Ventrolateral Prefrontal Cortex Research Articles

Altered functional connectivity subserving expressed emotion environments in schizophrenia: An fNIRS study

Living in high-expressed emotion (EE) environments, characterized by critical, hostile, or over-involved family attitudes, has been linked to increased relapse rates among individuals with schizophrenia (SZ). In our previous work (Wang et al., 2023), we conducted the first feasibility study of using functional near-infrared spectroscopy (fNIRS) with our developed EE stimuli to examine cortical hemodynamics in SZ. To better understand the neural mechanisms underlying EE environmental factors in SZ, we extended our investigation by employing functional connectivity (FC) analysis with a graph theory approach to fNIRS signals. Relative to healthy controls (N=40), individuals with SZ (N=37) exhibited altered connectivity across the medial prefrontal cortex (mPFC), left ventrolateral prefrontal cortex (vlPFC), and left superior temporal gyrus (STG) while exposed to EE environments. Notably, while individuals with SZ were exposed to high-EE environments, (i) reduced connectivity was observed in these brain regions and (ii) the left vlPFC-STG coupling was found to be associated with the negative symptom severity. Taken together, our FC findings suggest individuals with SZ experience a more extensive disruption in neural functioning and coordination, particularly indicating an increased susceptibility to high-EE environments. This further supports the potential utility of integrating fNIRS with the created EE stimuli for assessing EE environmental influences, paving the way for more targeted therapeutic interventions.

Asynchronous Involvement of VLPFC and DLPFC During Negative Emotion Processing: An Online Transcranial Magnetic Stimulation Study

The ventrolateral prefrontal cortex (VLPFC) and dorsolateral prefrontal cortex (DLPFC) have been found to play important roles in negative emotion processing. However, the specific time window of their involvement remains unknown. This study addressed this issue in three experiments using single-pulse transcranial magnetic stimulation (TMS). We found that TMS applied over the VLPFC at 400 ms after negative emotional exposure significantly enhanced negative feelings compared to the vertex condition. Furthermore, TMS applied over the DLPFC at both 0 ms and 600 ms after negative emotional exposure also resulted in deteriorated negative feelings. These findings provide potential evidence for the VLPFC-dependent semantic processing (∼400 ms) and the DLPFC-dependent attentional and cognitive control (∼0/600 ms) in negative emotion processing. The asynchronous involvement of these frontal cortices not only deepens our understanding of the neural mechanisms underlying negative emotion processing but also provides valuable temporal parameters for neurostimulation therapy targeting patients with mood disorders.

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and the underlying patterns of neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the amygdala of two male macaques. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5–14.5 Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-modal approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

Age-related changes in ventrolateral prefrontal cortex activation are associated with daily prosocial behaviors two years later

As adolescents acquire agency and become contributing members of society, it is necessary to understand how they help their community. Yet, it is unknown how prosocial behavior develops in the context of community-based prosocial behaviors that are relevant to adolescents, such as donating time to charities. In this longitudinal functional magnetic resonance imaging study, adolescents (N=172; mean age at wave 1=12.8) completed a prosocial task annually for three years (N=422 and 375 total behavioral and neural data points, respectively), and 14 days of daily diaries reporting on their prosocial behaviors two years later. During the task, adolescents decided how many minutes they would donate to a variety of local charities. We found that adolescents donated less time to charities from early to mid adolescence. Longitudinal whole-brain analyses revealed declines in ventrolateral prefrontal cortex (vlPFC) activation, as well as inverted U-shaped changes in precuneus activation when adolescents donated their time from early to mid adolescence. A less steep decrease in vlPFC activation predicted greater real-life prosocial behaviors in youth’s daily lives two years later. Our study elucidates the neurodevelopmental mechanisms of prosocial behavior from early to mid adolescence that have enduring effects on daily prosocial behaviors in late adolescence.

A.2 Understanding Grit in healthy older adults at-risk for Alzheimer’s disease

Background: Adherence to healthy lifestyle behaviours or to prescribed medication requires perseverance with stamina, and this is captured by Grit, a non-cognitive trait defined as perseverance and passion for long-term goals. Despite predicting cognitive decline and physical, emotional, and social functioning, Grit remains poorly understood and its neural substrates are unknown in cognitive aging. Methods: Ninety-five cognitively unimpaired older adults with a family history of Alzheimer’s disease were recruited through the PREVENT-AD longitudinal cohort. Participants completed tests that assess grit and conscientiousness and underwent resting-state functional magnetic resonance imaging (fMRI). Multivariate pattern analyses (MVPA), a rigorous data-driven whole-brain approach, were used to examine if resting-state functional connectivity of connectome-wide voxels were associated with grit scores, controlling for age, sex, APOE ε4 carriership, mean displacement, and conscientiousness. Results: Our analyses identified two large (≥54 voxels) and statistically significant (p<0.01 corrected for family-wise error) clusters in the right ventrolateral prefrontal cortex and the left orbitofrontal cortex underlying grit. Conclusions: Being the first to identify functional neural correlates supporting grit in the aging population while accounting for the variance of conscientiousness, our study provides unique insights into the construct which has important applications in adherence to clinical and empirical neurological interventions as well as in successful aging.

Brain activity during reappraisal and associations with psychotherapy response in social anxiety and major depression: a randomized trial.

Cognitive behavioral therapy (CBT) is an effective treatment for patients with social anxiety disorder (SAD) or major depressive disorder (MDD), yet there is variability in clinical improvement. Though prior research suggests pre-treatment engagement of brain regions supporting cognitive reappraisal (e.g. dorsolateral prefrontal cortex [dlPFC]) foretells CBT response in SAD, it remains unknown if this extends to MDD or is specific to CBT. The current study examined associations between pre-treatment neural activity during reappraisal and clinical improvement in patients with SAD or MDD following a trial of CBT or supportive therapy (ST), a common-factors comparator arm. Participants were 75 treatment-seeking patients with SAD (n = 34) or MDD (n = 41) randomized to CBT (n = 40) or ST (n = 35). Before randomization, patients completed a cognitive reappraisal task during functional magnetic resonance imaging. Additionally, patients completed clinician-administered symptom measures and a self-report cognitive reappraisal measure before treatment and every 2 weeks throughout treatment. Results indicated that pre-treatment neural activity during reappraisal differentially predicted CBT and ST response. Specifically, greater trajectories of symptom improvement throughout treatment were associated with less ventrolateral prefrontal cortex (vlPFC) activity for CBT patients, but more vlPFC activity for ST patients. Also, less baseline dlPFC activity corresponded with greater trajectories of self-reported reappraisal improvement, regardless of treatment arm. If replicated, findings suggest individual differences in brain response during reappraisal may be transdiagnostically associated with treatment-dependent improvement in symptom severity, but improvement in subjective reappraisal following psychotherapy, more broadly.

Neural mechanisms of the relationship between aerobic fitness and working memory in older adults: An fNIRS study

Abstract A growing number of studies have revealed that higher aerobic fitness is associated with better working memory (WM) performance in older adults. However, the underlying functional neural mechanisms of this association remain under debate. It has been reported that aging increases recruitment of the prefrontal cortex (PFC) during cognitive tasks, and that this is associated with task performance in a compensatory manner. Therefore, this study aimed to clarify the prefrontal activation pattern that is associated with the relationship between aerobic fitness and WM performance in older adults, focusing on age-related extended prefrontal recruitment. Forty-seven older adults (65–74 years, 29 females) and 49 younger adults (18–24 years, 23 female) performed verbal and spatial n-back tasks, which included 0-, 1-, and 2-back conditions. Reaction time (RT) and accuracy (ACC) were assessed as indices of task performance. Prefrontal activation during the experimental tasks was monitored using functional near-infrared spectroscopy (fNIRS) and analyzed using an adaptive GLM method. We compared task performance and prefrontal activation between age groups to find age-related prefrontal activation patterns. Only older adults underwent a graded exercise test (GXT) to determine their ventilation thresholds (VT) as a measure of aerobic fitness, and, subsequently, the relationships among aerobic fitness, n-back task performance, and prefrontal activation in older adults were examined using correlation analysis and mediation analysis controlling for possible covariates. A comparison of task performance between groups revealed that older adults had slower RT and lower ACC than did younger adults, especially in the higher WM load 2-back condition. Group comparisons of prefrontal activation showed that older adults exhibited additional or greater activation than younger adults mainly in the ventrolateral PFC (VLPFC) and front polar area (FPA) in both the verbal and spatial 2-back conditions. Correlation analysis showed a relationship between higher VT, shorter RT for the verbal 2-back condition, and greater prefrontal activation of the bilateral FPA and right VLPFC during verbal 2-back conditions in older adults. In addition, mediation analyses indicated the possibility of a mediation effect of the prefrontal activation on the relationship between VT and RT for the verbal 2-back condition. These results suggest that older adults with higher aerobic fitness levels recruited more extended PFC regions, possibly for compensatory activation, to enhance their performance of the verbal n-back task. This study sheds light on the neural mechanisms underpinning the relationship between aerobic fitness and cognitive function in older adults.

Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder.

Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD. A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci. In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E). Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.

Mesocorticolimbic system reactivity to alcohol use-related visual cues as a function of alcohol sensitivity phenotype: A pilot fMRI study

Low sensitivity (LS) to alcohol is a risk factor for alcohol use disorder (AUD). Compared to peers with high sensitivity (HS), LS individuals drink more, report more problems, and exhibit potentiated alcohol cue reactivity (ACR). Heightened ACR suggests LS confers AUD risk via incentive sensitization, which is thought to take place in the mesocorticolimbic system. This study examined neural ACR in LS and HS individuals. Young adults (N = 32, Mage=20.3) were recruited based on the Alcohol Sensitivity Questionnaire (HS: n = 16; LS: n = 16; 9 females/group). Participants completed an event-related fMRI ACR task. Group LS had higher ACR in left ventrolateral prefrontal cortex than group HS. In group LS, ACR in left caudomedial orbitofrontal cortex or left putamen was low at low alcohol use levels and high at heavier or more problematic alcohol use levels, whereas the opposite was true in group HS. Alcohol use level also was associated with the level of ACR in left substantia nigra among males in group LS. Taken together, results suggest elevated mesocorticolimbic ACR among LS individuals, especially those using alcohol at hazardous levels. Future studies with larger samples are warranted to determine the neurobiological loci underlying LS-based amplified ACR and AUD risk.

Event-related prefrontal activations during online video game playing are modulated by game mechanics, physiological arousal and the amount of daily playing

There is a trend to study human brain functions in ecological contexts and in relation to human factors. In this study, functional near-infrared spectroscopy (fNIRS) was used to record real-time prefrontal activities in 42 male university student habitual video game players when they played a round of multiplayer online battle arena game, League of Legends. A content-based event coding approach was used to analyze regional activations in relation to event type, physiological arousal indexed by heart rate (HR) change, and individual characteristics of the player. Game events Slay and Slain were found to be associated with similar HR and prefrontal responses before the event onset, but differential responses after the event onset. Ventrolateral prefrontal cortex (VLPFC) activation preceding the Slay onset correlated positively with HR change, whereas activations in dorsolateral prefrontal cortex (DLPFC) and rostral frontal pole area (FPAr) preceding the Slain onset were predicted by self-reported hours of weekly playing (HoWP). Together, these results provide empirical evidence to support the notion that event-related regional prefrontal activations during online video game playing are shaped by game mechanics, in-game dynamics of physiological arousal and individual characteristics the players.

Continuous decision to wait for a future reward is guided by fronto-hippocampal anticipatory dynamics.

Deciding whether to wait for a future reward is crucial for surviving in an uncertain world. While seeking rewards, agents anticipate a reward in the present environment and constantly face a trade-off between staying in their environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here, we show that anticipatory activity in the anterior prefrontal cortex, ventrolateral prefrontal cortex, and hippocampus underpins continuous stay-leave decision-making. Participants awaited real liquid rewards available after tens of seconds, and their continuous decision was tracked by dynamic brain activity associated with the anticipation of a reward. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When the dynamic anticipatory brain activity was enhanced in the anterior prefrontal cortex, participants remained in their current environment, but when this activity diminished, they left the environment. Moreover, while experiencing a delayed reward in a novel environment, the ventrolateral prefrontal cortex and hippocampus showed anticipatory activity. Finally, the activity in the anterior prefrontal cortex and ventrolateral prefrontal cortex was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced hippocampal activity. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision-making while anticipating a future reward.

7. Continuous Theta Burst Stimulation of Ventrolateral Prefrontal Cortex and Associated Reductions in Hypomanic Symptoms

7. Continuous Theta Burst Stimulation of Ventrolateral Prefrontal Cortex and Associated Reductions in Hypomanic Symptoms

Enhancing ventrolateral prefrontal cortex activation mitigates social pain and modifies subsequent social attitudes: Insights from TMS and fMRI

Social pain, a multifaceted emotional response triggered by interpersonal rejection or criticism, profoundly impacts mental well-being and social interactions. While prior research has implicated the right ventrolateral prefrontal cortex (rVLPFC) in mitigating social pain, the precise neural mechanisms and downstream effects on subsequent social attitudes remain elusive. This study employed transcranial magnetic stimulation (TMS) integrated with fMRI recordings during a social pain task to elucidate these aspects. Eighty participants underwent either active TMS targeting the rVLPFC (n = 41) or control stimulation at the vertex (n = 39). Our results revealed that TMS-induced rVLPFC facilitation significantly reduced self-reported social pain, confirming the causal role of the rVLPFC in social pain relief. Functional connectivity analyses demonstrated enhanced interactions between the rVLPFC and the dorsolateral prefrontal cortex, emphasizing the collaborative engagement of prefrontal regions in emotion regulation. Significantly, we observed that negative social feedback led to negative social attitudes, whereas rVLPFC activation countered this detrimental effect, showcasing the potential of the rVLPFC as a protective buffer against adverse social interactions. Moreover, our study uncovered the impact role of the hippocampus in subsequent social attitudes, a relationship particularly pronounced during excitatory TMS over the rVLPFC. These findings offer promising avenues for improving mental health within the intricate dynamics of social interactions. By advancing our comprehension of the neural mechanisms underlying social pain relief, this research introduces novel intervention strategies for individuals grappling with social distress. Empowering individuals to modulate rVLPFC activation may facilitate reshaping social attitudes and successful reintegration into communal life.

Preferences reveal dissociable encoding across prefrontal-limbic circuits.

Individual preferences for the flavor of different foods and fluids exert a strong influence on behavior. Most current theories posit that preferences are integrated with other state variables in the orbitofrontal cortex (OFC), which is thought to derive the relative subjective value of available options to guide choice behavior. Here, we report that instead of a single integrated valuation system in the OFC, another complementary one is centered in the ventrolateral prefrontal cortex (vlPFC) in macaques. Specifically, we found that the OFC and vlPFC preferentially represent outcome flavor and outcome probability, respectively, and that preferences are separately integrated into value representations in these areas. In addition, the vlPFC, but not the OFC, represented the probability of receiving the available outcome flavors separately, with the difference between these representations reflecting the degree of preference for each flavor. Thus, both the vlPFC and OFC exhibit dissociable but complementary representations of subjective value, both of which are necessary for decision-making.

Sex modulated the relationship between trait approach motivation and decision-making

It has been observed that one's Behavioral Approach System (BAS) can have an effect on decision-making under uncertainty, although the results have been mixed. To discern the underlying neural substrates, we hypothesize that sex may explain the conflicting results. To test this idea, a large sample of participants was studied using resting state fMRI, utilizing fractional Amplitude of Low Frequency Fluctuations (fALFF) and Resting-State Functional Connectivity (rsFC) techniques. The results of the Iowa Gambling Task (IGT) revealed an interaction between sex and BAS, particularly in the last 60 trials (decision-making under risk). Males with high BAS showed poorer performance than those with low BAS. fALFF analysis showed a significant interaction between BAS group and sex in the left superior occipital gyrus, as well as the functional connectivity between this region and the left ventrolateral prefrontal cortex. Additionally, this functional connectivity was further positively correlated with male performance in the IGT, particularly in the decision-making under risk stage. Furthermore, it was found that the functional connectivity between left ventrolateral prefrontal cortex and left superior occipital gyrus could mediate the relationship between BAS and decision-making in males, particularly in the decision-making under risk stage. These results suggest possible sex-based differences in decision-making, providing an explanation for the inconsistent results found in prior research. Since the research was carried out exclusively with Chinese university students, it is essential to conduct further studies to investigate whether the findings can be generalized.

Neural correlates of breath work, mental imagery of yoga postures, and meditation in yoga practitioners: a functional near-infrared spectroscopy study.

Previous research has shown numerous health benefits of yoga, a multicomponent physical and mental activity. The three important aspects of both traditional and modern yoga are breath work, postures, and meditation. However, the neural mechanisms associated with these three aspects of yoga remain largely unknown. The present study investigated the neural underpinnings associated with each of these three yoga components in long- and short-term yoga practitioners to clarify the neural advantages of yoga experience, aiming to provide a more comprehensive understanding of yoga's health-promoting effects. Participants were 40 Chinese women, 20 with a long-term yoga practice and 20 with a short-term yoga practice. Functional near-infrared spectroscopy was conducted while participants performed abdominal breathing, mental imagery of yoga postures, and mindfulness meditation. The oxygenated hemoglobin concentrations activated in the brain during these three tasks were used to assess the neural responses to the different aspects of yoga practice. The self-reported mastery of each yoga posture was used to assess the advantages of practicing yoga postures. Blood oxygen levels in the dorsolateral prefrontal cortex during breath work were significantly higher in long-term yoga practitioners than in short-term yoga practitioners. In the mental imagery of yoga postures task, self-reported data showed that long-term yoga practitioners had better mastery than short-term practitioners. Long-term yoga practitioners demonstrated lower activation in the ventrolateral prefrontal cortex, with lower blood oxygen levels associated with performing this task, than short-term yoga practitioners. In the mindfulness meditation task, blood oxygen levels in the orbitofrontal cortex and the ventrolateral prefrontal cortex were significantly higher in long-term yoga practitioners than in short-term yoga practitioners. The three core yoga components, namely, yogic breathing, postures, and meditation, showed differences and similarities in the activation levels of the prefrontal cortex. Long-term practice of each component led to the neural benefits of efficient activation in the prefrontal cortex, especially in the dorsolateral prefrontal cortex, orbitofrontal cortex, and ventrolateral prefrontal cortex.

Spontaneously emerging internal models of visual sequences combine abstract and event-specific information in the prefrontal cortex

When exposed to sensory sequences, do macaque monkeys spontaneously form abstract internal models that generalize to novel experiences? Here, we show that neuronal populations in macaque ventrolateral prefrontal cortex jointly encode visual sequences by separate codes for the specific pictures presented and for their abstract sequential structure. We recorded prefrontal neurons while macaque monkeys passively viewed visual sequences and sequence mismatches in the local-global paradigm. Even without any overt task or response requirements, prefrontal populations spontaneously form representations of sequence structure, serial order, and image identity within distinct but superimposed neuronal subspaces. Representations of sequence structure rapidly update following single exposure to a mismatch sequence, while distinct populations represent mismatches for sequences of different complexity. Finally, those representations generalize across sequences following the same repetition structure but comprising different images. These results suggest that prefrontal populations spontaneously encode rich internal models of visual sequences reflecting both content-specific and abstract information.

Abnormal prefrontal cortical activation during the GO/NOGO and verbal fluency tasks in adult patients with comorbid generalized anxiety disorder and attention-deficit/hyperactivity disorder: An fNIRS study

Generalized anxiety disorder (GAD) and adult attention-deficit/hyperactivity disorder (ADHD) are commonly reported comorbidities. Adult GAD patients with comorbid ADHD are often underdiagnosed and undertreated. To explore the clinical value of functional near-infrared spectroscopy (fNIRS) data for assisting in the accurate diagnosis of ADHD in individuals with GAD, haemoglobin (HbO) concentration changes in the prefrontal cortex (PFC) were detected via fNIRS in 49 patients with both GAD and ADHD, 46 patients with GAD, and 34 healthy controls (HCs) during a verbal fluency task (VFT) and a GO/NOGO task. The correlations between PFC fNIRS data and the severity of inattention and hyperactivity symptoms assessed using the adult ADHD Self-Report Scale (ASRS) were analyzed. Our results showed that, during the GO/NOGO task, channels in the left dorsolateral PFC (channels 28 and 29) were hyperactivated, while channels in the medial PFC (channels 36, 37, and 47) were hypoactivated in participants with ADHD and GAD compared with those with GAD alone. During the VFT, compared with the HC group, both the ADHD + GAD group and the GAD group exhibited significantly decreased HbO activation in the medial PFC (channels 37, 38, and 48) and in the left ventrolateral PFC (channel 39); moreover, no difference was found between the ADHD + GAD group and the GAD group. Activation in the left dorsolateral PFC (channels 28 and 29) during the GO/NOGO task showed a significant positive correlation with ASRS-inattention scores. Our results indicated that fNIRS data collected during the GO/NOGO task may help to distinguish patients with comorbid GAD and ADHD from those with GAD alone.

New organizational principles and 3D cytoarchitectonic maps of the dorsolateral prefrontal cortex in the human brain.

Areas of the dorsolateral prefrontal cortex (DLPFC) are part of the frontoparietal control, default mode, salience, and ventral attention networks. The DLPFC is involved in executive functions, like working memory, value encoding, attention, decision-making, and behavioral control. This functional heterogeneity is not reflected in existing neuroanatomical maps. For example, previous cytoarchitectonic studies have divided the DLPFC into two or four areas. Macroanatomical parcellations of this region rely on gyri and sulci, which are not congruent with cytoarchitectonic parcellations. Therefore, this study aimed to provide a microstructural analysis of the human DLPFC and 3D maps of cytoarchitectonic areas to help address the observed functional variability in studies of the DLPFC. We analyzed ten human post-mortem brains in serial cell-body stained brain sections and mapped areal boundaries using a statistical image analysis approach. Five new areas (i.e., SFG2, SFG3, SFG4, MFG4, and MFG5) were identified on the superior and middle frontal gyrus, i.e., regions corresponding to parts of Brodmann areas 9 and 46. Gray level index profiles were used to determine interregional cytoarchitectural differences. The five new areas were reconstructed in 3D, and probability maps were generated in commonly used reference spaces, considering the variability of areas in stereotaxic space. Hierarchical cluster analysis revealed a high degree of similarity within the identified DLPFC areas while neighboring areas (frontal pole, Broca's region, area 8, and motoric areas) were separable. Comparisons with functional imaging studies revealed specific functional profiles of the DLPFC areas. Our results indicate that the new areas do not follow a simple organizational gradient assumption in the DLPFC. Instead, they are more similar to those of the ventrolateral prefrontal cortex (Broca's areas 44, 45) and frontopolar areas (Fp1, Fp2) than to the more posterior areas. Within the DLPFC, the cytoarchitectonic similarities between areas do not seem to follow a simple anterior-to-posterior gradient either, but cluster along other principles. The new maps are part of the publicly available Julich Brain Atlas and provide a microstructural reference for existing and future imaging studies. Thus, our study represents a further step toward deciphering the structural-functional organization of the human prefrontal cortex.

Altered Lateral Prefrontal Cortex Functioning During Emotional Interference Resistance Is Associated With Affect Lability in Adults With Persisting Symptoms of Attention-Deficit/Hyperactivity Disorder From Childhood

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention and/or impulsivity/hyperactivity. ADHD, especially when persisting into adulthood, often includes emotional dysregulation, such as affect lability; however, the neural correlates of emotionality in adults with heterogeneous ADHD symptom persistence remain unclear. MethodsThe present study sought to determine shared and distinct functional neuroanatomical profiles of neural circuitry during emotional interference resistance using the emotional face n-back task in adult participants with persisting (n = 47), desisting (n = 93), or no (n = 42) childhood ADHD symptoms while undergoing functional magnetic resonance imaging. ResultsParticipants without any lifetime ADHD diagnosis performed significantly better (faster and more accurately) than participants with ADHD diagnoses on trials with high cognitive loads (2-back) that included task-irrelevant emotional distractors, tapping into executive functioning and emotion regulatory processes. In participants with persisting ADHD symptoms, more severe emotional symptoms were related to worse task performance. Heightened dorsolateral and ventrolateral prefrontal cortex activation was associated with more accurate and faster performance on 2-back emotional faces trials, respectively. Reduced activation was associated with greater affect lability in adults with persisting ADHD, and dorsolateral prefrontal cortex activation mediated the relationship between affect lability and task accuracy. ConclusionsThese findings suggest that alterations in dorsolateral prefrontal cortex function associated with greater interference in cognitive processes from emotion could represent a marker of risk for problems with emotional dysregulation in individuals with persisting ADHD and thus represent a potential therapeutic target for those with greater emotional symptoms of ADHD.