Towards a mechanistic understanding of mindfulness-based stress reduction (MBSR) using an RCT neuroimaging approach: Effects on regulating own stress in social and non-social situations.

Although much research has shown that mindfulness-based interventions (MBIs) can reduce psychological stress, it is less clear if effects generalize to everyday social situations, which range among the largest stress triggers. Furthermore, mechanisms of MBIs have not been fully established. Emotion regulation (ER) has been suggested as one key mechanism, yet the role of cognitive reappraisal and acceptance strategies is still under debate. To address these questions, a neuroimaging-based randomized controlled trial (RCT) was performed (n=68), comparing mindfulness-based stress reduction (MBSR) with a reading/listening intervention (READ), using a novel dyadic paradigm for self and other emotion regulation under stress as primary outcome on behavior and brain levels and established empathy measures (clinicatrials.gov NCT03035669). Compared to READ, MBSR led to self-reported stress reduction through both cognitive reappraisal and acceptance only when regulating self and not when regulating others' distress. In addition, MBSR led to increased brain activation over time for regulating own (parietal cortex) and others' (precuneus, TPJ) emotions through cognitive reappraisal and acceptance, albeit this effect was also seen for the reading intervention for regulating own stress via reappraisal. Brain changes did not scale with subjective stress reduction and amount of meditation practice. More distant generalization effects of MBSR on socio-emotional functioning (cognitive empathy and compassion) could also not be shown. This study identified both cognitive reappraisal and acceptance as two ER mechanisms of MBSR, but indicates that effects do not extend to social settings.

Regulating negative emotions of others reduces own stress: Neurobiological correlates and the role of individual differences in empathy.

BACKGROUND: While witnessing the suffering of other people results in personal distress, it is not clear whether regulating others' emotions in such situations also comes at an emotional cost for the observer. METHODS: This study included 62 subjects and used a newly developed functional Magnetic Resonance Imaging (fMRI) paradigm to investigate mechanisms of self and other emotion regulation via reappraisal while the subject and an interaction partner outside the scanner were facing the same distressing situation simultaneously. The relationship between distress levels and individual differences in emotional and cognitive empathy were also assessed. RESULTS: We found that individuals exhibited especially high levels of personal distress when relating with a partner while both being exposed to aversive photographs and that especially highly empathetic individuals were prone to such personal distress. Moreover, when engaging in social emotion regulation, personal distress was reduced in the observer at a similar rate as in self emotion regulation. FMRI analyses revealed increased activation for other vs. self emotion regulation in the precuneus and the left temporo-parietal junction, which are commonly engaged in social cognition. Furthermore, this activation was associated with lower self-reported stress and decreased sympathetic autonomic activity. While regulating others, precuneus activation exhibited a distinctive functional connectivity profile with parietal emotion regulation regions. CONCLUSIONS: This study demonstrates benefits of actively regulating another person's emotions for reducing one's own distress and identifies the precuneus as an important node for social emotion regulation. Given the novelty of the study design, the results are of exploratory and preliminary nature.

Effects of bariatric surgery on functional connectivity of the reward and default mode network: A pre-registered analysis.

Obesity imposes serious health risks and involves alterations in resting-state functional connectivity of brain networks involved in eating behavior. Bariatric surgery is an effective treatment, but its effects on functional connectivity are still under debate. In this pre-registered study, we aimed to determine the effects of bariatric surgery on major resting-state brain networks (reward and default mode network) in a longitudinal controlled design. Thirty-three bariatric surgery patients and 15 obese waiting-list control patients underwent magnetic resonance imaging at baseline, after 6 and 12 months. We conducted a pre-registered whole-brain time-by-group interaction analysis, and a time-by-group interaction analysis on within-network connectivity. In exploratory analyses, we investigated the effects of weight loss and head motion. Bariatric surgery compared to waiting did not significantly affect functional connectivity of the reward network and the default mode network (FWE-corrected p > .05), neither whole-brain nor within-network. In exploratory analyses, surgery-related BMI decrease (FWE-corrected p = .041) and higher average head motion (FWE-corrected p = .021) resulted in significantly stronger connectivity of the reward network with medial posterior frontal regions. This pre-registered well-controlled study did not support a strong effect of bariatric surgery, compared to waiting, on major resting-state brain networks after 6 months. Exploratory analyses indicated that head motion might have confounded the effects. Data pooling and more rigorous control of within-scanner head motion during data acquisition are needed to substantiate effects of bariatric surgery on brain organization.

Enhancement of task-switching performance with transcranial direct current stimulation over the right lateral prefrontal cortex.

Switching between two or more tasks is a key component in our modern world. Task switching, however, requires time-consuming executive control processes and thus produces performance costs when compared to task repetitions. While executive control during task switching has been associated with activation in the lateral prefrontal cortex (lPFC), only few studies so far have investigated the causal relation between lPFC activation and task-switching performance by modulating lPFC activation. In these studies, the results of lPFC modulation were not conclusive or limited to the left lPFC. In the present study, we aimed to investigate the effect of non-invasive transcranial direct current stimulation [tDCS; anodal tDCS (1 mA, 20 min) vs. cathodal tDCS (1 mA, 20 min) vs. sham tDCS (1 mA, 30 s)] over the right inferior frontal junction on task-switching performance in a well-established task-switching paradigm. In response times, we found a significant effect of tDCS Condition (atDCS, ctDCS vs. sham) on task-switching costs, indicating the modulation of task-switching performance by tDCS. In addition, we found a task-unspecific tDCS Condition effect in the first experimental session, in which participants were least familiar with the task, indicating a general enhancement of task performance in both task repetitions and task-switching trials. Taken together, our study provides evidence that the right lPFC is involved in task switching as well as in general task processing. Further studies are needed to investigate whether these findings can be translated into clinically relevant improvement in older subjects or populations with executive function impairment.

Weight loss reduces head motion: Revisiting a major confound in neuroimaging.

Head motion during magnetic resonance imaging (MRI) induces image artifacts that affect virtually every brain measure. In parallel, cross-sectional observations indicate a correlation of head motion with age, psychiatric disease status and obesity, raising the possibility of a systematic artifact-induced bias in neuroimaging outcomes in these conditions, due to the differences in head motion. Yet, a causal link between obesity and head motion has not been tested in an experimental design. Here, we show that a change in body mass index (BMI) (i.e., weight loss after bariatric surgery) systematically decreases head motion during MRI. In this setting, reduced imaging artifacts due to lower head motion might result in biased estimates of neural differences induced by changes in BMI. Overall, our finding urges the need to rigorously control for head motion during MRI to enable valid results of neuroimaging outcomes in populations that differ in head motion due to obesity or other conditions.

Using resting-state fMRI to assess the effect of aerobic exercise on functional connectivity of the DLPFC in older overweight adults.

Cardiovascular fitness is thought to exert beneficial effects on brain function and might delay the onset of cognitive decline. Empirical evidence of exercise-induced cognitive enhancement, however, has not been conclusive, possibly due to short intervention times in clinical trials. Resting-state functional connectivity (RSFC) has been proposed asan early indicator for intervention-induced changes. Here, we conducted a study in which healthy older overweight subjects took either part in a moderate aerobic exercise program over 6months (AE group; n=11) or control condition of non-aerobic stretching and toning (NAE group; n=18). While cognitive and gray matter volume changes were rather small (i.e., appeared only in certain sub-scores without Bonferroni correction for multiple comparisons or using small volume correction), we found significantly increased RSFC after training between dorsolateral prefrontal cortex and superior parietal gyrus/precuneus in the AE compared to the NAE group. This intervention study demonstrates an exercise-induced modulation of RSFC between key structures of the executive control and default mode networks, which might mediate an interaction between task-positive and task-negative brain activation required for task switching. Results further emphasize the value of RSFC asa sensitive biomarker for detecting early intervention-related cognitive improvements in clinical trials.

Age-dependent effects of brain stimulation on network centrality.

Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age-associated differential neural tDCS effects. Three "online" tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30 young and 30 older adults. Active stimulation targeted the left sensorimotor network (active electrode over left sensorimotor cortex with right supraorbital reference electrode). A graph-based rs-fMRI data analysis approach (eigenvector centrality mapping) and complementary seed-based analyses characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing patterns of tDCS-induced centrality modulation originated from differential effects of tDCS on functional coupling of the stimulated left paracentral lobule. Cathodal tDCS did not show significant effects. Our study provides first evidence for differential tDCS effects on neural network organization in young and older adults. Anodal stimulation mainly affected coupling of sensorimotor with ventromedial prefrontal areas in young and decoupling with posteromedial areas in older adults.

Caloric Restriction in Older Adults-Differential Effects of Weight Loss and Reduced Weight on Brain Structure and Function.

Dietary modifications such as caloric restriction (CR) have been suggested as a means to improve memory and prevent age-related decline. However, it is unclear whether those effects remain stable over time or are related specifically to negative energy balance during the weight loss phase of CR. Using a randomized interventional design, we investigated changes in recognition memory and neural correlates in postmenopausal obese women (n = 19): 1) after intense weight loss in the course of a 12-week low-caloric diet (reduced body weight and negative energy balance) and 2) after having sustained the reduced weight over 4 more weeks (reduced body weight, but energy balance equilibrium). Participants were contrasted to a control group (n = 18) instructed not to change dietary habits. In the CR group, we found improved recognition memory, paralleled by increased gray matter volume in inferior frontal gyrus and hippocampus, and augmented hippocampal resting-state functional connectivity to parietal areas. Moreover, effects were specific for transient negative energy balance and could not be detected after subsequent weight maintenance. Our data demonstrate for the first time in humans that beneficial effects of CR on brain structure and function are due to weight loss rather than an overall reduced weight.

Moral competence and brain connectivity: A resting-state fMRI study.

Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent and differentiated manner when judging moral issues. People greatly differ in terms of MC, however, little is known about how these differences are implemented in the brain. To investigate this question, we used functional magnetic resonance imaging and examined resting-state functional connectivity (RSFC) in n=31 individuals with MC scores in the highest 15% of the population and n=33 individuals with MC scores in the lowest 15%, selected from a large sample of 730 Master of Business Administration (MBA) students. Compared to individuals with lower MC, individuals with higher MC showed greater amygdala-ventromedial prefrontal connectivity, which may reflect better ability to cope with emotional conflicts elicited by moral dilemmas. Moreover, individuals with higher MC showed less inter-network connectivity between the amygdalar and fronto-parietal networks, suggesting a more independent operation of these networks. Our findings provide novel insights into how individual differences in moral judgment are associated with RSFC in brain circuits related to emotion processing and cognitive control.

Effects of empathic social responses on the emotions of the recipient.

Empathy is highly relevant for social behavior and can be verbally expressed by voicing sympathy and concern (emotional empathy) as well as by paraphrasing or stating that one can mentally reconstruct and understand another person's thoughts and feelings (cognitive empathy). In this study, we investigated the emotional effects and neural correlates of receiving empathic social responses after negative performance feedback and compared the effects of emotionally vs. cognitively empathic comments. 20 participants (10 male) underwent functional magnetic resonance imaging while receiving negative performance feedback for a cognitive task. Performance feedback was followed by verbal comments either expressing cognitive and emotional empathy or demonstrating a lack of empathy. Empathic comments in general led to less negative self-reported feelings and calmer breathing. At the neural level, empathic comments induced activity in regions associated with social cognition and emotion processing, specifically in right postcentral gyrus and left cerebellum (cognitively empathic comments), right precentral gyrus, the opercular part of left inferior frontal gyrus, and left middle temporal gyrus (emotionally empathic comments), as well as the orbital part of the left middle frontal gyrus and left superior parietal gyrus (emotionally empathic vs. unempathic comments). The study shows that cognitively and emotionally empathic comments appear to be processed in partially separable neural systems. Furthermore, confirming and expanding on another study on the same subject, the present results demonstrate that the social display of cognitive empathy exerts almost as positive effects on the recipient's feelings and emotions in states of distress as emotionally empathic response does. This can be relevant for professional settings in which strong negative emotions need to be de-escalated while maintaining professional impartiality, which may allow the display of cognitive but not emotional empathy.

Talking about social conflict in the MRI scanner: neural correlates of being empathized with.

This study investigated the emotional effects and neural correlates of being empathized with while speaking about a currently experienced real-life social conflict during fMRI. Specifically, we focused on the effects of cognitive empathy in the form of paraphrasing, a technique regularly used in conflict resolution. 22 participants underwent fMRI while being interviewed on their social conflict and receiving empathic or unempathic responses from the interviewer. Skin conductance response (SCR) and self-report ratings of feeling understood and emotional valence were used to assess emotional responses. Results confirm previous findings indicating that cognitive empathy exerts a positive short-term effect on emotions in social conflict, while at the same time increasing autonomic arousal reflected by SCR. Effects of paraphrasing and unempathic interventions as indicated by self-report ratings varied depending on self-esteem, pre-interview negative affect, and participants' empathy quotient. Empathic responses engaged a fronto-parietal network with activity in the right precentral gyrus (PrG), left middle frontal gyrus (MFG), left inferior parietal gyrus (IPG), and right postcentral gyrus (PoG). Processing unempathic responses involved a fronto-temporal network with clusters peaking in the left inferior frontal gyrus, pars triangularis (IFGTr), and right temporal pole (TP). A specific modeling of feeling misunderstood activated a network consisting of the IFG, left TP, left Heschl gyrus, IFGTr, and right precuneus, extending to several limbic regions, such as the insula, amygdala, putamen, and anterior cingulate cortex/right middle cingulum (ACC/MCC). The results support the effectiveness of a widely used conflict resolution technique, which may also be useful for professionals who regularly deal with and have to de-escalate situations highly charged with negative emotion, e.g. physicians or judges.

Positively biased processing of self-relevant social feedback.

Receiving social feedback such as praise or blame for one's character traits is a key component of everyday human interactions. It has been proposed that humans are positively biased when integrating social feedback into their self-concept. However, a mechanistic description of how humans process self-relevant feedback is lacking. Here, participants received feedback from peers after a real-life interaction. Participants processed feedback in a positively biased way, i.e., they changed their self-evaluations more toward desirable than toward undesirable feedback. Using functional magnetic resonance imaging we investigated two feedback components. First, the reward-related component correlated with activity in ventral striatum and in anterior cingulate cortex/medial prefrontal cortex (ACC/MPFC). Second, the comparison-related component correlated with activity in the mentalizing network, including the MPFC, the temporoparietal junction, the superior temporal sulcus, the temporal pole, and the inferior frontal gyrus. This comparison-related activity within the mentalizing system has a parsimonious interpretation, i.e., activity correlated with the differences between participants' own evaluation and feedback. Importantly, activity within the MPFC that integrated reward-related and comparison-related components predicted the self-related positive updating bias across participants offering a mechanistic account of positively biased feedback processing. Thus, theories on both reward and mentalizing are important for a better understanding of how social information is integrated into the human self-concept.

Brain volumes differ between diagnostic groups of violent criminal offenders.

Studies on structural abnormalities in antisocial individuals have reported inconsistent results, possibly due to inhomogeneous samples, calling for an investigation of brain alterations in psychopathologically stratified subgroups. We explored structural differences between antisocial offenders with either borderline personality disorder (ASPD-BPD) or high psychopathic traits (ASPD-PP) and healthy controls (CON) using region-of-interest-based and voxel-based morphometry approaches. Besides common distinct clusters of reduced gray matter volumes within the frontal pole and occipital cortex, there was remarkably little overlap in the regional distribution of brain abnormalities in ASPD-BPD and ASPD-PP, when compared to CON. Specific alterations of ASPD-BPD were detected in orbitofrontal and ventromedial prefrontal cortex regions subserving emotion regulation and reactive aggression and the temporal pole, which is involved in the interpretation of other peoples' motives. Volumetric reductions in ASPD-PP were most significant in midline cortical areas involved in the processing of self-referential information and self-reflection (i.e., dorsomedial prefrontal cortex, posterior cingulate/precuneus) and recognizing emotions of others (postcentral gyrus) and could reflect neural correlates of the psychopathic core features of callousness and poor moral judgment. The findings of this first exploratory study therefore may reflect correlates of prominent psychopathological differences between the two criminal offender groups, which have to be replicated in larger samples.

How Much of Me Do I See in Other Minds? Modulating Egocentricity in Emotion Judgments by tDCS.

When inferring the mental states of others, individuals' judgments are influenced by their own state of mind, an effect often referred to as egocentricity. Self-other differentiation is key for an accurate interpretation of other's mental states, especially when these differ from one's own states. It has been suggested that the right supramarginal gyrus (rSMG) is causally involved in overcoming egocentricity in the affective domain. In a double-blind randomized study, 47 healthy adults received anodal (1 mA, 20 min) or sham transcranial direct current stimulation (tDCS) to the rSMG prior to performing a newly developed paradigm, the self-other facial emotion judgment (SOFE) task. In this task, participants made judgments of facial emotional expressions while having been previously confronted with congruent or incongruent emotion-inducing situations. To differentiate between emotional and cognitive egocentricity, participants additionally completed an established visual perspective-taking task. Our results confirmed the occurrence of emotional egocentric biases during the SOFE task. No conclusive evidence of a general role of the rSMG in emotional egocentricity was found. However, active as compared to sham tDCS induced descriptively lower egocentric biases when judging incongruent fearful faces, and stronger biases when judging incongruent happy faces, suggesting emotion-specific tDCS effects on egocentric biases. Further, we found significant tDCS effects on cognitive egocentricity. Results of the present study expanded our understanding of emotional egocentricity and point towards emotion-specific patterns of the underlying functionality.

Impact of COMT val158met on tDCS-induced cognitive enhancement in older adults.

BACKGROUND: Previous studies suggest that genetic polymorphisms and aging modulate inter-individual variability in brain stimulation-induced plasticity. However, the relationship between genetic polymorphisms and behavioral modulation through transcranial direct current stimulation (tDCS) in older adults remains poorly understood. OBJECTIVE: Link individual tDCS responsiveness, operationalized as performance difference between tDCS and sham condition, to common genetic polymorphisms in healthy older adults. METHODS: 106 healthy older participants from five tDCS-studies were re-invited to donate blood for genotyping of apoliproprotein E (APOE: ε4 carriers and ε4 non-carriers), catechol-O-methyltransferase (COMT: val/val, val/met, met/met), brain-derived neurotrophic factor (BDNF: val/val, val/met, met/met) and KIdney/BRAin encoding gene (KIBRA: C/C, C/T, T/T). Studies had assessed cognitive performance during tDCS and sham in cross-over designs. We now asked whether the tDCS responsiveness was related to the four genotypes using a linear regression models. RESULTS: We found that tDCS responsiveness was significantly associated with COMT polymorphism; i.e., COMT val carriers (compared to met/met) showed higher tDCS responsiveness. No other significant associations emerged. CONCLUSION: Using data from five brain stimulation studies conducted in our group, we showed that only individual variation of COMT genotypes modulated behavioral response to tDCS. These findings contribute to the understanding of inherent factors that explain inter-individual variability in functional tDCS effects in older adults, and might help to better stratify participants for future clinical trials.

Bariatric Surgery and Brain Health-A Longitudinal Observational Study Investigating the Effect of Surgery on Cognitive Function and Gray Matter Volume.

Dietary modifications leading to weight loss have been suggested as a means to improve brain health. In morbid obesity, bariatric surgery (BARS)-including different procedures, such as vertical sleeve gastrectomy (VSG), gastric banding (GB), or Roux-en-Y gastric bypass (RYGB) surgery-is performed to induce rapid weight loss. Combining reduced food intake and malabsorption of nutrients, RYGB might be most effective, but requires life-long follow-up treatment. Here, we tested 40 patients before and six months after surgery (BARS group) using a neuropsychological test battery and compared them with a waiting list control group. Subsamples of both groups underwent structural MRI and were examined for differences between surgical procedures. No substantial differences between BARS and control group emerged with regard to cognition. However, larger gray matter volume in fronto-temporal brain areas accompanied by smaller volume in the ventral striatum was seen in the BARS group compared to controls. RYGB patients compared to patients with restrictive treatment alone (VSG/GB) had higher weight loss, but did not benefit more in cognitive outcomes. In sum, the data of our study suggest that BARS might lead to brain structure reorganization at long-term follow-up, while the type of surgical procedure does not differentially modulate cognitive performance.

Insular activity during passive viewing of aversive stimuli reflects individual differences in state negative affect.

People differ with regard to how they perceive, experience, and express negative affect. While trait negative affect reflects a stable, sustained personality trait, state negative affect represents a stimulus limited and temporally acute emotion. So far, little is known about the neural systems mediating the relationship between negative affect and acute emotion processing. To address this issue we investigated in a healthy female sample how individual differences in state negative affect are reflected in changes in blood oxygen level-dependent responses during passive viewing of emotional stimuli. To assess autonomic arousal we simultaneously recorded changes in skin conductance level. At the psychophysiological level we found increased skin conductance level in response to aversive relative to neutral pictures. However, there was no association of state negative affect with skin conductance level. At the neural level we found that high state negative affect was associated with increased left insular activity during passive viewing of aversive stimuli. The insula has been implicated in interoceptive processes and in the integration of sensory, visceral, and affective information thus contributing to subjective emotional experience. Greater recruitment of the insula in response to aversive relative to neutral stimuli in subjects with high state negative affect may represent increased processing of salient aversive stimuli.

Neuroticism influences pupillary responses during an emotional interference task.

We used behavioral and pupillary measures during an analogical reasoning task to investigate the processing of conceptual and emotional relations as well as their interaction. In particular, we examined how mental resource consumption is modulated by individual differences in neuroticism in healthy participants during conditions with emotional interference. Two word pairs were presented simultaneously, each with a conceptual and an emotional relation. In one experimental block, participants had to decide whether conceptual relations between the two word pairs were corresponding (conceptual task). In the other block, participants had to decide whether emotional relations were corresponding (emotional task). When participants had to focus on the correspondence of emotional relations, they were faster, more accurate, and showed greater pupillary responses than during the conceptual task. Moreover, participants with comparably higher neuroticism scores showed increased pupillary responses during conditions with emotional interference (i.e., during the conceptual task when they had to ignore incongruent information on the correspondence provided by the task-irrelevant emotional relations). These results demonstrate that affective aspects of stimuli (here: emotional relations) are preferentially selected for information processing. Moreover, increased mental resource consumption due to emotional interference in participants with comparably higher neuroticism scores might reflect a possible mechanism making these individuals more vulnerable to mood or anxiety disorders.

Neuronal and behavioral effects of multi-day brain stimulation and memory training.

Strategies for memory enhancement, especially for the older population, are of great scientific and public interest. Here, we aimed at investigating neuronal and behavioral effects of transcranial direct current stimulation (tDCS) paired with memory training. Young and older adults were trained on an object-location-memory task on 3 consecutive days with either anodal or sham tDCS. Recall performance was assessed immediately after training, 1 day and 1 month later, as well as performance on trained function and transfer task. Resting-state functional magnetic resonance imaging was conducted at baseline and at 1-day follow-up to analyze functional coupling in the default mode network. Anodal tDCS led to superior recall performance after training, an associated increase in default mode network strength and enhanced trained function and transfer after 1 month. Our findings suggest that tDCS-accompanied multi-day training improves performance on trained material, is associated with beneficial memory network alterations, and transfers to other memory tasks. Our study provides insight into tDCS-induced behavioral and neuronal alterations and will help to develop interventions against age-related cognitive decline.

Multimodal Assessment of Recurrent MTBI across the Lifespan.

Recurrent mild traumatic brain injuries (mTBI) and its neurological sequelae have been the focus of a large number of studies, indicating cognitive, structural, and functional brain alterations. However, studies often focused on single outcome measures in small cohorts of specific populations only. We conducted a multimodal evaluation of the impact of recurrent mTBI on a broad range of cognitive functions, regional brain volume, white matter integrity, and resting state functional connectivity (RSFC) in young and older adults in the chronic stage (>6 months after the last mTBI). Seventeen young participants with mTBI (age: 24.2 ± 2.8 (mean ± SD)) and 21 group-wise matched healthy controls (age: 25.8 ± 5.4 (mean ± SD)), as well as 17 older participants with mTBI (age: 62.7 ± 7.7 (mean ± SD)) and 16 group-wise matched healthy controls (age: 61.7 ± 5.9 (mean ± SD)) were evaluated. We found significant differences in the verbal fluency between young participants with mTBI and young healthy controls. Furthermore, differences in the regional volume of precuneus and medial orbitofrontal gyrus between participants with mTBI and controls for both age groups were seen. A significant age by group interaction for the right hippocampal volume was noted, indicating an accelerated hippocampal volume loss in older participants with mTBI. Other cognitive parameters, white matter integrity, and RSFC showed no significant differences. We confirmed some of the previously reported detrimental effects of recurrent mTBI, but also demonstrated inconspicuous findings for the majority of parameters.