Dorsolateral Prefrontal Regions Research Articles

Eye of the beholder: Neural synchrony of dynamically changing relations between parent praise and child affect.

In this study, we aimed to determine the role of parental praise and child affect in the neural processes underlying parent-child interactions, utilizing functional near-infrared spectroscopy (fNIRS) hyperscanning. We characterized the dynamic changes in interpersonal neural synchrony (INS) between parents and children (4-6 years old, n=40 dyads) during a cognitively challenging task. We then examined how changes in parent-child INS are influenced by parental feedback and child affect. Parent-child INS showed a quadratic change over time, indicating a decelerated decline during the interaction period. The relationship of parental praise, in the form of positive feedback, to change in INS was contingent upon the child's positive affect during the task. The highest levels of INS were observed when praise was present and child affect was positive. The left temporo-parietal regions of the child and the right dorsolateral prefrontal and right temporo-parietal regions of the parent demonstrated the strongest INS. The dynamic change in INS during the interaction was associated with children's independent performance on a standardized test of visuospatial processing. This research, leveraging fNIRS hyperscanning, elucidates the neural dynamics underlying the interaction between parent praise and child positive affect, thereby contributing to our broader understanding of parent-child dynamics. RESEARCH HIGHLIGHTS: The level of interpersonal neural synchrony between parents and children dynamically varies during a cognitively challenging (tangram) task. The left temporo-parietal regions of the child and the right dorsolateral prefrontal and right temporo-parietal regions of the parent demonstrate the strongest parent-child neural synchrony. The relationship between parental praise (positive feedback) and parent-child neural synchrony is contingent upon child positive affect during the task. Change in parent-child neural synchrony relates to children's performance on an independent visuospatial processing measure.

Unraveling the Prefrontal Cortex-Basolateral Amygdala Pathway's Role on Schizophrenia's Cognitive Impairments: A Multimodal Study in Patients and Mouse Models.

This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA. Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients. Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method.

Association between intra-individual variability and prefrontal cortex activity measured by functional Near Infrared Spectroscopy (fNIRS) in children with ADHD

ABSTRACT This study uses fNIRS to determine whether there is a difference in the relationship between intra-individual variability and frontal lobe activity between ADHD patients and typically developing children. A total of 28 subjects (14 in ADHD patient group and 14 in control group) participated in this study. The subjects were tested for K-SADS and intelligence, and then the frontal lobe activity of the subjects was measured by continuous performance test, using functional near-infrared spectroscopy (NIRSIT). Processing speed index was significantly lower in the ADHD patient group than in the control group (p = .04). The CPT test results showed a positive correlation in the activity of the right dorsolateral prefrontal region in the patient group, but not at a statistically significant level. In the control group, activity showed a significant level of negative correlation with commission and hit reaction time standard deviation (p = .023; p = .063 respectively). In contrary to ADHD patient group, activation of the right dorsolateral prefrontal area was significantly correlated with reduction of intra-individual variability. This result showing that the relationship between activation of the right dorsolateral prefrontal area of the ADHD patient group and intra-individual variability shows a different pattern from typically developing children.

Neuroregulatory Effects of Microcone Patch Stimulation on the Auricular Branch of the Vagus Nerve and the Prefrontal Cortex: A Feasibility Study.

Background: The primary purpose of this study was to preliminarily examine the effects of autonomic nervous system activity on the dorsolateral prefrontal cortex. Recent studies have examined approaches to modulating autonomic activity using invasive and non-invasive methods, but the effects of changes in autonomic activity during cognitive tasks on the dorsolateral prefrontal cortex have not been fully investigated. The purpose of this preliminary investigation was to examine changes in autonomic activity and blood oxygen saturation in the dorsolateral prefrontal cortex during reading tasks induced by vagus nerve stimulation using a microcone patch. Methods: A cohort of 40 typically developing adults was enrolled in this study. We carefully examined changes in autonomic nervous system activity and blood oxygen saturation in the dorsolateral prefrontal cortex during a reading task in two conditions: with and without microcone patch stimulation. Results: Significant changes in brain activation in the dorsolateral prefrontal cortext due to microcone patch stimulation were confirmed. In addition, hierarchical multiple regression analysis revealed specific changes in reading task-related blood oxygen saturation in the dorsolateral prefrontal region during microcone patch stimulation. Conclusions: It should be recognized that this study is a preliminary investigation and does not have immediate clinical applications. However, our results suggest that changes in autonomic nervous system activity induced by external vagal stimulation may affect activity in specific reading-related regions of the dorsolateral prefrontal cortex. Further research and evaluation are needed to fully understand the implications and potential applications of these findings.

Glucose-oxygen coupling can serve as a biomarker for neuroinflammation-related genetic variants.

Abstract The single-nucleotide polymorphism rs3197999 in the macrophage-stimulating protein 1 gene is a missense variant. Studies have indicated that macrophage-stimulating protein 1 mediates neuronal loss and synaptic plasticity damage, and overexpression of the macrophage-stimulating protein 1 gene leads to the excessive activation of microglial cells, thereby resulting in an elevation of cerebral glucose metabolism. Traditional diagnostic models may be disrupted by neuroinflammation, making it difficult to predict the pathological status of patients solely based on single-modal images. We hypothesize that the macrophage-stimulating protein 1 rs3197999 single-nucleotide polymorphism may lead to imbalances in glucose and oxygen metabolism, thereby influencing cognitive resilience and the progression of Alzheimer’s disease. In this study, we found that among 121 patients with mild cognitive impairment, carriers of the macrophage-stimulating protein 1 rs3197999 risk allele showed a significant reduction in the coupling of glucose and oxygen metabolism in the dorsolateral prefrontal cortex region. However, the rs3197999 variant did not induce significant differences in glucose metabolism and neuronal activity signals. Furthermore, the rs3197999 risk allele correlated with a higher rate of increase in clinical dementia score, mediated by the coupling of glucose and oxygen metabolism. Highlight

Top-down modulation of DLPFC in visual search: a study based on fMRI and TMS.

Effective visual search is essential for daily life, and attention orientation as well as inhibition of return play a significant role in visual search. Researches have established the involvement of dorsolateral prefrontal cortex in cognitive control during selective attention. However, neural evidence regarding dorsolateral prefrontal cortex modulates inhibition of return in visual search is still insufficient. In this study, we employed event-related functional magnetic resonance imaging and dynamic causal modeling to develop modulation models for two types of visual search tasks. In the region of interest analyses, we found that the right dorsolateral prefrontal cortex and temporoparietal junction were selectively activated in the main effect of search type. Dynamic causal modeling results indicated that temporoparietal junction received sensory inputs and only dorsolateral prefrontal cortex →temporoparietal junction connection was modulated in serial search. Such neural modulation presents a significant positive correlation with behavioral reaction time. Furthermore, theta burst stimulation via transcranial magnetic stimulation was utilized to modulate the dorsolateral prefrontal cortex region, resulting in the disappearance of the inhibition of return effect during serial search after receiving continuous theta burst stimulation. Our findings provide a new line of causal evidence that the top-down modulation by dorsolateral prefrontal cortex influences the inhibition of return effect during serial search possibly through the retention of inhibitory tagging via working memory storage.

Effect of Meditation on Brain Activity during an Attention Task: A Comparison Study of ASL and BOLD Task fMRI.

Focused attention meditation (FAM) training has been shown to improve attention, but the neural basis of FAM on attention has not been thoroughly understood. Here, we aim to investigate the neural effect of a 2-month FAM training on novice meditators in a visual oddball task (a frequently adopted task to evaluate attention), evaluated with both ASL and BOLD fMRI. Using ASL, activation was increased in the middle cingulate (part of the salience network, SN) and temporoparietal (part of the frontoparietal network, FPN) regions; the FAM practice time was negatively associated with the longitudinal changes in activation in the medial prefrontal (part of the default mode network, DMN) and middle frontal (part of the FPN) regions. Using BOLD, the FAM practice time was positively associated with the longitudinal changes of activation in the inferior parietal (part of the dorsal attention network, DAN), dorsolateral prefrontal (part of the FPN), and precentral (part of the DAN) regions. The effect sizes for the activation changes and their association with practice time using ASL are significantly larger than those using BOLD. Our study suggests that FAM training may improve attention via modulation of the DMN, DAN, SN, and FPN, and ASL may be a sensitive tool to study the FAM effect on attention.

The connectivity of the human frontal pole cortex, and a theory of its involvement in exploit versus explore.

The frontal pole is implicated in humans in whether to exploit resources versus explore alternatives. Effective connectivity, functional connectivity, and tractography were measured between six human frontal pole regions and for comparison 13 dorsolateral and dorsal prefrontal cortex regions, and the 360 cortical regions in the Human Connectome Project Multi-modal-parcellation atlas in 171 HCP participants. The frontal pole regions have effective connectivity with Dorsolateral Prefrontal Cortex regions, the Dorsal Prefrontal Cortex, both implicated in working memory; and with the orbitofrontal and anterior cingulate cortex reward/non-reward system. There is also connectivity with temporal lobe, inferior parietal, and posterior cingulate regions. Given this new connectivity evidence, and evidence from activations and damage, it is proposed that the frontal pole cortex contains autoassociation attractor networks that are normally stable in a short-term memory state, and maintain stability in the other prefrontal networks during stable exploitation of goals and strategies. However, if an input from the orbitofrontal or anterior cingulate cortex that expected reward, non-reward, or punishment is received, this destabilizes the frontal pole and thereby other prefrontal networks to enable exploration of competing alternative goals and strategies. The frontal pole connectivity with reward systems may be key in exploit versus explore.

Prefrontal activation in response to a plantar contact task under open and closed eye conditions in patients with cerebral infarction.

This study investigates the effect of a bilateral (paralyzed side, healthy side) plantar contact task on dorsolateral prefrontal activation in patients recovering from cerebral infarction under open and closed eye conditions. We selected 10 patients with cerebral infarction, admitted to the neurorehabilitation center of Beijing Rehabilitation Hospital, affiliated with Capital Medical University, from January 2019 to July 2020, who met our established criteria. Under open-eye and closed-eye conditions, the paralyzed and healthy sides performed the plantar contact tasks separately. The dorsolateral prefrontal region was monitored simultaneously with functional near-infrared spectroscopy (fNIRS), and activation was analyzed according to the curve-type changes of oxyhemoglobin and deoxyhemoglobin changes in the dorsolateral prefrontal cortex with 560 near-infrared monitoring channels. After stratifying the data based on the eyes-open and eyes-closed conditions, some degree of heterogeneity was observed between the layers. Under the eyes-closed condition, the Pearson χ2 was 0.142, with a p value of 0.706, indicating no significant impact of the eyes-closed condition on the activation of the dorsolateral prefrontal cortex during the plantar task, whether performed on the paralyzed or the healthy side.In contrast, the Pearson χ2 value was 15.15 for the eyes-open condition, with a p value of 0.002. This suggests that carrying out the plantar task, either on the paralyzed or the healthy side, with eyes open significantly influenced the activation of the dorsolateral prefrontal cortex. Furthermore, activation of the dorsolateral prefrontal cortex was 1.55 times higher when the task was executed with the paralyzed side compared to the healthy side. This implies that the paralyzed side was more likely to activate the dorsolateral prefrontal lobe when performing the plantar contact task under eyes-open conditions. Observations via fNIRS revealed that the plantar contact task elicited dorsolateral prefrontal cortex activation. Moreover, the activation effect was intensified when performed on the paralyzed side under eyes-open conditions. Therapeutic methods that leverage these findings-namely cognitive-motor therapies that promote the recovery of motor functions by activating cognitive control brain regions via perception (information construction)-may hold promise.

Causally informed activity flow models provide mechanistic insight into network-generated cognitive activations

Brain activity flow models estimate the movement of task-evoked activity over brain connections to help explain network-generated task functionality. Activity flow models have been shown to accurately generate task-evoked brain activations across a wide variety of brain regions and task conditions. However, these models have had limited explanatory power, given known issues with causal interpretations of the standard functional connectivity measures used to parameterize activity flow models. We show here that functional/effective connectivity (FC) measures grounded in causal principles facilitate mechanistic interpretation of activity flow models. We progress from simple to complex FC measures, with each adding algorithmic details reflecting causal principles. This reflects many neuroscientists’ preference for reduced FC measure complexity (to minimize assumptions, minimize compute time, and fully comprehend and easily communicate methodological details), which potentially trades off with causal validity. We start with Pearson correlation (the current field standard) to remain maximally relevant to the field, estimating causal validity across a range of FC measures using simulations and empirical fMRI data. Finally, we apply causal-FC-based activity flow modeling to a dorsolateral prefrontal cortex region (DLPFC), demonstrating distributed causal network mechanisms contributing to its strong activation during a working memory task. Notably, this fully distributed model is able to account for DLPFC working memory effects traditionally thought to rely primarily on within-region (i.e., not distributed) recurrent processes. Together, these results reveal the promise of parameterizing activity flow models using causal FC methods to identify network mechanisms underlying cognitive computations in the human brain.

The Relationship between Depression Severity and Prefrontal Hemodynamic Changes in Adolescents with Major Depression Disorder: A Functional Near-infrared Spectroscopy Study.

: Numerous studies have identified hemodynamic changes in adults with major depressive disorder (MDD) by using functional near-infrared spectroscopy (fNIRS). However, studies on adolescents with MDD are limited. As adolescence is a stage of rapid brain development, differences may occur depending on age. This study used fNIRS as an objective tool to investigate hemodynamic changes in the frontal lobe according to depression severity and age in adolescents with MDD. : Thirty adolescents (12 aged 12-15 years and 18 aged 16-18 years) were retrospectively investigated. The Children's Depression Inventory was used as a psychiatric evaluation scale, fNIRS was used as an objective brain function evaluation tool, and the Verbal Fluency Test was performed. : During the Verbal Fluency Test, in the younger MDD group, oxygenated-hemoglobin concentration increased in the right dorsolateral prefrontal cortex region as the severity of depression increased. In the older MDD group, the oxygenated-hemoglobin concentration decreased in the right dorsolateral prefrontal cortex region as the severity of depression increased. : These results suggest that fNIRS may be an objective tool for identifying age differences among adolescents with MDD. To generalize the results and verify fNIRS as a potential biomarker tool, follow-up studies with a larger sample group should be conducted.

Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management. Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical areas based on high-resolution MRI analysis. Gradients track region-to-region variations in intracortical lamination and myeloarchitecture, serving as a system-level measure of structural and functional reorganization. Comparing cortex-wide microstructural gradients between 21 patients and 35 healthy controls, we observed a reorganization of this gradient in TLE driven by reduced microstructural differentiation between paralimbic cortices and the remaining cortex with marked abnormalities in ipsilateral temporopolar and dorsolateral prefrontal regions. Findings were replicated in an independent cohort. Using an independent post-mortem dataset, we observed that in vivo findings reflected topographical variations in cortical cytoarchitecture. We indeed found that macroscale changes in microstructural differentiation in TLE reflected increased similarity of paralimbic and primary sensory/motor regions. Disease-related transcriptomics could furthermore show specificity of our findings to TLE over other common epilepsy syndromes. Finally, microstructural dedifferentiation was associated with cognitive network reorganization seen during an episodic memory functional MRI paradigm and correlated with interindividual differences in task accuracy. Collectively, our findings showing a pattern of reduced microarchitectural differentiation between paralimbic regions and the remaining cortex provide a structurally-grounded explanation for large-scale functional network reorganization and cognitive dysfunction characteristic of TLE.

Modelling the differential effects of age on transcranial magnetic stimulation induced electric fields

Objective. The therapeutic application of noninvasive brain stimulation modalities such as transcranial magnetic stimulation (TMS) has expanded in terms of indications and patient populations. Often neurodevelopmental and neurodegenerative changes are not considered in research studies and clinical applications. This study sought to examine TMS dosing across time points in the life cycle. Approach. TMS induced electric fields with a figure-of-eight coil was simulated at left dorsolateral prefrontal cortex regions and taken in vertex as a control region. Realistic magnetic resonance imaging-based head models (N = 48) were concurrently examined in a cross-sectional study of three different age groups (children, adults, and elderlies). Main results. Age had a negative correlation with electric field peaks in white matter, grey matter and cerebrospinal fluid (P < 0.001). Notably, the electric field map in children displayed the widest cortical surface spread of TMS induced electric fields. Significance. Age-related anatomical geometry beneath the coil stimulation site had a significant impact on the TMS induced electric fields for different age groups. Safety considerations for TMS applications and protocols in children are warranted based on the present electric field findings.

Prefrontal and somatosensory-motor cortex effective connectivity in humans.

Effective connectivity, functional connectivity, and tractography were measured between 57 cortical frontal and somatosensory regions and the 360 cortical regions in the Human Connectome Project (HCP) multimodal parcellation atlas for 171 HCP participants. A ventral somatosensory stream connects from 3b and 3a via 1 and 2 and then via opercular and frontal opercular regions to the insula, which then connects to inferior parietal PF regions. This stream is implicated in "what"-related somatosensory processing of objects and of the body and in combining with visual inputs in PF. A dorsal "action" somatosensory stream connects from 3b and 3a via 1 and 2 to parietal area 5 and then 7. Inferior prefrontal regions have connectivity with the inferior temporal visual cortex and orbitofrontal cortex, are implicated in working memory for "what" processing streams, and provide connectivity to language systems, including 44, 45, 47l, TPOJ1, and superior temporal visual area. The dorsolateral prefrontal cortex regions that include area 46 have connectivity with parietal area 7 and somatosensory inferior parietal regions and are implicated in working memory for actions and planning. The dorsal prefrontal regions, including 8Ad and 8Av, have connectivity with visual regions of the inferior parietal cortex, including PGs and PGi, and are implicated in visual and auditory top-down attention.

Enhancing Immediate Memory, Potential Learning, and Working Memory with Transcranial Direct Current Stimulation in Healthy Older Adults.

Background: Transcranial direct current stimulation (tDCS) has emerged as a prevention method or minimizer of the normal cognitive deterioration that occurs during the aging process. tDCS can be used to enhance cognitive functions such as immediate memory, learning, or working memory in healthy subjects. The objective of this study was to analyze the effect of two 20-min sessions of anodal transcranial direct stimulation on immediate memory, learning potential, and working memory in healthy older adults. Methods: A randomized, single-blind, repeated-measures, sham-controlled design was used. The sample is made up of 31 healthy older adults, of whom 16 were in the stimulation group and 15 were in the sham group. The anode was placed on position F7, coinciding with the left dorsolateral prefrontal cortex region, and the cathode was placed on Fp2, the right supraorbital area (rSO). Results: When comparing the results of the treatment group and the sham group, differences were observed in working memory and learning potential; however, no differences in immediate memory were found. Conclusion: The results showed that tDCS is a non-invasive and safe tool to enhance cognitive processes in healthy older adults interested in maintaining some cognitive function.

Effect of the anodal transcranial direct current electrical stimulation on cognition of medical residents with acute sleep deprivation.

BackgroundMedical residents must sustain acute sleep deprivation, which can lead to nonfatal and fatal consequences in hospitals due to cognitive decline. Anodal transcranial direct current stimulation (a-tDCS) is a safe noninvasive neuromodulation technique that can induce depolarization of neurons. Previous studies in pilots have shown benefits against fatigue increasing wakefulness and cognitive performance. However, the effects of a-tDCS on cognition in acute sleep deprived healthcare workers remains unknown.PurposeTo evaluate cognitive changes in sleep deprived medical residents after one session of a-tDCS.MethodsOpen clinical test-re-test study including 13 medical residents with acute sleep deprivation. Subjects received 1 session of bifrontal a-tDCS (2mAx20min), anodal over the left dorsolateral prefrontal region. Pre-and-post treatment subjects were tested with Beck anxiety inventory, Beck depression and HVLT tests, Rey´s and Taylor´s figures, Trail Making A/B, Stroop, Aleatory Digit retention test (WAIS), Digits and symbols and MoCA tests. Post-intervention was added the Executive functions and Frontal Lobes Neuropsychological Battery (BANFE2) test and changing the Taylor figure for Reyfigure.ResultsTwelve medical residents were analyzed; 8 men and 4 women, 29.5 (+/-2.2) years mean age. All had a mean of 21.6 (+/-1.3) hours of sleep deprivation. There were no serious adverse events. We found statistically significant difference in Rey´s/Taylor´s figures (p=0.002), Trail Making Test (p=0.005), WAIS IV symbols (p=0.003), Word Stroop (p=0.021). BANFE-2 showed that the main affected area was the orbito-medial prefrontal region.Conclusiona-tDCS appears safe and improves working memory, attention, response time and distractors elimination in acute sleep deprived medical residents.

Prof K C Dube Poster Award

INTRODUCTION:Clinical, neurophysiological and functional neuroimaging studies in schizophrenia suggest impaired frontal lobe function, especially of the dorsolateral prefrontal cortex (DLPFC). Prefrontal dysfunction has been found to be associated with negative symptoms. Despite these findings, structural neuroimaging studies have failed to show consistent abnormalities in the frontal lobe. This may be because existing techniques are not sensitive enough to detect structural abnormalities or that dysfunction in the frontal lobe is caused by lesions elsewhere.AIM:We aimed to measure N-acetylaspartate (NAA), a neuronal marker, to evaluate the neuronal integrity of the dorsolateral prefrontal region in schizophrenic patients with persistent negative symptoms and in healthy comparison subjects, using proton magnetic resonance spectroscopy (1H-MRS).METHODOLOGY:Thirty six patients who fulfilled ICD-10 criteria for schizophrenia and with SANS score of more than 20 were compared to 15 healthy controls matched for age and gender. Proton Magnetic Resonance spectra were collected from the left dorsolateral prefrontal region with a voxel size of a 1.5cm3. In vivo 1H-MRS analyses were processed using Tarquin 4.3.10 software. Total NAA corresponding to the sum of NAA and N-Acetyl-Aspartyl-Glutamate (NAAG), was determined. NAA levels were calculated relative to the unsuppressed water signal from the same voxel.RESULTS:There were no significant differences between the two groups for NAA levels. There was no significant correlation between severity of symptoms and NAA concentration in the schizophrenic patients.CONCLUSION:The lack of significant mean difference in NAA between the two groups suggests that there is no marked neuronal loss in the dorsolateral prefrontal region in schizophrenia.

Four-modality imaging of unmedicated subjects with schizophrenia: 18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, and MRI

Diminished prefrontal function, dopaminergic abnormalities in the striatum and thalamus, reductions in white matter integrity and frontotemporal gray matter deficits are the most replicated findings in schizophrenia. We used four imaging modalities (18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, structural MRI) in 19 healthy and 25 schizophrenia subjects to assess the relationship between functional (dopamine D2/D3 receptor binding potential, glucose metabolic rate) and structural (fractional anisotropy, MRI) correlates of schizophrenia and their additive diagnostic prediction potential. Multivariate ANOVA was used to compare structural and functional image sets for identification of schizophrenia. Integration of data from all four modalities yielded better predictive power than less inclusive combinations, specifically in the thalamus, left dorsolateral prefrontal and temporal regions. Among the modalities, fractional anisotropy showed highest discrimination in white matter whereas 18F-fallypride binding showed highest discrimination in gray matter. Structural and functional modalities displayed comparable discriminative power but different topography, with higher sensitivity of structural modalities in the left prefrontal region. Combination of functional and structural imaging modalities with inclusion of both gray and white matter appears most effective in diagnostic discrimination. The highest sensitivity of 18F-fallypride PET to gray matter changes in schizophrenia supports the primacy of dopaminergic abnormalities in its pathophysiology.

A review and meta-analysis of gene expression profiles in suicide

Suicide claims over 800,000 deaths worldwide, making it a serious public health problem. The etiopathophysiology of suicide remains unclear and is highly complex, and postmortem gene expression studies can offer insights into the molecular biological mechanism underlying suicide. In the current study, we conducted a meta-analysis of postmortem brain gene expression in relation to suicide. We identified five gene expression datasets for postmortem orbitofrontal, prefrontal, or dorsolateral prefrontal cortical brain regions from the Gene Expression Omnibus repository. After quality control, the total sample size was 380 (141 suicide deaths and 239 deaths from other causes). We performed the analyses using two meta-analytic approaches. We further performed pathway and cell-set enrichment analyses. We found reduced expression of the KCNJ2 (Potassium Inwardly Rectifying Channel Subfamily J Member 2), A2M (Alpha-2-Macroglobulin), AGT (Angiotensinogen), PMP2 (Peripheral Myelin Protein 2), and VEZF1 (Vascular Endothelial Zinc Finger 1) genes (FDR p<0.05). Our findings support the involvement of astrocytes, stress response, immune system, and microglia in suicide. These findings will require further validation in additional large datasets.

Increased amygdala and decreased frontolimbic r esting- s tate functional connectivity in children with aggressive behavior.

Childhood maladaptive aggression is associated with disrupted functional connectivity within amygdala-prefrontal circuitry. In this study, neural correlates of childhood aggression were probed using the intrinsic connectivity distribution, a voxel-wise metric of global resting-state brain connectivity. This sample included 38 children with aggressive behavior (26 boys, 12 girls) ages 8–16 years and 21 healthy controls (14 boys, 6 girls) matched for age and IQ. Functional MRI data were acquired during resting state, and differential patterns of intrinsic functional connectivity were tested in a priori regions of interest implicated in the pathophysiology of aggressive behavior. Next, correlational analyses tested for associations between functional connectivity and severity of aggression measured by the Reactive-Proactive Aggression Questionnaire in children with aggression. Children with aggressive behavior showed increased global connectivity in the bilateral amygdala relative to controls. Greater severity of aggressive behavior was associated with decreasing global connectivity in the dorsal anterior cingulate and ventromedial prefrontal cortex. Follow-up seed analysis revealed that aggression was also positively correlated with left amygdala connectivity with the dorsal anterior cingulate, ventromedial and dorsolateral prefrontal cortical regions. These results highlight the potential role of connectivity of the amygdala and medial prefrontal and anterior cingulate cortices in modulating the severity of aggressive behavior in treatment-seeking children.