Dorsolateral Prefrontal Cortex Regions Research Articles

Reconfiguration of Functional Dynamics in Cortico-Thalamo-Cerebellar Circuit in Schizophrenia Following High-Frequency Repeated Transcranial Magnetic Stimulation.

Schizophrenia is a serious mental illness characterized by a disconnection between brain regions. Transcranial magnetic stimulation is a non-invasive brain intervention technique that can be used as a new and safe treatment option for patients with schizophrenia with drug-refractory symptoms, such as negative symptoms and cognitive impairment. However, the therapeutic effects of transcranial magnetic stimulation remain unclear and would be investigated using non-invasive tools, such as functional connectivity (FC). A longitudinal design was adopted to investigate the alteration in FC dynamics using a dynamic functional connectivity (dFC) approach in patients with schizophrenia following high-frequency repeated transcranial magnetic stimulation (rTMS) with the target at the left dorsolateral prefrontal cortex (DLPFC). Two groups of schizophrenia inpatients were recruited. One group received a 4-week high-frequency rTMS together with antipsychotic drugs (TSZ, n = 27), while the other group only received antipsychotic drugs (DSZ, n = 26). Resting-state functional magnetic resonance imaging (fMRI) and psychiatric symptoms were obtained from the patients with schizophrenia twice at baseline (t1) and after 4-week treatment (t2). The dynamics was evaluated using voxel- and region-wise FC temporal variability resulting from fMRI data. The pattern classification technique was used to verify the clinical application value of FC temporal variability. For the voxel-wise FC temporary variability, the repeated measures ANCOVA analysis showed significant treatment × time interaction effects on the FC temporary variability between the left DLPFC and several regions, including the thalamus, cerebellum, precuneus, and precentral gyrus, which are mainly located within the cortico-thalamo-cerebellar circuit (CTCC). For the ROI-wise FC temporary variability, our results found a significant interaction effect on the FC among CTCC. rTMS intervention led to a reduced FC temporary variability. In addition, higher alteration in FC temporal variability between left DLPFC and right posterior parietal thalamus predicted a higher remission ratio of negative symptom scores, indicating that the decrease of FC temporal variability between the brain regions was associated with the remission of schizophrenia severity. The support vector regression (SVR) results suggested that the baseline pattern of FC temporary variability between the regions in CTCC could predict the efficacy of high-frequency rTMS intervention on negative symptoms in schizophrenia. These findings confirm the potential relationship between the reduction in whole-brain functional dynamics induced by high-frequency rTMS and the improvement in psychiatric scores, suggesting that high-frequency rTMS affects psychiatric symptoms by coordinating the heterogeneity of activity between the brain regions. Future studies would examine the clinical utility of using functional dynamics patterns between specific brain regions as a biomarker to predict the treatment response of high-frequency rTMS.

Expansion of Schizophrenia Gene Network Knowledge Using Machine Learning Selected Signals From Dorsolateral Prefrontal Cortex and Amygdala RNA-seq Data.

It is widely accepted, given the complex nature of schizophrenia (SCZ) gene networks, that a few or a small number of genes are unlikely to represent the underlying functional pathways responsible for SCZ pathogenesis. Several studies from large cohorts have been performed to search for key SCZ network genes using different analytical approaches, such as differential expression tests, genome-wide association study (GWAS), copy number variations, and differential methylations, or from the analysis of mutations residing in the coding regions of the genome. However, only a small portion (<10%) of candidate genes identified in these studies were considered SCZ disease-associated genes in SCZ pathways. RNA sequencing (RNA-seq) has been a powerful method to detect functional signals. In this study, we used RNA-seq data from the dorsolateral prefrontal cortex (DLPFC) from 254 individuals and RNA-seq data from the amygdala region from 46 individuals. Analysis was performed using machine learning methods, including random forest and factor analysis, to prioritize the numbers of genes from previous SCZ studies. For genes most differentially expressed between SCZ and healthy controls, 18 were added to known SCZ-associated pathways. These include three genes (GNB2, ITPR1, and PLCB2) for the glutamatergic synapse pathway, six genes (P2RX6, EDNRB, GHR, GRID2, TSPO, and S1PR1) for neuroactive ligand–receptor interaction, eight genes (CAMK2G, MAP2K1, RAF1, PDE3A, RRAS2, VAV1, ATP1B2, and GLI3) for the cAMP signaling pathway, and four genes (GNB2, CAMK2G, ITPR1, and PLCB2) for the dopaminergic synapse pathway. Besides the previously established pathways, 103 additional gene interactions were expanded to SCZ-associated networks, which were shared among both the DLPFC and amygdala regions. The novel knowledge of molecular targets gained from this study brings opportunities for a more complete picture of the SCZ pathogenesis. A noticeable fact is that hub genes, in the expanded networks, are not necessary differentially expressed or containing hotspots from GWAS studies, indicating that individual methods, such as differential expression tests, are not enough to identify the underlying SCZ pathways and that more integrative analysis is required to unfold the pathobiology of SCZ.

Blue light exposure increases functional connectivity between dorsolateral prefrontal cortex and multiple cortical regions.

ObjectiveBlue light is a powerful environmental stimulus that can produce significant phase shifts in the circadian rhythm of melatonin and sleep propensity as well as acute effects on alertness of neurobehavioral performance. Here, we undertook an expansion and reanalysis of our previously published findings to examine the effect of acute blue light exposure on the strength of resting-state functional connectivity (rsFC) between a previously identified region of the left dorsolateral prefrontal cortex (DLPFC) and 106 cortical and subcortical regions.MethodsTwenty-nine healthy adults (16 men and 13 women; age 18–32 years) completed a psychomotor vigilance test (PVT) before and after a single 30-min exposure to either blue (λ = 469 nm; n = 17) or amber wavelength (λ = 578 nm; n = 12) light, immediately followed by an rsFC scan.ResultsCompared with amber light, blue light exposure produced significantly greater functional connectivity between the left DLPFC seed region and 30 cortical and subcortical regions (P < 0.05; false discovery rate–corrected). Although neurobehavioral performance did not differ between light conditions, only those exposed to blue light showed a significant association between rsFC and sustained PVT performance. Better sustained PVT performance was associated with greater connectivity between the left DLPFC and regions associated with visuospatial awareness/motion detection (right temporal-occipital middle temporal gyrus) and memory (left hippocampus), as well as reduced connectivity in a circuit associated with cognitive rumination and distraction (left parahippocampal gyrus).ConclusionFindings suggest that blue-wavelength light may facilitate acute alertness and improved cognitive performance through enhanced rsFC between the left DLPFC and cortical regions associated with visuospatial awareness.

Aching face and hand: the interoceptive attentiveness and social context in relation to empathy for pain

This research explored how the manipulation of interoceptive attentiveness (IA) can influence the frontal (dorsolateral prefrontal cortex (DLPFC) and somatosensory cortices) activity associated with the emotional regulation and sensory response of observing pain in others. 20 individuals were asked to observe face versus hand, painful/non-painful stimuli in an individual versus social condition while brain hemodynamic response (oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) components) was measured via functional Near-Infrared Spectroscopy (fNIRS). Images represented either a single person (individual condition) or two persons in social interaction (social condition) both for the pain and body part set of stimuli. The participants were split into experimental (EXP) and control (CNT) groups, with the EXP explicitly required to concentrate on its interoceptive correlates while observing the stimuli. Quantitative statistical analyses were applied to both oxy- and deoxy-Hb data. Firstly, significantly higher brain responsiveness was detected for pain in comparison to no-pain stimuli in the individual condition. Secondly, a left/right hemispheric lateralization was found for the individual and social condition, respectively, in both groups. Besides, both groups showed higher DLPFC activation for face stimuli presented in the individual condition compared to hand stimuli in the social condition. However, face stimuli activation prevailed for the EXP group, suggesting the IA phenomenon has certain features, namely it manifests itself in the individual condition and for pain stimuli. We can conclude that IA promoted the recruitment of internal adaptive regulatory strategies by engaging both DLPFC and somatosensory regions towards emotionally relevant stimuli.

Is There Any Relationship Between Biochemical Indices and Anthropometric Measurements With Dorsolateral Prefrontal Cortex Activation Among Older Adults With Mild Cognitive Impairment?

Working memory is developed in one region of the brain called the dorsolateral prefrontal cortex (DLPFC). The dysfunction of this region leads to synaptic neuroplasticity impairment. It has been reported that several biochemical parameters and anthropometric measurements play a vital role in cognition and brain health. This study aimed to investigate the relationships between cognitive function, serum biochemical profile, and anthropometric measurements using DLPFC activation. A cross-sectional study was conducted among 35 older adults (≥60 years) who experienced mild cognitive impairment (MCI). For this purpose, we distributed a comprehensive interview-based questionnaire for collecting sociodemographic information from the participants and conducting cognitive tests. Anthropometric values were measured, and fasting blood specimens were collected. We investigated their brain activation using the task-based functional MRI (fMRI; N-back), specifically in the DLPFC region. Positive relationships were observed between brain-derived neurotrophic factor (BDNF) (β = 0.494, p < 0.01) and Mini-Mental State Examination (MMSE) (β = 0.698, p < 0.01); however, negative relationships were observed between serum triglyceride (β = −0.402, p < 0.05) and serum malondialdehyde (MDA) (β = −0.326, p < 0.05) with right DLPFC activation (R2 = 0.512) while the participants performed 1-back task after adjustments for age, gender, and years of education. In conclusion, higher serum triglycerides, higher oxidative stress, and lower neurotrophic factor were associated with lower right DLPFC activation among older adults with MCI. A further investigation needs to be carried out to understand the causal-effect mechanisms of the significant parameters and the DLPFC activation so that better intervention strategies can be developed for reducing the risk of irreversible neurodegenerative diseases among older adults with MCI.

Brain Activity Measurement during a Mental Arithmetic Task in fNIRS Signal Using Continuous Wavelet Transform

Purpose: Functional Near-Infrared Spectroscopy (fNIRS) is a non-invasive imaging technology with widespread use in cognitive sciences and clinical studies. It indirectly measures neural activation by measuring alterations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) in tissues. This study used mental arithmetic task for analyzing the activation of the frontal cortex. Materials and methods: The fNIRS instrument was used for measuring the alterations of HbO2 and Hb in healthy subjects during the task. Then the recorded signals were filtered in the frequency range of 3 to 80 mHz. The Continuous Wavelet Transform (CWT) of each of the HbO2 and Hb signals in each channel was calculated in the intended frequency range, followed by the calculation of the energy of obtained coefficients. Finally, for the performed tasks, the average energy of each channel in each region was obtained. Then the energies of spatially symmetric channel pairs in the two hemispheres were compared using the t-test. Results: Results demonstrated that the average energy of HbO2 signal for corresponding channels in the temporal, Medial Prefrontal Cortex (MPFC), and Dorsolateral Prefrontal Cortex (DLPFC) regions had significant differences (P&lt;0.05). Also, a significant difference was observed in the temporal, medial prefrontal, and Ventrolateral Prefrontal Cortex (VLPFC) regions for Hb signal. Conclusion: The obtained results indicate activation in both HbO2 and Hb signals in the DLPFC, temporal, and MPFC regions, considering the performance of memory and the frontal cortex under mental arithmetic tasks. Therefore, it can be concluded that this technique is effective and appropriate for analyzing alterations of brain oxygen levels during cognitive activity.

Anatomical and fMRI-network comparison of multiple DLPFC targeting strategies for repetitive transcranial magnetic stimulation treatment of depression

BackgroundThe efficacy of repetitive transcranial magnetic stimulation (rTMS) for depression may vary depending on the subregion stimulated within the dorsolateral prefrontal cortex (DLPFC). Clinical TMS typically uses scalp-based landmarks for DLPFC targeting, rather than individualized MRI guidance. ObjectiveIn rTMS patients, determine the brain systems targeted by multiple DLPFC stimulation rules by computing several surrogate measures: underlying brain targets labeled with connectivity-based atlases, subgenual cingulate anticorrelation strength, and functionally connected networks. MethodsForty-nine patients in a randomized controlled trial of rTMS therapy for treatment resistant major depression underwent structural and functional MRI. DLPFC rules were applied virtually using MR-image guidance. Underlying cortical regions were labeled, and connectivity with the subgenual cingulate and whole-brain computed. ResultsScalp-targeting rules applied post hoc to these MRIs that adjusted for head size, including Beam F3, were comparably precise, successful in directly targeting classical DLPFC and frontal networks, and anticorrelated with the subgenual cingulate. In contrast, all rules involving fixed distances introduced variability in regions and networks targeted. The 5 cm rule targeted a transitional DLPFC region with a different connectivity profile from the adjusted rules. Seed-based connectivity analyses identified multiple regions, such as posterior cingulate and inferior parietal lobe, that warrant further study in order to understand their potential contribution to clinical response. ConclusionEEG-based rules consistently targeted DLPFC brain regions with resting-state fMRI features known to be associated with depression response. These results provide a bridge from lab to clinic by enabling clinicians to relate scalp-targeting rules to functionally connected brain systems.

Individualized tDCS modeling predicts functional connectivity changes within the working memory network in older adults

BackgroundWorking memory decline has been associated with normal aging. The frontal brain structure responsible for this decline is primarily located in the prefrontal cortex (PFC). Our previous neuroimaging study demonstrated a significant change in functional connectivity between the left dorsolateral PFC (DLPFC) and left ventrolateral PFC (VLPFC) when applying 2 mA tDCS in MRI scanner during an N-Back task. These regions were part of the working memory network. The present study is the first study that utilizes individualized finite element models derived from older adults’ MRI to predict significant changes of functional connectivity observed from an acute tDCS application. MethodsIndividualized head models from 15 healthy older adults (mean age = 71.3 years) were constructed to create current density maps. Each head model was segmented into 11 tissue types: white matter, gray matter, CSF, muscle, blood vessels, fat, eyes, air, skin, cancellous, and cortical bone. Electrodes were segmented from T1-weighted images and added to the models. Computed median and maximum current density values in the left DLPFC and left VLPFC regions of interest (ROIs) were correlated with beta values as functional connectivity metrics measured in different timepoint (baseline, during stimulation) and stimulation condition (active and sham). Main resultsPositive significant correlations (R2 = 0.523 for max J, R2 = 0.367 for median J, p < 0.05) were found between the beta values and computed current densities in the left DLPFC ROIs for active stimulation, but no significant correlation was found during sham stimulation. We found no significant correlation between connectivity and current densities computed in the left VLPFC for both active and sham stimulation. ConclusionsThe amount of current within the left DLPFC ROIs was found positively correlated with changes in functional connectivity between left DLPFC and left VLPFC during active 2 mA stimulation. Future work may include expansion of number of participants to further test the accuracy of tDCS models used to predict tDCS-induced functional connectivity changes within the working memory network.

Functional Interactions between Sensory and Memory Networks for Adaptive Behavior.

The brain’s capacity to adapt to sensory inputs is key for processing sensory information efficiently and interacting in new environments. Following repeated exposure to the same sensory input, brain activity in sensory areas is known to decrease as inputs become familiar, a process known as adaptation. Yet, the brain-wide mechanisms that mediate adaptive processing remain largely unknown. Here, we combine multimodal brain imaging (functional magnetic resonance imaging [fMRI], magnetic resonance spectroscopy) with behavioral measures of orientation-specific adaptation (i.e., tilt aftereffect) to investigate the functional and neurochemical mechanisms that support adaptive processing. Our results reveal two functional brain networks: 1) a sensory-adaptation network including occipital and dorsolateral prefrontal cortex regions that show decreased fMRI responses for repeated stimuli and 2) a perceptual-memory network including regions in the parietal memory network (PMN) and dorsomedial prefrontal cortex that relate to perceptual bias (i.e., tilt aftereffect). We demonstrate that adaptation relates to increased occipito-parietal connectivity, while decreased connectivity between sensory-adaptation and perceptual-memory networks relates to GABAergic inhibition in the PMN. Thus, our findings provide evidence that suppressive interactions between sensory-adaptation (i.e., occipito-parietal) and perceptual-memory (i.e., PMN) networks support adaptive processing and behavior, proposing a key role of memory systems in efficient sensory processing.

Neurophysiological effects of repetitive transcranial magnetic stimulation (rTMS) in treatment resistant depression

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) is effective for treatment resistant depression (TRD), but little is known about rTMS’ effects on neurophysiological markers. We previously identified neurophysiological markers in depression (N45 and N100) of GABA receptor mediated inhibition. Here, we indexed TMS-electroencephalographic (TMS-EEG) effects of rTMS. MethodsTMS-EEG data was analyzed from a double blind 2:1 randomized active (10 Hz left/bilateral):sham rTMS TRD trial. Participants underwent TMS-EEG over left dorsolateral prefrontal cortex (DLPFC) before and after 6 weeks of rTMS. 30 had useable datasets. TMS-evoked potentials (TEP) and components (N45, N100, P60) were examined with global mean field analysis (GMFA) and locally in DLPFC regions of interest. ResultsThe N45 amplitude differed between active and sham groups over time, N100 amplitude did not. N45 (t = 2.975, p = 0.007) and N100 amplitudes (t = 2.177, p = 0.042) decreased after active rTMS, demonstrating alterations in cortical inhibition. TEP amplitudes decreased after active rTMS in left (t = 4.887, p < 0.001) and right DLPFC (t = 4.403, p < 0.001) not sham rTMS, demonstrating alterations in cortical excitability. ConclusionsOur results provide important new knowledge regarding rTMS effects on TMS-EEG measures in TRD, suggesting rTMS reduces neurophysiological markers of inhibition and excitability. SignificanceThese findings uncover potentially important neurophysiological mechanisms of rTMS action.

Support for an inhibitory model of word retrieval

Word retrieval may involve an inhibitory process in which a target word is activated and related words are suppressed. In the current functional magnetic resonance imaging (fMRI) study, we examined the inhibition of language processing cortex by the left dorsolateral prefrontal cortex (DLPFC) during word retrieval using an anagram-solving paradigm. Participants were presented with a distractor that was read aloud followed by a to-be-solved anagram. Distractor types were defined relative to orthographic overlap with the subsequent anagram solution and included related words with one letter different (e.g., “gripe” for the anagram of “price”), related pseudo-words, and unrelated words (i.e., all five letters were different). The anagram solution reaction time was slower in both the related word and related pseudo-word distractor conditions as compared to the unrelated word distractor condition, which can be attributed to greater inhibition following related distractors. The contrast of related words and unrelated words produced one activation in the left DLPFC, a region that has been associated with memory inhibition. To identify the regions that were negatively correlated with activity in the left DLPFC for related distractors, we conducted a functional connectivity analysis between this left DLPFC region and the rest of the brain. We found negatively correlated activity between the DLPFC and language processing cortex for the related word distractor condition (and the related pseudo-word distractor condition at a relaxed threshold). These findings suggest that that the left DLPFC may inhibit related word (and pseudo-word) representations in language processing cortex.

An Examination of the Association Between Subjective Distress and Functional Connectivity During Discarding Decisions in Hoarding Disorder

BackgroundIndividuals with hoarding disorder (HD) demonstrate exaggerated subjective distress and hyperactivation of cingulate and insular cortex regions when discarding personal possessions. No prior study has sought to determine whether this subjective distress is associated with specific profiles of abnormal brain function in individuals with HD. MethodsWe used multimodal canonical correlation analysis plus joint independent component analysis to test whether five hoarding-relevant domains of subjective distress when deciding to discard possessions (anxiety, sadness, monetary value, importance, and sentimental attachment) are associated with functional magnetic resonance imaging–measured whole-brain functional connectivity in 72 participants with HD and 44 healthy controls. ResultsThree extracted components differed between HD participants and healthy control subjects. Each of these components depicted an abnormal profile of functional connectivity in HD participants relative to control subjects during discarding decisions, and a specific distress response profile. One component pair showed a relationship between anxiety ratings during discarding decisions and connectivity among the pallidum, perirhinal ectorhinal cortex, and dorsolateral prefrontal cortex. Another component comprised sadness ratings during discarding decisions and connectivity in the pallidum, nucleus accumbens, amygdala, and dorsolateral prefrontal cortex. The third component linked HD brain connectivity in several dorsolateral prefrontal cortex regions with perceived importance ratings during discarding decisions. ConclusionsThe findings indicate that in patients with HD, the subjective intensity of anxiety, sadness, and perceived possession importance is related to abnormal functional connectivity in key frontal and emotional processing brain regions. The findings are discussed in terms of emerging neurobiological models of HD.

Measurement of brain activity related to behavior acquisition by imitation learning using near-infrared spectroscopy

According to David Marr, three levels are needed to understand information processing systems. Those are “computational theory”, “representation” and “algorithm and hardware implementation”. This idea improves understanding brain function and technological application in a mutually complementary manner. On the other hand, the development of measuring brain function enabled us to apply brain activities to engineering. Measuring brain activity have been used for the evaluation method to information that is difficult to quantify such as emotion and learning levels. This work investigates the relationships between learning levels and brain activities. In the conducted experiment, subjects firstly learned a set of procedures for assembling work by observation and then imitated the procedures in the tasks. After several practices, they participated in the same tasks. The results indicates that activities of regions of dorsolateral prefrontal cortex (DLPFC) have increased at pre-learning and a wide region of prefrontal area have increased at post-learning during the observation. In the imitation, regions of DLPFC were activated at pre-learning. At the post-learning, the regions of DLPFC, frontopolar cortex and inferior prefrontal gyrus were activated. These findings are accorded with the results of the previous studies and suggest the necessity of considering the effects of a default mode network on the brain activities of imitation learning.

Fronto-limbic neuroimaging biomarkers for diagnosis and prediction of treatment responses in major depressive disorder

The neuroimaging is an important tool for understanding the biomarkers and predicting treatment responses in major depressive disorder (MDD). The potential biomarkers and prediction of treatment response in MDD will be addressed in the review article. The brain regions of cognitive control and emotion regulation, such as the frontal and limbic regions, might represent the potential targets for MDD biomarkers. The potential targets of frontal lobes might include anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). For the limbic system, hippocampus and amygdala might be the potentially promising targets for MDD. The potential targets of fronto-limbic regions have been found in the studies of several major neuroimaging modalities, such as the magnetic resonance imaging, near-infrared spectroscopy, electroencephalography, positron emission tomography, and single-photon emission computed tomography. Additional regions, such as brainstem and midbrain, might also play a part in the MDD biomarkers. For the prediction of treatment response, the gray matter volumes, white matter tracts, functional representations and receptor bindings of ACC, DLPFC, OFC, amygdala, and hippocampus might play a role in the prediction of antidepressant responses in MDD. For the response prediction of psychotherapies, the fronto-limbic, reward regions, and insula will be the potential targets. For the repetitive transcranial magnetic stimulation, the DLPFC, ACC, limbic, and visuospatial regions might represent the predictive targets for treatment. The neuroimaging targets of MDD might be focused in the fronto-limbic regions. However, the neuroimaging targets for the prediction of treatment responses might be inconclusive and beyond the fronto-limbic regions.

Repeatability of Neural and Autonomic Responses to Acute Psychosocial Stress.

FMRI Montreal Imaging Stress Tasks (MIST) have been shown to activate endocrine and autonomic stress responses that are mediated by a prefrontal cortex (PFC)-hippocampus-amygdala circuit. However, the stability of the neurobehavioral responses over time and the ability to monitor response to clinical interventions has yet to be validated. The objective of this study was to compare the fMRI and physiologic responses to acute psychosocial stress in healthy volunteers during initial and follow-up visits approximately 13 weeks later, simulating a typical duration of clinical intervention. We hypothesized that responses to stress would remain highly conserved across the 2 visits in the absence of an intervention. 15 healthy volunteers completed a variant of control math task (CMT) and stress math task (SMT) conditions based on MIST. Neural responses were modeled using an event-related design with estimates for math performance and auditory feedback for each task condition. For each visit, measures of stress reactivity included differential fMRI and heart rate (SMT-CMT), as well as salivary alpha-amylase before and after scanning sessions. The results revealed that differential fMRI, as well as increased heart rate and salivary alpha-amylase from before and after scanning remained similar between visits. Intraclass correlation coefficient (ICC) values revealed areas of reliable task-dependent BOLD fMRI signal response across visits for peaks of clusters for the main effect of condition (SMT vs CMT) within dorsal anterior cingulate cortex (ACC), insula, and hippocampus regions during math performance and within subgenual ACC, posterior cingulate cortex, dorsolateral PFC regions during auditory feedback. Given that the neurobehavioral response to acute stress remained highly conserved across visits in the absence of an intervention, this study confirms the utility for MIST for assessing longitudinal changes in controlled trials that can identify underlying neurobiological mechanisms involved in mediating the efficacy of stress-reduction interventions.

Relationship between neural responses to stress and mental health symptoms in psychogenic nonepileptic seizures after traumatic brain injury.

To utilize traumatic brain injury (TBI) as a model for investigating functioning during acute stress experiences in psychogenic nonepileptic seizures (PNES) and to identify neural mechanisms underlying the link between changes in processing of stressful experiences and mental health symptoms in PNES. We recruited 94 participants: 50 with TBI only (TBI-only) and 44 with TBI and PNES (TBI+PNES). Participants completed mood (Beck Depression Inventory-II), anxiety (Beck Anxiety Inventory), and posttraumatic stress disorder (PTSD) symptom (PTSD Checklist-Specific Event) assessments before undergoing functional magnetic resonance imaging during an acute psychosocial stress task. Linear mixed-effects analyses identified clusters of significant interactions between group and neural responses to stressful math performance and stressful auditory feedback conditions within limbic brain regions (volume-corrected α=.05). Spearman rank correlation tests compared mean cluster signals to symptom assessments (false discovery rate-corrected α=.05). Demographic and TBI-related measures were similar between groups; TBI+PNES demonstrated worse clinical symptom severity compared to TBI-only. Stressful math performance induced relatively greater reactivity within dorsomedial prefrontal cortex (PFC) and right hippocampal regions and relatively reduced reactivity within left hippocampal and dorsolateral PFC regions for TBI+PNES compared to TBI-only. Stressful auditory feedback induced relatively reduced reactivity within ventral PFC, cingulate, hippocampal, and amygdala regions for TBI+PNES compared to TBI-only. Changes in responses to stressful math within hippocampal and dorsal PFC regions were correlated with increased mood, anxiety, and PTSD symptom severity. Corticolimbic functions underlying processing of stressful experiences differ between patients with TBI+PNES and those with TBI-only. Relationships between these neural responses and symptom assessments suggest potential pathophysiologic mechanisms in PNES.

Independent Contributions of Dorsolateral Prefrontal Structure and Function to Working Memory in Healthy Older Adults.

Age-related differences in dorsolateral prefrontal cortex (DLPFC) structure and function have each been linked to working memory. However, few studies have integrated multimodal imaging to simultaneously investigate relationships among structure, function, and cognition. We aimed to clarify how specifically DLPFC structure and function contribute to working memory in healthy older adults. In total, 138 participants aged 65-88 underwent 3T neuroimaging and were divided into higher and lower groups based on a median split of in-scanner n-back task performance. Three a priori spherical DLPFC regions of interest (ROIs) were used to quantify blood-oxygen-level-dependent (BOLD) signal and FreeSurfer-derived surface area, cortical thickness, and white matter volume. Binary logistic regressions adjusting for age, sex, education, and scanner type revealed that greater left and right DLPFC BOLD signal predicted the probability of higher performing group membership (P values<.05). Binary logistic regressions also adjusting for total intracranial volume revealed left DLPFC surface area that significantly predicted the probability of being in the higher performing group (P = 0.017). The left DLPFC BOLD signal and surface area were not significantly associated and did not significantly interact to predict group membership (P values>.05). Importantly, this suggests BOLD signal and surface area may independently contribute to working memory performance in healthy older adults.

Reduced striatal GABA in unmedicated children with ADHD at 7T

Attention-deficit hyperactive disorder (ADHD) is characterized by inattention and increased impulsive and hypermotoric behaviors.Despite the high prevalence and impact of ADHD, little is known about the underlying neurophysiology of ADHD. The main inhibitory and excitatory neurotransmitters γ-aminobutyric acid (GABA) and glutamate are receiving increased attention in ADHD and can be measured using Magnetic Resonance Spectroscopy (MRS). However, MRS studies in ADHD are limited. We measured GABA and glutamate in young unmedicated participants, utilizing high magnetic field strength. Fifty unmedicated children (26 with ADHD, 24 controls) aged 5–9 years completed MRS at 7T and behavioral testing. GABA and glutamate were measured in dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), premotor cortex (PMC), and striatum, and estimated using LCModel. Children with ADHD showed poorer inhibitory control and significantly reduced GABA/Cr in the striatum, but not in ACC, DLPFC, or PMC regions. There were no significant group differences for Glu/Cr levels, or correlations with behavioral manifestations of ADHD. The primary finding of this study is a reduction of striatal GABA levels in unmedicated children with ADHD at 7T. These findings provide guidance for future studies or interventions. Reduced striatal GABA may be a marker for specific GABA-related treatment for ADHD.

Context-dependency in the Cognitive Bias Task and Resting-state Functional Connectivity of the Dorsolateral Prefrontal Cortex.

Goldberg, the author of the "novelty-routinization" framework, suggested a new pair of cognitive styles for agent-centered decision-making (DM), context-dependency/independency (CD/CI), quantified by the Cognitive Bias Task (CBT) and supposedly reflecting functional brain hemispheric specialization. To date, there are only three lesion and activation neuroimaging studies on the CBT with the largest sample of 12 participants. The present study is the first to analyze whole-brain functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC), involved in contextual agent-centered DM. We compared whole-brain resting-state FC of the DLPFC between CD (n = 24) and CI (n = 22) healthy participants. Additionally, we investigated associations between CD/CI and different aspects of executive functions. CD participants had stronger positive FC of the DLPFC with motor and visual regions; FC of the left DLPFC was more extensive. CI participants had stronger positive FC of the left DLPFC with right prefrontal and parietal-occipital areas and of the left and right DLPFC with ipsilateral cerebellar hemispheres. No sex differences were found. CD/CI had nonlinear associations with working memory. The findings suggest that CD and CI are associated with different patterns of DLPFC FC. While CD is associated with FC between DLPFC and areas presumably involved in storing representations of current situation, CI is more likely to be associated with FC between DLPFC and right-lateralized associative regions, probably involved in the inhibition of the CD response and switching from processing of incoming perceptual information to creation of original response strategies.

How does the non-conscious become conscious?

In this My Word, Joseph LeDoux describes how his work as a graduate student got him interested in human consciousness. Although he has not studied this topic since 1970s, he never stopped thinking and writing about it during his four-decade career exploring how non-conscious processes involving the amygdala detect and respond to danger. Here, he tells us what is on his mind about consciousness these days.