Brodmann Areas Research Articles

Regional cerebral blood flow in behavioral variant of FTD: hypoperfusion patterns and clinical associations.

Findings from functional neuroimaging techniques, such as single-photon emission computed tomography (SPECT), may add useful evidence improving Frontotemporal Dementia (FTD) diagnosis. The aim of the present study was to investigate patterns of hypoperfusion in a group of patients diagnosed with the behavioral variant of FTD (bvFTD) and to explore the relationship between brain perfusion and clinical characteristics. Brain perfusion of 23 bvFTD patients was measured with SPECT scintigraphy in lobes and Brodmann areas (BAs) and the NeurogamTM software was used for image analysis. To assess behavioral disturbances and dementia severity, patients' informants completed the Frontotempotal Behavioral Inventory and the Frontotemporal Dementia Rating Scale. Descriptive statistics were used for the detection of pathological hypoperfusion in lobes and selected BAs. Associations among patients' clinical characteristics and perfusion in lobes were explored via non-parametric correlations. Participants presented pathological hypoperfusion in frontal, limbic and temporal lobes. The most prominent deficit was observed in limbic lobes, where all participants showed pathological hypoperfusion. Decreased perfusion was also observed in limbic, frontal and temporal BAs. Perfusion in the left and right frontal lobe was associated with behavioral disturbances and disease severity, which was also correlated with perfusion in right limbic, left and right temporal areas. Patterns of limbic, frontal and temporal hypopefusion were reported in the present study, along with associations between brain perfusion, behavioral disturbance and severity of dementia. Perfusion patterns can help to understand further associated brain biomarkers, contributing to early diagnosis and intervention in bvFTD.

Genome-wide association study meta-analysis of 9,619 cases with tic disorders

Despite the significant personal and societal burden of tic disorders (TD), treatment outcomes remain modest, necessitating a deeper understanding of their etiology. Family history is the biggest known risk factor and identifying risk genes could accelerate progress in the field. Expanding upon previous sample size limitations, we added 4,800 new TD cases and 971,560 controls, conducting a GWAS meta-analysis with 9,619 cases and 981,048 controls of European ancestry. We attempted to replicate the results in an independent deCODE Genetics GWAS (885 TD cases and 310,367 controls). To characterize GWAS findings, we conducted several post-GWAS gene-based and enrichment analyses. A genome-wide significant hit (rs79244681, p=2.27x10-08) within MCHR2-AS1 was identified, though it was not replicated. Post-GWAS analyses revealed a 13.8% SNP-heritability and three significant genes: BCL11B, NDFIP2, and RBM26. Common variant risk for TD was enriched within genes preferentially expressed in the cortico-striato-thalamo-cortical circuit (including the putamen, caudate, nucleus accumbens, and Brodman area 9) and five brain cell types (excitatory and inhibitory telencephalon-, inhibitory- di- and mesencephalon, hindbrain-, and medium spiny neurons). TD polygenic risk was enriched within loss-of-function intolerant genes (p=0.0017) and high-confidence neurodevelopmental disorder genes (p=0.0108). Of 112 genetic correlations, 43 were statistically significant, showing high positive correlations with most psychiatric disorders. Of the two SNPs previously associated with TD, one (rs2453763) replicated in an independent sub-sample of our GWAS (p=0.00018). This GWAS was still underpowered to identify high-confidence, replicable loci, but the results suggest imminent discovery of common genetic variants for TD.

Unveiling Functional Biomarkers in Schizophrenia: Insights from Region of Interest Analysis Using Machine Learning.

Schizophrenia is a complex and disabling mental disorder that represents one of the most important challenges for neuroimaging research. There were many attempts to understand these basic mechanisms behind the disorder, yet we know very little. By employing machine learning techniques with age-matched samples from the auditory oddball task using multi-site functional magnetic resonance imaging (fMRI) data, this study aims to address these challenges. The study employed a three-stage model to gain a better understanding of the neurobiology underlying schizophrenia and techniques that could be applied for diagnosis. At first, we constructed four-level hierarchical sets from each fMRI volume of 34 schizophrenia patients (SZ) and healthy controls (HC) individually in terms of hemisphere, gyrus, lobes, and Brodmann areas. Second, we employed statistical methods, namely, t-tests and Pearson's correlation, to assess the group differences in cortical activation. Finally, we assessed the predictive power of the brain regions for machine learning algorithms using K-nearest Neighbor (KNN), Naive Bayes, Decision Tree (DT), Random Forest (RF), Support Vector Machines (SVMs), and Extreme Learning Machine (ELM). Our investigation depicts promising results, obtaining an accuracy of up to 84% when applying Pearson's correlation-selected features at lobes and Brodmann region level (81% for Gyrus), as well as Hemispheres involving different stages. Thus, the results of our study were consistent with previous studies that have revealed some functional abnormalities in several brain regions. We also discovered the involvement of other brain regions which were never sufficiently studied in previous literature, such as the posterior lobe (posterior cerebellum), Pyramis, and Brodmann Area 34. We present a unique and comprehensive approach to investigating the neurological basis of schizophrenia in this study. By bridging the gap between neuroimaging and computable analysis, we aim to improve diagnostic accuracy in patients with schizophrenia and identify potential prognostic markers for disease progression.

Voxel-Based Lesion Analysis of Ideomotor Apraxia.

Ideomotor apraxia is a cognitive disorder most often resulting from acquired brain lesions (i.e., strokes or tumors). Neuroimaging and lesion studies have implicated several brain regions in praxis and apraxia, but most studies have described (sub)acute patients. This study aimed to extend previous research by analyzing data from 115 left hemisphere chronic stroke patients using the praxis subtest of the Western Aphasia Battery, which is divided into four action types: facial, upper limb, complex, and instrumental. Lesion-symptom mapping was used to identify brain regions most critically associated with difficulties in each of the four subtests. Complex and instrumental action deficits were associated with left precentral, postcentral, and superior parietal gyri (Brodmann areas 2, 3, 4, 5, and 6), while the facial and upper limb action deficits maps were restricted to left inferior, middle, and medial temporal gyri (Brodmann areas 20, 21, 22, and 48). We discuss ideas about neuroplasticity and cortical reorganization in chronic stroke and how different methodologies can reveal different aspects of lesion and recovery networks in apraxia.

Volume electron microscopy analysis of synapses in primary regions of the human cerebral cortex.

Functional and structural studies investigating macroscopic connectivity in the human cerebral cortex suggest that high-order associative regions exhibit greater connectivity compared to primary ones. However, the synaptic organization of these brain regions remains unexplored. In the present work, we conducted volume electron microscopy to investigate the synaptic organization of the human brain obtained at autopsy. Specifically, we examined layer III of Brodmann areas 17, 3b, and 4, as representative areas of primary visual, somatosensorial, and motor cortex. Additionally, we conducted comparative analyses with our previous datasets of layer III from temporopolar and anterior cingulate associative cortical regions (Brodmann areas 24, 38, and 21). 9,690 synaptic junctions were 3D reconstructed, showing that certain synaptic characteristics are specific to particular regions. The number of synapses per volume, the proportion of the postsynaptic targets, and the synaptic size may distinguish one region from another, regardless of whether they are associative or primary cortex. By contrast, other synaptic characteristics were common to all analyzed regions, such as the proportion of excitatory and inhibitory synapses, their shapes, their spatial distribution, and a higher proportion of synapses located on dendritic spines. The present results provide further insights into the synaptic organization of the human cerebral cortex.

Ground-truth validation of uni- and multivariate lesion inference approaches.

Lesion analysis aims to reveal the causal contributions of brain regions to brain functions. Various strategies have been used for such lesion inferences. These approaches can be broadly categorized as univariate or multivariate methods. Here we analysed data from 581 patients with acute ischaemic injury, parcellated into 41 Brodmann areas, and systematically investigated the inferences made by two univariate and two multivariate lesion analysis methods via ground-truth simulations, in which we defined a priori contributions of brain areas to assumed brain function. Particularly, we analysed single-region models, with only single areas presumed to contribute functionally, and multiple-region models, with two contributing regions that interacted in a synergistic, redundant or mutually inhibitory mode. The functional contributions could vary in proportion to the lesion damage or in a binary way. The analyses showed a considerably better performance of the tested multivariate than univariate methods in terms of accuracy and mis-inference error. Specifically, the univariate approaches of Lesion Symptom Mapping as well as Lesion Symptom Correlation mis-inferred substantial contributions from several areas even in the single-region models, and also after accounting for lesion size. By contrast, the multivariate approaches of Multi-Area Pattern Prediction, which is based on machine learning, and Multi-perturbation Shapley value Analysis, based on coalitional game theory, delivered consistently higher accuracy and specificity. Our findings suggest that the tested multivariate approaches produce largely reliable lesion inferences, without requiring lesion size consideration, while the application of the univariate methods may yield substantial mis-localizations that limit the reliability of functional attributions.

Sex Differences in the Effect of Brain-derived Neurotrophic Factor (BDNF) Val66Met Polymorphism on Baseline EEG Connectivity

Dependent on Val66Met polymorphism in BDNF gene secretion of neurotrophin affects morphological and functional changes in the developing and mature nervous system, in particular, may contribute to associated with white matter degradation changes in connectivity observed with aging. It was also shown that the associated with Val66Met polymorphism differences in connectivity between cortical structures are moderated by the sex of the subjects. However, there are no studies examining the effect of polymorphism on connectivity, taking into account age and gender differences. In this regard, the present study examined the associations of the Val66Met polymorphism of the BDNF gene with the characteristics of delayed phase synchronization based on EEG data in 223 younger (from 18 to 35 years old) and 134 older (over 55 years old) men and women. The analysis included connections between 84 cortical areas, identified on the basis of 42 Brodmann areas located in the left and right hemispheres. A statistically significant effect, including the factor of polymorphism, was the SEX × GENOTYPE interaction when considering associations at the frequency of the α1-rhythm: in Val/Met men, the strength of thirty-three connections was higher compared to Val/Val. Strengthening of connections was observed mainly between the parahippocampal regions of different hemispheres. At the frequency of the gamma rhythm, associated with the genotype differences in connectivity depended on gender and age. In young subjects, the scores of connectivity in Val/Val women were lower in comparison with men, however, no differences between Val/Val and Met carriers were found in any age group. The combined effect of sex and BDNF genotype on the baseline EEG parameters of brain connectivity may be a background for further study of the role of these factors in the formation of basic characteristics of brain activity.

The effect of transcranial alternating current stimulation on cognitive flexibility and attention of children with intellectual disability: a case report

BackgroundIntellectual disability is a neurodevelopmental disorder characterized by significant impairments in intellectual functioning and adaptive behavior. Cognitive flexibility and attention are crucial cognitive domains often affected in children with intellectual disability. This case report explores the novel use of transcranial alternating current stimulation, a noninvasive brain stimulation technique, to enhance these cognitive functions. The study’s novelty lies in its focus on alpha-wave frequency transcranial alternating current stimulation targeting specific Brodmann areas and its potential sustained impact on cognitive flexibility and attention in the pediatric population with intellectual disability.Case presentationThe case study involved two elementary school students, both 7 years old with mild intellectual disability, one male and one female, both with Turkic ethnicity, from Shahid Fahmideh School for Exceptional Children in Khosrowshah, Iran. Both participants underwent a 2-week intervention with daily 20-minute sessions of transcranial alternating current stimulation at an alpha-wave frequency (10 Hz), targeting Brodmann areas F3 and P3. Cognitive flexibility and attention were assessed using the Wisconsin Card Sorting Test and the Clock Test, administered at four time points: pre-intervention, week 1, week 2, and 1 month post-intervention. Statistical analysis showed significant improvements in both Wisconsin Card Sorting Test and Clock Test scores for both participants compared with baseline, with sustained enhancement over time.ConclusionThe findings from this case report indicate that transcranial alternating current stimulation may be a promising intervention for improving cognitive flexibility and attention in children with intellectual disability. The significant and sustained improvements observed suggest that transcranial alternating current stimulation could have a meaningful clinical impact on the cognitive development of this population. However, further research is needed to confirm the efficacy of transcranial alternating current stimulation and to explore its broader applicability and long-term effects in larger, more diverse populations.

Disentangling transcriptomic heterogeneity within the human subgenual anterior cingulate cortex.

The subgenual anterior cingulate cortex (sgACC) is a critical site for understanding the neural correlates of affect and emotion. While the activity of the sgACC is functionally homogenous, it is comprised of multiple Brodmann Areas (BAs) that possess different cytoarchitectures. In some sgACC BAs, Layer 5 is sublaminated into L5a and L5b which has implications for its projection targets. To understand how the transcriptional profile differs between the BAs, layers, and sublayers of human sgACC, we collected layer strips using laser capture microdissection followed by RNA sequencing. We found no significant differences in transcript expression in these specific cortical layers between BAs within the sgACC. In contrast, we identified striking differences between Layers 3 and 5a or 5b that were concordant across sgACC BAs. We found that sublayers 5a and 5b were transcriptionally similar. Pathway analyses of L3 and L5 revealed overlapping biological processes related to synaptic function. However, L3 was enriched for pathways related to cell-to-cell junction and dendritic spines whereas L5 was enriched for pathways related to brain development and presynaptic function, indicating potential functional differences across layers. Our study provides important insight into normative transcriptional features of the sgACC.

Morphological and Molecular Characteristics of Perineuronal Nets in the Human Prefrontal Cortex-A Possible Link to Microcircuitry Specialization.

Perineuronal nets (PNNs) are a type of extracellular matrix (ECM) that play a significant role in synaptic activity and plasticity of interneurons in health and disease. We researched PNNs' regional and laminar representation and molecular composition using immunohistochemistry and transcriptome analysis of Brodmann areas (BA) 9, 14r, and 24 in 25 human postmortem brains aged 13-82 years. The numbers of VCAN- and NCAN-expressing PNNs, relative to the total number of neurons, were highest in cortical layers I and VI while WFA-binding (WFA+) PNNs were most abundant in layers III-V. The ECM glycosylation pattern was the most pronounced regional difference, shown by a significantly lower proportion of WFA+ PNNs in BA24 (3.27 ± 0.69%) compared to BA9 (6.32 ± 1.73%; P = 0.0449) and BA14 (5.64 ± 0.71%; P = 0.0278). The transcriptome of late developmental and mature stages revealed a relatively stable expression of PNN-related transcripts (log2-transformed expression values: 6.5-8.5 for VCAN and 8.0-9.5 for NCAN). Finally, we propose a classification of PNNs that envelop GABAergic neurons in the human cortex. The significant differences in PNNs' morphology, distribution, and molecular composition strongly suggest an involvement of PNNs in specifying distinct microcircuits in particular cortical regions and layers.

Neural Functioning in Late-Life Depression: An Activation Likelihood Estimation Meta-Analysis.

Late-life depression (LLD) is a relatively common and debilitating mental disorder, also associated with cognitive dysfunctions and an increased risk of mortality. Considering the growing elderly population worldwide, LLD is increasingly emerging as a significant public health issue, also due to the rise in direct and indirect costs borne by healthcare systems. Understanding the neuroanatomical and neurofunctional correlates of LLD is crucial for developing more targeted and effective interventions, both from a preventive and therapeutic standpoint. This ALE meta-analysis aims to evaluate the involvement of specific neurofunctional changes in the neurophysiopathology of LLD by analysing functional neuroimaging studies conducted on patients with LLD compared to healthy subjects (HCs). We included 19 studies conducted on 844 subjects, divided into 439 patients with LLD and 405 HCs. Patients with LLD, compared to HCs, showed significant hypoactivation of the right superior and medial frontal gyri (Brodmann areas (Bas) 8, 9), left cingulate cortex (BA 24), left putamen, and left caudate body. The same patients exhibited significant hyperactivation of the left superior temporal gyrus (BA 42), left inferior frontal gyrus (BA 45), right anterior cingulate cortex (BA 24), right cerebellar culmen, and left cerebellar declive. In summary, we found significant changes in activation patterns and brain functioning in areas encompassed in the cortico-limbic-striatal network in LLD. Furthermore, our results suggest a potential role for areas within the cortico-striatal-cerebellar network in the neurophysiopathology of LLD.

Neural correlates of musical timbre: an ALE meta-analysis of neuroimaging data.

Timbre is a central aspect of music that allows listeners to identify musical sounds and conveys musical emotion, but also allows for the recognition of actions and is an important structuring property of music. The former functions are known to be implemented in a ventral auditory stream in processing musical timbre. While the latter functions are commonly attributed to areas in a dorsal auditory processing stream in other musical domains, its involvement in musical timbre processing is so far unknown. To investigate if musical timbre processing involves both dorsal and ventral auditory pathways, we carried out an activation likelihood estimation (ALE) meta-analysis of 18 experiments from 17 published neuroimaging studies on musical timbre perception. We identified consistent activations in Brodmann areas (BA) 41, 42, and 22 in the bilateral transverse temporal gyri, the posterior superior temporal gyri and planum temporale, in BA 40 of the bilateral inferior parietal lobe, in BA 13 in the bilateral posterior Insula, and in BA 13 and 22 in the right anterior insula and superior temporal gyrus. The vast majority of the identified regions are associated with the dorsal and ventral auditory processing streams. We therefore propose to frame the processing of musical timbre in a dual-stream model. Moreover, the regions activated in processing timbre show similarities to the brain regions involved in processing several other fundamental aspects of music, indicating possible shared neural bases of musical timbre and other musical domains.

Cerebral hemodynamics underlying ankle force sense modulated by high-definition transcranial direct current stimulation.

This study aimed to investigate the effects of high-definition transcranial direct current stimulation on ankle force sense and underlying cerebral hemodynamics. Sixteen healthy adults (8 males and 8 females) were recruited in the study. Each participant received either real or sham high-definition transcranial direct current stimulation interventions in a randomly assigned order on 2 visits. An isokinetic dynamometer was used to assess the force sense of the dominant ankle; while the functional near-infrared spectroscopy was employed to monitor the hemodynamics of the sensorimotor cortex. Two-way analyses of variance with repeated measures and Pearson correlation analyses were performed. The results showed that the absolute error and root mean square error of ankle force sense dropped more after real stimulation than after sham stimulation (dropped by 23.4% vs. 14.9% for absolute error, and 20.0% vs. 10.2% for root mean square error). The supplementary motor area activation significantly increased after real high-definition transcranial direct current stimulation. The decrease in interhemispheric functional connectivity within the Brodmann's areas 6 was significantly correlated with ankle force sense improvement after real high-definition transcranial direct current stimulation. In conclusion, high-definition transcranial direct current stimulation can be used as a potential intervention for improving ankle force sense. Changes in cerebral hemodynamics could be one of the explanations for the energetic effect of high-definition transcranial direct current stimulation.

Expression of guanylate cyclase C in human prefrontal cortex depends on sex and feeding status.

Guanylate cyclase C (GC-C) has been detected in the rodent brain in neurons of the cerebral cortex, amygdala, midbrain, hypothalamus, and cerebellum. In this study we determined GC-C protein expression in Brodmann areas (BA) 9, BA10, BA11, and BA32 of the human prefrontal cortex involved in regulation of feeding behavior, as well as in the cerebellar cortex, arcuate nucleus of hypothalamus and substantia nigra in brain samples of human 21 male and 13 female brains by ELISA with postmortem delay < 24 h. GC-C was found in all tested brain areas and it was expressed in neurons of the third cortical layer of BA9. The regulation of GC-C expression by feeding was found in male BA11 and BA10-M, where GC-C expression was in negative correlation to the volume of stomach content during autopsy. In female BA11 there was no correlation detected, while in BA10-M there was even positive correlation. This suggests sex differences in GC-C expression regulation in BA11 and BA10-M. The amount of GC-C was higher in female BA9 only when the death occurred shortly after a meal, while expression of GC-C was higher in BA10-O only when the stomach was empty. The expression of GC-C in female hypothalamus was lower when compared to male hypothalamus only when the stomach was full, suggesting possibly lower satiety effects of GC-C agonists in women. These results point toward the possible role of GC-C in regulation of feeding behavior. Since, this is first study of GC-C regulation and its possible function in prefrontal cortex, to determine exact role of GC-C in different region of prefrontal cortex, especially in humans, need further studies.

Changes in the visual areas of the cerebral cortex in children with left-sided anisometropic amblyopia according to structural MRI and resting-state fMRI

Thanks to the development of structural and functional magnetic resonance imaging (MRI) methods, in recent decades there has been a lot of research aimed at elucidating brain abnormalities caused by amblyopia. In the cases of this prevalent visual disorder, the anomalies causing decreased visual acuity and other visual disabilities cannot be determined by standard ophthalmologic examination. Since there are several types of this disorder that are fundamentally different in etiology, it is natural to suggest the presence of different types of corresponding brain abnormalities. In this regard, before obtaining a general picture of the pathogenesis of amblyopia, studies conducted on groups of specially selected similar patients are very important. This paper presents the results of a study of school-age children with left-sided anisometropic amblyopia. In the patients investigated, MRI data revealed interhemispheric differences in the thickness of the lateral occipital cortex, and resting-state fMRI revealed interhemispheric differences in the local coherence of the hemodynamic signal within 17 Brodmann area and in the functional connectivity between 17 and 18+19 Brodmann areas. The data obtained contribute to the creation of a general MRI database on the pathophysiology of amblyopia, help clarify some controversial issues and indicate the advisability of using resting-state fMRI in ophthalmology.

Aberrant Brain Networks and Relative Band Power in Patients with Acute Anti-NMDA Receptor Encephalitis: A Study of Resting-State EEG.

The alterations of the functional network (FN) in anti-N-methyl-Daspartate receptor (NMDAR) encephalitis have been recognized by functional magnetic resonance imaging studies. However, few studies using the electroencephalogram (EEG) have been performed to explore the possible FN changes in anti-NMDAR encephalitis. In this study, the aim was to explore any FN changes in patients with anti-NMDAR encephalitis. Twenty-nine anti-NMDAR encephalitis patients and 29 age- and gender-matched healthy controls (HC) were assessed using 19-channel EEG examination. For each participant, five 10-second epochs of resting state EEG with eyes closed were extracted. The cortical source signals of 84 Brodmann areas were calculated using the exact low resolution brain electromagnetic tomography (eLORETA) inverse solution by LORETA-KEY. Phase Lag Index (PLI) matrices were then obtained and graph and relative band power (RBP) analyses were performed. Compared with healthy controls, functional connectivity (FC) in the delta, theta, beta 1 and beta 2 bands significantly increased within the 84 cortical source signals of anti-NMDAR encephalitis patients (p < 0.05) and scalp FC in the alpha band decreased within the 19 electrodes. Additionally, the anti-NMDAR encephalitis group exhibited higher local efficiency and clustering coefficient compared to the healthy control group in the four bands. The slowing band RBP increased while the fast band RBP decreased in multiple-lobes and some of these changes in RBP were correlated with the modified Rankin Scale (mRS) and Mini-mental State Examination (MMSE) in anti-NMDAR encephalitis patients. This study further deepens the understanding of related changes in the abnormal brain network and power spectrum of anti-NMDA receptor encephalitis. The decreased scalp alpha FC may indicate brain dysfunction, while the increased source beta FC may indicate a compensatory mechanism for brain function in anti-NMDAR encephalitis patients. These findings extend understanding of how the brain FN changes from a cortical source perspective. Further studies are needed to detect correlations between altered FNs and clinical features and characterize their potential value for the management of anti-NMDAR encephalitis.

Lower levels of TRAF1 in Brodmann's area 24, but not 46, in bipolar disorders are not detectable in major depressive disorders

IntroductionMultiple lines of research implicate inflammation-related pathways in the molecular pathology of mood disorders, with our data suggesting a critical role for aberrant cortical tumour necrosis factor α (TNF)-signaling in the molecular pathology of bipolar disorders (BPD) and major depressive disorders (MDD). MethodsTo extend our understanding of changes in TNF-signaling pathways in mood disorders we used Western blotting to measure levels of tumour necrosis factor receptor associated factor 1 (TRAF1) and transmembrane TNF receptor superfamily member 1B (tmTNFRSF1B) in Brodmann's areas (BA) 24 and 46 from people with BPD and MDD. These proteins are key rate-limiting components within TNF-signaling pathways. ResultsCompared to controls, there were higher levels of TRAF1 of large effect size (η = 0.19, Cohen's d = 0.97) in BA 24, but not BA 46, from people with BPD. Levels of TRAF1 were not altered in MDD and levels of tmTNFRSF1B were not altered in either disorder. LimitationsThe cases studied had been treated with psychotropic drugs prior to death which is an unresolvable study confound. Cohort sizes are relatively small but not untypical of postmortem CNS studies. ConclusionsTo facilitate post-synaptic signaling, TRAF1 is known to associate with tmTNFRSF1B after that receptor takes its activated conformation which occurs predominantly after it binds to transmembrane TNF (tmTNF). Simultaneously, when tmTNFRSF1B binds to tmTNF reverse signaling through tmTNF is activated. Hence our findings in BA 24 argues that bidirectional TNF-signaling may be an important component of the molecular pathology of BPD.

Brodmann Areas, V1 Atlas and Cognitive Impairment: Assessing Cortical Thickness for Cognitive Impairment Diagnostics.

Background and Objectives: Magnetic resonance imaging is vital for diagnosing cognitive decline. Brodmann areas (BA), distinct regions of the cerebral cortex categorized by cytoarchitectural variances, provide insights into cognitive function. This study aims to compare cortical thickness measurements across brain areas identified by BA mapping. We assessed these measurements among patients with and without cognitive impairment, and across groups categorized by cognitive performance levels using the Montreal Cognitive Assessment (MoCA) test. Materials and Methods: In this cross-sectional study, we included 64 patients who were divided in two ways: in two groups with (CI) or without (NCI) impaired cognitive function and in three groups with normal (NC), moderate (MPG) and low (LPG) cognitive performance according to MoCA scores. Scans with a 3T MRI scanner were carried out, and cortical thickness data was acquired using Freesurfer 7.2.0 software. Results: By analyzing differences between the NCI and CI groups cortical thickness of BA3a in left hemisphere (U = 241.000, p = 0.016), BA4a in right hemisphere (U = 269.000, p = 0.048) and BA28 in left hemisphere (U = 584.000, p = 0.005) showed significant differences. In the LPG, MPG and NC cortical thickness in BA3a in left hemisphere (H (2) = 6.268, p = 0.044), in V2 in right hemisphere (H (2) = 6.339, p = 0.042), in BA28 in left hemisphere (H (2) = 23.195, p < 0.001) and in BA28 in right hemisphere (H (2) = 10.015, p = 0.007) showed significant differences. Conclusions: Our study found that cortical thickness in specific Brodmann Areas-BA3a and BA28 in the left hemisphere, and BA4a in the right-differ significantly between NCI and CI groups. Significant differences were also observed in BA3a (left), V2 (right), and BA28 (both hemispheres) across LPG, MPG, NC groups. Despite a small sample size, these findings suggest cortical thickness measurements can serve as effective biomarkers for cognitive impairment diagnosis, warranting further validation with a larger cohort.

Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories.

The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the entorhinal and parahippocampal cortices as well as Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 μm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized slices spaced 5 mm apart (pixel size 0.4 μm at 20× magnification). Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while the definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists' agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed less saliently. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed neuroimaging research on the human MTL cortex.

New organizational principles and 3D cytoarchitectonic maps of the dorsolateral prefrontal cortex in the human brain.

Areas of the dorsolateral prefrontal cortex (DLPFC) are part of the frontoparietal control, default mode, salience, and ventral attention networks. The DLPFC is involved in executive functions, like working memory, value encoding, attention, decision-making, and behavioral control. This functional heterogeneity is not reflected in existing neuroanatomical maps. For example, previous cytoarchitectonic studies have divided the DLPFC into two or four areas. Macroanatomical parcellations of this region rely on gyri and sulci, which are not congruent with cytoarchitectonic parcellations. Therefore, this study aimed to provide a microstructural analysis of the human DLPFC and 3D maps of cytoarchitectonic areas to help address the observed functional variability in studies of the DLPFC. We analyzed ten human post-mortem brains in serial cell-body stained brain sections and mapped areal boundaries using a statistical image analysis approach. Five new areas (i.e., SFG2, SFG3, SFG4, MFG4, and MFG5) were identified on the superior and middle frontal gyrus, i.e., regions corresponding to parts of Brodmann areas 9 and 46. Gray level index profiles were used to determine interregional cytoarchitectural differences. The five new areas were reconstructed in 3D, and probability maps were generated in commonly used reference spaces, considering the variability of areas in stereotaxic space. Hierarchical cluster analysis revealed a high degree of similarity within the identified DLPFC areas while neighboring areas (frontal pole, Broca's region, area 8, and motoric areas) were separable. Comparisons with functional imaging studies revealed specific functional profiles of the DLPFC areas. Our results indicate that the new areas do not follow a simple organizational gradient assumption in the DLPFC. Instead, they are more similar to those of the ventrolateral prefrontal cortex (Broca's areas 44, 45) and frontopolar areas (Fp1, Fp2) than to the more posterior areas. Within the DLPFC, the cytoarchitectonic similarities between areas do not seem to follow a simple anterior-to-posterior gradient either, but cluster along other principles. The new maps are part of the publicly available Julich Brain Atlas and provide a microstructural reference for existing and future imaging studies. Thus, our study represents a further step toward deciphering the structural-functional organization of the human prefrontal cortex.