Midfrontal Gyrus Research Articles

Cytoarchitectonic gradients of laminar degeneration in behavioural variant frontotemporal dementia.

Behavioral variant frontotemporal dementia (bvFTD) is a clinical syndrome primarily caused by either tau (bvFTD-tau) or TDP-43 (bvFTD-TDP) proteinopathies. We previously found lower cortical layers and dorsolateral regions accumulate greater tau than TDP-43 pathology; however, patterns of laminar neurodegeneration across diverse cytoarchitecture in bvFTD is understudied. We hypothesized that bvFTD-tau and bvFTD-TDP have distinct laminar distributions of pyramidal neurodegeneration along cortical gradients, a topologic order of cytoarchitectonic subregions based on increasing pyramidal density and laminar differentiation. Here, we tested this hypothesis in a frontal cortical gradient consisting of five cytoarchitectonic types (i.e., periallocortex, agranular mesocortex, dysgranular mesocortex, eulaminate-I isocortex, eulaminate-II isocortex) spanning anterior cingulate, paracingulate, orbitofrontal, and mid-frontal gyri in bvFTD-tau (n=27), bvFTD-TDP (n=47), and healthy controls (HC; n=32). We immunostained all tissue for total neurons (NeuN; neuronal-nuclear protein) and pyramidal neurons (SMI32; non-phosphorylated neurofilament) and digitally quantified NeuN-immunoreactivity (ir) and SMI32-ir in supragranular II-III, infragranular V-VI, and all I-VI layers in each cytoarchitectonic type. We used linear mixed-effects models adjusted for demographic and biologic variables to compare SMI32-ir between groups and examine relationships with the cortical gradient, long-range pathways, and clinical symptoms. We found regional and laminar distributions of SMI32-ir expected for HC, validating our measures within the cortical gradient framework. While SMI32-ir loss was relatively uniform along the cortical gradient in bvFTD-TDP, SMI32-ir progressively decreased along the cortical gradient of bvFTD-tau and included greater SMI32-ir loss in supragranular eulaminate-II isocortex in bvFTD-tau versus bvFTD-TDP (p=0.039). Using a ratio of SMI32-ir to model known long-range connectivity between infragranular mesocortex and supragranular isocortex, we found a larger laminar ratio in bvFTD-tau versus bvFTD-TDP (p=0.019), suggesting select long-projecting pathways may contribute to isocortical-predominant degeneration in bvFTD-tau. In cytoarchitectonic types with the highest NeuN-ir, we found lower SMI32-ir in bvFTD-tau versus bvFTD-TDP (p=0.047), suggesting pyramidal neurodegeneration may occur earlier in bvFTD-tau. Lastly, we found that reduced SMI32-ir related to behavioral severity and frontal-mediated letter fluency, not temporal-mediated confrontation naming, demonstrating the clinical relevance and specificity of frontal pyramidal neurodegeneration to bvFTD-related symptoms. Our data suggest loss of neurofilament-rich pyramidal neurons is a clinically relevant feature of bvFTD that selectively worsens along a frontal cortical gradient in bvFTD-tau, not bvFTD-TDP. Therefore, tau-mediated degeneration may preferentially involve pyramidal-rich layers that connect more distant cytoarchitectonic types. Moreover, the hierarchical arrangement of cytoarchitecture along cortical gradients may be an important neuroanatomical framework for identifying which types of cells and pathways are differentially involved between proteinopathies.

Decoding auditory deprivation: resting-state fMRI insights into deafness and brain plasticity.

Deafness, as a profound manifestation of sensory deprivation, prompts a cascade of intricate cerebral adaptations. In this study, involving 35 deaf individuals and 35 hearing controls, we utilized resting-state functional magnetic resonance imaging (rs-fMRI) to delve into the depths of functional connectivity nuances distinguishing deaf individuals from their hearing counterparts. Leading our analytical approach was the application of multi-voxel pattern analysis (fc-MVPA). This advanced method provided a refined perspective, revealing amplified neural connectivity within the deaf population. Notably, regions such as the left postcentral somatosensory association cortex, the anterior and posterior corridors of the left superior temporal gyrus (STG), and the left mid-temporal lobe were identified as hotspots of heightened connectivity. Further, fc-MVPA shed light on intricate interaction effects, which became more pronounced when examining variables such as the duration of auditory deprivation and the extent of sign language exposure. These interactions were particularly evident in the premotor and left frontal mid-orbital regions. Complementing this, seed-based connectivity assessments illuminated pronounced coupling dynamics within the left STG spectrum. Concurrently, local correlation (LCOR) value analysis in the deaf group revealed significant shifts in the right superior STG and bilateral precuneus. In addition, amplitude of low-frequency fluctuation (ALFF) evaluations indicated modulations in the bilateral mid cingulum and left superior mid frontal gyrus. This comprehensive, fc-MVPA-driven exploration uncovers the multifaceted functional adaptations resulting from deafness, highlighting the profound plasticity of the human brain and its potential implications for targeted rehabilitative strategies.

Task-related oxygenation in the prefrontal cortex as a function of mask-wearing frequency: An empirical test using functional near-infrared spectroscopy

ObjectiveIntroduction of brain hypoxia by frequent mask-wearing is a concern voiced by some who resist masking mandates. Studies have examined acute effects of one-shot mask-wearing on peripheral and cerebral oxygenation in the laboratory, but not effects of everyday mask-wearing frequencies on task-related functional activation. The objective of the current study was to examine whether frequency of mask-wearing in daily life is associated with lower task-related brain oxygenation levels, and whether the magnitude of any such effects vary by age and sex. MethodsParticipants were 78 community-dwelling adults between the ages of 18 and 84 years, all of whom were vaccinated at the time of participation; 65.4% (n = 51) were female. Frequency of mask-wearing was assessed using survey questions on mask-wearing practice during an active COVID-19 mask mandate. Recordings of task-related cerebral oxygenation were taken during the completion of a simple reaction time task using 16-channel functional near-infrared spectroscopy (fNIRS). ResultsThe psychomotor vigilance task elicited reliable increases in cerebral oxygenation within the right mid-frontal gyrus (F(1,61.345) = 15.975, p < .001). However, there was no significant association between everyday masking frequency and performance on the psychomotor vigilance task (b = 0.059, SE = 0.092 (95% CI [-0.122, 0.241]), t = .646, p = .520), nor any association between everyday masking frequency and task-related brain oxygenation on any measurement channel (all ps < .05). ConclusionsHigher mask-wearing frequency in daily life is not associated with significantly lower levels of task-related brain oxygenation, or worse performance on a sustained attention task.

The Chromatin Structure at the MECP2 Gene and In Silico Prediction of Potential Coding and Non-Coding MECP2 Splice Variants.

Methyl CpG binding protein 2 (MeCP2) is an epigenetic reader that binds to methylated CpG dinucleotides and regulates gene transcription. Mecp2/MECP2 gene has 4 exons, encoding for protein isoforms MeCP2E1 and MeCP2E2. MeCP2 plays key roles in neurodevelopment, therefore, its gain- and loss-of-function mutations lead to neurodevelopmental disorders including Rett Syndrome. Here, we describe the structure, functional domains, and evidence support for potential additional alternatively spliced MECP2 transcripts and protein isoforms. We conclude that NCBI MeCP2 isoforms 3 and 4 contain certain MeCP2 functional domains. Our in silico analysis led to identification of histone modification and accessibility profiles at the MECP2 gene and its cis-regulatory elements. We conclude that the human MECP2 gene associated histone post-translational modifications exhibit high similarity between males and females. Between brain regions, histone modifications were found to be less conserved and enriched within larger genomic segments named as "S1-S11". We also identified highly conserved DNA accessibility regions in different tissues and brain regions, named as "A1-A9" and "B1-B9". DNA methylation profile was similar between mid-frontal gyrus of donors 35 days-25 years of age. Based on ATAC-seq data, the identified hypomethylated regions "H1-H8" intersected with most regions of the accessible chromatin (A regions).

CNS imaging characteristics in fibromyalgia patients with and without peripheral nerve involvement

We tested the hypothesis that reduced skin innervation in fibromyalgia syndrome is associated with specific CNS changes. This prospective case–control study included 43 women diagnosed with fibromyalgia syndrome and 40 healthy controls. We further compared the fibromyalgia subgroups with reduced (n = 21) and normal (n = 22) skin innervation. Brains were analysed for cortical volume, for white matter integrity, and for functional connectivity. Compared to controls, cortical thickness was decreased in regions of the frontal, temporal and parietal cortex in the fibromyalgia group as a whole, and decreased in the bilateral pericalcarine cortices in the fibromyalgia subgroup with reduced skin innervation. Diffusion tensor imaging revealed a significant increase in fractional anisotropy in the corona radiata, the corpus callosum, cingulum and fornix in patients with fibromyalgia compared to healthy controls and decreased FA in parts of the internal capsule and thalamic radiation in the subgroup with reduced skin innervation. Using resting-state fMRI, the fibromyalgia group as a whole showed functional hypoconnectivity between the right midfrontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. The subgroup with reduced skin innervation showed hyperconnectivity between the inferior frontal gyrus, the angular gyrus and the posterior parietal gyrus. Our results suggest that the subgroup of fibromyalgia patients with pronounced pathology in the peripheral nervous system shows alterations in morphology, structural and functional connectivity also at the level of the encephalon. We propose considering these subgroups when conducting clinical trials.

The Changes of Brain Function After Spinal Manipulation Therapy in Patients with Chronic Low Back Pain: A Rest BOLD fMRI Study.

ObjectiveTo investigate the changes of regional homogeneity (Reho) values before and after spinal manipulative therapy (SMT) in patients with chronic low back pain (CLBP) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI).MethodsPatients with CLBP (Group 1, n = 20) and healthy control subjects (Group 2, n = 20) were recruited. The fMRI was performed three times in Group 1 before SMT (time point 1, TP1), after the first SMT (time point 2, TP2), after the sixth SMT (time point 3, TP3), and for one time in Group 2, which received no intervention. The clinical scales were finished in Group 1 every time before fMRI was performed. The Reho values were compared among Group 1 at different time points, and between Group 1 and Group 2. The correlation between Reho values with the statistical differences and the clinical scale scores were calculated.ResultsThe bilateral precuneus and right mid-frontal gyrus in Group 1 had different Reho values compared with Group 2 at TP1. The Reho values were increased in the left precuneus and decreased in the left superior frontal gyrus in Group 1 at TP2 compared with TP1. The Reho values were increased in the left postcentral gyrus and decreased in the left posterior cingulate cortex and the superior frontal gyrus in Group 1 at TP3 compared with TP1. The ReHo values of the left precuneus in Group 1 at TP1 were negatively correlated with the pain degree at TP1 and TP2 (r = −0.549, −0.453; p = 0.012, 0.045). The Reho values of the middle temporal gyrus in Group 1 at TP3 were negatively correlated with the changes of clinical scale scores between TP3 and TP1 (r = 0.454, 0.559; p = 0.044, 0.01).ConclusionPatients with CLBP showed abnormal brain function activity, which was altered after SMT. The Reho values of the left precuneus could predict the immediate analgesic effect of SMT.

Brain insulin signaling and cerebrovascular disease in human postmortem brain.

Diabetes is associated with impaired insulin metabolism and increased dementia risk. Insulin is important in brain function and alterations may be associated with neuropathology. We examined associations of insulin resistance in the human postmortem brain, as assessed by molecular signaling measures including insulin receptor substrate (IRS1) and serine/threonine-protein kinase [AKT], with pathologically-defined cerebrovascular disease. Subjects were 150 elderly deceased and autopsied persons with or without diabetes, matched 1:1 by sex on age-at-death and education. ELISA, immunohistochemistry, and ex vivo stimulation with insulin, of midfrontal gyrus cortex tissue, documented insulin signaling. Postmortem neuropathologic data identified cerebrovascular disease. We examined associations of brain insulin signaling measures with cerebrovascular pathology, and specifically with brain infarcts (including by size and location) and cerebral vessel pathologies including atherosclerosis, arteriolosclerosis, and amyloid angiopathy. We also examined whether diabetes affected associations of the insulin measures with cerebrovascular pathology. In a regression analysis, greater AKT1 phosphorylation at T308 following ex vivo stimulation of human postmortem brain tissue with insulin was associated with more cerebrovascular disease, and specifically more brain infarcts (OR=1.916; estimate=0.650; p=0.007). This association was present regardless of diabetes status. In secondary analyses, we also found that a greater pS616 IRS1 immunolabeling in neuronal cytoplasm was associated with more brain infarcts (OR=1.610; estimate=0.476; p=0.013), and that this association was higher among persons without diabetes. We also showed consistent results of pS616 IRS1 associations with each of gross infarcts and microinfarcts separately. No other association including by infarct location (cortical or subcortical) was found. No association was found between other measures of insulin resistance including levels of proteins by ELISA, with any of the infarct outcomes including cortical or subcortical infarct outcomes. Other analyses with vessel pathologies as outcomes showed no association of the insulin resistance and related markers with atherosclerosis or arteriolosclerosis, except for pS473 AKT1 following insulin stimulation being associated with less amyloid angiopathy. In this study of elderly autopsied persons with or without diabetes, we found that insulin resistance in the human brain is associated with cerebrovascular disease and especially infarcts (in number and different sizes), even among persons without diabetes. The underlying pathophysiologic mechanisms need further elucidation.

Brain insulin signaling and cerebrovascular disease in human postmortem brain

Insulin is an important hormone for brain function, and alterations in insulin metabolism may be associated with neuropathology. We examined associations of molecular markers of brain insulin signaling with cerebrovascular disease. Participants were enrolled in the Religious Orders Study (ROS), an ongoing epidemiologic community-based, clinical-pathologic study of aging from across the United States. Using cross-sectional analyses, we studied a subset of ROS: 150 persons with or without diabetes, matched 1:1 by sex on age-at-death and education. We used ELISA, immunohistochemistry, and ex vivo stimulation with insulin, to document insulin signaling in postmortem midfrontal gyrus cortex tissue. Postmortem neuropathologic data identified cerebrovascular disease including brain infarcts, classified by number (as none for the reference; one; and more than one), size (gross and microscopic infarcts), and brain region/location (cortical and subcortical). Cerebral vessel pathologies were assessed, including severity of atherosclerosis, arteriolosclerosis, and amyloid angiopathy. In separate regression analyses, greater AKT1 phosphorylation at T308 following ex vivo stimulation with insulin (OR = 1.916; estimate = 0.650; p = 0.007) and greater pS616IRS1 immunolabeling in neuronal cytoplasm (OR = 1.610; estimate = 0.476; p = 0.013), were each associated with a higher number of brain infarcts. Secondary analyses showed consistent results for gross infarcts and microinfarcts separately, but no other association including by infarct location (cortical or subcortical). AKT S473 phosphorylation following insulin stimulation was associated with less amyloid angiopathy severity, but not with other vessel pathology including atherosclerosis and arteriolosclerosis. In summary, insulin resistance in the human brain, even among persons without diabetes, is associated with cerebrovascular disease and especially infarcts. The underlying pathophysiologic mechanisms need further elucidation. Because brain infarcts are known to be associated with lower cognitive function and dementia, these data are relevant to better understanding the link between brain metabolism and brain function.

Neurocognitive markers of passive suicidal ideation in late-life depression.

(1) To delineate whether cognitive flexibility and inhibitory ability are neurocognitive markers of passive suicidal ideation (PSI), an early stage of suicide risk in depression and (2) to determine whether PSI is associated with volumetric differences in regions of the prefrontal cortex (PFC) in middle-aged and older adults with depression. Cross-sectional study. University medical school. Forty community-dwelling middle-aged and older adults with depression from a larger study of depression and anxiety (NIMH R01 MH091342-05 PI: O'Hara). Psychiatric measures were assessed for the presence of a DSM-5 depressive disorder and PSI. A neurocognitive battery assessed cognitive flexibility, inhibitory ability, as well as other neurocognitive domains. The PSI group (n = 18) performed significantly worse on cognitive flexibility and inhibitory ability, but not on other neurocognitive tasks, compared to the group without PSI (n = 22). The group with PSI had larger left mid-frontal gyri (MFG) than the no-PSI group. There was no association between cognitive flexibility/inhibitory ability and left MFG volume. Findings implicate a neurocognitive signature of PSI: poorer cognitive flexibility and poor inhibitory ability not better accounted for by other domains of cognitive dysfunction and not associated with volumetric differences in the left MFG. This suggests that there are two specific but independent risk factors of PSI in middle- and older-aged adults.

442 - Neurocognitive markers of passive suicidal ideation in late life depression

Aims:Late life suicide is an international public health crisis, yet the mechanisms underlying late life suicide risk are far less understood compared to younger age groups. Executive dysfunction is widely documented in late life depression (LLD), and cognitive flexibility and inhibition are specifically hypothesized as vulnerabilities for suicide risk. There is some evidence that LLD patients with suicidal ideation or attempt suicide have worse executive dysfunction than LLD patients that do not; however, it is unknown whether these differences exist in Passive Suicidal Ideation (PSI), which may be an important early stage of suicide risk. Delineating the mechanisms of risk for PSI in LLD is a crucial direction for late life suicide research. The purpose of our study was to examine whether cognitive flexibility and inhibitory ability are neurocognitive markers of PSI. The secondary purpose of our study was to determine if neurocognitive differences due to PSI are mediated by volumetric differences in the prefrontal cortex.Methods:Forty community-dwelling middle- and older-aged adults with LLD (18 with PSI, 22 without) completed a neurocognitive battery that assessed cognitive flexibility, inhibitory ability, as well as other neurocognitive domains, and underwent structural neuroimaging.Results:The PSI group performed significantly worse on cognitive flexibility and inhibitory ability, but not on other neurocognitive tasks which included other measures of executive function. The PSI group had a larger left mid-frontal gyrus (LMFG) than those without PSI, but there was no association between LMFG and cognitive flexibility or inhibitory ability, nor was there statistical evidence of mediation.Conclusions:Our findings implicate a unique neurocognitive signature in LLD with PSI: poorer cognitive flexibility and poorer inhibitory ability not better accounted for by other domains of cognitive dysfunction and not mediated by volumetric differences in the prefrontal cortex. Volumetric brain differences in the LMFG appear unrelated to differences in cognitive flexibility and inhibitory ability, which suggests two specific but independent risk factors for PSI in middle- and older-aged adults.

The effects of gastrointestinal symptoms on structural grey matter volume in youth.

Previous neuroimaging studies have examined the association between changes in brain structure and gastrointestinal symptoms (GIS), seen in disorders such as Irritable Bowel Syndrome and Irritable Bowel Disease. Studies in adults have found changes in white and grey matter volume (GMV) in patients with various gastrointestinal disorders. However, it is unclear whether GIS-related structural changes in the brain are limited to adults or could be present throughout the lifespan. Given that gastrointestinal disorders are typically diagnosed between 4 and 18years old, we investigated GIS-induced morphological changes in pre-adolescents (8-10), adolescents (12-16years) and young adults (17-21years). Using a voxel-based morphometry (VBM) analysis, we compared regional grey matter volume (GMV) between participants with GIS and controls, using structural brain images from the Philadelphia Neurodevelopmental Cohort (PNC) database. A total of 211 participants (107 participants with GISs and 104 control participants) who had undergone structural magnetic resonance imaging were analysed. VBM analysis was used to objectively analyse GMV across the whole brain and compare between participants with GIS and controls. Participants experiencing GIS showed smaller GMV in regions within the limbic system/basal ganglia (bilateral caudate, bilateral ventral hippocampus, bilateral amygdala and bilateral superior orbital frontal cortex), and larger GMV in regions within the pain-matrix (thalamus, bilateral putamen, right mid-frontal gyrus) compared to controls. These differences were most prominent in the adolescent and young adult groups compared to pre-adolescents. In conclusion, the structural differences found in participants with GIS support the need for further research into the neurophysiological impact of these symptoms.

A Sleeping rs-fMRI Study of Preschool Children with Autism Spectrum Disorders.

The brain functional network of autism spectrum disorders (ASDs) in the earlier stages of life has been almost unknown due to difficulties in obtaining a resting-state functional magnetic resonance imaging (rs-fMRI). This study aimed to perform rs-MRI under a sedated sleep state and reveal possible alterations in the brain functional network. Rs-fMRI was performed in a group of preschool children (aged 2-6 years, 53 with ASD, 63 as controls) under a sedated sleeping state. Based on graph theoretical analysis, global and local topological metrics were calculated to investigate alterations in brain functional networks. Besides, correlation analyses were conducted between the abnormal attribute values and the Childhood Autism Rating Scale (CARS) scores. The graph theoretical analysis showed that the nodal degree of the right medial frontal gyrus and the nodal efficiency of the right lingual gyrus in the ASD group were higher than those in the control group (P<0.05). There was a statistically significant positive correlation (R=0.318, P<0.05) between the right midfrontal gyrus nodal degree values and CARS scores in the ASD patients. Alterations of some nodal attributes in the brain network occurred in preschool autistic children which could serve as potential imaging biomarkers for evaluating ASD in earlier stages.

Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia

RationaleThere is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce.ObjectivesThe aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC).MethodsIn a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions.ResultsCompared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6).ConclusionsThese findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of interest.

Improving brain function of pediatric acute lymphoblastic leukemia patients after induction chemotherapy, a pilot self-contrast study by fractional amplitude of low-frequency fluctuation

Our previous study revealed altered resting-stated brain function in children with acute lymphoblastic leukemia (ALL) on new-onset stage. To investigate the effects after induction chemotherapy, a pilot self-contrast study was conducted to compare the difference in resting-stated brain function between pre- and post-induction chemotherapy of ALL. Fractional amplitude of low-frequency fluctuation (fALFF) was employed for fMRI data analysis. Clinical and resting state functional magnetic resonance imaging (RS-fMRI) data of 14 new-onset pediatric ALL patients were collected before and after 3 months of induction chemotherapy. Fourteen age- and gender-matched healthy controls (HCs) were recruited for comparison. Before induction chemotherapy, fALFF values of ALL patients decreased globally, especially in the default mode network (DMN), left frontal lobe, left occipital lobe, and bilateral postcentral gyri as compared to HCs. After induction chemotherapy, fALFF values of ALL patients decreased significantly in the bilateral cuneus, left lingual and calcarine gyri, and left mid frontal gyrus. Paired-sample t-tests and self-contrast analysis showed fALFF increased in the left precuneus, bilateral cuneus, left occipital lobe, bilateral frontal gyri, and bilateral temporal lobes, whereas fALFF in the bilateral precuneus decreased in the ALL patients after induction, which suggests potential side-effects of the treatment. The alteration of fALFF values suggested that resting brain function was impaired before induction chemotherapy and mostly recovered after treatment. This study suggested that fALFF is a reliable and feasible tool in detecting spontaneous brain activity to monitor early neurocognitive impairments in pediatric ALL to better understand the underlying neurobiological mechanisms of chemotherapy on the brain.

Using subjective expectations to model the neural underpinnings of proactive inhibition.

Proactive inhibition – the anticipation of having to stop a response – relies on objective information contained in cue‐related contingencies in the environment, as well as on the subjective interpretation derived from these cues. To date, most studies of brain areas underlying proactive inhibition have exclusively considered the objective predictive value of environmental cues, by varying the probability of stop‐signals. However, by only taking into account the effect of different cues on brain activation, the subjective component of how cues affect behavior is ignored. We used a modified stop‐signal response task that includes a measurement for subjective expectation, to investigate the effect of this subjective interpretation. After presenting a cue indicating the probability that a stop‐signal will occur, subjects were asked whether they expected a stop‐signal to occur. Furthermore, response time was used to retrospectively model brain activation related to stop‐expectation. We found more activation during the cue period for 50% stop‐signal probability, when contrasting with 0%, in the mid and inferior frontal gyrus, inferior parietal lobe and putamen. When contrasting expected vs. unexpected trials, we found modest effects in the mid frontal gyrus, parietal, and occipital areas. With our third contrast, we modeled brain activation during the cue with trial‐by‐trial variances in response times. This yielded activation in the putamen, inferior parietal lobe, and mid frontal gyrus. Our study is the first to use the behavioral effects of proactive inhibition to identify the underlying brain regions, by employing an unbiased task‐design that temporally separates cue and response.

Extravascular CD3+ T Cells in Brains of Alzheimer Disease Patients Correlate with Tau but Not with Amyloid Pathology: An Immunohistochemical Study

Background: Strong genetic and epidemiological evidence points to a crucial role of the immune system in the development of Alzheimer disease (AD). CD3+ T lymphocytes have been described in brains of postmortem AD patients and in transgenic models of AD-like cerebral amyloidosis and tau pathology. However, the occurrence of T cells in AD brains is still controversial; furthermore, the relationship between T cells and hallmarks of AD pathology (amyloid plaques and neurofibrillary tangles) remains to be established. Objectives: We have studied the occurrence of T cells in postmortem hippocampi and mid frontal gyrus (MFG) samples of AD patients (Braak stage V-VI) and nondemented control subjects and correlated it with amyloid and tau pathology burden. Methods: Confocal microscopy and bright-field immunohistochemistry were used to identify brain-associated T cells. Extravascular CD3+ T cells were quantified and compared to nondemented controls. In addition, numbers of extravascular CD3+ T cells were correlated with amyloid (6E10 staining) and tau pathology (AT8 staining) in the same sections. Results: Several CD3+, extravascular T cells were observed in the brains of AD patients, mostly of the CD8+ subtype. AD hippocampi harbored significantly increased numbers of extravascular CD3+ T cells compared to nondemented controls. CD3+ T cells significantly correlated with tau pathology but not with amyloid plaques in AD samples. Conclusions: Our data support the notion of T-cell occurrence in AD brains and suggest that, in advanced stages of AD, T-cell extravasation is driven by tau-related neurodegenerative changes rather than by cerebral amyloidosis. T cells could be crucial for driving the amyloid-independent phase of the AD pathology.

Intracranial source activity (eLORETA) related to scalp-level asymmetry scores and depression status.

Frontal EEG alpha asymmetry provides a promising index of depression risk, yet very little is known about the neural sources of alpha asymmetry. To identify these sources, this study examined alpha asymmetry using a distributed inverse solution: exact low resolution brain electromagnetic tomography (eLORETA). Findings implicated a generator in lateral midfrontal regions that contributed to both surface asymmetry and depression risk. Participants with any lifetime history of depressive episodes were characterized by less left than right activity in the precentral gyrus and midfrontal gyrus. Anhedonia accounted for a significant portion of the relationship between alpha asymmetry and lifetime major depressive disorder. Results are suggestive of convergence between motivational and capability models of asymmetry and replicate results from experimental studies in a large resting-state data set. The capability model of frontal alpha asymmetry is contextualized in terms of motor preparedness following emotional mobilization.

Autobiographical memory loss following a right prefrontal lobe tumour resection: a case report and review of the literature

IntroductionThe right prefrontal lobe has not traditionally been considered eloquent brain. Resection of tumours within this region does not typically lead to permanent functional impairment. In this report, we highlight the case of a patient who developed autobiographical memory loss following an uncomplicated resection of a right prefrontal tumour.Case materialA previously fit and well 15-year old presented with a persistent right-sided headache. An MRI demonstrated an expanded right mid-frontal gyrus with changes consistent with a low-grade tumour. The patient underwent a right-sided craniotomy and resection of the lesion which was confirmed as a WHO grade II diffuse astrocytoma. Postoperatively, the patient reported profound retrograde amnesia for a range of memory components, in particular autobiographical memory and semantic memory. Postoperative imaging showed a good resection margin with no evidence of underlying brain injury. Over an 18-month period, the patient showed no improvement in autobiographical memory; however, significant relearning of semantic knowledge took place and her academic performance was found to be in line with expectations for her age.ConclusionIn this report, we discuss a case and review the literature on the role of the right prefrontal cortex in memory and caution on the perception of right prefrontal non-eloquence.

Brain function in patients with diarrhea type irritable bowel syndrome after rectal balloon distention

Objective To investigate the correlation between activated brain regions examined by functional magnetic resonance imaging (fMRI) after rectal balloon distention and intestinal symptoms, psychological status, and quality of life in patients with diarrhea type irritable bowel syndrome (IBS-D) at different stages of disease. Methods According to the symptoms status, patients with IBS-D were divided into onset group (seven patients), remission group (five patients) and persistence group (six patients), and six healthy individuals were selected as healthy controls at the same time. After stimulated with rectal balloon distention at first sensation thresholds, continual defecation thresholds or 80% of maximum tolerable thresholds, patients received fMRI examination. Analysis of variance and two-sample t test were used to compare the difference in activated brain areas between two groups. Pearson analysis was performed to analyze the correlations between activated brain areas and scores of irritable bowel syndrome (IBS) intestinal symptom, Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and irritable bowel syndrome special quality of life scale (IBS-QOL). Results There was no significant difference in first sensation thresholds, continual defecation thresholds or 80% of maximum tolerable thresholds between patients of different groups. After rectal balloon distention, there were differences in such brain areas: bilateral anterior cingulate cortex (ACC), left inferior parietal lobe, and left middle frontal gyrus. Compared with those of control group, the activation of ACC, inferior parietal lobe and middle frontal gyrus lowered in patients of onset group (both P<0.05). There was positive correlation between the activation of middle frontal gyrus and intestinal symptom scores in persistence group(r=0.823, P=0.048). There were negative correlations between the activation of inferior parietal lobe (r =-0.816, P=0.048), middle frontal gyrus(r=-0.860, P=0.028) of persistence group, activation of middle frontal gyrus (r=-0.892, P=0.042) of remission group and HAMD score. There were positive correlations between the activation of inferior parietal lobe (r =0.818, P=0.047), middle frontal gyrus(r = 0.907, P=0.013) of persistence group, activation of midfrontal gyrus (r = 0.914, P=0.030) of remission group and scores of IBS-QOL. Conclusion The brain regions were activated during the rectal balloon distention both in IBS-D patients and healthy controls, and there were differences in activated brain regions among different stages of IBS-D. Key words: Irritable bowel syndrome; diarrhea; Magnetic resonance imaging; Brain region activities; Rectal balloon distention

Side effects for placebo poppers.

Neuroscience Patients in clinical trials may see their conditions improve, sometimes dramatically, even when they are in the control arm of the study. Tetreault et al. used brain imaging to analyze the connectivity during placebo and pain relief treatment for arthritis-induced knee pain. Brain activity associated with the placebo effect was recorded in the right midfrontal gyrus circuitry of about half of the participants. In contrast, duloxetine-induced analgesia stimulated activity deep in the right parahippo-campal gyrus. In some patients, duloxetine interfered adversely with the placebo effect. The responses of individuals can now be differentiated, and their exposure to ineffective therapies can be monitored. PLOS Biol. 10.1371/journal. pbio. 1002570 (2016).