Bilateral Ventrolateral Prefrontal Cortex Research Articles

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.

Frontostriatal circuitry and the tryptophan kynurenine pathway in major psychiatric disorders.

An imbalance of the tryptophan kynurenine pathway (KP) commonly occurs in psychiatric disorders, though the neurocognitive and network-level effects of this aberration are unclear. In this study, we examined the connection between dysfunction in the frontostriatal brain circuits, imbalances in the tryptophan kynurenine pathway (KP), and neurocognition in major psychiatric disorders. Forty first-episode medication-naive patients with schizophrenia (SCZ), fifty patients with bipolar disorder (BD), fifty patients with major depressive disorder (MDD), and forty-two healthy controls underwent resting-state functional magnetic resonance imaging. Plasma levels of KP metabolites were measured, and neurocognitive function was evaluated. Frontostriatal connectivity and KP metabolites were compared between groups while controlling for demographic and clinical characteristics. Canonical correlation analyses were conducted to explore multidimensional relationships between frontostriatal circuits-KP and KP-cognitive features. Patient groups shared hypoconnectivity between bilateral ventrolateral prefrontal cortex (vlPFC) and left insula, with disorder-specific dysconnectivity in SCZ related to PFC, left dorsal striatum hypoconnectivity. The BD group had higher anthranilic acid and lower xanthurenic acid levels than the other groups. KP metabolites and ratios related to disrupted frontostriatal dysconnectivity in a transdiagnostic manner. The SCZ group and MDD group separately had high-dimensional associations between KP metabolites and cognitive measures. The findings suggest that KP may influence cognitive performance across psychiatric conditions via frontostriatal dysfunction.

Differentiating people with schizophrenia from healthy controls in a developing Country: An evaluation of portable functional near infrared spectroscopy (fNIRS) as an adjunct diagnostic tool.

This study aimed to evaluate portable functional near-infrared spectroscopy (fNIRS) device as an adjunct diagnostic tool in Vietnam to assess hemodynamics when people with schizophrenia and healthy controls performed cognitive tasks. One hundred fifty-seven participants were divided into schizophrenia (n = 110) and healthy controls group (n = 47), which were recruited by match of age, and gender. Hemodynamic responses in the frontal cortex were monitored with a 48-channel portable device during the Stroop Color-Word Test (SCWT) and Verbal Fluency Test (VFT). General linear model compared the differences in oxyhemoglobin (HbO2) levels between the two groups. The Receiver Operating Characteristic (ROC) graph was generated for each neuroanatomical area. People with schizophrenia did not show significant activation in the frontal lobe during the SCWT and VFT as compared to pre-task. During the VFT, the area under the ROC curve of the bilateral dorsolateral prefrontal cortex, bilateral orbitofrontal cortex, bilateral frontopolar prefrontal cortex, and bilateral ventrolateral prefrontal cortex were greater than 0.7 (p < 0.001). The area under the ROC curve (AUC) for the right orbitofrontal cortex was maximal during the VFT (AUC = 0.802, 95%CI = 0.731-0.872). The Youden's index reached a peak (0.57) at the optimal cut-point value (HbO2 cutoff <0.209 μmol/ml for schizophrenia) in which the sensitivity was 85%; specificity was 72%; positive predictive value (PPV) was 0.88; negative predictive value (NPV) was 0.68 and correct classification rate was 76%. Assessing hemodynamics during VFT by portable fNIRS offers the potential as an adjunct diagnostic tool for schizophrenia in developing countries.

The impact of visual cross-modal conflict with semantic and nonsemantic distractors on working memory task: A functional near-infrared spectroscopy study.

Cross-modal conflicts arise when information from multisensory modalities is incongruent. Most previous studies investigating audiovisual cross-modal conflicts have focused on visual targets with auditory distractors, and only a few studies have focused on auditory targets with visual distractors. Moreover, no study has investigated the differences in the impact of visual cross-modal conflict with semantic and nonsemantic competition and its neural basis. This cross-sectional study aimed to characterize the impact of 2 types of visual cross-modal conflicts with semantic and nonsemantic distractors through a working memory task and associated brain activities. The participants were 33 healthy, right-handed, young male adults. The paced auditory serial addition test was performed under 3 conditions: no-distractor and 2 types of visual distractor conditions (nonsemantic and semantic distractor conditions). Symbols and numbers were used as nonsemantic and semantic distractors, respectively. The oxygenated hemoglobin (Oxy-Hb) concentration in the frontoparietal regions, bilateral ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex, and inferior parietal cortex (IPC) were measured during the task under each condition. The results showed significantly lower paced auditory serial addition test performances in both distractor conditions than in the no-distractor condition, but no significant difference between the 2 distractor conditions. For brain activity, a significantly increased Oxy-Hb concentration in the right VLPFC was only observed in the nonsemantic distractor condition (corrected P = .015; Cohen d = .46). The changes in Oxy-Hb in the bilateral IPC were positively correlated with changes in task performance for both types of visual cross-modal distractor conditions. Visual cross-modal conflict significantly impairs auditory working memory task performance, regardless of the presence of semantic or nonsemantic distractors. The right VLPFC may be a crucial region to inhibit visual nonsemantic information in cross-modal conflict situations, and bilateral IPC may be closely linked with the inhibition of visual cross-modal distractor, regardless of the presence of semantic or nonsemantic distractors.

Percentage amplitude of fluctuation and structural covariance changes of subjective cognitive decline in patients: A multimodal imaging study.

Back groundSubjective cognitive decline (SCD) may be the first clinical sign of Alzheimer’s disease (AD). The possible neural mechanisms of SCD are not well known. This study aimed to compare percent amplitude of fluctuation (PerAF) and structural covariance patterns in patients with SCD and healthy controls (HCs).MethodsWe enrolled 53 patients with SCD and 65 HCs. Resting-state functional magnetic resonance imaging (MRI) data and T1-weighted anatomical brain 3.0-T MRI scans were collected. The PerAF approach was applied to distinguish altered brain functions between the two groups. A whole-brain voxel-based morphometry analysis was performed, and all significant regions were selected as regions of interest (ROIs) for the structural covariance analysis. Statistical analysis was performed using two-sample t-tests, and multiple regressions were applied to examine the relationships between neuroimaging findings and clinical symptoms.ResultsFunctional MRI results revealed significantly increased PerAF including the right hippocampus (HIPP) and right thalamus (THA) in patients with SCD relative to HCs. Gray matter volume (GMV) results demonstrated decreased GMV in the bilateral ventrolateral prefrontal cortex (vlPFC) and right insula in patients with SCD relative to HCs. Taking these three areas including the bilateral vlPFC and right insula as ROIs, differences were observed in the structural covariance of the ROIs with several regions between the two groups. Additionally, significant correlations were observed between neuroimaging findings and clinical symptoms.ConclusionOur study investigated the abnormal PerAF and structural covariance patterns in patients with SCD, which might provide new insights into the pathological mechanisms of SCD.

Different Roles of the Left and Right Ventrolateral Prefrontal Cortex in Cognitive Reappraisal: An Online Transcranial Magnetic Stimulation Study.

The ventrolateral prefrontal cortex (VLPFC) plays a pivotal role in cognitive reappraisal. Previous studies suggested a functional asymmetry of the bilateral VLPFC, but the evidence is still insufficient during cognitive reappraisal. In this study, we conducted an online single-pulse transcranial magnetic stimulation (spTMS) to investigate the causal and distinct roles of the left and right VLPFC in reappraisal. Participants were instructed to reappraise (down-regulate) or attend to pictures depicting social exclusion scenarios while the spTMS was applied over the left or right VLPFC of the participants’ brains. The results showed that spTMS of either the left or the right VLPFC would increase reappraisal difficulty. Meanwhile, the outcome of reappraisal (measured by self-reported negative feelings) significantly deteriorated when the right (but not the left) VLPFC was temporally interrupted by spTMS, while the verbal fluency during oral reporting of the reappraisal strategy was significantly reduced when the left VLPFC was interrupted by spTMS. Taken together, these findings provide causal evidence for the involvement of left and right VLPFC with distinct roles: while the left VLPFC is responsible for the linguistic especially semantic process of generating and selecting appraisals according to the goal of emotion regulation, the right VLPFC plays a critical role in inhibiting inappropriate negative emotions and thoughts generated by the effective scenarios. These findings deepen our understanding of the neurocognitive mechanism of emotion regulation.

Symptom Profiles, But Not Prefrontal Neurochemistry, Differentiate ADHD Youth With and Without a Family History of Bipolar I Disorder

Objective: To identify clinical and central features that differentiate ADHD youth with and without familial risk for bipolar I disorder (BD). Methods: Psychostimulant-free ADHD youth (10–18 years) with and without a first-degree relative with BD and healthy controls were enrolled. Bilateral ventrolateral prefrontal cortex (VLPFC) proton magnetic resonance spectroscopy (1H MRS) scans and a range of symptom ratings were performed. Results: A total of n = 145 youth were enrolled. ADHD youth with a family history of BD exhibited greater manic and depressive symptom severity, ADHD hyperactivity/impulsive symptom severity, and higher parent-reported ratings of dysregulation compared with ADHD youth without a BD family history. Although VLPFC metabolite levels did not differ across groups, choline levels in the left VLPFC correlated with different symptom ratings. Conclusion: Symptom profiles including more severe mood and externalizing symptoms, but not VLPFC neurochemistry, differentiate psychostimulant-free ADHD youth with and without a family history of BD.

Frontal asymmetry as a core feature of major depression: a functional near-infrared spectroscopy study.

Background:Frontal asymmetry plays a major role in depression. However, patients with treatment-resistant depression (TRD) have widespread hypofrontality. We investigated whether patients with TRD have a characteristic frontal activation pattern in functional near-infrared spectroscopy (fNIRS) findings and how the frontal cortex responds to different levels of cognitive tasks.Methods:We enrolled 27 right-handed patients with TRD, 27 patients without TRD and 27 healthy controls. We used multichannel fNIRS to evaluate activation of the bilateral dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and left motor area in response to 3 tasks: finger tapping, a low cognitive–load motor task; verbal fluency, a moderate cognitive–load task; and a dual task involving simultaneous finger tapping and verbal fluency, a high cognitive–load task.Results:We found significant between-group differences in left DLPFC activation for all 3 tasks. The healthy controls had cortical activation in the left motor area during finger tapping and the bilateral frontal cortex during the dual task. However, patients without TRD had right VLPFC activation during finger tapping and left DLPFC activation during the dual task. Patients with TRD had bilateral DLPFC activation during finger tapping but exhibited increased bilateral VLPFC and left motor area activation during verbal fluency and increased left motor area activation during the dual task. In healthy controls and patients without TRD, we found that the right VLPFC was positively correlated with depression severity.Limitations:Our cohort included only patients with late-onset depression.Conclusion:We found different patterns of abnormal frontal activation between patients with and without TRD. In patients without TRD, the right prefrontal cortex (PFC) was recruited during simple motor tasks. However, in patients with TRD, the bilateral PFC was recruited during simple tasks and motor cortical resources were used compensatorily during PFC-demanding complex cognitive tasks.

Hemodynamic changes in the right ventrolateral prefrontal cortex relate to the psychological mood profile

Previous reports indicate that the right ventrolateral prefrontal cortex (VLPFC) is involved in emotional regulation. However, most such studies were performed under unphysiological conditions, like the administration of transcranial direct current or repetitive transcranial magnetic stimulation. We have shown that the right VLPFC is stimulated by an acute bout of daily activity, such as cleaning. Here, we investigated the relationship between the right VLPFC and mood changes using this system. Fourteen young adults vacuumed a floor as a cleaning task and kept a standing position as a control task on separate days. The oxyhemoglobin (oxy-Hb) and deoxy-hemoglobin (deoxy-Hb) signals of the prefrontal cortex were measured during the tasks. The mood scale scores of Profile of Mood States 2nd edition (POMS) and Two-Dimensional Mood Scale (TDMS) were measured before and after both tasks. The differences in subscale scores between pre- and post-tasks in both scales were calculated as ΔPOMS and ΔTDMS. The cleaning task significantly increased the oxy-Hb signal in the bilateral VLPFC and right frontopolar, but did not affect the deoxy-Hb signals. The control task significantly decreased the oxy-Hb signal in some brain regions. The Confusion–Bewilderment score in POMS changed after the cleaning task. Importantly, the oxy-Hb signal in the right VLPFC was negatively correlated with the ΔPOMS Confusion–Bewilderment score. The activity of the right VLPFC stimulated by the cleaning task might have a correlation with the Confusion–Bewilderment mood state.

Effect of Audiovisual Cross-Modal Conflict during Working Memory Tasks: A Near-Infrared Spectroscopy Study.

Cognitive conflict effects are well characterized within unimodality. However, little is known about cross-modal conflicts and their neural bases. This study characterizes the two types of visual and auditory cross-modal conflicts through working memory tasks and brain activities. The participants consisted of 31 healthy, right-handed, young male adults. The Paced Auditory Serial Addition Test (PASAT) and the Paced Visual Serial Addition Test (PVSAT) were performed under distractor and no distractor conditions. Distractor conditions comprised two conditions in which either the PASAT or PVSAT was the target task, and the other was used as a distractor stimulus. Additionally, oxygenated hemoglobin (Oxy-Hb) concentration changes in the frontoparietal regions were measured during tasks. The results showed significantly lower PASAT performance under distractor conditions than under no distractor conditions, but not in the PVSAT. Oxy-Hb changes in the bilateral ventrolateral prefrontal cortex (VLPFC) and inferior parietal cortex (IPC) significantly increased in the PASAT with distractor compared with no distractor conditions, but not in the PVSAT. Furthermore, there were significant positive correlations between Δtask performance accuracy and ΔOxy-Hb in the bilateral IPC only in the PASAT. Visual cross-modal conflict significantly impairs auditory task performance, and bilateral VLPFC and IPC are key regions in inhibiting visual cross-modal distractors.

Alterations of Regional Homogeneity in Children With Congenital Sensorineural Hearing Loss: A Resting-State fMRI Study.

Background: Brain functional alterations have been observed in children with congenital sensorineural hearing loss (CSNHL). The purpose of this study was to assess the alterations of regional homogeneity in children with CSNHL.Methods: Forty-five children with CSNHL and 20 healthy controls were enrolled into this study. Brain resting-state functional MRI (rs-fMRI) for regional homogeneity including the Kendall coefficient consistency (KCC-ReHo) and the coherence-based parameter (Cohe-ReHo) was analyzed and compared between the two groups, i.e., the CSNHL group and the healthy control group.Results: Compared to the healthy controls, children with CSNHL showed increased Cohe-ReHo values in left calcarine and decreased values in bilateral ventrolateral prefrontal cortex (VLPFC) and right dorsolateral prefrontal cortex (DLPFC). Children with CSNHL also had increased KCC-ReHo values in the left calcarine, cuneus, precentral gyrus, and right superior parietal lobule (SPL) and decreased values in the left VLPFC and right DLPFC. Correlations were detected between the ReHo values and age of the children with CSNHL. There were positive correlations between ReHo values in the pre-cuneus/pre-frontal cortex and age (p < 0.05). There were negative correlations between ReHo values in bilateral temporal lobes, fusiform gyrus, parahippocampal gyrus and precentral gyrus, and age (p < 0.05).Conclusion: Children with CSNHL had RoHo alterations in the auditory, visual, motor, and other related brain cortices as compared to the healthy controls with normal hearing. There were significant correlations between ReHo values and age in brain regions involved in information integration and processing. Our study showed promising data using rs-fMRI ReHo parameters to assess brain functional alterations in children with CSNHL.

Ventrolateral prefrontal hemodynamic responses in autism spectrum disorder with and without depression.

In clinical settings, autism spectrum disorder (ASD) with comorbid depression is often difficult to diagnose, and should be considered in treatment. However, to our knowledge, no functional imaging study has examined the difference between ASD adolescents with and without comorbid depression. We aimed to compare the characteristics and prefrontal brain function of ASD with and without depression in order to identify a biological marker that can be used to detect the difference. Twenty-eight drug-naïve adolescents with ASD (14 ASD with and 14 ASD without depression) and 14 age- and gender-matched adolescents with typical development were evaluated using several variables. These included intelligence quotient, autism quotient, depression severity using the Beck Depression Inventory 2nd edition (BDI-II), and level of social functioning using the Social Adaptation Self-evaluation Scale (SASS). In addition, frontotemporal hemodynamic responses during a verbal fluency task (VFT) were measured using functional near-infrared spectroscopy (fNIRS). The ASD group, including both of the ASD with and ASD without depression groups, showed smaller hemodynamic responses than the typical development group in portions of the left dorsolateral prefrontal cortex (DLPFC), bilateral ventrolateral prefrontal cortex (VLPFC) and anterior part of the temporal cortex (aTC) during the VFT. Moreover, the smaller hemodynamic responses in the right VLPFC during the VFT in the ASD group were associated with the worse BDI-II and SASS scores. Furthermore, the ASD with depression group showed smaller hemodynamic responses in the right VLPFC during the VFT than the ASD without depression group in a direct comparison. Adolescents with ASD showed reduced activation in broad frontotemporal regions during a cognitive task compared with those with typical development. More specifically, the right VLPFC activation reflected the level of self-estimated depression and social functioning in the ASD subjects, and could be used to discriminate between ASD adolescents with and without depression.

FNIRS Evidence for Distinguishing Patients With Major Depression and Healthy Controls.

In recent years, major depressive disorder (MDD) has been shown to negatively impact physical recovery in a variety of patients. Functional near-infrared spectroscopy (fNIRS) is a tool that can potentially supplement clinical interviews and mental state examinations to establish a psychiatric diagnosis and monitor treatment progress. Thirty-two subjects, including 16 patients clinically diagnosed with MDD and 16 healthy controls (HCs), participated in the study. Brain oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) responses were recorded using a 22-channel continuous-wave fNIRS device while the subjects performed the emotional sound test. This study evaluated the difference between MDD patients and HCs using a variety of methods. In a comparison of the Pearson correlation coefficients between the HbO/HbR responses of each fNIRS channel and four scores, MDD patients and HCs had significantly different Athens Insomnia Scale (AIS) scores. By quantitative evaluation of the functional association, we found that MDD patients had aberrant functional connectivity compared with HCs. Furthermore, we concluded that compared with HCs, there were marked abnormalities in blood oxygen in the bilateral ventrolateral prefrontal cortex (VLPFC) and bilateral dorsolateral prefrontal cortex (DLPFC). Four statistical-based features extracted from HbO signals and four vector-based features from both HbO and HbR served as inputs to four simple neural networks (multilayer neural network (MNN), feedforward neural network (FNN), cascade forward neural network (CFNN) and recurrent neural network (RNN)). Through an analysis of combinations of different features, the combination of 4 common features (mean, STD, area under the receiver operating characteristic curve (AUC) and slope) yielded the highest classification accuracy of 89.74% for fear emotion. The combination of four novel feature (CBV, COE, |L | and K) resulted in a classification accuracy of 99.94% for fear emotion. The top 10 common and novel features were selected by the ReliefF feature selection algorithm, resulting in classification accuracies of 83.52% and 91.99%, respectively. This study identified the AUC and angle K as specific neuromarkers for predicting MDD across specific depression-related regions of the prefrontal cortex (PFC). These findings suggest that the fNIRS measurement of the PFC may serve as a supplementary test in routine clinical practice to further support a diagnosis of MDD.

Differentiating between bipolar and unipolar depression using prefrontal activation patterns: Promising results from functional near infrared spectroscopy (fNIRS) findings

BackgroundBipolar depression (BD) is a unique, severe and prevalent mental illness that shares many similarities in symptoms with unipolar depression (UD). Improving precision of their diagnoses would enhance treatment outcome and prognosis for both conditions. This study aims to provide evidence from functional Near-Infrared Spectroscopy (fNIRS) as a potential tool to differentiate UD and BD based on their differences in hemodynamic change in the prefrontal cortex during verbal fluency tasks (VFT). MethodsWe enrolled 179 participants with clinically confirmed diagnoses, including 69 UD patients, 68 BD patients and 42 healthy controls(HC). Every participant was assessed using a 45-channel fNIRS and various clinical scales. FindingsCompared with HC, region-specific fNIR leads show UD patients had significant lower hemodynamic activation in 4 particular pre-frontal regions: 1) the left dorsolateral prefrontal cortex (DLPFC), 2) orbitofrontal cortex (OFC), 3) bilateral ventrolateral prefrontal cortex (VLPFC) and 4) left inferior frontal gyrus (IFG). In contrast, BD vs. HC comparisons showed only significant lower hemodynamic activation in the LIFG area. Furthermore, compared to BD patients, UD patients showed decreased hemodynamic activation changes in the VLPFC region. ConclusionOur results show significant frontal lobe activation pattern differences between UD and BD groups. fNIRS can be a potential tool to increase diagnostic precision for these conditions. In particular, the VLPFC area holds promise to be a useful site for such differentiation for further investigations.

Effects of Fish Oil Monotherapy on Depression and Prefrontal Neurochemistry in Adolescents at High Risk for Bipolar I Disorder: A 12-Week Placebo-Controlled Proton Magnetic Resonance Spectroscopy Trial.

Objectives: To evaluate the clinical and neurochemical effects of 12-week fish oil, a source of omega-3 polyunsaturated fatty acids (n-3 PUFAs), in depressed adolescents with a family history of bipolar I disorder. Methods: Adolescents with a current Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision diagnosis of Major Depressive Disorder or Depressive Disorder not otherwise specified, a Childhood Depression Rating Scale-Revised (CDRS-R) Version raw score of ≥40, and at least one biological parent with bipolar I disorder were randomized to double-blind treatment with fish oil (2100 mg/day) or placebo for 12 weeks. The primary outcome measure was change in CDRS-R total score, and secondary outcomes measures were change in manic symptoms (Young Mania Rating Scale), global symptom and functioning measures (Clinical Global Impression-Severity [CGI-S] /CGI Improvement [CGI-I], Children's Global Assessment Scale, and Child Behavior Checklist), safety and laboratory measures, and anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex neurometabolite concentrations using proton magnetic resonance spectroscopy at 4 T. Results: Fifty-six patients were randomized, and 42 completed the 12-week trial (placebo: n = 21; fish oil, n = 21). Subjects randomized to fish oil, but not placebo, exhibited a significant baseline to endpoint increase in erythrocyte n-3 PUFAs. Reductions in CDRS-R scores did not differ between treatment groups (p = 0.15), and similar remission (p = 0.58) and response (p = 0.77) rates were observed. Fish oil produced a significantly greater decrease in CGI-S (p = 0.0042) and CGI-I (p = 0.036) scores compared with placebo. Baseline to endpoint change in ACC creatine (p = 0.004) and ACC choline (Cho) (p = 0.024) differed significantly between groups. Baseline ACC Cho levels were inversely correlated with baseline and baseline to endpoint change in CDRS-R scores, and baseline to endpoint change in ACC Cho correlated with baseline-endpoint change in CDRS-R scores and n-3 PUFA. There were no group differences in safety and tolerability ratings or laboratory measures. Conclusions: Fish oil monotherapy was not superior to placebo for reducing depressive symptoms in high-risk youth as assessed by the CDRS-R, but was safe and well tolerated and superior to placebo on clinician ratings of global symptom improvement. Associations among ACC Cho levels, depression symptom severity, and n-3 PUFA warrant additional investigation.

Individual prediction of symptomatic converters in youth offspring of bipolar parents using proton magnetic resonance spectroscopy.

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (1H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time. Baseline 1H-MRS data were obtained from anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex (VLPFC). Glutamate (Glu), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and phosphocreatine plus creatine (PCr + Cr) levels were calculated. SVM with a linear kernel was adopted to classify converters and non-converters based on their baseline metabolites. SVM allowed the significant classification of converters and non-converters across all regions for Cho (accuracy = 76.0%), but not for other metabolites. Considering all metabolites within each region, SVM allowed the significant classification of converters and non-converters for left VLPFC (accuracy = 76.5%), but not for right VLPFC or ACC. The combined mI, PCr + Cr, and Cho from left VLPFC achieved the highest accuracy differentiating converters from non-converters (79.0%). Our findings from this exploratory study suggested that 1H-MRS levels of mI, Cho, and PCr + Cr from left VLPFC might be useful to predict the development of first mood episode in youth bipolar offspring using machine learning. Future studies that prospectively examine and validate these metabolites as predictors of mood episodes in high-risk individuals are necessary.

Association of Residents' Neural Signatures With Stress Resilience During Surgery

Intraoperative stressors may compound cognitive load, prompting performance decline and threatening patient safety. However, not all surgeons cope equally well with stress, and the disparity between performance stability and decline under high cognitive demand may be characterized by differences in activation within brain areas associated with attention and concentration such as the prefrontal cortex (PFC). To compare PFC activation between surgeons demonstrating stable performance under temporal stress with those exhibiting stress-related performance decline. Cohort study conducted from July 2015 to September 2016 at the Imperial College Healthcare National Health Service Trust, England. One hundred two surgical residents (postgraduate year 1 and greater) were invited to participate, of which 33 agreed to partake. Participants performed a laparoscopic suturing task under 2 conditions: self-paced (SP; without time-per-knot restrictions), and time pressure (TP; 2-minute per knot time restriction). A composite deterioration score was computed based on between-condition differences in task performance metrics (task progression score [arbitrary units], error score [millimeters], leak volume [milliliters], and knot tensile strength [newtons]). Based on the composite score, quartiles were computed reflecting performance stability (quartile 1 [Q1]) and decline (quartile 4 [Q4]). Changes in PFC oxygenated hemoglobin concentration (HbO2) measured at 24 different locations using functional near-infrared spectroscopy were compared between Q1 and Q4. Secondary outcomes included subjective workload (Surgical Task Load Index) and heart rate. Of the 33 participants, the median age was 33 years, the range was 29 to 56 years, and 27 were men (82%). The Q1 residents demonstrated task-induced increases in HbO2 across the bilateral ventrolateral PFC (VLPFC) and right dorsolateral PFC in the SP condition and in the VLPFC in the TP condition. In contrast, Q4 residents demonstrated decreases in HbO2 in both conditions. The magnitude of PFC activation (change in HbO2) was significantly greater in Q1 than Q4 across the bilateral VLPFC during both SP (mean [SD] left VLPFC: Q1, 0.44 [1.30] μM; Q4, -0.21 [2.05] μM; P < .001; right VLPFC: Q1, 0.46 [1.12] μM; Q4, -0.15 [2.14] μM; P < .001) and TP (mean [SD] left VLPFC: Q1, 0.44 [1.36] μM; Q4, -0.03 [1.83] μM; P = .001; right VLPFC: Q1, 0.49 [1.70] μM; Q4, -0.32 [2.00] μM; P < .001) conditions. There were no significant between-group differences in Surgical Task Load Index or heart rate in either condition. Performance stability within TP is associated with sustained prefrontal activation indicative of preserved attention and concentration, whereas performance decline is associated with prefrontal deactivation that may represent task disengagement.

Neurophysiological effects of multiple mood episodes in bipolar disorder.

Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. First- and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel (1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; (1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from (1 H)MRS were compared across bipolar groups. Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects. Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions.

Traditional medicine for antipsychotic drugs induced constipation: a bibliometric analysis of clinical studies

In people with psychoses, Self-Reflectiveness may rely on the right ventrolateral prefrontal cortex (VLPFC). We used functional magnetic resonance imaging (fMRI) and a novel virtual reality paradigm to evaluate the role of the VLPFC for Self-Reflectiveness in 25 first-episode of schizophrenia (FES) participants and 24 controls. Participants first viewed 20 characters each paired with a unique object/location, and later completed source memory judgements during fMRI scanning. Self-Reflectiveness, measured with the Beck Cognitive Insight Scale, was significantly and positively correlated to activation in bilateral VLPFC in FES, but not in controls, providing further evidence that the VLPFC supports Self-Reflectiveness in FES.

Ventral attention-network effective connectivity predicts individual differences in adolescent depression

BackgroundStimulus-driven negative attention bias is a central deficit in depression and might play an important role in vulnerability to depression Adolescents are susceptible to depression. Thus, investigating the neural correlates of attention bias in adolescents is a critical step for identifying neural markers of early onset of depression. Previous studies have shown that the ventral attention network (VAN), which includes bilateral ventrolateral prefrontal cortex (VLPFC) and bilateral temporal-parietal junction (TPJ), is the key brain network for stimulus-driven attention. However, the relationship between depression and effective connectivity within the VAN in adolescents is poorly understood. MethodWe employed resting-state fMRI to assess the relationship between directional effective connectivity within the VAN and depression scores in 216 healthy adolescents. ResultsUsing stochastic dynamic modeling, we found that individuals who exhibited higher self-reported depression showed stronger effective connectivity between right VLPFC and left TPJ within the VAN. LimitationThe level of depression in this study was assessed with self-reported questionnaire. This measure might be more influenced by current mood in adolescents than that in adults. Future studies should emplo more objective measures to index levels of depression. ConclusionsOur findings indicate that effective connectivity between right VLPFC and left TPJ could at least partially serve as a biomarker for bottom-up processing of depression in adolescents.