Prefrontal Cortex Functional Connectivity Research Articles

Assessing resting-state brain functional connectivity in adolescents and young adults with narcolepsy using functional near-infrared spectroscopy.

This study aimed to elucidate the alterations in the prefrontal cortex's functional connectivity and network topology in narcolepsy patients using functional near-infrared spectroscopy (fNIRS). Twelve narcolepsy-diagnosed patients from Guangxi Zhuang Autonomous Region's People's Hospital Sleep Medicine Department and 11 matched healthy controls underwent resting fNIRS scans. Functional connectivity and graph theory analyses were employed to assess the prefrontal cortex network's properties and their correlation with clinical features. Results indicated increased functional connectivity in these adolescent and young adult patients with narcolepsy, with significant variations in metrics like average degree centrality and node efficiency, particularly in the left middle frontal gyrus. These alterations showed correlations with clinical symptoms, including depression and sleep efficiency. However, the significance of these findings was reduced post False Discovery Rate adjustment, suggesting a larger sample size is needed for validation. In conclusion, the study offers initial observations that alterations in the prefrontal cortex's functional connectivity may potentially act as a neurobiological indicator of narcolepsy, warranting further investigation with a larger cohort to substantiate these findings and understand the underlying mechanisms.

Lower cerebrovascular reactivity in prefrontal cortex and weaker negative functional connectivity between prefrontal cortex and insula contribute to white matter hyperintensity-related anxiety or depression

BackgroundWhite matter hyperintensities (WMHs) are associated with higher anxiety or depression (A/D) incidence. We investigated associations of WMHs with A/D, cerebrovascular reactivity (CVR), and functional connectivity (FC) to identify potential pathomechanisms. MethodsParticipants with WMH (n = 239) and normal controls (NCs, n = 327) were assessed for A/D using the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The CVR and FC maps were constructed from resting-state functional MRI. Two-way analysis of covariance with fixed factors A/D and WMH was performed to identify regional CVR abnormalities. Seed-based FC analyses were then conducted on regions with WMH × A/D interaction effects on CVR. Logistic regression models were constructed to examine the utility of these measurements for identifying WMH-related A/D. ResultsParticipants with WMH related A/D exhibited significantly greater CVR in left insula and lower CVR in right superior frontal gyrus (SFG.R), and HAMA scores were negatively correlated with CVR in SFG.R (r = −0.156, P = 0.016). Insula–SFG.R negative FC was significantly weaker in WMH patients with suspected or definite A/D. A model including CVR plus FC changes identified WMH-associated A/D with highest sensitivity and specificity. In contrast, NCs with A/D exhibited greater CVR in prefrontal cortex and stronger FC within the default mode network (DMN) and between the DMN and executive control network. LimitationsThis cross-sectional study requires validation by longitudinal and laboratory studies. ConclusionsImpaired CVR in SFG.R and weaker negative FC between prefrontal cortex and insula may contribute to WMH-related A/D, providing potential diagnostic imaging markers and therapeutic targets.

Prefrontal cortex functional connectivity changes during verbal fluency test in adults with short-term insomnia disorder: a functional near-infrared spectroscopy study.

Individuals suffering from short-term insomnia disorder (SID) experience difficulties in falling or staying asleep, often leading to daytime fatigue and impaired concentration. However, the underlying mechanisms of SID remain unclear. This study aims to investigate the alterations in brain activation patterns and functional connectivity in patients with SID. The study enrolled a total of 31 adults diagnosed with SID and 31 healthy controls (HC). Functional near-infrared spectroscopy (fNIRS) was utilized to assess the concentrations of oxyhemoglobin (Oxy-Hb) and functional connectivity in the prefrontal cortex of each participant while performing the verbal fluency test (VFT) task. In the VFT task, no significant difference was found between the SID group and the HC group in terms of integral values, centroid values, and mean Oxy-Hb variations. These findings suggest that both groups exhibit similar hemodynamic responses. However, the functional connectivity analysis revealed significant differences in inter-channel connectivity strength between the two groups. The SID group showed significantly lower average inter-channel connectivity strength compared to the HC group. Moreover, six channel pairs (right frontopolar cortex - left frontopolar cortex, left orbitofrontal cortex - left temporopolar cortex, left temporopolar cortex - left frontopolar cortex, left frontopolar cortex-Ch38, left frontopolar cortex - right pre-motor and supplementary motor cortex, and left frontopolar cortex - right dorsolateral prefrontal cortex) exhibited significantly higher connectivity strength in the HC group compared to the SID group (FDR corrected, p < 0.05). Specifically, channel 27 exhibited the highest frequency of significant connectivity across different channel pairs, occurring five times in total. The channel pair Ch27-Ch39, representing left frontopolar cortex and right dorsolateral prefrontal cortex, exhibited a negative correlation with PSQI scores (r = -0.422, p = 0.018). Our findings suggest that patients with SID may exhibit altered brain connectivity during the VFT task, as measured by fNIRS. These results provide valuable insights into the functional brain differences associated with SID. Further research is needed to validate and expand upon these findings.

Patterns of Neural Network Functional Connectivity Associated With Mania/Hypomania and Depression Risk in 3 Independent Young Adult Samples

Mania/hypomania is the pathognomonic feature of bipolar disorder (BD). Established, reliable neural markers denoting mania/hypomania risk to help with early risk detection and diagnosis and guide the targeting of pathophysiologically informed interventions are lacking. To identify patterns of neural responses associated with lifetime mania/hypomania risk, the specificity of such neural responses to mania/hypomania risk vs depression risk, and the extent of replication of findings in 2 independent test samples. This cross-sectional study included 3 independent samples of young adults aged 18 to 30 years without BD or active substance use disorder within the past 3 months who were recruited from the community through advertising. Of 603 approached, 299 were ultimately included and underwent functional magnetic resonance imaging at the University of Pittsburgh, Pittsburgh, Pennsylvania, from July 2014 to May 2023. Activity and functional connectivity to approach-related emotions were examined using a region-of-interest mask supporting emotion processing and emotional regulation. The Mood Spectrum Self-Report assessed lifetime mania/hypomania risk and depression risk. In the discovery sample, elastic net regression models identified neural variables associated with mania/hypomania and depression risk; multivariable regression models identified the extent to which selected variables were significantly associated with each risk measure. Multivariable regression models then determined whether associations in the discovery sample replicated in both test samples. A total of 299 participants were included. The discovery sample included 114 individuals (mean [SD] age, 21.60 [1.91] years; 80 female and 34 male); test sample 1, 103 individuals (mean [SD] age, 21.57 [2.09] years; 30 male and 73 female); and test sample 2, 82 individuals (mean [SD] age, 23.43 [2.86] years; 48 female, 29 male, and 5 nonbinary). Associations between neuroimaging variables and Mood Spectrum Self-Report measures were consistent across all 3 samples. Bilateral amygdala-left amygdala functional connectivity and bilateral ventrolateral prefrontal cortex-right dorsolateral prefrontal cortex functional connectivity were positively associated with mania/hypomania risk: discovery omnibus χ2 = 1671.7 (P < .001); test sample 1 omnibus χ2 = 1790.6 (P < .001); test sample 2 omnibus χ2 = 632.7 (P < .001). Bilateral amygdala-left amygdala functional connectivity and right caudate activity were positively associated and negatively associated with depression risk, respectively: discovery omnibus χ2 = 2566.2 (P < .001); test sample 1 omnibus χ2 = 2935.9 (P < .001); test sample 2 omnibus χ2 = 1004.5 (P < .001). In this study of young adults, greater interamygdala functional connectivity was associated with greater risk of both mania/hypomania and depression. By contrast, greater functional connectivity between ventral attention or salience and central executive networks and greater caudate deactivation were reliably associated with greater risk of mania/hypomania and depression, respectively. These replicated findings indicate promising neural markers distinguishing mania/hypomania-specific risk from depression-specific risk and may provide neural targets to guide and monitor interventions for mania/hypomania and depression in at-risk individuals.

Tai Chi exercise reduces circulating levels of inflammatory oxylipins in postmenopausal women with knee osteoarthritis: results from a pilot study.

Tai Chi (TC) controls pain through mind-body exercise and appears to alter inflammatory mediators. TC actions on lipid biomarkers associated with inflammation and brain neural networks in women with knee osteoarthritic pain were investigated. A single-center, pre- and post-TC group (baseline and 8 wk) exercise pilot study in postmenopausal women with knee osteoarthritic pain was performed. 12 eligible women participated in TC group exercise. The primary outcome was liquid chromatography tandem mass spectrometry determination of circulating endocannabinoids (eCB) and oxylipins (OxL). Secondary outcomes were correlations between eCB and OxL levels and clinical pain/limitation assessments, and brain resting-state function magnetic resonance imaging (rs-fMRI). Differences in circulating quantitative levels (nM) of pro-inflammatory OxL after TC were found in women. TC exercise resulted in lower OxL PGE1 and PGE2 and higher 12-HETE, LTB4, and 12-HEPE compared to baseline. Pain assessment and eCB and OxL levels suggest crucial relationships between TC exercise, inflammatory markers, and pain. Higher plasma levels of eCB AEA, and 1, 2-AG were found in subjects with increased pain. Several eCB and OxL levels were positively correlated with left and right brain amygdala-medial prefrontal cortex functional connectivity. TC exercise lowers pro-inflammatory OxL in women with knee osteoarthritic pain. Correlations between subject pain, functional limitations, and brain connectivity with levels of OxL and eCB showed significance. Findings indicate potential mechanisms for OxL and eCB and their biosynthetic endogenous PUFA precursors that alter brain connectivity, neuroinflammation, and pain. ClinicalTrials.gov, identifier: NCT04046003.

Maternal anxiety during pregnancy is associated with weaker prefrontal functional connectivity in adult offspring

BackgroundThe connectome, constituting a unique fingerprint of a person’s brain, may be influenced by its prenatal environment, potentially affecting later-life resilience and mental health.MethodsWe conducted a prospective resting-state functional Magnetic Resonance Imaging study in 28-year-old offspring (N = 49) of mothers whose anxiety was monitored during pregnancy. Two offspring anxiety subgroups were defined: “High anxiety” (n = 13) group versus “low-to-medium anxiety” (n = 36) group, based on maternal self-reported state anxiety at 12–22 weeks of gestation. To predict resting-state functional connectivity of 32 by 32 ROIs, maternal state anxiety during pregnancy was included as a predictor in general linear models for both ROI-to-ROI and graph theoretical metrics. Sex, birth weight and postnatal anxiety were included as covariates.ResultsHigher maternal anxiety was associated with weaker functional connectivity of medial prefrontal cortex with left inferior frontal gyrus (t = 3.45, pFDR < 0.05). Moreover, network-based statistics (NBS) confirmed our finding and revealed an additional association of weaker connectivity between left lateral prefontal cortex with left somatosensory motor gyrus in the offspring. While our results showed a general pattern of lower functional connectivity in adults prenatally exposed to maternal anxiety, we did not observe significant differences in global brain networks between groups.ConclusionsWeaker (medial) prefrontal cortex functional connectivity in the high anxiety adult offspring group suggests a long-term negative impact of prenatal exposure to high maternal anxiety, extending into adulthood. To prevent mental health problems at population level, universal primary prevention strategies should aim at lowering maternal anxiety during pregnancy.

0162 The neural bases of emotion dysregulation in rotating shift workers

Abstract Introduction Shift work is known to be associated with sleep disturbance and circadian misalignment and may contribute to alterations in the brain implicated in emotion dysregulation. In this study, we examined 1) neural correlates of emotion dysregulation, including emotional reactivity and regulation in shift workers and 2) relationships between neural correlates of emotion dysregulation, sleep disturbance, and circadian misalignment. Methods Fifty-six rotating shift workers (SW, 42 females, 30.80 ± 6.94 years old) who had non-standard shift schedules and 52 healthy controls (HC, 36 females, 31.69 ± 7.86 years old) who did not work as shift schedules participated in this study. Both SW and HC completed self-reported measures of sleep and mood problems, and wrote sleep diary and wore actigraphy to assess sleep quality and circadian rhythms. They also underwent one night polysomnography and were scanned while they were performing the emotion regulation task. We analyzed group differences in mood, sleep, circadian rhythms, and neural bases of emotional reactivity and regulation, and examined relationships between these variables. Results SW showed significant differences in actigraphy-estimated sleep (i.e., lower sleep efficiency) and circadian rhythms (e.g., greater motor activity [M10] and lower interdaily stability) compared to HC. SW also exhibited increased anterior insula (AI) activation in response to negative pictures, but reduced activation in the dorsomedial prefrontal cortex (dMPFC) and AI-dMPFC functional connectivity during emotion regulation compared to HC. AI activation and AI-dMPFC functional connectivity were significantly associated with sleep disturbance (i.e., sleep diary-estimated sleep onset latency) and circadian misalignment (e.g., M10 and interdaily stability). Furthermore, a mediation analysis revealed that shift work was associated with increased motor activity during the most active 10-hour period, which then contributed to increased AI activation in response to negative pictures. Conclusion Our findings suggest that shift work may contribute to sleep disturbance and circadian misalignment, and neural alterations associated with emotional reactivity and regulation. Furthermore, the mediation result suggests that increased motor activity along with misaligned circadian rhythm may serve as a pathway, through shift work contributes to heightened emotional reactivity to negative information. Support (if any) National Research Foundation (No. 2022R1A2C2008417, NRF-2022R1A2C1008209) and Korea Institute for Advancement of Technology (No. 20009210).

Lower Dorsal Lateral Prefrontal Cortex Functional Connectivity in Late-Life Depression With Suicidal Ideation

The dorsal lateral prefrontal cortex (DLPFC) has been identified as a neuromodulation target for alleviating suicidal ideation. Dysfunctional DLPFC has been implicated in suicidality in depression. This study aimed to investigate the functional connectivity (FC) of the DLPFC in late-life depression (LLD) with suicidal ideation. Resting-state functional magnetic resonance imaging (fMRI) data from 32 LLD patients with suicidal ideation (LLD-S), 41 LLD patients without suicidal ideation (LLD-NS), and 54 healthy older adults (HOA) were analyzed using DLPFC seed-based FC analyses. Group differences in FC were examined, and machine learning was applied to explore the potential of DLPFC-FC for classifying LLD-S from LLD-NS. Abnormal DLPFC-FC patterns were observed in LLD-S, characterized by lower connectivity with the angular gyrus, precuneus, and superior frontal gyrus compared to LLD-NS and healthy controls. A classification model based on the identified DLPFC-FC achieved an accuracy of 75%. The lower FC of DLPFC networks may contribute to the neurobiological mechanism of suicidal ideation in late-life depression. These findings may facilitate suicide prevention for LLD by providing potential neuroimaging markers and network-based neuromodulation targets. However, further confirmation with larger sample sizes and experimental designs is warranted.

Neural Circuit Markers of Familial Risk for Depression Among Healthy Youths in the Adolescent Brain Cognitive Development Study

BackgroundFamily history of depression is a robust predictor of early-onset depression, which may confer risk through alterations in neural circuits that have been implicated in reward and emotional processing. These alterations may be evident in youths who are at familial risk for depression but who do not currently have depression. However, the identification of robust and replicable findings has been hindered by few studies and small sample sizes. In the current study, we sought to identify functional connectivity (FC) patterns associated with familial risk for depression. MethodsParticipants included healthy (i.e., no lifetime psychiatric diagnoses) youths at high familial risk for depression (HR) (n = 754; at least one parent with a history of depression) and healthy youths at low familial risk for psychiatric problems (LR) (n = 1745; no parental history of psychopathology) who were 9 to 10 years of age and from the Adolescent Brain Cognitive Development (ABCD) Study sample. We conducted whole-brain seed-to-voxel analyses to examine group differences in resting-state FC with the amygdala, caudate, nucleus accumbens, and putamen. We hypothesized that HR youths would exhibit global amygdala hyperconnectivity and striatal hypoconnectivity patterns primarily driven by maternal risk. ResultsHR youths exhibited weaker caudate–angular gyrus FC than LR youths (α = 0.04, Cohen’s d = 0.17). HR youths with a history of maternal depression specifically exhibited weaker caudate–angular gyrus FC (α = 0.03, Cohen’s d = 0.19) as well as weaker caudate–dorsolateral prefrontal cortex FC (α = 0.04, Cohen’s d = 0.21) than LR youths. ConclusionsWeaker striatal connectivity may be related to heightened familial risk for depression, primarily driven by maternal history. Identifying brain-based markers of depression risk in youths can inform approaches to improving early detection, diagnosis, and treatment.

Heart rate variability covaries with amygdala functional connectivity during voluntary emotion regulation

The Neurovisceral Integration Model posits that shared neural networks support the effective regulation of emotions and heart rate, with heart rate variability (HRV) serving as an objective, peripheral index of prefrontal inhibitory control. Prior neuroimaging studies have predominantly examined both HRV and associated neural functional connectivity at rest, as opposed to contexts that require active emotion regulation. The present study sought to extend upon previous resting-state functional connectivity findings, examining task-related HRV and corresponding amygdala functional connectivity during a cognitive reappraisal task. Seventy adults (52 older and 18 younger adults, 18–84 years, 51% male) received instructions to cognitively reappraise negative affective images during functional MRI scanning. HRV measures were derived from a finger pulse signal throughout the scan. During the task, younger adults exhibited a significant inverse association between HRV and amygdala-medial prefrontal cortex (mPFC) functional connectivity, in which higher task-related HRV was correlated with weaker amygdala-mPFC coupling, whereas older adults displayed a slight positive, albeit non-significant correlation. Furthermore, voxelwise whole-brain functional connectivity analyses showed that higher task-based HRV was linked to weaker right amygdala-posterior cingulate cortex connectivity across older and younger adults, and in older adults, higher task-related HRV correlated positively with stronger right amygdala-right ventrolateral prefrontal cortex connectivity. Collectively, these findings highlight the importance of assessing HRV and neural functional connectivity during active regulatory contexts to further identify neural concomitants of HRV and adaptive emotion regulation.

Cover Image

The cover image is based on the Original Article Glutamate levels in the ventromedial prefrontal cortex and resting-state functional connectivity within reward circuits in alcohol-dependent patients by Yiting Hu et al.,https://doi.org/10.1111/adb.13272.

Prefrontal Cortex Hemodynamics and Functional Connectivity Changes during Performance Working Memory Tasks in Older Adults with Sleep Disorders

Older adults with sleep disorders (SDs) show impaired working memory abilities, and working memory processes are closely related to the prefrontal cortex (PFC). However, the neural mechanism of working memory impairment in older adults with SD remains unclear. This study aimed to investigate changes in PFC function among older adults with SD when carrying out the N-back task by functional near-infrared spectroscopy (fNIRS). A total of 37 older adults with SDs were enrolled in this study and matched with 37 healthy older adults by gender, age, and years of education. Changes in PFC function were observed by fNIRS when carrying out the N-back task. The accuracy on the 0-back and 2-back tasks in the SD group was significantly lower than that in the healthy controls (HC) group. The oxygenated hemoglobin (oxy-Hb) concentration of channel 8 which located in the dorsolateral prefrontal cortex (DLPFC) was significantly reduced in the SD group during the 2-back task, and the channel-to-channel connectivity between the PFC subregions was significantly decreased. These results suggest that patients with sleep disorders have a weak performance of working memory; indeed, the activation and functional connectivity in the prefrontal subregions were reduced in this study. This may provide new evidence for working memory impairment and brain function changes in elderly SDs.

Glutamate levels in the ventromedial prefrontal cortex and resting-state functional connectivity within reward circuits in alcohol-dependent patients.

Great progress has been made in understanding the neural mechanisms associated with alcohol-dependent (AD) patients. However, the interactions within the reward circuits of the patients need further exploration. Glutamatergic projections from the prefrontal cortex to some brain regions are present in the reward circuit. However, little is known about the potential implications of glutamate levels in the prefrontal cortex on abnormal interactions within reward circuits in AD patients. To determine the potential roles of reward circuits in drinking, we investigated differences in resting-state functional connectivity (RSFC) and multivariate Granger causality analysis between 20 AD patients and 20 healthy controls (HC). The neuroimaging findings were then correlated with clinical variables (alcohol use disorder identification test). The ventromedial prefrontal cortex (VmPFC) is believed to play a critical role in addiction disorders, and glutamatergic projections from the prefrontal cortex to several regions of the brain are present in reward circuits. Proton magnetic resonance spectroscopy was also performed to assess the difference in glutamate levels in VmPFC between AD patients and HC. The results showed that the strength of functional connectivity in the reward circuit was generally attenuated in AD patients, and the reciprocal enhancement of activity between the right insula, left thalamus and VmPFC was found to be significantly greater in AD patients. It is worth noting that although glutamate levels in the VmPFC did not show significant differences between the two groups, the level of glutamate in the VmPFC was significantly correlated with RSFC. We hope that the current findings will help us to develop new intervention models based on the important role of the VmPFC in AD.

Sleep fails to depotentiate amygdala-reactivity to negative emotional stimuli in youth with elevated symptoms of anxiety.

Sleep-related problems often precede escalating anxiety in early adolescence. Pushing beyond broad sleep-mental health associations and toward mechanistic theories of their interplay can inform etiological models of psychopathology. Recent studies suggest that sleep depotentiates neural (e.g., amygdala) reactivity during reexposure to negative emotional stimuli in adults. Persistent amygdala reactivity to negative experiences and poor sleep characterize anxiety, particularly at the transition to adolescence. We propose that sleep depotentiates amygdala reactivity in youth but fails to do so among youth with anxiety. Participants (n = 34; 18 males; age, mean [M] = 11.35, standard deviation [SD] = 2.00) recruited from the community and specialty anxiety clinics viewed valenced images (positive, negative, and neutral) across two fMRI sessions (Study, Test), separated by a 10-12-hour retention period of sleep or wake (randomized). Mixed linear models regressed basolateral amygdala (BLA) activation and BLA-medial prefrontal cortex (mPFC) functional connectivity to negative images on Time, Condition, and Anxiety Severity. There were greater reductions in BLA activations to negative target images from Study to Test in the Sleep Condition, which was blunted with higher anxiety (b = -0.065, z = -2.355, p = 0.019). No such sleep- or anxiety-related effects were observed for BLA-mPFC functional connectivity (ps > 0.05). Sleep supports depotentiation of amygdala reactivity to negative stimuli in youth, but this effect is blunted at higher levels of anxiety. Disruptions in sleep-related affective habituation may be a critical, modifiable driver of anxiety.

Resting-state connectivity and neural response to emotional images in patients with severe health anxiety: An fMRI study

BackgroundSevere health anxiety is a disorder characterized by a persistent preoccupation with one's health. In behavioral studies, biases in the processing of health-related stimuli (e.g., pictures, words) are consistently associated with health anxiety symptoms. The neural correlates of the observed behavioral abnormalities remain however poorly understood. MethodsIn this functional magnetic resonance imaging study, 22 treatment-seeking patients with severe health anxiety and 22 control participants performed a resting-state and a picture matching task. Immediately after the resting-state, participants completed a questionnaire quantifying their thoughts and feelings during rest along several dimensions. The picture task included images of health-related and neutral scenes and of disgusted and neutral faces. ResultsCompared to controls, patients with health anxiety showed increased functional connectivity in the dorsolateral prefrontal cortex within the left fronto-parietal resting-state network, which correlated positively with the self-reported thought dimensions of Self, Health Concern, and Thought Suppression. In the picture matching task, no significant group differences were found in the hypothesised regions (amygdala and insula) or at a whole-brain level in response to either health-related versus neural scenes or disgust versus neutral faces contrasts. LimitationsA relatively small sample size and that no information about patients declining to participate was obtained. ConclusionsOur findings suggest that behavioral biases in health anxiety may be related to aberrant left dorsolateral prefrontal cortex functional connectivity at rest. In contrast, the health anxiety patients did not show significant hyperactivations of amygdala and insula during processing of emotional stimuli, contrasting findings in other anxiety disorders.

Longitudinal investigation of executive function development employing task-based, teacher reports, and fNIRS multimethodology in 4- to 5-year-old children.

Increased focus on resting-state functional connectivity (rsFC) and the use and accessibility of functional near-infrared spectroscopy (fNIRS) have advanced knowledge on the interconnected nature of neural substrates underlying executive function (EF) development in adults and clinical populations. Less is known about the relationship between rsFC and developmental changes in EF during preschool years in typically developing children, a gap the present study addresses employing task-based assessment, teacher reports, and fNIRS multimethodology. This preregistered study contributes to our understanding of the neural basis of EF development longitudinally with 41 children ages 4-5. Changes in prefrontal cortex (PFC) rsFC utilizing fNIRS, EF measured with a common task-based assessment (Day-Night task), and teacher reports of behavior (BRIEF-P) were monitored over multiple timepoints: Initial Assessment, 72 h follow-up, 1 Month Follow-up, and 4 Month Follow-up. Measures of rsFC were strongly correlated 72h apart, providing evidence of high rsFC measurement reliability using fNIRS with preschool-aged children. PFC rsFC was positively correlated with performance on task-based and report-based EF assessments. Children's PFC functional connectivity at rest uniquely predicted later EF, controlling for verbal IQ, age, and sex. Functional connectivity at rest using fNIRS may potentially show the rapid changes in EF development in young children, not only neurophysiologically, but also as a correlate of task-based EF performance and ecologically-relevant teacher reports of EF in a classroom context.

Reduced subgenual cingulate–dorsolateral prefrontal connectivity as an electrophysiological marker for depression

Major Depressive Disorder (MDD) is a widespread mental illness that causes considerable suffering, and neuroimaging studies are trying to reduce this burden by developing biomarkers that can facilitate detection. Prior fMRI- and neurostimulation studies suggest that aberrant subgenual Anterior Cingulate (sgACC)—dorsolateral Prefrontal Cortex (DLPFC) functional connectivity is consistently present within MDD. Combining the need for reliable depression markers with the electroencephalogram’s (EEG) high clinical utility, we investigated whether aberrant EEG sgACC–DLPFC functional connectivity could serve as a marker for depression. Source-space Amplitude Envelope Correlations (AEC) of 20 MDD patients and 20 matched controls were contrasted using non-parametric permutation tests. In addition, extracted AEC values were used to (a) correlate with characteristics of depression and (b) train a Support Vector Machine (SVM) to determine sgACC–DLPFC connectivity’s discriminative power. FDR-thresholded statistical maps showed reduced sgACC–DLPFC AEC connectivity in MDD patients relative to controls. This diminished AEC connectivity is located in the beta-1 (13–17 Hz) band and is associated with patients’ lifetime number of depressive episodes. Using extracted sgACC–DLPFC AEC values, the SVM achieved a classification accuracy of 84.6% (80% sensitivity and 89.5% specificity) indicating that EEG sgACC–DLPFC connectivity has promise as a biomarker for MDD.

Aberrant prefrontal functional connectivity during verbal fluency test is associated with reading comprehension deficits in autism spectrum disorder: An fNIRS study.

Children with autism spectrum disorder (ASD) show marked difficulties in reading comprehension, a complex cognitive skill fundamental to successful daily functioning that is associated with core executive functions. However, the neurophysiological mechanisms underlying reading comprehension deficits in these children remain elusive. Twenty-one right-handed males with high-functioning ASD (mean age = 10.24 years) and 23 age-, IQ-, educational level-, sex- and handedness-matched typically developing (TD; mean age = 10.14 years) individuals underwent a reading comprehension test and the semantic verbal fluency test that tapped core executive functions underlying reading comprehension during concurrent prefrontal functional near-infrared spectroscopy (fNIRS) measurement. Participants’ information processing efficiency was also assessed. High-functioning ASD children exhibited general reading comprehension [main effect of group: F(1,40) = 7.58, p = 0.009], selective verbal fluency deficits [Group × category interaction: F(1,42) = 4.90, p = 0.032] and slower processing speed (t42 = 2.36, p = 0.023). Regarding the hemodynamics of the prefrontal cortex (PFC), although ASD individuals showed comparable patterns of PFC brain activation to their healthy counterparts, lower PFC intrahemispheric [main effect of group: F(1,42) = 11.36, p = 0.002] and interhemispheric [main effect of group: F(1,42) = 7.79, p = 0.008] functional connectivity were evident during the semantic verbal fluency test. At the whole-group level, poorer reading comprehension performance was associated with poorer performance in the semantic verbal fluency test (r42 = 0.508, p < 0.001). Moreover, poorer semantic verbal fluency test performance was associated with slower information processing speed (r42 = –0.312, p = 0.044), which is associated with reduced left medial PFC functional connectivity (r42 = –0.319, p = 0.040). Abnormal intrahemispheric and interhemispheric prefrontal hypoconnectivity is associated with deficits in executive processes essential for reading comprehension in ASD. Our study has provided important implications for the neuropsychological and neurophysiological mechanisms underlying reading comprehension deficits in ASD.

Cingulate-Prefrontal Connectivity During Dynamic Cognitive Control Mediates Association Between p Factor and Adaptive Functioning in a Transdiagnostic Pediatric Sample

BackgroundCovariation among psychiatric symptoms is being actively pursued for transdiagnostic dimensions of psychopathology with predictive utility. A superordinate dimension, the p factor, reflects overall psychopathology burden and has support from genetic and neuroimaging correlates. However, the neurocognitive correlates that link an elevated p factor to maladaptive outcomes are unknown. We tested the mediating potential of dynamic adjustments in cognitive control rooted in functional connections anchored by the dorsal anterior cingulate cortex (dACC) in a transdiagnostic pediatric sample. MethodsA multiple mediation model tested the association between the p factor (derived by principal component analysis of Child Behavior Checklist syndrome scales) and outcome measured with the Vineland Adaptive Behavior Scale-II in 89 children ages 8 to 13 years (23 female) with a variety of primary neurodevelopmental diagnoses who underwent functional magnetic resonance imaging during a socioaffective Stroop-like task with eye gaze as distractor. Mediators included functional connectivity of frontoparietal- and salience network–affiliated dACC seeds during conflict adaptation. ResultsHigher p factor scores were related to worse adaptive functioning. This effect was partially mediated by conflict adaptation–dependent functional connectivity between the frontoparietal network–affiliated dACC seed and the right dorsolateral prefrontal cortex. Post hoc follow-up indicated that the p factor was related to all Vineland Adaptive Behaviors Scale-II domains; the association was strongest for socialization followed by daily living skills and then communication. Mediation results remained significant for socialization only. ConclusionsHigher psychopathology burden was associated with worse adaptive functioning in early adolescence. This association was mediated by weaker dACC–dorsolateral prefrontal cortex functional connectivity underlying modulation of cognitive control in response to contextual contingencies. Our results contribute to the identification of transdiagnostic and developmentally relevant neurocognitive endophenotypes of psychopathology.

Early life stress, systemic inflammation, and neural correlates of implicit emotion regulation in adolescents

Exposure to early life stress (ELS) increases the risk for developing psychopathology; however, the mechanisms underlying this association are not clear. In this study we examined systemic inflammation as a pathway that may link exposure to stress to altered neural correlates of implicit emotion regulation in adolescents with varying levels of exposure to ELS (n = 83; 52 females, 31 males; 15.63 ± 1.10 years). We measured ventrolateral prefrontal cortex (vlPFC) activation and functional connectivity (FC) between the bilateral amygdala and the vlPFC as adolescents completed an affect labeling task in the scanner and assessed concentrations of C-reactive protein (CRP) using a dried blood spot protocol. We found that CRP levels were negatively associated with vlPFC activation during implicit regulation of negatively-valenced stimuli, and that cumulative severity of ELS exposure moderated this neuroimmune association. Severity of ELS also significantly moderated the association between CRP levels and FC between the bilateral amygdala and l-vlPFC during implicit emotion regulation: in adolescents who had been exposed to more severe ELS, higher CRP was associated with more negative frontoamygdala FC during implicit regulation of negatively-valenced stimuli. Thus, ELS may disrupt the normative association between the immune system and the neural processes that underlie socioemotional functioning potentially increasing adolescents’ risk for maladaptive outcomes.