Temporal Pole Cortex Research Articles

Regional Brain Volume Changes in Catholic Nuns: A Cross-Sectional Study Using Deep Learning-Based Brain MRI Segmentation.

Objective Religious behaviors are considered as complex brain-based phenomena that may be associated with structural brain change. To identify the pattern of regional brain volume change in nuns, we investigated structural alterations in the brains of nuns using a fast processing automated segmentation method based on deep learning algorithms. Methods We retrospectively reviewed the medical records of the catholic sisters between the ages of 31 and 80 who are members of the charity of St. Vincent de Paul of Korea. A total of 193 asymptomatic subjects (86 nuns and 107 control subjects) received comprehensive health screening and underwent brain MRI scans. We compared cortical and sub-cortical volume between groups across multiple locations using our in-house U-Net++ deep learning-based automatic segmentation tool. Results Compared to the control group, the nun group displayed increased gray matter volume in the right lingual cortex, left isthmus-cingulate, posterior-cingulate, rostral-middle-frontal, superior-frontal, supramarginal, temporal-pole cortices, and bilateral pars-triangularis cortices after correction for multiple comparisons. On the other hand, the nun group showed reduced gray matter volume in the temporal and parietal regions relative to healthy controls. Conclusion Our study suggests that spiritual practice may affect brain structure, especially in several frontal regions involved in a higher level of insight function.

Increase in Right Temporal Cortex Thickness Is Related to Decline of Overall Cognitive Function in Patients With Hypertension.

Background: Hypertension is associated with poorer cognitive functions, but the mechanisms are unclear.Objective: This research aims to explore the cognitive status of elderly patients with hypertension and the possible mechanisms of hypertension affecting cognitive function.Methods: Data were obtained from the China Longitudinal Aging Study (CLAS), and a total of 128 residents, aged 60 years and above, were recruited in this study. Based on whether they had hypertension, these 128 people were divided into the hypertension (n = 64) and non-hypertension groups (n = 64). The Beijing version of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess the overall cognitive function of the subjects, while digit span, language fluency, Wechsler mapping, and Wechsler wood block were used to assess their domain-specific cognitive function (both at baseline and follow-up stages). At the same time, we also examined baseline blood biochemical indicators (such as total protein, fasting plasma glucose (FPG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol, and triglyceride) and baseline MRI data of hippocampus and amygdala volume and temporal polar cortex thickness.Results: The total protein and thickness of temporal polar cortex in patients with hypertension were significantly higher than those in normal controls, but the scores on MMSE, MoCA, digit span, Wechsler mapping and Wechsler wood block at baseline were significantly lower than those in normal controls (p < 0.05). By linear regression analysis and correlation analysis (age and education were controlled), we found that baseline Wechsler mapping scores were negatively correlated with total protein (B = −0.243, t = −3,735, p < 0.001, 95% confidence interval (CI): −0.371 to −0.114); and both the follow-up MMSE score (B = 2.657, t = 2.002, p = 0.049, 95% CI: 0.009~5.306) and the change score of MMSE (r = −0.025, p = 0.047) were related to the thickness of the right temporal pole cortex. Then, by linear regression analysis (mediating model), we found that hypertension may influence follow-up MMSE scores by influencing the cortical thickness of the right temporal pole (B = 1.727, p = 0.022, 95% CI: 0.261–3.193).Conclusions: Elderly patients with hypertension exhibit poorer overall cognitive function and executive function, and the mechanism may be related to the effect of hypertension on the cortical thickness of the right temporal pole.

Structural brain assessment of temporal lobe epilepsy based on voxel-based and surface-based morphological features.

This study aimed to assess the cerebral voxel-based and surface-based morphological abnormalities of patients with temporal lobe epilepsy (TLE). A total of 100 healthy adults and 73 patients with TLE were enrolled in this study, and their 3D T1-weighted MRI data were collected. Voxel-based morphology (VBM) and surface-based morphology (SBM) tools were used to compare the morphological differences between healthy adults and patients with TLE. Receiver-operating characteristic (ROC) curves were used to acquire the boundary values for detecting morphological abnormalities in regions of interest from the corrected VBM and SBM analysis. Our results showed that cortical voxels and decreased thickness areas were located in the widespread cortex and subcortical structures in the TLE group. However, after completing the analysis, we found that the left-TLE lesions were limited to the left temporal pole and left hippocampus, while the right-TLE lesions were located in the bilateral medial temporal lobe, including the right hippocampus and bilateral amygdala. ROC-curve results showed that the volume of the left hippocampus at 4,124.45 mm3 and the thickness of the left temporal pole cortex at 3.50 mm could be used as optimal boundary values based on the curves of the left-TLE group. The right-TLE group curves were poor. Widespread cerebral morphological TLE abnormalities were represented in this study. However, the lesions may be limited after completing a corrected comparison with clinical information. Boundary values of left-TLE group lesions were also obtained.

Left temporal pole contributes to creative thinking via an individual semantic network.

The neural substrates that contribute to creative thinking through the recruitment of semantic memory structures remain largely unknown. This study sought to investigate the properties of semantic networks using a semantic judgment rating task at the individual level and explore the relationship among creative abilities, the topological properties of semantic networks, and their underlying brain structures. We first used a semantic judgment rating to assess individual semantic networks and computed their topological properties. The analysis confirmed a significant correlation between the creative thinking abilities assessed by an alternate uses task and all three topological properties. In addition, voxel-based morphometry was employed to assess the neural correlates of gray matter volume (GMV) related to different topological properties of the semantic network. Results revealed a positive correlation between global efficiency and the left temporal pole cortex, considered to be involved in semantic information transmission and processing. Furthermore, mediation analysis found that the global efficiency of the individual semantic network mediated the association between the left temporal pole GMV and creative thinking, showing that the relationship between left temporal pole GMV and creative thinking may be affected by the semantic networks. To the best of our knowledge, this study is the first to combine a behavioral investigation of semantic networks with magnetic resonance imaging to shed light on the cerebral structural basis of semantic memory networks, in addition to their relationship to creativity.

T22. RELATIONSHIP BETWEEN CORTICAL THICKNESS AND FUNCTIONAL OUTCOME IN INDIVIDUALS AT RISK OF PSYCHOSIS

BackgroundPrevious magnetic resonance imaging (MRI) studies in patients with schizophrenia have demonstrated reduced cortical thickness predominantly in the fronto-temporal regions, but several MRI studies of regional cortical thickness in individuals at clinical high-risk for psychosis have reported inconsistent results. In addition, it remains elusive whether abnormalities of the cortical thickness in individuals at risk of psychosis, if present, are related to their functional outcome.MethodsT1-weighted structural MR scans were obtained from 107 individuals with at-risk mental state (ARMS), of whom 21 (19.6%) later developed psychosis during clinical follow-up (mean = 4.9 years, SD = 2.6 years), as well as 104 age- and gender- matched healthy control subjects recruited at 4 scanning sites (University of Toyama, Toho University, Tohoku University, and The University of Tokyo). ARMS individuals were subdivided into good (ARMS-G, n = 77) and poor (ARMS-P, n = 13) outcome groups based on the Global Assessment of Functioning (GAF) scores both at baseline and 1-year follow-up. After preprocessing MR images using FreeSurfer software (ver.5.3.), we continuously measured the cortical thickness of entire cortex. A general linear model controlling for age, gender, and sites was used to estimate group differences. To correct for multiple comparisons, a Monte Carlo simulation procedure was used. This study was approved by the Committees on Medical Ethics of each site. After a complete description of the study was provided, written informed consent was obtained from all subjects.ResultsCompared with the controls, ARMS individuals exhibited significantly reduced cortical thickness in the superior and inferior frontal gyri, parahippocampal gyri, fusiform gyri, temporal pole cortices, and insula cortices bilaterally, as well as in the left middle frontal gyrus and right precuneus cortex. ARMS individuals also showed significantly increased cortical thickness in the left pre- and postcentral gyrus and right pericalcarine cortex in comparison to the controls. Within ARMS population, ARMS-P individuals had significantly reduced cortical thickness in the right paracentral lobule compared with ARMS-G individuals.DiscussionCortical thinning in the fronto-temporal regions as well as cortical thickening in the posterior cortices seen in ARMS individuals might be associated with general vulnerability to psychopathology. Furthermore, cortical thickness of the right paracentral lobule could be a predictive marker for functional outcome in ARMS population.

Brain perfusion during manic episode and at 6-month follow-up period in bipolar disorder patients: Correlation with cognitive functions.

BackgroundPatterns of altered cerebral perfusion and cognitive dysfunction have been described in Bipolar Disorder (BD) acute episodes and euthymia. Knowledge of the relationship between cognitive function and perfusion in a manic state and status when followed up is still limited.ObjectiveTo describe brain perfusion alterations and its relationship with cognitive impairment in patients with BD during manic episodes and after 6 months.MethodsObservational‐prospective study in 10 type I BD adults during moderate‐severe manic episodes. We assessed sociodemographic data and clinical variables as well as cognitive function through Screening for Cognitive Impairment in Psychiatry (SCIP‐S). Finally, we performed a Brain Perfusion SPECT using a Tc99m‐ethyl cysteine dimer.ResultsDuring manic episodes, patients showed cognitive impairment with a mean SCIP‐S score of 63.8 ± 17.16. This was positively correlated with perfusion measured as relative reuptake index (RRI) at the right temporal pole (ρ = 0.65 p = .0435) and negatively correlated with right the orbitofrontal cortex (ρ = −0.70 p = .0077) and the right subgenual cingulate cortex (ρ = −0.70 p = .0256). Episode severity measured by the Young Mania Rating Scale (YMRS) positively correlated with RRI at the right temporal pole (ρ = 0.75, p = .01). At follow‐up, six patients were taking treatment and were euthymic, we found a negative correlation with the YMRS and RRI at the bilateral orbitofrontal cortex (ρ = −0.8827, p = .019). They did not show significant improvement in cognitive performance at SCIP‐S, and there was negative correlation with the following of the SCIP‐S subscales; processing speed with the bilateral dorsolateral prefrontal, the bilateral medial prefrontal, the left temporal pole cortex RRI, and verbal fluency with the bilateral anterior cingulate cortex RRI.ConclusionCognitive impairment was correlated with brain perfusion patterns at baseline and follow‐up. Large sample size studies with longer follow‐up are needed to describe the changes in perfusion and cognitive functions in BD.

Genome-wide DNA methylomic differences between dorsolateral prefrontal and temporal pole cortices of bipolar disorder

Dorsolateral prefrontal cortex (DLPFC) and temporal pole (TP) are brain regions that display abnormalities in bipolar disorder (BD) patients. DNA methylation — an epigenetic mechanism both heritable and sensitive to the environment — may be involved in the pathophysiology of BD. To study BD-associated DNA methylomic differences in these brain regions, we extracted genomic DNA from the postmortem tissues of Brodmann Area (BA) 9 (DLPFC) and BA38 (TP) gray matter from 20 BD, ten major depression (MDD), and ten control age-and-sex-matched subjects. Genome-wide methylation levels were measured using the 850 K Illumina MethylationEPIC BeadChip. We detected striking differences between cortical regions, with greater numbers of between-brain-region differentially methylated positions (DMPs; i.e., CpG sites) in all groups, most pronounced in the BD group, and with substantial overlap across groups. The genes of DMPs common to both BD and MDD (hypothetically associated with their common features such as depression) and those distinct to BD (hypothetically associated with BD-specific features such as mania) were enriched in pathways involved in neurodevelopment including axon guidance. Pathways enriched only in the BD-MDD shared list pointed to GABAergic dysregulation, while those enriched in the BD-only list suggested glutamatergic dysregulation and greater impact on synaptogenesis and synaptic plasticity. We further detected group-specific between-brain-region gene expression differences in ODC1, CALY, GALNT2, and GABRD, which contained significant between-brain-region DMPs. In each brain region, no significant DMPs or differentially methylated regions (DMRs) were found between diagnostic groups. In summary, the methylation differences between DLPFC and TP may provide molecular targets for further investigations of genetic and environmental vulnerabilities associated with both unique and common features of various mood disorders and suggest directions of future development of individualized treatment strategies.

White Matter Damage in the Semantic Variant of Primary Progressive Aphasia.

The semantic variant of primary progressive aphasia (svPPA) is a form of dementia, mainly featuring language impairment, for which the extent of white matter (WM) damage is less described than its associated grey matter (GM) atrophy. Our study aimed to characterise the extent of this damage using a sensitive and unbiased approach. We conducted a between-group study comparing 10 patients with a clinical diagnosis of svPPA, recruited between 2011 and 2014 at a tertiary reference centre, with 9 cognitively healthy, age-matched controls. From diffusion tensor imaging (DTI) data, we extracted fractional anisotropy (FA) values using a tract-based spatial statistics approach. We further obtained GM volumetric data using the Freesurfer automated segmentation tool. We compared both groups using non-parametric Wilcoxon rank-sum tests, correcting for multiple comparisons. Demographic data showed that patients and controls were comparable. As expected, clinical data showed lower results in svPPA than controls on cognitive screening tests. Tractography showed impaired diffusion in svPPA patients, with FA mostly decreased in the longitudinal, uncinate, cingulum and external capsule fasciculi. Volumetric data show significant atrophy in svPPA patients, mostly in the left entorhinal, amygdala, inferior temporal, middle temporal, superior temporal and temporal pole cortices, and bilateral fusiform gyri. This syndrome appears to be associated not only with GM but also significant WM degeneration. Thus, DTI could play a role in the differential diagnosis of atypical dementia by specifying WM damage specific to svPPA.

Exploring the Neuroplastic Effects of Biofeedback Training on Smokers.

Smoking and stress cooccur in different stages of a nicotine addiction cycle, affecting brain function and showing additive impact on different physiological responses. Resting-state functional connectivity has shown potential in identifying these alterations. Nicotine addiction has been associated with detrimental effects on functional integrity of the central nervous system, including the organization of resting-state networks. Prolonged stress may result in enhanced activation of the default mode network (DMN). Considering that biofeedback has shown promise in alleviating physiological manifestations of stress, we aimed to explore the possible neuroplastic effects of biofeedback training on smokers. Clinical, behavioral, and neurophysiological (resting-state EEG) data were collected from twenty-seven subjects before and after five sessions of skin temperature training. DMN functional cortical connectivity was investigated. While clinical status remained unaltered, the degree of nicotine dependence and psychiatric symptoms were significantly improved. Significant changes in DMN organization and network properties were not observed, except for a significant increase of information flow from the right ventrolateral prefrontal cortex and right temporal pole cortex towards other DMN components. Biofeedback aiming at stress alleviation in smokers could play a protective role against maladaptive plasticity of connectivity. Multiple sessions, individualized interventions and more suitable methods to promote brain plasticity, such as neurofeedback training, should be considered.

TDP-43 pathology in anterior temporal pole cortex in aging and Alzheimer\u2019s disease

TDP-43 pathology was investigated in the anterior temporal pole cortex (ATPC) and orbital frontal cortex (OFC), regions often degenerated in frontotemporal lobar degenerations (FTLD), in aging and Alzheimer’s disease (AD). Diagnosis of dementia in the 1160 autopsied participants from 3 studies of community-dwelling elders was based on clinical evaluation and cognitive performance tests which were used to create summary measures of the five cognitive domains. Neuronal and glial TDP-43 cytoplasmic inclusions were quantitated in 8 brain regions by immunohistochemistry, and used in ANOVA and regression analyses. TDP-43 pathology was present in 547 (49.4%) participants in whom ATPC (41.9%) was the most frequently involved neocortical region and in 15.5% of these cases, ATPC was the only neocortical area with TDP-43 pathology suggesting not only that ATPC is involved early by TDP-43 but that ATPC may represent an intermediate stage between mesial temporal lobe involvement by TDP-43 and the last stage with involvement of other neocortical areas. To better study this intermediary neocortical stage, and to integrate with other staging schemes, our previous 3 stage distribution of TDP-43 pathology was revised to a 5 stage distribution scheme with stage 1 showing involvement of the amygdala only; stage 2 showed extension to hippocampus and/or entorhinal cortex; stage 3 showed extension to the ATPC; stage 4 – showed extension to the midtemporal cortex and/or OFC and finally in stage 5, there was extension to the midfrontal cortex. Clinically, cases in stages 2 to 5 had impaired episodic memory, however, stage 3 was distinct from stage 2 since stage 3 cases had significantly increased odds of dementia. The proportion of cases with hippocampal sclerosis increased progressively across the stages with stage 5 showing the largest proportion of hippocampal sclerosis cases. Stage 5 cases differed from other stages by having impairment of semantic memory and perceptual speed, in addition to episodic memory impairment. These data suggest that of the regions studied, TDP-43 pathology in the ATPC is an important early neocortical stage of TDP-43 progression in aging and AD while extension of TDP-43 pathology to the midfrontal cortex is a late stage associated with more severe and global cognitive impairment.

Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey.

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long-term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown.

Real-time FMRI neurofeedback training of amygdala activity in patients with major depressive disorder.

BackgroundAmygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD), and normalize with remission. Real-time functional MRI neurofeedback (rtfMRI-nf) offers a non-invasive method to modulate this regional activity. We examined whether depressed participants can use rtfMRI-nf to enhance amygdala responses to positive autobiographical memories, and whether this ability alters symptom severity.MethodsUnmedicated MDD subjects were assigned to receive rtfMRI-nf from either left amygdala (LA; experimental group, n = 14) or the horizontal segment of the intraparietal sulcus (HIPS; control group, n = 7) and instructed to contemplate happy autobiographical memories (AMs) to raise the level of a bar representing the hemodynamic signal from the target region to a target level. This 40s Happy condition alternated with 40s blocks of rest and counting backwards. A final Transfer run without neurofeedback information was included.ResultsParticipants in the experimental group upregulated their amygdala responses during positive AM recall. Significant pre-post scan decreases in anxiety ratings and increases in happiness ratings were evident in the experimental versus control group. A whole brain analysis showed that during the transfer run, participants in the experimental group had increased activity compared to the control group in left superior temporal gyrus and temporal polar cortex, and right thalamus.ConclusionsUsing rtfMRI-nf from the left amygdala during recall of positive AMs, depressed subjects were able to self-regulate their amygdala response, resulting in improved mood. Results from this proof-of-concept study suggest that rtfMRI-nf training with positive AM recall holds potential as a novel therapeutic approach in the treatment of depression.

Comparative neuroanatomical parcellation of the human and nonhuman primate temporal pole

The temporal pole is unique to nonhuman and human primates, although other species also present temporal cortex. A clear distinction is made between the gross anatomical, macroscopic temporal pole, located at the tip of the temporal lobe, and the temporal polar cortex, which is a general term that encompasses all reported divisions and can be applied to both nonhuman and human primates. In the 19th century early neuroanatomists identified the temporal polar cortex as a different entity, independent from the remainder of the temporal lobe. More recently, the temporal polar cortex has been subdivided into different fields. The analysis of the different portions that make up the temporal polar cortex was first described in the nonhuman primate, and later on in humans. In this review we examine the historical course of the concepts about the extension, structure, and main cytoarchitectonic areas. The different descriptions are presented in chronological order and their relevance is discussed. In general, some common features arise in nonhuman and human primates temporopolar cortex, namely, an increased thickness of this cortical area, a predominant dysgranular type of cortex, and a more restricted extension in humans relative to earlier accounts. A common pattern of cytoarchitectonic areas results from the criteria of previous authors, although the sulcal anatomy of the human temporal pole has great variability. The understanding of the extension, composition, and limits of the temporal polar cortex is crucial for identification of separate regions in neuroimaging studies. J. Comp. Neurol. 521:4163-4176, 2013. © 2013 Wiley Periodicals, Inc.

Dynamic Changes In The Medial Temporal Lobe During Incidental Learning Of Object–Location Associations

The role of the medial temporal lobe (MTL) in associative memory encoding has been the focus of many memory experiments. However, there has been surprisingly little investigation of whether the contributions of different MTL subregions (amygdala, hippocampus [HPC], parahippocampal [PHc], perirhinal cortex [PRc], and temporal polar cortex [TPc]) shift across multiple presentations during associative encoding. We examined this issue using event-related functional magnetic resonance imaging and a multivoxel pattern classification analysis. Subjects performed a visual search task, becoming faster with practice to locate objects whose locations were held constant across trials. The classification analysis implicated right HPC and amygdala early in the task when the speed-up from trial to trial was greatest. The same analysis implicated right PRc and TPc late in learning when speed-up was minimal. These results suggest that associative encoding relies on complex patterns of neural activity in MTL that cannot be expressed by simple increases or decreases of blood oxygenation level-dependent signal during learning. Involvement of MTL subregions during encoding of object-location associations depends on the nature of the learning phase. Right HPC and amygdala support active integration of object and location information, while right PRc and TPc are involved when object and spatial representations become unitized into a single representation.

Neuroanatomical correlates of attention‐deficit–hyperactivity disorder accounting for comorbid oppositional defiant disorder and conduct disorder

An increasing number of neuroimaging studies have been conducted to uncover the pathophysiology of attention-deficit-hyperactivity disorder (ADHD). The findings are inconsistent, however, at least partially due to methodological differences. In the present study voxel-based morphometry (VBM) was used to evaluate brain morphology in ADHD subjects after taking into account the confounding effect of oppositional defiant disorder (ODD) and conduct disorder (CD) comorbidity. Eighteen children with ADHD and 17 age- and gender-matched typically developing subjects underwent high-spatial resolution magnetic resonance imaging. The regional gray matter volume differences between the children with ADHD and controls were examined with and without accounting for comorbid ODD and CD in a voxel-by-voxel manner throughout the entire brain. The VBM indicated significantly smaller regional gray matter volume in regions including the bilateral temporal polar and occipital cortices and the left amygdala in subjects with ADHD compared with controls. Significantly smaller regional gray matter volumes were demonstrated in more extensive regions including the bilateral temporal polar cortices, bilateral amygdala, right occipital cortex, right superior temporal sulcus, and left middle frontal gyrus after controlling for the confounding effect of comorbid ODD and CD. Morphological abnormalities in ADHD were seen not only in the regions associated with executive functioning but also in the regions associated with social cognition. When the effect of comorbid CD and ODD was taken into account, there were more extensive regions with significantly smaller volume in ADHD compared to controls.

Genetic Variation and Neuroimaging Measures in Alzheimer Disease

To investigate whether genome-wide association study (GWAS)-validated and GWAS-promising candidate loci influence magnetic resonance imaging measures and clinical Alzheimer's disease (AD) status. Multicenter case-control study of genetic and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative. Multicenter GWAS. Patients A total of 168 individuals with probable AD, 357 with mild cognitive impairment, and 215 cognitively normal control individuals recruited from more than 50 Alzheimer's Disease Neuroimaging Initiative centers in the United States and Canada. All study participants had APOE and genome-wide genetic data available. We investigated the influence of GWAS-validated and GWAS-promising novel AD loci on hippocampal volume, amygdala volume, white matter lesion volume, entorhinal cortex thickness, parahippocampal gyrus thickness, and temporal pole cortex thickness. Markers at the APOE locus were associated with all phenotypes except white matter lesion volume (all false discovery rate-corrected P values < .001). Novel and established AD loci identified by prior GWASs showed a significant cumulative score-based effect (false discovery rate P = .04) on all analyzed neuroimaging measures. The GWAS-validated variants at the CR1 and PICALM loci and markers at 2 novel loci (BIN1 and CNTN5) showed association with multiple magnetic resonance imaging characteristics (false discovery rate P < .05). Loci associated with AD also influence neuroimaging correlates of this disease. Furthermore, neuroimaging analysis identified 2 additional loci of high interest for further study.

Parcellation of human temporal polar cortex: A combined analysis of multiple cytoarchitectonic, chemoarchitectonic, and pathological markers

Although the human temporal polar cortex (TPC), anterior to the limen insulae, is heavily involved in high-order brain functions and many neurological diseases, few studies on the parcellation and extent of the human TPC are available that have used modern neuroanatomical techniques. The present study investigated the TPC with combined analysis of several different cellular, neurochemical, and pathological markers and found that this area is not homogenous, as at least six different areas extend into the TPC, with another area being unique to the polar region. Specifically, perirhinal area 35 extends into the posterior TPC, whereas areas 36 and TE extend more anteriorly. Dorsolaterally, an area located anterior to the typical area TA or parabelt auditory cortex is distinguishable from area TA and is defined as area TAr (rostral). The polysensory cortical area located primarily in the dorsal bank of the superior temporal sulcus, separate from area TA, extends for some distance into the TPC and is defined as the TAp (polysensory). Anterior to the limen insulae and the temporal pyriform cortex, a cortical area, characterized by its olfactory fibers in layer Ia and lack of layer IV, was defined as the temporal insular cortex and named as area TI after Beck (J. Psychol. Neurol. 1934;41:129-264). Finally, a dysgranular TPC region that capped the tip with some extension into the dorsal aspect of the TPC is defined as temporopolar area TG. Therefore, the human TPC actually includes areas TAr and TI, anterior parts of areas 35, 36, TE, and TAp, and the unique temporopolar area TG.

Clinical characteristics in patients with hippocampal sclerosis with or without cortical dysplasia.

Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) constitutes a distinct clinical syndrome with variable pathogenesis. Extrahippocampal regions may be affected in MTLE/HS, association with cortical dysplasia is common and temporal polar cortex is frequently involved in seizure onset. Patients with dual pathology may have favourable outcome from the surgery provided that both pathologies are removed. The aim of the study was to review clinical variables of MTLE/HS patients in order to distinguish preoperatively patients with associated microscopic cortical dysplasia in the temporal pole. A series of 38 patients with the clinical diagnosis of MTLE and histopathologically proven HS were analysed. Patients were divided into two groups on the basis of histopathological finding in the temporal polar cortex: HS associated with malformation of cortical development (group HS+, n = 19) and a group with isolated HS (group HS, n = 19). Demographic, clinical, electrographic and seizure semiology variables were obtained and their prevalence compared between both groups. At least one insult was identified in early childhood history of 18 patients in the HS group in comparison to 10 patients in the HS+ group (p < 0.01). Complicated febrile seizures were found in both groups with similar prevalence, the history of early childhood CNS infection prevailed in the HS group (p < 0.01). Absence of aura was reported in HS group only. Patients in the the HS+ group had earlier surgery (p < 0.05) but the seizure outcome was comparable between groups. Microscopic dual pathology is common in MTLE/HS patients. This group of patients is difficult to distinguish preoperatively on the basis of noninvasive electrographic features or ictal clinical semiology. Detailed information regarding the possible precipitating insult in the history may be of critical importance.

The temporopolar cortex plays a pivotal role in temporal lobe seizures

We investigated the role of the temporal pole (TP) in 48 consecutive patients with drug-refractory temporal lobe epilepsy (TLE). Chronic depth recordings of TP cortex activity were used in association with video recording of ictal symptoms during 48 spontaneous seizures. In 23 cases (48%, group 1) the TP was involved at the onset of the seizure, before or concurrently with the hippocampus. In the remaining 25 patients (52%, group 2) the TP was involved 16.4 +/- 13.8 s after the hippocampus. A past history of febrile seizures was found in both groups, with no statistical difference. Ictal symptoms did not differentiate TP seizures from seizures originating in the hippocampus but the first clinical sign occurred sooner in group 1 compared with group 2 (respectively 10.56 +/- 9 and 25.7 +/- 19 s, respectively, P = 0.005). Loss of awareness also occurred sooner in the case of TP seizures compared with mesiotemporal lobe (MTL) seizures (22.9 +/- 22.6 versus 42.2 +/- 18.6 s, P = 0.0002). MRI data analysis showed that hippocampal sclerosis was present in both groups of patients, although it was more frequent in patients with MTL onset. Anterior temporal white matter changes were found ipsilateral to the epileptogenic area and tended to be more frequent in patients with TP seizures. All the patients underwent tailored anterior temporal lobectomy that included the TP, the hippocampus, the parahippocampal gyrus and the anterior part of the lateral temporal cortex. A better postoperative outcome was achieved in group 1 compared with group 2 (Engel class 1, 95 and 72% respectively, P = 0.04). We conclude that the frequent TP involvement at the onset of seizures could be a supplementary explanation for some failures of selective amygdalohippocampectomy, which should be addressed preferentially to well-selected patients. Moreover, the involvement of the TP cortex at the onset of the seizures is a good predicting factor for postoperative seizure outcome.

Relationship of Prefrontal Connections to Inhibitory Systems in Superior Temporal Areas in the Rhesus Monkey

The prefrontal cortex selects relevant signals and suppresses irrelevant signals in behavior, as exemplified by its functional interaction with superior temporal cortices. We addressed the structural basis of this process by investigating quantitatively the relationship of prefrontal pathways to inhibitory interneurons in superior temporal cortices. Pathways were labeled with neural tracers, and two neurochemical classes of inhibitory interneurons were labeled with parvalbumin (PV) and calbindin (CB), which differ in mode of inhibitory control. Both markers varied significantly and systematically across superior temporal areas. Calbindin neurons were more prevalent than PV neurons, with the highest densities found in posterior high-order auditory association cortices. Axons from anterior lateral, medial prefrontal and orbitofrontal areas terminated in the anterior half of the superior temporal gyrus, targeting mostly the superficial layers (I to upper III), where CB neurons predominated. Reciprocal projection neurons were intermingled with PV neurons, and emanated mostly from the deep part of layer III and to a lesser extent from layers V-VI, in proportions matching the laminar density of inhibitory interneurons. In marked contrast, prefrontal connections in temporal polar cortex were found mostly in the deep layers, showing mismatch with the predominant upper laminar distribution of interneurons. Differences in the relationship of connections to inhibitory neurons probably affect the dynamics in distinct superior temporal cortices. These findings may help explain the reduced efficacy of inhibitory control in superior temporal areas after prefrontal cortical damage.