researchers to directly test causal contributions of stimulated brain regions, answering questions about the physiology and neural mechanisms underlying behaviour. Despite the promise of the technique, advances have been hampered by technical challenges and methodological variability between studies, confounding comparability/replicability. Methods: Here tDCS-fMRI at 3T was developed for a series of experiments investigating language recovery after stroke. To validate the method, one healthy volunteer completed an fMRI paradigm with three conditions: No-tDCS, Sham-tDCS, Anodal-tDCS. MR data were analysed with region-of-interest (ROI) analyses of the electrodes and reference site. Results: Quality assessment indicated no visible signal dropouts or distortions in the brain introduced by the tDCS equipment. After modelling scanner drift, motion-related variance, and temporal autocorrelation, we found that functional MR sensitivity was not degraded or adversely affected by the tDCS set-up and stimulation protocol across conditions in grey matter and in the three ROIs. Discussion: Key safety factors and risk mitigation strategies that must be taken into consideration when integrating tDCS into an fMRI environment are outlined. To obtain reliable results, we provide practical solutions to technical challenges and complications of the method. It is hoped that sharing these data and Standard Operation Procedure (SOP) will promote methodological replication in future studies, enhancing the quality of tDCS-fMRI application, and improve the reliability of scientific results in this field. Conclusions: Our method and data provide a technically safe, reliable tDCS-fMRI procedure to obtain high quality MR data. The detailed framework of the SOP systematically reports the technical and procedural elements of our tDCS-fMRI approach, which can be adopted and prove useful in future studies.

Differential neural reward reactivity in response to food advertising medium in children.

Food cues including food advertisements (ads) activate brain regions related to motivation and reward. These responses are known to correlate with eating behaviors and future weight gain. The objective of this study was to compare brain responses to food ads by different types of ad mediums, dynamic (video) and static (images), to better understand how medium type impacts food cue response. Children aged 9-12 years old were recruited to complete a functional magnetic resonance imaging (fMRI) paradigm that included both food and non-food dynamic and static ads. Anatomical and functional images were preprocessed using the fMRIPrep pipeline. A whole-brain analysis and a targeted region-of-interest (ROI) analysis for reward regions (nucleus accumbens, orbitofrontal cortex, amygdala, insula, hypothalamus, ventral tegmental area, substantia nigra) were conducted. Individual neural responses to dynamic and static conditions were compared using a paired t-test. Linear mixed-effects models were then constructed to test the differential response by ad condition after controlling for age, sex, BMI-z, physical activity, and % of kcal consumed of a participant's estimated energy expenditure in the pre-load prior to the MRI scan. A total of 115 children (mean=10.9 years) completed the fMRI paradigm. From the ROI analyses, the right and left hemispheres of the amygdala and insula, and the right hemisphere of the ventral tegmental area and substantia nigra showed significantly higher responses for the dynamic food ad medium after controlling for covariates and a false discovery rate correction. From the whole-brain analysis, 21 clusters showed significant differential responses between food ad medium including the precuneus, middle temporal gyrus, superior temporal gyrus, and inferior frontal gyrus, and all regions remained significant after controlling for covariates. Advertising medium has unique effects on neural response to food cues. Further research is needed to understand how this differential activation by ad medium ultimately affects eating behaviors and weight outcomes.

Action viewing and language in adolescents with autism spectrum disorder.

The mirror neuron system consists of fronto-parietal regions and responds to both goal-directed action execution and observation. The broader action observation network is specifically involved in observation of actions and is thought to play a role in understanding the goals of the motor act, the intention of others, empathy, and language. Many, but not all, studies have found mirror neuron system or action observation network dysfunction in autism spectrum disorder. The objective of this study was to use observation of a goal-directed action fMRI paradigm to examine the action observation network in autism spectrum disorder and to determine whether fronto-parietal activation is associated with language ability. Adolescents with autism spectrum disorder (n = 23) were compared to typically developing adolescents (n = 20), 11-17years. Overall, there were no group differences in activation, however, the autism spectrum group with impaired expressive language (n = 13) had significantly reduced inferior frontal and inferior parietal activation during action viewing. In controls, right supramarginal gyrus activation was associated with higher expressive language; bilateral supramarginal and left pars opercularis activation was associated with better verbal-gesture integration. Results suggest that action-observation network dysfunction may characterize a subgroup of individuals with autism spectrum disorder with expressive language deficits. Therefore, interventions that target this dysfunctional network may improve expressive language in this autism spectrum subgroup. Future treatment studies should individualize therapeutic approaches based on brain-behavior relationships.

The brain-esophagus axis in subjects with and without obesity assessed by esophageal acid perfusion and functional brain imaging.

Gastroesophageal reflux disease (GERD) has a complex pathophysiology and a heterogeneous symptom profile. The brain-esophageal axis in GERD has been studied with functional brain imaging during the last decades, but data from obese patients was just recently reported. A comparison of such a group with non-obese subjects is lacking in the literature. This study aimed to evaluate heartburn perception and brain connectivity responses during esophageal acid stimulation in subjects with and without obesity, controlling for the presence of typical reflux symptoms. In this cross-sectional study, 25 patients with obesity (body mass index ≥30 kg/m2) and 46 subjects without obesity underwent functional magnetic resonance imaging (fMRI) of the brain with esophageal water and acid perfusion. The fMRI paradigm and connectivity were assessed. About two-thirds of the participants had reflux symptoms. Heartburn perception during fMRI did not differ between subjects with and without obesity. The presence of reflux symptoms was associated with lower activation in frontal brain regions during acid perfusion compared to water perfusion. Compared to subjects without obesity, patients with obesity presented significantly lower connectivity within the anterior salience network. Corrected clusters included left caudate, left putamen and left anterior cingulate gyrus. The brain-esophagus axis showed differences between subjects with and without obesity. Even without symptomatic differences following esophageal acid perfusion, patients with reflux symptoms showed less brain activation in frontal areas, while obese individuals presented lower connectivity within the anterior salience network.

Validation of novel fMRI paradigms in gambling disorder

Validation of novel fMRI paradigms in gambling disorder

Self-blame-selective hyper-connectivity between anterior temporal and subgenual cortices predicts prognosis in major depressive disorder

BackgroundSelf-blame-related fMRI measures were shown to predict subsequent recurrence in remitted major depressive disorder (MDD). Their role in current MDD, however, is unknown. We hypothesised that these neural signatures reflect a highly recurrent but remitting course of MDD and therefore predict favourable outcomes over a four-month follow-up period in current MDD. MethodsForty-five participants with current MDD and non-responders to at least two serotonergic antidepressants, were encouraged to optimise their medication and followed up after receiving four months of primary care treatment-as-usual. Prior to their medication review, participants completed an fMRI paradigm in which they viewed self- and other-blame emotion-evoking statements. Thirty-nine participants met pre-defined fMRI data minimum quality thresholds. Psychophysiological interaction analysis was used to determine baseline connectivity of the right superior anterior temporal lobe (RSATL), with an a priori BA25 region-of-interest for self-blaming vs other-blaming emotions, using Quick Inventory of Depressive Symptomatology (16-item) percentage change as a covariate. ResultsWe corroborated our pre-registered hypothesis that a favourable clinical outcome was associated with higher self-blame-selective RSATL-BA25 connectivity (Family-Wise Error-corrected p <.05 over the a priori BA25 region-of-interest; rs(34) = −0.47, p =.005). This generalised to the sample including participants with suboptimal fMRI quality (rs(39) = −0.32, p =.05). ConclusionsThis study shows that neural signatures of overgeneralised self-blame are relevant for prognostic stratification of current treatment-resistant MDD. Future studies need to confirm whether this neural signature indeed represents a trait-like feature of a fully remitting subtype of MDD, or whether it is also modulated by depressive state and related to treatment effects.

The role of left insula mediating impaired error processing in response inhibition in adult heavy drinkers.

Identification of neurobiological mechanisms underlying development of alcohol use disorder is critical to ensuring the appropriate early-phase treatment and prevention of the disorder. To this aim, we tried to elucidate the disturbance of neural functions in heavy drinking, which can lead to alcohol use disorder. Because response inhibition is affected by alcohol use disorder, we examined neural activation and task performance for response inhibition using the Go/No-Go task in an fMRI paradigm in adult non-dependent heavy and light drinkers. We examined the neural activation for error processing and inhibitory control, components of response inhibition. We then investigated the mediating effect of the relevant neural substrate on the relationship between the level of alcohol drinking and task performance using mediation analysis. We found that heavy drinking significantly decreased activation in the left insula during error processing and increased the mean commission error rate for No-Go trials compared with light drinking. Mediation analysis demonstrated full mediation of the left insula activation during error processing for the relationship between drinking level and commission error rate. Our results suggested that left insula activation may be a neural marker pivotal for potential conversion to alcohol use disorder in individuals with high clinical risk such as heavy drinking.

The Angiotensin Antagonist Losartan Modulates Social Reward Motivation and Punishment Sensitivity via Modulating Midbrain-Striato-Frontal Circuits.

Social deficits and dysregulations in dopaminergic midbrain-striato-frontal circuits represent transdiagnostic symptoms across psychiatric disorders. Animal models suggest that interactions between the dopamine (DA) and renin-angiotensin system (RAS) may modulate learning and reward-related processes. The present study therefore examined the behavioral and neural effects of the Angiotensin II type 1 receptor (AT1R) antagonist losartan on social reward and punishment processing in humans. A preregistered randomized double-blind placebo-controlled between-subject pharmacological design was combined with a social incentive delay (SID) functional MRI (fMRI) paradigm during which subjects could avoid social punishment or gain social reward. Healthy volunteers received a single-dose of losartan (50 mg, n = 43, female = 17) or placebo (n = 44, female = 20). We evaluated reaction times (RTs) and emotional ratings as behavioral and activation and functional connectivity as neural outcomes. Relative to placebo, losartan modulated the reaction time and arousal differences between social punishment and social reward. On the neural level the losartan-enhanced motivational salience of social rewards was accompanied by stronger ventral striatum-prefrontal connectivity during reward anticipation. Losartan increased the reward-neutral difference in the ventral tegmental area (VTA) and attenuated VTA associated connectivity with the bilateral insula in response to punishment during the outcome phase. Thus, losartan modulated approach-avoidance motivation and emotional salience during social punishment versus social reward via modulating distinct core nodes of the midbrain-striato-frontal circuits. The findings document a modulatory role of the renin-angiotensin system in these circuits and associated social processes, suggesting a promising treatment target to alleviate social dysregulations.SIGNIFICANCE STATEMENT Social deficits and anhedonia characterize several mental disorders and have been linked to the midbrain-striato-frontal circuits of the brain. Based on initial findings from animal models we here combine the pharmacological blockade of the Angiotensin II type 1 receptor (AT1R) via losartan with functional MRI (fMRI) to demonstrate that AT1R blockade enhances the motivational salience of social rewards and attenuates the negative impact of social punishment via modulating the communication in the midbrain-striato-frontal circuits in humans. The findings demonstrate for the first time an important role of the AT1R in social reward processing in humans and render the AT1R as promising novel treatment target for social and motivational deficits in mental disorders.