Bilateral Prefrontal Cortex Research Articles

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.

Brain structural and perfusion changes in amyotrophic lateral sclerosis-frontotemporal dementia patients with cognitive and motor onset: a preliminary study

Amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) is rare but exhibits worse prognosis than either ALS or FTD alone. However, cognitive onset ALS-FTD (ALS-FTD-C) confers significantly better patient survival than does motor onset ALS-FTD (ALS-FTD-M), underscoring a meager understanding of pathological group differences. This study aimed to assess disparities in cortical atrophy and perfusion shown by patients with the above disease variants. A total of 38 participants (ALS-FTD-C, 8; ALS-FTD-M, 6; simultaneous-onset ALS-FTD [ALS-FTD-S], 4; healthy controls [HC], 20) qualified for the study and underwent magnetic resonance imaging scan. Three-dimensional T1-weighted structural brain imaging and 3D-pseudocontinuous arterial spin-labeled imaging were routinely collected. Gray matter volume (GMV) and cerebral blood flow (CBF) in ALS-FTD-C and ALS-FTD-M were compared through voxel-based analysis. Correlations between imaging parameters and clinical data were also assessed. Compared with HC, ALS-FTD had significant GMV reduction mainly in bilateral limbic system. GMV reduction in ALS-FTD-C was similar in pattern but less widespread, whereas ALS-FTD-M lacked any significant GMV reduction. In CBF analyses, ALS-FTD displayed hypoperfusion in bilateral motor cortex, frontotemporal lobe, and left basal ganglia. Hypoperfusion involved bilateral temporal lobe, prefrontal cortex, and putamen in ALS-FTD-C but was limited to left parahippocampal gyrus in ALS-FTD-M. Correlations between clinical data and GMV/CBF changes in specific regions were also identified in ALS-FTD. Group-specific patterns of cortical atrophy and perfusion were evident in ALS-FTD-C and ALS-FTD-M. ALS-FTD-C showed pronounced cortical atrophy and hypoperfusion, which were otherwise minimal in ALS-FTD-M. Above findings preliminarily revealed the pathological group differences that may help in classifying patients with ALS-FTD.

Improved Regional Homogeneity in Chronic Insomnia Disorder After Amygdala-Based Real-Time fMRI Neurofeedback Training.

BackgroundChronic insomnia disorder (CID) is a highly prevalent sleep disorder, which influences people's daily life and is even life threatening. However, whether the resting-state regional homogeneity (ReHo) of disrupted brain regions in CID can be reshaped to normal after treatment remains unclear.MethodsA novel intervention real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) was used to train 28 CID patients to regulate the activity of the left amygdala for three sessions in 6 weeks. The ReHo methodology was adopted to explore its role on resting-state fMRI data, which were collected before and after training. Moreover, the relationships between changes of clinical variables and ReHo value of altered regions were determined.ResultsResults showed that the bilateral dorsal medial pre-frontal cortex, supplementary motor area (SMA), and left dorsal lateral pre-frontal cortex had decreased ReHo values, whereas the bilateral cerebellum anterior lobe (CAL) had increased ReHo values after training. Some clinical scores markedly decreased, including Pittsburgh Sleep Quality Index, Insomnia Severity Index, Beck Depression Inventory, and Hamilton Anxiety Scale (HAMA). Additionally, the ReHo values of the left CAL were positively correlated with the change in the Hamilton depression scale score, and a remarkable positive correlation was found between the ReHo values of the right SMA and the HAMA score.ConclusionOur study provided an objective evidence that amygdala-based rtfMRI-NF training could reshape abnormal ReHo and improve sleep in patients with CID. The improved ReHo in CID provides insights into the neurobiological mechanism for the effectiveness of this intervention. However, larger double-blinded sham-controlled trials are needed to confirm our results from this initial study.

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.

Evaluating interhemispheric synchronization and cortical activity in acute stroke patients using optical hemodynamic oscillations

Objective. An understanding of functional interhemispheric asymmetry in ischemic stroke patients is a crucial factor in the designs of efficient programs for post-stroke rehabilitation. This study evaluates interhemispheric synchronization and cortical activities in acute stroke patients with various degrees of severity and at different post-stroke stages. Approach. Twenty-three patients were recruited to participate in the experiments, including resting-state and speed finger-tapping tasks at week-1 and week-3 post-stroke. Multichannel near-infrared spectroscopy (NIRS) was used to measure the changes in hemodynamics in the bilateral prefrontal cortex (PFC), the supplementary motor area (SMA), and the sensorimotor cortex (SMC). The interhemispheric correlation coefficient (IHCC) measuring the synchronized activities in time and the wavelet phase coherence (WPCO) measuring the phasic activity in time-frequency were used to reflect the symmetry between the two hemispheres within a region. The changes in oxyhemoglobin during the finger-tapping tasks were used to present cortical activation. Main results. IHCC and WPCO values in the severe-stroke were significantly lower than those in the minor-stroke at low frequency bands during week-3 post-stroke. Cortical activation in all regions in the affected hemisphere was significantly lower than that in the unaffected hemisphere in the moderate-severe stroke measured in week-1, however, the SMC activation on the affected hemisphere was significantly enhanced in week-3 post-stroke. Significance. In this study, non-invasive NIRS was used to observe dynamic synchronization in the resting-state based on the IHCC and WPCO results as well as hemodynamic changes in a motor task in acute stroke patients. The findings suggest that NIRS could be used as a tool for early stroke assessment and evaluation of the efficacy of post-stroke rehabilitation.

Gray Matter Deficits of Cortical-striatal-limbic Circuit in Social Anxiety Disorder

IntroductionThe extant findings have been of great heterogeneity due to partial volume effects in the investigation of cortical gray matter volume (GMV), high comorbidity with other psychiatric disorders, and concomitant therapy in the neuroimaging studies of social anxiety disorder (SAD).Objectives To identity gray matter deficits in cortical and subcortical structures in non-comorbid never-treated patients, so as to explore the “pure” SAD-specific pathophysiology and neurobiology.Methods Thirty-two non-comorbid free-of-treatment patients with SAD and 32 demography-matched healthy controls were recruited to undergo high-resolution 3.0-Tesla T1-weighted MRI. Cortical thickness (CT) and subcortical GMV were estimated using FreeSurfer; then the whole-brain vertex-wise analysis was performed to compare group differences in CT. Besides, differences in subcortical GMV of priori selected regions-of-interest: amygdala, hippocampus, putamen, and pallidum were compared by an analysis of covariance with age, gender, and total subcortical GMV as covariates.ResultsThe SAD patients demonstrated significantly decreased CT near-symmetrically in the bilateral prefrontal cortex (Monte Carlo simulations of P < 0.05). Besides, smaller GMV in the left hippocampus and pallidum were also observed in the SAD cohort (two-sample t-test of P < 0.05).ConclusionsFor the first time, the current study investigated the structural alterations of CT and subcortical GMV in non-comorbid never-treated patients with SAD. Our findings provide preliminary evidences that structural deficits in cortical-striatal-limbic circuit may contribute to the psychopathological basis of SAD, and offer more detailed structural substrates for the involvement of such aberrant circuit in the imbalance between defective bottom-up response and top-down control to external stimuli in SAD.DisclosureNo significant relationships.

Study Protocol of tDCS Based Pain Modulation in Head and Neck Cancer Patients Under Chemoradiation Therapy Condition: An fNIRS-EEG Study.

BackgroundMultiple therapeutic strategies have been adopted to reduce pain, odynophagia, and oral mucositis in head and neck cancer patients. Among them, transcranial direct current stimulation (tDCS) represents a unique analgesic modality. However, the details of tDCS mechanisms in pain treatment are still unclear.Aims(1) to study the analgesic effects of a protocol that encompassed supervised-remote and in-clinic tDCS sessions applied in head and neck patients undergoing chemoradiation therapy; (2) to explore the underlining brain mechanisms of such modulation process, using a novel protocol that combined functional near-infrared spectroscopy (fNIRS), and electroencephalograph (EEG), two distinct neuroimaging methods that bring information regarding changes in the hemodynamic as well as in the electrical activity of the brain, respectively.MethodsThis proof-of-concept study was performed on two subjects. The study protocol included a 7-week-long tDCS stimulation procedure, a pre-tDCS baseline session, and two post-tDCS follow-up sessions. Two types of tDCS devices were used. One was used in the clinical setting and the other remotely. Brain imaging was obtained in weeks 1, 2, 5, 7, 8, and after 1 month.ResultsThe protocol implemented was safe and reliable. Preliminary results of the fNIRS analysis in weeks 2 and 7 showed a decrease in functional connections between the bilateral prefrontal cortex (PFC) and the primary sensory cortex (S1) (p < 0.05, FDR corrected). Changes in EEG power spectra were found in the PFC when comparing the seventh with the first week of tDCS.ConclusionThe protocol combining remote and in-clinic administered tDCS and integrated fNIRS and EEG to evaluate the brain activity is feasible. The preliminary results suggest that the mechanisms of tDCS in reducing the pain of head and neck cancer patients may be related to its effects on the connections between the S1 and the PFC.

Hyper-connectivity between the left motor cortex and prefrontal cortex is associated with the severity of dysfunction of the descending pain modulatory system in fibromyalgia.

IntroductionThe association between descending pain modulatory system (DPMS) dysfunction and fibromyalgia has been previously described, but more studies are required on its relationship with aberrant functional connectivity (FC) between the motor and prefrontal cortices.ObjectivesThe objective of this cross-sectional observational study was to compare the intra- and interhemispheric FC between the bilateral motor and prefrontal cortices in women with fibromyalgia, comparing responders and nonresponders to the conditioned pain modulation (CPM) test.MethodsA cross-sectional sample of 37 women (23 responders and 14 nonresponders to the CPM test) with fibromyalgia diagnosed according to the American College of Rheumatology criteria underwent a standardized clinical assessment and an FC analysis using functional near-infrared spectroscopy. DPMS function was inferred through responses to the CPM test, which were induced by hand immersion in cold water (0–1°C). A multivariate analysis of covariance for main effects between responders and nonresponders was conducted using the diagnosis of multiple psychiatric disorders and the use of opioid and nonopioid analgesics as covariates. In addition, we analyzed the interaction between the CPM test response and the presence of multiple psychiatric diagnoses.ResultsNonresponders showed increased FC between the left motor cortex (lMC) and the left prefrontal cortex (lPFC) (t = −2.476, p = 0.01) and right prefrontal cortex (rPFC) (t = −2.363, p = 0.02), even when both were considered as covariates in the regression analysis (lMC–lPFC: β = −0.127, t = −2.425, p = 0.021; lMC–rPFC: β = −0.122, t = −2.222, p = 0.033). Regarding main effects, a significant difference was only observed for lMC–lPFC (p = 0.035). A significant interaction was observed between the psychiatric disorders and nonresponse to the CPM test in lMC−lPFC (β = −0.222, t = −2.275, p = 0.03) and lMC−rPFC (β = −0.211, t = −2.2, p = 0.035). Additionally, a significant interaction was observed between the CPM test and FC in these two region-of-interest combinations, despite the psychiatric diagnoses (lMC−lPFC: β = −0.516, t = −2.447, p = 0.02; lMC−rPFC: β = −0.582, t = −2.805, p = 0.008).ConclusionsHigher FC between the lMC and the bilateral PFC may be a neural marker of DPMS dysfunction in women with fibromyalgia, although its interplay with psychiatric diagnoses also seems to influence this association.

Network alterations underlying anxiety symptoms in early multiple sclerosis

BackgroundAnxiety, often seen as comorbidity in multiple sclerosis (MS), is a frequent neuropsychiatric symptom and essentially affects the overall disease burden. Here, we aimed to decipher anxiety-related networks functionally connected to atrophied areas in patients suffering from MS.MethodsUsing 3-T MRI, anxiety-related atrophy maps were generated by correlating longitudinal cortical thinning with the severity of anxiety symptoms in MS patients. To determine brain regions functionally connected to these maps, we applied a technique termed “atrophy network mapping”. Thereby, the anxiety-related atrophy maps were projected onto a large normative connectome (n = 1000) performing seed‐based functional connectivity. Finally, an instructed threat paradigm was conducted with regard to neural excitability and effective connectivity, using transcranial magnetic stimulation combined with high-density electroencephalography.ResultsThinning of the left dorsal prefrontal cortex was the only region that was associated with higher anxiety levels. Atrophy network mapping identified functional involvement of bilateral prefrontal cortex as well as amygdala and hippocampus. Structural equation modeling confirmed that the volumes of these brain regions were significant determinants that influence anxiety symptoms in MS. We additionally identified reduced information flow between the prefrontal cortex and the amygdala at rest, and pathologically increased excitability in the prefrontal cortex in MS patients as compared to controls.ConclusionAnxiety-related prefrontal cortical atrophy in MS leads to a specific network alteration involving structures that resemble known neurobiological anxiety circuits. These findings elucidate the emergence of anxiety as part of the disease pathology and might ultimately enable targeted treatment approaches modulating brain networks in MS.

Effects of Quinolinate-Induced Lesion of the Medial Prefrontal Cortex on Prefrontal and Striatal Concentrations of D-Serine in the Rat.

D-Serine has been shown to play an important role in the expression and control of a variety of brain functions by acting as the endogenous coagonist for the N-methyl-D-aspartate type glutamate receptor (NMDAR), at least, in the forebrain. To obtain further insight into the still debatable cellular localization of the D-amino acid, we have examined the effects of the selective destruction of the neuronal cell bodies by quinolinate on the tissue or extracellular D-serine concentrations in the medial prefrontal cortex of the rat. A local quinolinate infusion into the bilateral medial prefrontal cortex produced a cortical lesion with a marked (- 65%) and non-significant alteration (- 5%) in the cortical and striatal tissue D-serine concentrations, respectively, 7days post-infusion. In vivo microdialysis experiments in the right prefrontal lesion site 9days after the quinolinate application revealed that the basal extracellular D-serine levels were also dramatically reduced (- 64%). A prominent reduction in the tissue levels of GABA in the interneurons of the prefrontal cortex (- 78%) without significant changes in those in the striatum (+ 12%) verified that a major lesion part was confined to the cortical portion. The lack of a significant influence of the prefrontal quinolinate lesion on its dopamine concentrations in the mesocortical dopamine projections suggests that the nerve terminals and axons in the lesion site may be spared. These findings are consistent with the perikarya-selective nature of the present quinolinate-induced lesion and further support the view that neuronal cell bodies of intrinsic neurons in the prefrontal cortical region contain substantial amounts of D-serine, which may sustain the basal extracellular concentrations of D-serine.

Auditory cortical stimulability in non habilitated individuals – An evidence from CAEPs

ObjectiveThe effect of long term auditory deprivation on Cortical Auditory Evoked Potentials (CAEPs) especially in human models is not well explored. Hence, the current study was aimed to investigate the effects of long-term auditory deprivation and stimulability of auditory cortex in non habilitated congenitally deaf adolescents and adults using CAEPs. Methods and ResultsA total of 27 non-habilitated congenitally deaf adolescents/adults with age and gender matched normal hearing adolescents/adults participated in the study. The congenitally deaf group was fitted with high gain hearing aids (first fit). Further, the CAEPs were recorded. The obtained CAEP components were assessed for group effect, source and topographical differences. The between group analysis for CAEP responses showed a significant difference only for P2 latency and amplitude. The source analysis revealed that, in the normal hearing group for CAEPs, the sources were within the temporal regions. However, in the congenitally deaf group, along with the temporal cortex, the bilateral prefrontal cortex also was activated. ConclusionThe findings revealed that it is possible to stimulate and evoke a matured CAEP response from a long deprived auditory system with adequate acoustic stimulation. The presence of CAEP responses is indicative of the functionality of the innate auditory pathway and the crossmodal plasticity in long auditory deprived individuals.

Similarities and differences in working memory and neurometabolism of obsessive-compulsive disorder and major depressive disorder

BackgroundObsessive-compulsive disorder (OCD) and major depressive disorder (MDD) both showed cognitive impairment, and the altered neurometabolic may associate with cognitive impairment. However, there are limited comparative working memory (WM) and neuroimaging studies on these two disorders. Therefore, we investigated the characteristics of WM and neurometabolic changes in patients with OCD and MDD. MethodsA total of 64 unmedicated patients (32 OCD and 32 MDD), and 33 healthy controls (HC) were included to conduct WM assessment comprising Digit Span Test (DST), 2-back task and Stroop Color and Word Test (SCWT). Additionally, all subjects underwent protons magnetic resonance spectroscopy (1H-MRS) to collect neurometabolic ratios of N-acetyl aspartate (NAA) and choline-containing compounds (Cho) to creatine (Cr) in the prefrontal cortex (PFC) and lentiform nucleus (LN). Finally, differential and correlation analysis were conducted to investigate their characteristics and relationships. ResultsCompared with HC, both OCD and MDD patients exhibited a lower accuracy rate in the 2-back task, and only MDD patients performed worse in DST scores and longer reaction times in SCWT (all p < 0.05). Both OCD and MDD patients had lower NAA/Cr ratios in bilateral PFC (all p < 0.05). And the decreased NAA/Cr ratios in right PFC were positively correlated to DST scores in MDD group (r = 0.518, p = 0.003). ConclusionsBoth OCD and MDD showed WM impairment and neurometabolic alterations in PFC. Besides, MDD performed more severe and broader WM impairment compared to OCD. Moreover, the dysfunction of PFC may underlie the neural basis of WM impairment in MDD.

Comparison of Acute Followed by Maintenance ECT vs Clozapine on Psychopathology and Regional Cerebral Blood Flow in Treatment-Resistant Schizophrenia: A Randomized Controlled Trial.

In treatment-resistant schizophrenia (TRS), Clozapine is only approved treatment with undesirable side-effects, warranting better alternatives. Our hypothesis is acute followed by maintenance Electroconvulsive Therapy (M-ECT) will be comparable in efficacy and safety to Clozapine in TRS. In this open-label trial, 60 TRS patients were randomized equally to M-ECT (following an acute-course) or Clozapine. Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Schizophrenia Scale (CGI-SCH), Montreal Cognitive Assessment (MoCA), and Global assessment of functioning (GAF) were measured and compared within and between the groups at baseline, 6 weeks, 12 weeks, and 24 weeks. SPECT-CT brain was done at baseline and 24 weeks to compare the changes in regional cerebral perfusion between the groups and correlate with the changes in the outcome-measures. The PANSS-T scores changes from baseline over the observation-points were significant in both M-ECT and clozapine groups (P < .001), with comparatively better reduction with M-ECT (P < .001). Similar trends were observed in PANSS subscales, CGI-SCH and GAF in both groups, with significantly better improvement with M-ECT over the study-period. After 24 weeks, there was significantly better perfusion with M-ECT in bilateral prefrontal and temporal cortices (P < .05). With M-ECT, a positive correlation was found between changes in PANSS-P scores and left-lateral Temporal cortical perfusion (r = .465, P = .017). Acute followed by M-ECT was more effective than clozapine over 6 months in reducing the positive and negative symptoms, general psychopathology, illness-severity, and improving the global functionality in TRS [clinicaltrials.gov: NCT03807882].

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.

Cortical Activity During Pain Relief: A Functional Near-infrared Spectroscopy Study of Offset Analgesia

Offset analgesia is defined by a dramatic drop in perceived pain intensity with a relatively small decrease in noxious input. Although functional magnetic resonance imaging studies implicate subcortical descending inhibitory circuits during offset analgesia, the role of cortical areas remains unclear. The current study performed task-based and connectivity analyses to elucidate the cortical correlates of offset analgesia using functional near infrared spectroscopy (fNIRS). This study was approved by the University of Pittsburgh IRB. After providing informed consent, twenty-four healthy volunteers (18-50 years old) underwent fNIRS scanning at rest and then during offset (OS) and control (Con) heat stimuli applied to the forearm. NIRS data were collected with a head probe targeting bilateral frontal and somatomotor cortices (NIRx NIRSport2). Pain intensity was recorded continuously on a computerized visual analogue scale (COVAS, Medoc). NIRS data were preprocessed and analyzed in NIRS Toolbox, a free analysis package based in Matlab. After controlling for non-neural hemodynamic responses in superficial tissues, widespread increases in cortical oxygenated hemoglobin concentration were observed, reflecting cortical activation during heat pain. OS – Con contrasts revealed deactivations in bilateral medial prefrontal cortex (mPFC) and bilateral somatosensory cortex (SSC) associated with offset analgesia. Right dorsolateral prefrontal cortex (dlPFC) showed activation only during OS. Functional connectivity analyses are ongoing. These data demonstrate opposing cortical activation patterns during offset analgesia and support a model in which right dlPFC underlies ongoing evaluation of pain intensity change. With predictions of decreasing pain intensity, right dlPFC activation likely inhibits ascending noxious input via subcortical pathways resulting in SSC and mPFC deactivation. This study identifies cortical circuitry underlying offset analgesia and introduces the use of fNIRS to study pain modulation in an outpatient clinical environment. Grant support from NIGMS T32GM075770 (BA), NIBIB R01EB028248-01 (TH), the Virginia Kaufman Endowment Fund in the form of a Pitt CTSI competitive research grant (BA, HS, AW, TH), and the International Anesthesia Research Society in the form of the Mentored Research Award (BA).

Modulation of Interhemispheric Synchronization and Cortical Activity in Healthy Subjects by High-Definition Theta-Burst Electrical Stimulation.

Background Various forms of theta-burst stimulation (TBS) such as intermittent TBS (iTBS) and continuous TBS (cTBS) have been introduced as novel facilitation/suppression schemes during repetitive transcranial magnetic stimulation (rTMS), demonstrating a better efficacy than conventional paradigms. Herein, we extended the rTMS-TBS schemes to electrical stimulation of high-definition montage (HD-TBS) and investigated its neural effects on the human brain. Methods In a within-subject design, fifteen right-handed healthy adults randomly participated in 10 min and 2 mA HD-TBS sessions: unilateral (Uni)-iTBS, bilateral (Bi)-cTBS/iTBS, and sham stimulation over primary motor cortex regions. A 20-channel near-infrared spectroscopy (NIRS) system was covered on the bilateral prefrontal cortex (PFC), sensory motor cortex (SMC), and parietal lobe (PL) for observing cerebral hemodynamic responses in the resting-state and during fast finger-tapping tasks at pre-, during, and poststimulation. Interhemispheric correlation coefficient (IHCC) and wavelet phase coherence (WPCO) from resting-state NIRS and concentration of oxyhemoglobin during fast finger-tapping tasks were explored to reflect the symmetry between the two hemispheres and cortical activity, respectively. Results The IHCC and WPCO of NIRS data in the SMC region under Bi-cTBS/iTBS showed relatively small values at low-frequency bands III (0.06–0.15 Hz) and IV (0.02–0.06), indicating a significant desynchronization in both time and frequency domains. In addition, the SMC activation induced by fast finger-tapping exercise was significantly greater during Uni-iTBS as well as during and post Bi-cTBS/iTBS sessions. Conclusions It appears that a 10 min and 2 mA Bi-cTBS/iTBS applied over two hemispheres within the primary motor cortex region could effectively modulate the interhemispheric synchronization and cortical activation in the SMC of healthy subjects. Our study demonstrated that bilateral HD-TBS approaches is an effective noninvasive brain stimulation scheme which could be a novel therapeutic for inducing effects of neuromodulation on various neurological disorders caused by ischemic stroke or traumatic brain injuries.

Not the Master of Your Volitional Mind? The Roles of the Right Medial Prefrontal Cortex and Personality Traits in Unconscious Introjections Versus Self-Chosen Goals.

Humans are unconditionally confronted with social expectations and norms, up to a degree that they, or some of them, have a hard time recognizing what they actually want. This renders them susceptible for introjection, that is, to unwittingly or “unconsciously” mistake social expectations for self-chosen goals. Such introjections compromise an individual’s autonomy and mental health and have been shown to be more prevalent in individuals with rumination tendencies and low emotional self-awareness. In this brain imaging study, we draw on a source memory task and found that introjections, as indicated by imposed tasks that are falsely recognized as self-chosen, involved the bilateral medial prefrontal cortex (MPFC) and the dorsal anterior cingulate cortex (ACC). Notably, reduced right MPFC activation within this condition correlated with trait scores of ruminations and reduced emotional self-awareness, but also introversion. Moreover, correct recognition of tasks as self-chosen involved the right MPFC. Accordingly, the right MPFC may play a role in supporting the maintenance of psychological autonomy and counteract introjection, which individuals with certain personality traits seem to be prone to. This research has significant implications for the study of mechanisms underlying autonomous motivation, goal and norm internalization, decision-making, persuasion, education, and clinical conditions such as depression and burnout.

Cortical Thickness Abnormalities at Different Stages of the Illness Course in Schizophrenia

Questions of whether and how cortical thickness (CTh) alterations differ over the course of schizophrenia (SCZ) have yet to be resolved. To characterize CTh alterations across illness stages in SCZ. PubMed, Embase, Web of Science, and Science Direct were screened for CTh studies published before June 15, 2021. Original studies comparing whole-brain CTh alterations from healthy controls in individuals at clinical high-risk (CHR), first episode of psychosis (FEP), and long-term illness stages of SCZ were included. This preregistered systematic review and meta-analysis followed PRISMA reporting guidelines. Separate and pooled meta-analyses were performed using seed-based d mapping. Meta-regression analyses were conducted. Cortical thickness differences from healthy control individuals across illness stages. Ten studies comprising 859 individuals with CHR (mean [SD] age, 21.02 [2.66] years; male, 573 [66.7%]), 12 studies including 671 individuals with FEP (mean [SD] age, 22.87 [3.99] years; male, 439 [65.4%]), and 10 studies comprising 579 individuals with long-term SCZ (mean [SD] age, 41.58 [6.95] years; male, 396 [68.4%]) were included. Compared with healthy control individuals, individuals with CHR showed cortical thinning in bilateral medial prefrontal cortex (z = -1.01; P < .001). Individuals with FEP showed cortical thinning in right lateral superior temporal cortex (z = -1.34; P < .001), right anterior cingulate cortex (z = -1.44; P < .001), and right insula (z = -1.14; P = .002). Individuals with long-term SCZ demonstrated CTh reductions in right insula (z = -3.25; P < .001), right inferior frontal cortex (z = -2.19; P < .001), and left (z = -2.37; P < .001) and right (z = -1.94; P = .002) temporal pole. There were no significant CTh differences between CHR and FEP. Individuals with long-term SCZ showed greater cortical thinning in right insula (z = -2.58; P < .001), right inferior frontal cortex (z = -2.32; P < .001), left lateral temporal cortex (z = -1.91; P = .002), and right temporal pole (z = -1.82; P = .002) than individuals with FEP. Combining all studies on SCZ, accelerated age-related CTh reductions were found in bilateral lateral middle temporal cortex and right pars orbitalis in inferior frontal cortex. The absence of significant differences between FEP and CHR noted in this systematic review and meta-analysis suggests that the onset of psychosis was not associated with robust CTh reduction. The greater cortical thinning in long-term SCZ compared with FEP with accelerated age-related reduction in CTh suggests progressive neuroanatomic alterations following illness onset. Caution in interpretation is needed because heterogeneity in samples and antipsychotic treatment may confound these results.

Offset analgesia is associated with opposing modulation of medial versus dorsolateral prefrontal cortex activations: A functional near-infrared spectroscopy study.

Offset analgesia is defined by a dramatic drop in perceived pain intensity with a relatively small decrease in noxious input. Although functional magnetic resonance imaging studies implicate subcortical descending inhibitory circuits during offset analgesia, the role of cortical areas remains unclear. The current study identifies cortical correlates of offset analgesia using functional near infrared spectroscopy (fNIRS). Twenty-four healthy volunteers underwent fNIRS scanning during offset (OS) and control (Con) heat stimuli applied to the forearm. After controlling for non-neural hemodynamic responses in superficial tissues, widespread increases in cortical oxygenated hemoglobin concentration were observed, reflecting cortical activation during heat pain. OS–Con contrasts revealed deactivations in bilateral medial prefrontal cortex (mPFC) and bilateral somatosensory cortex (SSC) associated with offset analgesia. Right dorsolateral prefrontal cortex (dlPFC) showed activation only during OS. These data demonstrate opposing cortical activation patterns during offset analgesia and support a model in which right dlPFC underlies ongoing evaluation of pain intensity change. With predictions of decreasing pain intensity, right dlPFC activation likely inhibits ascending noxious input via subcortical pathways resulting in SSC and mPFC deactivation. This study identifies cortical circuitry underlying offset analgesia and introduces the use of fNIRS to study pain modulation in an outpatient clinical environment.

Disorder- and cognitive demand-specific neurofunctional alterations during social emotional working memory in generalized anxiety disorder and major depressive disorder

BackgroundGeneralized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) are both characterized by cognitive and social impairments. Determining disorder-specific neurobiological alterations in GAD and MDD by means of functional magnetic resonance imaging (fMRI) may promote determination of precise diagnostic markers. MethodsThis study aimed to examine disorder-specific behavioral and neural alterations at the intersection of social and cognitive processing in treatment-naïve first-episode GAD (n = 35) and MDD (n = 37) patients compared to healthy controls (n = 35) by employing a social-emotional n-back fMRI paradigm. ResultsNo behavioral differences between patients and healthy controls were observed. However, GAD patients exhibited decreased bilateral dorsomedial prefrontal cortex (dmPFC) engagement during the 0-back condition yet increased dmPFC engagement during the 1-back condition compared to MDD and healthy participants. In contrast, MDD patients exhibited increased dmPFC-insula coupling during 0-back, yet decreased coupling during 1-back, compared to GAD and healthy participants. Dimensional symptom-load analysis confirmed that increased dmPFC-insula connectivity during 0-back was positively associated with depressive symptom load. LimitationsThe moderate sample size in the present study did not allow us to further explore gender differences. In addition, some patients exhibited GAD and MDD comorbidity according to the M.I.N.I. interview. Finally, the paradigm we used did not allow to further disentangle emotion-specific effects on working memory. ConclusionsThese findings suggest that the dmPFC engaged in integrating affective and cognitive components and self-other processing exhibits GAD-specific neurofunctional dysregulations whereas functional dmPFC communication with the insula, a region involved in salience processing, may represent an MDD-specific neurofunctional deficit.