Dorsomedial PFC Research Articles

Theta Transcranial Alternating Current Stimulation Is Not Effective in Improving Working Memory Performance.

There is an extensive body of research showing a significant relationship between frontal midline theta activity in the 4- to 8-Hz range and working memory (WM) performance. Transcranial alternating current stimulation (tACS) is recognized for inducing lasting changes in brain oscillatory activity. Across two experiments, we tested whether WM could be improved through tACS of dorsomedial pFC and ACC, by affecting executive control networks associated with frontal midline theta. In Experiment 1, after either a 20-min verum or sham stimulation applied to Fpz-CPz at 1 mA and 6 Hz, 31 participants performed WM tasks, while EEG was recorded. The tasks required participants to either mentally manipulate memory items or retain them in memory as they were originally presented. No significant effects were observed in behavioral performance, and we found no change in theta activity during rest and task after stimulation. However, alpha activity during retention or manipulation of information in WM was less strongly enhanced during the delay period after verum stimulation as compared with sham. In Experiment 2 (n = 25), tACS was administered during the task in two separate sessions. Here, we changed the order of the stimulation blocks: A 25-min task block was either accompanied first by sham stimulation and then by verum stimulation, or vice versa. Again, we found no improvements in WM through either tACS after-effects or online stimulation. Taken together, our results demonstrate that theta frequency tACS applied at the midline is not an effective method for enhancing WM.

Corticotropin releasing hormone receptor 1 in the medial prefrontal cortex mediates aversion resistant alcohol intake.

Alcohol consumption despite negative consequences is a core symptom of Alcohol Use Disorder. In animal models, this is studied by pairing aversive stimuli with alcohol access, and continuation of drinking under these conditions is known as aversion resistance. Previously, we found that female mice are more aversion resistant than males. Corticotropin releasing hormone (Crh) and the Crh receptor 1 (Crhr1) regulate stress-induced reinstatement, alcohol dependence, and binge-like drinking. However, the role of the Crh system in aversion resistance has not been assessed. We aimed to identify sex differences in the Crh system during quinine-adulterated alcohol intake. We used two-bottle choice and adulterated the alcohol solution with quinine. Next, we measured Crh and Crhr1 levels in brain tissue using real-time polymerase chain reaction (RT-qPCR) and RNAscope in situ hybridization. We then infused a Crhr1 antagonist into the medial prefrontal cortex (mPFC) prior to quinine-alcohol intake. After quinine-alcohol consumption, females exhibited increased mPFC Crhr1 mRNA levels as measured by RT-qPCR. This was confirmed with greater anatomical specificity using RNAscope, with females exhibiting an increased number of Crhr1 + cells in the dorsomedial PFC and the ventromedial PFC. mPFC Crhr1 antagonist treatment reduced quinine-alcohol consumption in females but did not impact consumption in males. Quinine-free alcohol intake was unaffected by Crhr1 antagonist treatment. Our findings suggest that Crhr1 in mPFC plays a role in aversion resistant alcohol intake in females. Future experiments will examine the sources of Crh innervation to the mPFC and their distinct roles in alcohol seeking.

Roles of the Default Mode Network in Different Aspects of Self-representation When Remembering Social Autobiographical Memories.

Autobiographical memory (AM) is episodic memory for personally experienced events, in which self-representation is more important than that in laboratory-based memory. Theoretically, self-representation in a social context is categorized as the interpersonal self (IS) referred to in a social interaction with a person or the social-valued self (SS) based on the reputation of the self in the surrounding society. Although functional neuroimaging studies have demonstrated the involvement of the default mode network (DMN) in self-representation, little is known about how the DMN subsystems contribute differentially to IS-related and SS-related AMs. To elucidate this issue, we used fMRI to scan healthy young adults during the recollection of AMs. We performed multivariate pattern analysis (MVPA) and assessed functional connectivity in the DMN subsystems: the midline core, medial temporal lobe (MTL), and dorsomedial pFC (dmPFC) subsystems. The study yielded two main sets of findings. First, MVPA revealed that all DMN subsystems showed significant classification accuracy between IS-related and nonsocial-self-related AMs, and IS-related functional connectivity of the midline core regions with the retrosplenial cortex of the MTL subsystem and the dmPFC of the dmPFC subsystem was significant. Second, MVPA significantly distinguished between SS-related and nonsocial-self-related AMs in the midline core and dmPFC subsystems but not in the MTL subsystem, and SS-related functional connectivity with the midline core regions was significant in the temporal pole and TPJ of the dmPFC subsystem. Thus, dissociable neural mechanisms in the DMN could contribute to different aspects of self-representation in social AMs.

Users’ reactions to website designs: A neuroimaging study based on evolutionary psychology with a focus on color and button shape

Website design decisions consider visual stimuli that have a significant impact on user behavior. We use evolutionary psychology as a theoretical lens for studying the effects of color and shapes on e-commerce websites. Referring to their evolutionary meaning, we derive hypotheses that are tested in a neuroimaging experiment utilizing functional near-infrared spectroscopy (fNIRS). The self-report results reveal significantly more pleasure, arousal, less distrust, and positive attitude toward colored versus uncolored websites. Neural results reveal a deactivation in the right dorsolateral prefrontal cortex (dlPFC) when comparing colored versus uncolored websites. Further, a significant deactivation in the left medial PFC areas and the left dlPFC is identified for the blue website. These results signify a cognitive relief for the use of color on websites in general, and for the use of blue in particular. For button shape, significant increases in the dorsomedial PFC, as well as in the right medial PFC areas, were identified for rounded shapes. These results signify users’ preference toward interaction with rounded rather than sharp button shapes on websites. Altogether, the present study shows that neural mechanisms indicate how the meaning of website elements is still derived from their evolutionary meaning, and that users are not necessarily aware of this.

Effects of a dissociative drug on fronto-limbic resting-state functional connectivity in individuals with posttraumatic stress disorder: a randomized controlled pilot study

RationaleA subanesthetic dose of ketamine, a non-competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist, elicits dissociation in individuals with posttraumatic stress disorder (PTSD), who also often suffer from chronic dissociative symptoms in daily life. These debilitating symptoms have not only been linked to worse PTSD trajectories, but also to increased resting-state functional connectivity (RSFC) between medial prefrontal cortex (mPFC) and amygdala, supporting the conceptualization of dissociation as emotion overmodulation. Yet, as studies were observational, causal evidence is lacking.ObjectivesThe present randomized controlled pilot study examines the effect of ketamine, a dissociative drug, on RSFC between mPFC subregions and amygdala in individuals with PTSD.MethodsTwenty-six individuals with PTSD received either ketamine (0.5mg/kg; n = 12) or the control drug midazolam (0.045mg/kg; n = 14) during functional magnetic resonance imaging (fMRI). RSFC between amygdala and mPFC subregions, i.e., ventromedial PFC (vmPFC), dorsomedial PFC (dmPFC) and anterior-medial PFC (amPFC), was assessed at baseline and during intravenous drug infusion.ResultsContrary to pre-registered predictions, ketamine did not promote a greater increase in RSFC between amygdala and mPFC subregions from baseline to infusion compared to midazolam. Instead, ketamine elicited a stronger transient decrease in vmPFC-amygdala RSFC compared to midazolam.ConclusionsA dissociative drug did not increase fronto-limbic RSFC in individuals with PTSD. These preliminary experimental findings contrast with prior correlative findings and call for further exploration and, potentially, a more differentiated view on the neurobiological underpinning of dissociative phenomena in PTSD.

Conscious expectancy rather than associative strength elicits brain activity during single-cue fear conditioning.

The neurocognitive processes underlying Pavlovian conditioning in humans are still largely debated. The conventional view is that conditioned responses (CRs) emerge automatically as a function of the contingencies between a conditioned stimulus (CS) and an unconditioned stimulus (US). As such, the associative strength model asserts that the frequency or amplitude of CRs reflects the strength of the CS-US associations. Alternatively, the expectation model asserts that the presentation of the CS triggers conscious expectancy of the US, which is responsible for the production of CRs. The present study tested the hypothesis that there are dissociable brain networks related to the expectancy and associative strength theories using a single-cue fear conditioning paradigm with a pseudo-random intermittent reinforcement schedule during functional magnetic resonance imaging. Participants' (n = 21) trial-by-trial expectations of receiving shock displayed a significant linear effect consistent with the expectation model. We also found a positive linear relationship between the expectancy model and activity in frontoparietal brain areas including the dorsolateral prefrontal cortex (PFC) and dorsomedial PFC. While an exploratory analysis found a linear relationship consistent with the associated strength model in the insula and early visual cortex, our primary results are consistent with the view that conscious expectancy contributes to CRs.

Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine

Ketamine shows rapid antidepressant effects peaking 24 h after administration. The antidepressant effects may occur through changes in glutamatergic metabolite levels and resting-state functional connectivity (rsFC) within the default mode network (DMN). A multistage drug effect of ketamine has been suggested, inducing acute effects on dysfunctional network configuration and delayed effects on homeostatic synaptic plasticity. Whether the DMN-centered delayed antidepressant-related changes are associated with the immediate changes remains unknown. Thirty-five healthy male participants (25.1 ± 4.2 years) underwent 7 T magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (rsfMRI) before, during, and 24 h after a single S-ketamine or placebo infusion. Changes in glutamatergic measures and rsFC in the DMN node pregenual anterior cingulate cortex (pgACC) were examined. A delayed rsFC decrease of the pgACC to inferior parietal lobe (family-wise error corrected p (pFWEc) = 0.018) and dorsolateral prefrontal cortex (PFC; pFWEc = 0.002) was detected that was preceded by an immediate rsFC increase of the pgACC to medial PFC (pFWEc < 0.001) and dorsomedial PFC (pFWEc = 0.005). Additionally, the immediate rsFC reconfigurations correlated with the delayed pgACC glutamate (Glu) level increase (p = 0.024) after 24 h at trend level (p = 0.067). Baseline measures of rsFC and MRS were furthermore associated with the magnitude of the respective delayed changes (p’s < 0.05). In contrast, the delayed changes were not associated with acute psychotomimetic side effects or plasma concentrations of ketamine and its metabolites. This multimodal study suggests an association between immediate S-ketamine-induced network effects and delayed brain changes at a time point relevant in its clinical context.

The neuroanatomy of social trust predicts depression vulnerability

Trust attitude is a social personality trait linked with the estimation of others’ trustworthiness. Trusting others, however, can have substantial negative effects on mental health, such as the development of depression. Despite significant progress in understanding the neurobiology of trust, whether the neuroanatomy of trust is linked with depression vulnerability remains unknown. To investigate a link between the neuroanatomy of trust and depression vulnerability, we assessed trust and depressive symptoms and employed neuroimaging to acquire brain structure data of healthy participants. A high depressive symptom score was used as an indicator of depression vulnerability. The neuroanatomical results observed with the healthy sample were validated in a sample of clinically diagnosed depressive patients. We found significantly higher depressive symptoms among low trusters than among high trusters. Neuroanatomically, low trusters and depressive patients showed similar volume reduction in brain regions implicated in social cognition, including the dorsolateral prefrontal cortex (DLPFC), dorsomedial PFC, posterior cingulate, precuneus, and angular gyrus. Furthermore, the reduced volume of the DLPFC and precuneus mediated the relationship between trust and depressive symptoms. These findings contribute to understanding social- and neural-markers of depression vulnerability and may inform the development of social interventions to prevent pathological depression.

Exposure to Violence as an Environmental Pathway Linking Low Socioeconomic Status with Altered Neural Processing of Threat and Adolescent Psychopathology.

Low childhood socioeconomic status (SES) is associated with increased risk for psychopathology, in part because of heightened exposure to environmental adversity. Adverse experiences can be characterized along dimensions, including threat and deprivation, that contribute to psychopathology via distinct mechanisms. The current study investigated a neural mechanism through which threat and deprivation may contribute to socioeconomic disparities in psychopathology. Participants were 177 youths (83 girls) aged 10-13 years recruited from a cohort followed since the age of 3 years. SES was assessed using the income-to-needs ratio at the age of 3 years. At the age of 10-13 years, retrospective and current exposure to adverse experiences and symptoms of psychopathology were assessed. At this same time point, participants also completed a face processing task (passive viewing of fearful and neutral faces) during an fMRI scan. Lower childhood SES was associated with greater exposure to threat and deprivation experiences. Both threat and deprivation were associated with higher depression symptoms, whereas threat experiences were uniquely linked to posttraumatic stress disorder symptoms. Greater exposure to threat, but not deprivation, was associated with higher activation in dorsomedial pFC to fearful compared with neutral faces. The dorsomedial pFC is a hub of the default mode network thought to be involved in internally directed attention and cognition. Experiences of threat, but not deprivation, are associated with greater engagement of this region in response to threat cues. Threat-related adversity contributes to socioeconomic disparities in adolescent psychopathology through distinct mechanisms from deprivation.

Differential Developmental Associations of Material Hardship Exposure and Adolescent Amygdala-Prefrontal Cortex White Matter Connectivity.

Accumulating literature has linked poverty to brain structure and function, particularly in affective neural regions; however, few studies have examined associations with structural connections or the importance of developmental timing of exposure. Moreover, prior neuroimaging studies have not used a proximal measure of poverty (i.e., material hardship, which assesses food, housing, and medical insecurity) to capture the lived experience of growing up in harsh economic conditions. The present investigation addressed these gaps collectively by examining the associations between material hardship (ages 1, 3, 5, 9, and 15 years) and white matter connectivity of frontolimbic structures (age 15 years) in a low-income sample. We applied probabilistic tractography to diffusion imaging data collected from 194 adolescents. Results showed that material hardship related to amygdala-prefrontal, but not hippocampus-prefrontal or hippocampus-amygdala, white matter connectivity. Specifically, hardship during middle childhood (ages 5 and 9 years) was associated with greater connectivity between the amygdala and dorsomedial pFC, whereas hardship during adolescence (age 15 years) was related to reduced amygdala-orbitofrontal (OFC) and greater amygdala-subgenual ACC connectivity. Growth curve analyses showed that greater increases of hardship across time were associated with both greater (amygdala-subgenual ACC) and reduced (amygdala-OFC) white matter connectivity. Furthermore, these effects remained above and beyond other types of adversity, and greater hardship and decreased amygdala-OFC connectivity were related to increased anxiety and depressive symptoms. Results demonstrate that the associations between material hardship and white matter connections differ across key prefrontal regions and developmental periods, providing support for potential windows of plasticity for structural circuits that support emotion processing.

Functional Magnetic Resonance Imaging Signal Variability Is Associated With Neuromodulation in Fibromyalgia

ObjectivesAlthough primary motor cortex (M1) transcranial direct current stimulation (tDCS) has an analgesic effect in fibromyalgia (FM), its neural mechanism remains elusive. We investigated whether M1-tDCS modulates a regional temporal variability of blood-oxygenation-level-dependent (BOLD) signals, an indicator of the brain's flexibility and efficiency and if this change is associated with pain improvement. Materials and MethodsIn a within-subjects cross-over design, 12 female FM patients underwent sham and active tDCS on five consecutive days, respectively. Each session was performed with an anode placed on the left M1 and a cathode on the contralateral supraorbital region. The subjects also participated in resting-state functional magnetic resonance imaging (fMRI) at baseline and after sham and active tDCS. We compared the BOLD signal variability (SDBOLD), defined as the standard deviation of the BOLD time-series, between the tDCS conditions. Baseline SDBOLD was compared to 15 healthy female controls. ResultsAt baseline, FM patients showed reduced SDBOLD in the ventromedial prefrontal cortex (vmPFC), lateral PFC, and anterior insula and increased SDBOLD in the posterior insula compared to healthy controls. After active tDCS, compared to sham, we found an increased SDBOLD in the left rostral anterior cingulate cortex (rACC), lateral PFC, and thalamus. After sham tDCS, compared to baseline, we found a decreased SDBOLD in the dorsomedial PFC and posterior cingulate cortex/precuneus. Interestingly, after active tDCS compared to sham, pain reduction was correlated with an increased SDBOLD in the rACC/vmPFC but with a decreased SDBOLD in the posterior insula. ConclusionOur findings suggest that M1-tDCS might revert temporal variability of fMRI signals in the rACC/vmPFC and posterior insula linked to FM pain. Changes in neural variability would be part of the mechanisms underlying repetitive M1-tDCS analgesia in FM.

A Commentary on “Can Neuroscience Provide a New Foundation for the Rorschach Variables?” (Jimura et al., 2021)

A Commentary on “Can Neuroscience Provide a New Foundation for the Rorschach Variables?” (Jimura et al., 2021)

Regional prefrontal cortical atrophy predicts specific cognitive-behavioral symptoms in ALS-FTD.

Amyotrophic Lateral Sclerosis-Frontotemporal Dementia (ALS-FTD) may present typical behavioral variant FTD symptoms. This study aims to determine whether profile and severity of cognitive-behavioral symptoms in ALS/ALS-FTD are predicted by regional cortical atrophy. The hypothesis is that executive dysfunction can be predicted by dorsolateral prefrontal cortical (dlPFC) atrophy, apathy by dorsomedial PFC (dmPFC) and anterior cingulate cortical (ACC) atrophy, disinhibition by orbitofrontal cortical (OFC) atrophy. 3.0 Tesla MRI scans were acquired from 22 people with ALS or ALS-FTD. Quantitative cortical thickness analysis was performed with FreeSurfer. A priori-defined regions of interest (ROI) were used to measure cortical thickness in each participant and calculate magnitude of atrophy in comparison to 115 healthy controls. Spearman correlations were used to evaluate associations between frontal ROI cortical thickness and cognitive-behavioral symptoms, measured by Neuropsychiatric Inventory Questionnaire (NPI-Q) and Clinical Dementia Rating (CDR) scale. ALS-FTD participants exhibited variable degrees of apathy (NPI-Q/apathy: 1.6 ± 1.2), disinhibition (NPI-Q/disinhibition: 1.2 ± 1.2), executive dysfunction (CDR/judgment-problem solving: 1.7 ± 0.8). Within the ALS-FTD group, executive dysfunction correlated with dlPFC atrophy (ρ:-0.65;p < 0.05); similar trends were seen for apathy with ACC (ρ:-0.53;p < 0.10) and dmPFC (ρ:-0.47;p < 0.10) atrophy, for disinhibition with OFC atrophy (ρ:-0.51;p < 0.10). Compared to people with ALS, those with ALS-FTD showed more diffuse atrophy involving precentral gyrus, prefrontal, temporal regions. Profile and severity of cognitive-behavioral symptoms in ALS-FTD are predicted by regional prefrontal atrophy. These findings are consistent with established brain-behavior models and support the role of quantitative MRI in diagnosis, management, counseling, monitoring and prognostication for a neurodegenerative disorder with diverse phenotypes.

Natural sleep loss is associated with lower mPFC activity during negative distracter processing

Previous research has demonstrated that loss of sleep has a negative impact on both emotional and cognitive functioning. We examined whether subjectively reported natural sleep loss is associated with the interplay between emotion and cognition, as was probed by brain activity in response to emotional distraction during a working memory task. Forty-six healthy male adults reported their typical weekly sleep pattern using the Munich Chronotype Questionnaire (MCTQ), while recent sleep loss was enquired using a sleep diary in the 7 days preceding scanning. Participants performed a delayed match-to-sample task with negative and neutral distracters during the delay period inside the MRI scanner. Activity differences between negative and neutral distracters were associated to both sleep loss measures across participants. The amount of typically encountered sleep loss indicated by the MCTQ, but not sleep diary, was negatively associated with activity in the rostral anterior cingulate cortex and dorsomedial prefrontal cortex during emotionally negative compared to neutral distraction (p < 0.025, whole brain corrected). Participants showed less distracter-related activity in the ACC and dorsomedial PFC with increasing sleep loss, which, in the long run, might contribute to less adaptive emotional processing, and therefore a greater vulnerability to develop affective disorders.

Mutual influence between emotional language and inhibitory control processes. Evidence from an event-related potential study.

There is abundant literature demonstrating that processing emotional stimuli modulates inhibitory control processes. However, the reverse effects, namely, how cognitive inhibition influences the processing of emotional stimuli, have been considerably neglected. This ERP study tries to fill this gap by studying the bidirectional interactions between emotional language and inhibitory processes. To this end, participants read emotional sentences, embedded in a cue-based Go-NoGo task. In Experiment 1, the critical emotional adjective preceded the Go-NoGo visual cue. The ERPs showed a significant reduction in the inhibition-related N2 component in NoGo trials when they were preceded by negative adjectives, compared to positive or neutral adjectives, indicating a priming-like effect on inhibitory control. Consistently, the estimated source of this interaction was the dorsomedial PFC, a region associated with inhibitory and control processes. In Experiment 2, the Go-NoGo cue preceded the emotional adjective, and the ERPs showed a sustained, broadly distributed LPP-like positivity for NoGo negative trials, relative to all the other conditions. In this case, the presetting of an inhibition state modulated the processing of negatively charged words. Together, the two experiments suggest a mutual facilitation between inhibitory control and negative valence, supporting thereby recent integrative theories of cognition-emotion interactions.

Network Localization of Executive Function Deficits in Patients with Focal Thalamic Lesions.

The human thalamus has been suggested to be involved in executive function, based on animal studies and correlational evidence from functional neuroimaging in humans. Human lesion studies, examining behavioral deficits associated with focal brain injuries, can directly test the necessity of the human thalamus for executive function. The goal of our study was to determine the specific lesion location within the thalamus as well as the potential disruption of specific thalamocortical functional networks, related to executive dysfunction. We assessed executive function in 15 patients with focal thalamic lesions and 34 comparison patients with lesions that spared the thalamus. We found that patients with mediodorsal thalamic lesions exhibited more severe impairment in executive function when compared to both patients with thalamic lesions that spared the mediodorsal nucleus and to comparison patients with lesions outside the thalamus. Furthermore, we employed a lesion network mapping approach to map cortical regions that show strong functional connectivity with the lesioned thalamic subregions in the normative functional connectome. We found that thalamic lesion sites associated with more severe deficits in executive function showed stronger functional connectivity with ACC, dorsomedial PFC, and frontoparietal network, compared to thalamic lesions not associated with executive dysfunction. These are brain regions and functional networks whose dysfunction could contribute to impaired executive functioning. In aggregate, our findings provide new evidence that delineates a thalamocortical network for executive function.

Assessment of Neighborhood Poverty, Cognitive Function, and Prefrontal and Hippocampal Volumes in Children

The association between poverty and unfavorable cognitive outcomes is robust, but most research has focused on individual household socioeconomic status (SES). There is increasing evidence that neighborhood context explains unique variance not accounted for by household SES. To evaluate whether neighborhood poverty (NP) is associated with cognitive function and prefrontal and hippocampal brain structure in ways that are dissociable from household SES. This cross-sectional study used a baseline sample of the ongoing longitudinal Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study will follow participants for assessments each year for 10 years. Data were collected at 21 US sites, mostly within urban and suburban areas, between September 2019 and October 2018. School-based recruitment was used to create a participant sample reflecting the US population. Data analysis was conducted from March to June 2019. NP and household SES were included as factors potentially associated with National Institutes of Health Toolbox Cognitive Battery subtests and hippocampal and prefrontal (dorsolateral prefrontal cortex [DLPFC], dorsomedial PFC [DMPFC], superior frontal gyrus [SFG]) volumes. Independent variables were first considered individually and then together in mixed-effects models with age, sex, and intracranial volume as covariates. Structural equation modeling (SEM) was used to assess shared variance in NP to brain structure and cognitive task associations. The tested hypotheses were formulated after data collection. A total of 11 875 children aged 9 and 10 years (5678 [47.8%] girls) were analyzed. Greater NP was associated with lower scores across all cognitive domains (eg, total composite: β = -0.18; 95% CI, -0.21 to -0.15; P < .001) and with decreased brain volume in the DLPFC (eg, right DLPFC: β = -0.09; 95% CI, -0.12 to -0.07; P < .001), DMPFC (eg, right DMPC: β = -0.07; 95% CI, -0.09 to -0.05; P < .001), SFG (eg, right SFG: β = -0.05; 95% CI, -0.08 to -0.03; P < .001), and right hippocampus (β = -0.04; 95% CI, -0.06 to -0.01; P = .01), even when accounting for household income. Greater household income was associated with higher scores across all cognitive domains (eg, total composite: β = 0.30; 95% CI, 0.28 to 0.33; P < .001) and larger volume in all prefrontal and hippocampal brain regions (eg, right hippocampus: β = 0.04; 95% CI, 0.02 to 0.07; P < .001) even when accounting for NP. The SEM model was a good fit across all cognitive domains, with prefrontal regions being associated with NP relations to language (picture vocabulary: estimate [SE], -0.03 [0.01]; P < .001; oral reading: estimate [SE], -0.02 [0.01]; P < .001), episodic memory (picture sequence: estimate [SE], -0.02 [0.01]; P = .008), and working memory (dimensional card sort: estimate [SE], -0.02 [0.01]; P = .001; flanker inhibitory control: estimate [SE], -0.01 [0.01]; P = .01; list sorting: estimate [SE], -0.03 [0.01]; P < .001) and hippocampal regions being associated with NP associations with language (picture vocabulary: estimate [SE], -0.01 [0.004]; P < .001) and episodic memory (picture sequence: estimate [SE], -0.01 [0.004]; P < 0.001). In this study, NP accounted for unique variance in cognitive function and prefrontal and right hippocampal brain volume. These findings demonstrate the importance of including broader environmental influences when conceptualizing early life adversity.

Intermittent theta burst stimulation over the dorsomedial prefrontal cortex modulates resting-state connectivity in depressive patients: A sham-controlled study

The mechanisms underlying repetitive transcranial magnetic stimulation (rTMS) treatment are largely unknown. Although there is a general lack of sham controlled studies, findings show altered functional connectivity to the stimulated region following treatment. When targeting the dorsolateral prefrontal cortex (dlPFC), connectivity with the subgenual anterior cingulate cortex (sgACC) is predictive of response, but less is known about the effects on functional connectivity of targeting the dorsomedial PFC (dmPFC). Here, 30 patients with an ongoing depressive episode were recruited and randomized to 20 sessions at target intensity of either active or sham intermittent theta burst stimulation (iTBS) over dmPFC. Those receiving sham were offered active treatment in a subsequent open phase. A seven minute resting-state scan and depressive symptom assessment was performed before and after treatment. After exclusions due to attrition and excessive head movements 23 patients remained for analysis. Seed-based resting-state connectivity was calculated using two seeds for the dmPFC target as well as the sgACC. A symptom related increase in dmPFC connectivity after active treatment, compared to sham treatment, was found. The effect was observed in a region overlapping the precuneus and the posterior cingulate cortex (PCC), suggesting an increase in the connectivity between the targeted salience network and the default mode network mediating improvement in depressive symptoms. Connectivity between the precuneus and both the sgACC and the treatment target was predictive of symptom improvement following active treatment. The findings have implications for understanding the mechanisms behind iTBS and may inform future efforts to individualize the treatment.

How Does Motivation Modulate the Operation of the Mentalizing Network in Person Evaluation?

The mentalizing network is theorized to play a central role in making sense of people (compared with nonsocial targets), but is its involvement affected when we make sense of people in a nondispassionate manner (e.g., favoritism toward others on the basis of group membership)? First, mixed findings and small samples have prevented strong conclusions about whether intergroup evaluation increases or decreases activation regions associated with the mentalizing network. Second, little is known about the psychological mechanism underlying mentalizing network activation shaped by ingroup versus outgroup evaluations. Psychological models suggest two hypotheses that can be challenging to disentangle with self-report: Ingroup trait evaluations may benefit from a priori expectations and/or preferential evidence accumulation. Therefore, the current study (n = 50) drew on a combination of drift diffusion modeling and fMRI to examine how group membership affects the engagement of the mentalizing network for trait evaluation and whether group-differentiated activation is associated with a priori expectations and/or preferential evidence accumulation. Outgroup trait evaluations engaged dorsomedial pFC activation, whereas ingroup trait evaluations engaged ventromedial pFC activation as well as other regions associated with mentalizing such as precuneus, posterior cingulate cortex, and right TPJ. Furthermore, the ventromedial pFC and posterior cingulate cortex activation was associated with differential expectations applied to ingroup trait evaluation. The current findings demonstrate the importance of combining motivational factors, computational modeling, and fMRI to deepen our understanding of the neural basis of person evaluation.

Longitudinal changes in DLPFC activation during childhood are related to decreased aggression following social rejection

Regulating aggression after social feedback is an important prerequisite for developing and maintaining social relations, especially in the current times with larger emphasis on online social evaluation. Studies in adults highlighted the role of the dorsolateral prefrontal cortex (DLPFC) in regulating aggression. Little is known about the development of aggression regulation following social feedback during childhood, while this is an important period for both brain maturation and social relations. The current study used a longitudinal design, with 456 twins undergoing two functional MRI sessions across the transition from middle (7 to 9 y) to late (9 to 11 y) childhood. Aggression regulation was studied using the Social Network Aggression Task. Behavioral aggression after social evaluation decreased over time, whereas activation in the insula, dorsomedial PFC and DLPFC increased over time. Brain-behavior analyses showed that increased DLPFC activation after negative feedback was associated with decreased aggression. Change analyses further revealed that children with larger increases in DLPFC activity from middle to late childhood showed stronger decreases in aggression over time. These findings provide insights into the development of social evaluation sensitivity and aggression control in childhood.