Mesial Temporal Cortex Research Articles

Neurosurgical management of posterior communicating artery aneurysmal perforators

Background: Posterior communicating artery (PCom) aneurysms are prevalent intracranial aneurysms, frequently leading to subarachnoid haemorrhage and third nerve palsy. "True" perforators originating directly from the PCom aneurysmal sac are rare and pose unique surgical challenges. We present two illustrative cases where "true" PCom perforators were identified during surgery, necessitating tailored microsurgical approaches. Case Reports: In case one, a 35-year-old female presented with a large PCom aneurysm. During surgery, a modified clipping technique successfully preserved a perforator originating from the aneurysmal sac. In case two, a 36-year-old male with a PCom aneurysm was found to have a perforator supplying the mesial temporal cortex. Sacrificing this perforator was necessary for aneurysm clipping. Conclusion: This paper underscores the rarity of "true" PCom perforators and their impact on microsurgical approaches. Preoperative imaging techniques often fail to detect these small-calibre vessels, highlighting the importance of intraoperative identification. Tailored approaches based on individual anatomy and clinical context are essential. While endovascular procedures provide alternatives, adaptability in microsurgical techniques remains crucial for cases requiring intraoperative perforator management. Overall, understanding the complex vascular intricacies of PCom aneurysms, including "true" perforators, is vital for neurosurgeons. The delicate balance between preservation and necessity, along with ongoing research for improved preoperative identification, stands as the cornerstone for enhancing surgical outcomes in these complex cases.

Posterior cingulate epilepsy: Seizure semiology and intracranial electrical stimulation using SEEG

PurposeThis study aimed to explore seizure semiology and the effects of intracerebral electrical stimulation on the human posterior cingulate cortex (PCC) using Stereoelectroencephalography (SEEG) to deepen our comprehension of posterior cingulate epilepsy (PCE). MethodsThis study examined the characteristics of seizures through video documentation, by assessing the outcomes of intracranial electrical stimulation (iES) during SEEG. We further identified the connection between the observed semiology and precise anatomical locations within the PCC subregions where seizure onset zones (SOZ) were identified. ResultsAnalysis was conducted on 59 seizures from 15 patients recorded via SEEG. Behavioural arrest emerged as the predominant manifestation across the PCC subregions. Where ictal activity extended to both the mesial and lateral temporal cortex, automatism was predominantly observed in seizures originating from the ventral PCC (vPCC). The retrosplenial cortex (RSC) is associated with complex motor behaviour, with seizure discharges spreading to the temporal lobe. Seizures originating from the PCC include axial tonic and autonomic seizures. Only one case of positive clinical seizures was documented. High frequencies of iES within the PCC induced various clinical responses, categorised as vestibular, visual, psychological, and autonomic, with vestibular reactions primarily occurring in the dorsal PCC (dPCC) and RSC, visual responses in the left RSC, and autonomic reactions in the vPCC and RSC. ConclusionThe manifestations of seizures in PCE vary according to the SOZ and the patterns of seizure propagation. The occurrence of seizures induced by iES is exceedingly rare, indicating that mapping of the PCC could pinpoint the primary sector of PCC.

Preliminary evidence for preserved synaptic density in late-life depression

Late-life depression has been consistently associated with lower gray matter volume, the origin of which remains largely unexplained. Recent in-vivo PET findings in early-onset depression and Alzheimer’s Disease suggest that synaptic deficits contribute to the pathophysiology of these disorders and may therefore contribute to lower gray matter volume in late-life depression. Here, we investigate synaptic density in vivo for the first time in late-life depression using the synaptic vesicle glycoprotein 2A receptor radioligand 11C-UCB-J. We included 24 currently depressed adults with late-life depression (73.0 ± 6.2 years, 16 female, geriatric depression scale = 19.5 ± 6.8) and 36 age- and gender-matched healthy controls (70.4 ± 6.2 years, 21 female, geriatric depression scale = 2.7 ± 2.9) that underwent simultaneous 11C-UCB-J positron emission tomography (PET) and 3D T1- and T2-FLAIR weighted magnetic resonance (MR) imaging on a 3-tesla PET-MR scanner. We used analyses of variance to test for 11C-UCB-J binding and gray matter volumes differences in regions implicated in depression. The late-life depression group showed a trend in lower gray matter volumes in the hippocampus (p = 0.04), mesial temporal (p = 0.02) and prefrontal cortex (p = 0.02) compared to healthy control group without surviving correction for multiple comparison. However, no group differences in 11C-UCB-J binding were found in these regions nor were any associations between 11C-UCB-J and depressive symptoms. Our data suggests that, in contrast to Alzheimer’s Disease, lower gray matter volume in late-life depression is not associated with synaptic density changes. From a therapeutic standpoint, preserved synaptic density in late-life depression may be an encouraging finding.

Cognitive flexibility impairment in temporal lobe epilepsy: The impact of epileptic foci lateralization on executive functions

IntroductionTemporal Lobe Epilepsy (TLE) has been associated with memory impairments, which are typically linked to hippocampal and mesial temporal cortex lesions. Considering the presence of extensive bidirectional frontotemporal connections, it can be hypothesized that executive dysfunction in TLE is modulated by the lateralization of the epileptic foci. Material and MethodsA comprehensive neuropsychological executive functions protocol was administered to 63 participants, including 42 individuals with temporal lobe epilepsy (20 with right-TLE and 22 with left-TLE) and 21 healthy controls aged 20–49. ResultsThe results indicate that TLE patients exhibit poorer executive performance compared to healthy controls in working memory (F(2,60) = 4.18, p <.01), planning (F(2,60) = 4.71, p <.05), set shifting (F(2,60) = 10.1, p <.001), phonetic verbal fluency (F(2,60) = 11.71, p <.01) and semantic verbal fluency (F(2,60) = 9.61, p <.001. No significant differences were found in cognitive inhibition. Furthermore, right-TLE patients showed lower performance than left-TLE in set shifting (F(1,61) = 6.45, p <.05), while no significant differences were observed in working memory, planning, inhibition, and verbal fluency. ConclusionsThis research emphasize the importance of considering the lateralization of the temporal lobe focus to achieve a more accurate neuropsychological characterization. The cognitive differences between left and right TLE patients highlight the need for individualized approaches in their treatment and care.

Astrocyte reactivity potentiates longitudinal tau tangle accumulation in cognitively unimpaired individuals

AbstractBackgroundAβ accumulation precedes tau pathology in cognitively unimpaired (CU) individuals, which is an event closely related to the development of cognitive symptoms. However, Aβ leads to tau pathology in some individuals, but not in others, suggesting the presence of other processes triggering the deleterious effects of Aβ in the early Alzheimer’s disease (AD) stages. It was already demonstrated that glial fibrillary acidic protein (GFAP)‐positive astrocytes can internalize tau and might contribute to its propagation. Here we investigated whether astrocyte reactivity is a key element to determining the longitudinal accumulation and spreading of tau pathology in CU individuals.MethodWe assessed 147 CU individuals from the TRIAD cohort with available baseline Aβ‐ and Tau‐PET, plasma p‐tau181 and GFAP. Individuals were classified as positive (Ast+) or negative (Ast‐) for astrocyte reactivity using a cutoff based on plasma GFAP levels of younger Aβ‐ individuals. Longitudinal analysis included 71 CU individuals with Tau‐PET (mean follow‐up:2.3 years).Voxel‐wise associations between biomarkers were tested using linear regressions accounting for age, sex, and adjusting for multiple comparisons. We measured the annual rate of progression in Tau uptake as the difference between follow‐up and baseline uptakes divided by the time between scans. To assess individuals’ percentage of abnormal regions, we used composite brain regions corresponding to Braak histopathological stages.ResultTau‐PET deposition occurred as a function of Aβ burden only in CU Ast+ and in regions expected to present the earliest tau deposition (Fig.1a). In the longitudinal analysis, we observed that the annual rate of tau‐PET accumulation was higher in the CU Ast+ group (Fig.2a) and predicted by baseline Aβ burden only in CU Ast+ (Fig.2b). Interestingly, while the baseline association was confined to the mesial temporal cortex, the longitudinal tau‐PET accumulation as a function of Aβ/Ast presented initial tau spread over the neocortex in Braak III‐IV regions (Fig.2c).ConclusionWe observed that Tau‐PET accumulation was highest in CU Ast+ individuals, with astrocyte reactivity being necessary for the spreading of tau over the neocortex. Our findings suggest that astrocyte reactivity is an important upstream event to unleash tau accumulation and spread in CU individuals, which might have implications for selecting individuals for early preventive clinical trials.

Role of FDG PET/CT in definitive and presumed autoimmune encephalitis.

F-18 Fluorodeoxyglucose PET/CT (FDG-PET) is emerging as a useful imaging adjunct to MRI in the initial diagnostic evaluation of autoimmune encephalitis (AIE)-though presently it is not included in the diagnostic criteria. In this prospective study we enrolled a total of 52 patients with clinically diagnosed and treated AIE. MRI evaluation was done in each case along with CSF and EEG where feasible. FDG-PET was done for all and images were interpreted visually and using SPM. The mean age group of patients included was 38.5 ± 22.6 years with 31 females and 21 males. 23 antibody-positive cases underwent PET, the most common antibody detected was anti-NMDAR type followed by anti-LGI 1. Most common metabolic pattern in NMDARE was hypermetabolism in basal ganglia and hypometabolism in parieto-occipital cortices and ovarian teratoma was detected in two of these patients on whole-body PET. A metabolic pattern consistent with AIE was demonstrated in 22/29 (75.8%) antibody-negative patients with hypermetabolism in basal ganglia and mesial temporal cortices. The overall sensitivity of FDG PET was 86% (45/52). MRI abnormalities were detected in 22/52 (42%) cases, 10/23 antibody positive and 12/29 antibody negative cases. PET was positive in 23/30 (76%) MRI negative cases. Sensitivity of FDG PET for supporting a diagnosis of AIE was higher compared to MRI in both antibody-positive (definitive) and antibody-negative (presumed) AIE. Specific metabolic patterns can be demonstrated on FDG PET in AIE, prompting an early diagnosis so that timely treatment can be instituted.

60 Are all Embedded Measures Created Equal? A look at Embedded PVTs in Major Neurocognitive Disorder

Objective:Although performance validity is critical in determining the quality and accuracy of test data, research suggests not all neuropsychologists incorporate performance validity tests (PVTs) in dementia evaluations (McGuire et al., 2019). Furthermore, well-validated embedded measures, such as Reliable Digit Span (RDS) from the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV), have evidenced an unusually high number of failures in a dementia population when utilizing typical clinical cut-offs (Zenisek et al., 2016). The objective of this study is to explore performance on embedded PVTs among older adults who have a major neurocognitive disorder (MND), specifically among Alzheimer disease (AD) and non-AD patients.Participants and Methods:Archival data from outpatient neuropsychological evaluations were analyzed. All participants were at least 65 years of age, diagnosed with a MND, and completed Digit Span from the WAIS-IV, Brief Visuospatial Memory Test- Revised (BVMT-R), and Hopkins Verbal Learning Test-Revised (HVLT-R). In total, 84 participants, aged 67-96 (M=78.44, SD=6.11) with 6-20 years of education (M=13.47, SD=3.30), were included. The sample predominantly identified as female (n=60) and White (n=61). More individuals were diagnosed with AD (n=50) than non-AD dementia (n=34). Common non-AD diagnoses included Vascular (n=44), Lewy bodies (n=8), and Parkinson’s (n=2) dementias. Fisher’s Exact Test of Independence was used to account for the smaller sample to determine if there was a nonrandom association between diagnosis (AD vs non-AD) and embedded PVT performance: RDS&lt; 7, BVMT-R Hits&lt;4, BVMT-R Recognition Discrimination (RD) &lt; 4, and HVLT-R RD &lt; 5 (Bailey et al., 2018).Results:The Fisher’s Exact Test of Independence revealed a statistically significant association between neurocognitive diagnosis and RDS (p= .008), BVMT-R RD (p&lt;.001), and HVLT-R RD (p&lt;.001). BVMT-R Hits were not significantly associated with diagnosis (p = 0.10). These measures evidenced opposite patterns with RDS demonstrating a higher percentage of fails for the non-AD (63%) versus AD (20%) group. The AD group had a higher percentage of fails for BVMT-R RD (58% for AD and 13% for non-AD groups) and HLVT-R RD (66% for AD and 29% for non-AD group).Conclusions:The current study suggests performance on embedded PVTs vary across MND diagnoses. Individuals with a non-AD diagnosis were more likely to fail RDS than those with AD. This is likely secondary to attention and working memory demands that are mediated by the frontal-subcortical networks, which are less impacted by AD pathology (Bonelli &amp; Cummings, 2022; Loring et al., 2016). In contrast, AD patients were more likely to fail embedded PVTs within memory measures, which are largely mediated by the mesial temporal cortex associated with AD (Pluta, 2022). These results suggest embedded measures operate differently based on diagnosis and neuroanatomical systems affected. The clinical relevance of these findings includes potentially using alternative PVTs or different cut-offs based on diagnosis. Future research should attempt to better delineate more appropriate, as well as time efficient, PVTs among the dementia population.

Explainable Deep-Learning-Based Diagnosis of Alzheimer’s Disease Using Multimodal Input Fusion of PET and MRI Images

PurposeAlzheimer’s disease (AD) is a progressive, incurable human brain illness that impairs reasoning and retention as well as recall. Detecting AD in its preliminary stages before clinical manifestations is crucial for timely treatment. Magnetic Resonance Imaging (MRI) provides valuable insights into brain abnormalities by measuring the decrease in brain volume expressly in the mesial temporal cortex and other regions of the brain, while Positron Emission Tomography (PET) measures the decrease of glucose concentration in the temporoparietal association cortex. When these data are combined, the performance of AD diagnostic methods could be improved. However, these data are heterogeneous and there is a need for an effective model that will harness the information from both data for the accurate prediction of AD.MethodsTo this end, we present a novel heuristic early feature fusion framework that performs the concatenation of PET and MRI images, while a modified Resnet18 deep learning architecture is trained simultaneously on the two datasets. The innovative 3-in-channel approach is used to learn the most descriptive features of fused PET and MRI images for effective binary classification of AD.ResultsThe experimental results show that the proposed model achieved a classification accuracy of 73.90% on the ADNI database. Then, we provide an Explainable Artificial Intelligence (XAI) model, allowing us to explain the results.ConclusionOur proposed model could learn latent representations of multimodal data even in the presence of heterogeneity data; hence, the proposed model partially solved the issue with the heterogeneity of the MRI and PET data.

γ-Aminobutyric acid as a biomarker of the lateralizing and monitoring drug effect in patients with magnetic resonance imaging-negative temporal lobe epilepsy.

Despite verifying proton magnetic resonance spectroscopy (1H-MRS) for focal localization in magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE), it is necessary to illustrate metabolic changes and screen for effective biomarkers for monitoring therapeutic effect. We used 1H-MRS to investigate the role of metabolic levels in MRI-negative TLE. Thirty-seven patients (n = 37, 14 women) and 20 healthy controls (n = 20, 11 women) were investigated by 1H-MRS. We compared the metabolite level changes in the epileptic and contralateral sides on the mesial temporal and dorsolateral prefrontal cortices and analyzed their association with clinical symptoms. γ-Aminobutyric acid (GABA) levels were significantly lower on the epileptic side (2.292 ± 0.890) than in the contralateral side (2.662 ± 0.742, p = 0.029*) in patients on the mesial temporal lobe. N-acetylaspartate (NAA) levels were significantly lower on the epileptic side (7.284 ± 1.314) than on the contralateral side (7.655 ± 1.549, p = 0.034*). NAA + N-acetylaspartylglutamate levels were significantly lower on the epileptic side (7.668 ± 1.406) than on the contralateral side (8.086 ± 1.675, p = 0.032*). Glutamate levels were significantly lower on the epileptic side (7.773 ± 1.428) than on the contralateral side (8.245 ± 1.616, p = 0.040*). Moreover, a significant negative correlation was found between GABA levels in the epileptic mesial temporal lobe and tonic-clonic seizure frequency (r = -0.338, p = 0.046*). γ-Aminobutyric acid (GABA) is a potential biomarker for lateralization and monitoring seizure frequency in MRI-negative TLE.

Evaluation of tau deposition using 18F-PI-2620 PET in MCI and early AD subjects—a MissionAD tau sub-study

BackgroundThe ability of 18F-PI-2620 PET to measure the spatial distribution of tau pathology in Alzheimer’s disease (AD) has been demonstrated in previous studies. The objective of this work was to evaluate tau deposition using 18F-PI-2620 PET in beta-amyloid positive subjects with a diagnosis of mild cognitive impairment (MCI) or mild AD dementia and characterize it with respect to amyloid deposition, cerebrospinal fluid (CSF) assessment, hippocampal volume, and cognition.MethodsSubjects with a diagnosis of MCI due to AD or mild AD dementia and a visually amyloid-positive 18F-florbetaben PET scan (n=74, 76 ± 7 years, 38 females) underwent a baseline 18F-PI-2620 PET, T1-weighted magnetic resonance imaging (MRI), CSF assessment (Aβ42/Aβ40 ratio, p-tau, t-tau) (n=22) and several cognitive tests. A 1-year follow-up 18F-PI-2620 PET scans and cognitive assessments were done in 15 subjects.ResultsPercentage of visually tau-positive scans increased with amyloid-beta deposition measured in 18F-florbetaben Centiloids (CL) (7.7% (<36 CL), 80% (>83 CL)). 18F-PI-2620 standardized uptake value ratio (SUVR) was correlated with increased 18F-florbetaben CL in several regions of interest. Elevated 18F-PI-2620 SUVR (fusiform gyrus) was associated to high CSF p-tau and t-tau (p=0.0006 and p=0.01, respectively). Low hippocampal volume was associated with increased tau load at baseline (p=0.006 (mesial temporal); p=0.01 (fusiform gyrus)). Significant increases in tau SUVR were observed after 12 months, particularly in the mesial temporal cortex, fusiform gyrus, and inferior temporal cortex (p=0.04, p=0.047, p=0.02, respectively). However, no statistically significant increase in amyloid-beta load was measured over the observation time. The MMSE (Recall score), ADAS-Cog14 (Word recognition score), and CBB (One-card learning score) showed the strongest association with tau deposition at baseline.ConclusionsThe findings support the hypothesis that 18F-PI-2620 PET imaging of neuropathologic tau deposits may reflect underlying neurodegeneration in AD with significant correlations with hippocampal volume, CSF biomarkers, and amyloid-beta load. Furthermore, quantifiable increases in 18F-PI-2620 SUVR over a 12-month period in regions with early tau deposition are consistent with the hypothesis that cortical tau is associated with cognitive impairment. This study supports the utility of 18F-PI-2620 PET to assess tau deposits in an early AD population. Quantifiable tau load and its corresponding increase in early AD cases could be a relevant target engagement marker in clinical trials of anti-amyloid and anti-tau agents.Trial registrationData used in this manuscript belong to a tau PET imaging sub-study of the elenbecestat MissionAD Phase 3 program registered in ClinicalTrials.gov (NCT02956486; NCT03036280).

Disruptions of the Human Connectome Associated With Hemispatial Neglect.

Background and ObjectivesHemispatial neglect is a heterogeneous and complex disorder that can be classified by frame of reference for “left” vs “right,” including viewer-centered neglect (VCN, affecting the contralesional side of the view), stimulus-centered neglect (SCN, affecting the contralesional side of the stimulus, irrespective of its location with respect to the viewer), or both. We investigated the effect of acute stroke lesions on the connectivity of neural networks that underlie VCN or SCN.MethodsA total of 174 patients within 48 hours of acute right hemispheric infarct underwent a detailed hemispatial neglect assessment that included oral reading, scene copy, line cancellation, gap detection, horizontal line bisection tests, and MRI. Each patient's connectivity map was generated. We performed a linear association analysis between network connectivity strength and continuous measures of neglect to identify lesion-induced disconnections associated with the presence or severity of VCN and SCN. Results were corrected for multiple comparisons.ResultsAbout 42% of the participants with right hemisphere stroke had at least one type of neglect. The presence of any type of neglect was associated with lesions to tracts connecting the right inferior parietal cortex, orbitofrontal cortex, and right thalamus to other right-hemispheric structures. VCN only was strongly associated with tracts connecting the right putamen to other brain regions and tracts connecting right frontal regions with other brain regions. The presence of both types of neglect was most strongly associated with tracts connecting the right inferior and superior parietal cortex to other brain regions and those connecting left or right mesial temporal cortex to other brain regions.DiscussionOur study provides new evidence for the specific white matter tracts where disruption can cause hemispatial neglect in a relatively large number of participants and homogeneous time after onset. We obtained MRI and behavioral testing acutely, before the opportunity for rehabilitation or substantial recovery.Classification of EvidenceThis study provides Class II evidence that damage to specific white matter tracts identified on MRI are associated with the presence of neglect following right hemispheric stroke.

Clinical features of automatisms and correlation with the seizure onset zones: A cluster analysis of 74 surgically-treated cases

ObjectivesTo identify semiologic features of automatisms correlating to different seizure onset zones (SOZ). MethodsIn total, 204 seizures from 74 patients with either oral or manual automatisms were assessed. Patients were divided into four groups depending on the SOZ into frontal, posterior, neocortical temporal, and mesial temporal cortex groups. A k-means analysis was applied on 11 semiologic features on a multi-criteria scale. Then, the resulting clinical patterns were correlated with the SOZs determined by presurgical anatomy-electroclinical data (25 cases with stereo-EEG). ResultsFour clinical patterns of automatisms with different accompanying symptoms were identified. The clinical features of clusters 1 and 4 were mostly found in temporal epilepsy whereas clusters 2 and 3 were more frequent in extratemporal epilepsy. Cluster 1 was significantly correlated with mesial temporal lobe epilepsy (p = .017) and was characterised by aura, postictal confusion, short automatisms delay. Cluster 3 included 1/3 patients with frontal lobe epilepsy and was characterised by emotionality. Cluster 4 was related to neocortical temporal lobe epilepsy and characterised by dystonia and short automatism delay (p = .011). ConclusionThe distinct semiologic patterns of automatisms may provide information which may allow clinicians to define the SOZs. These findings could improve diagnostic accuracy and surgical outcome.

Connectivity and Patterns of Regional Cerebral Blood Flow, Cerebral Glucose Uptake, and Aβ-Amyloid Deposition in Alzheimer's Disease (Early and Late-Onset) Compared to Normal Ageing.

The aim of this study was to investigate the differences in early (EOAD) and late (LOAD) onset of Alzheimer´s disease, as well as glucose uptake, regional cerebral blood flow (R1), amyloid depositions, and functional brain connectivity between normal young (YC) and Old Controls (OC). The study included 22 YC (37 ± 5 y), 22 OC (73 ± 5.9 y), 18 patients with EOAD (63 ± 9.5 y), and 18 with LOAD (70.6 ± 7.1 y). Patients underwent FDG and PIB PET/CT. R1 images were obtained from the compartmental analysis of the dynamic PIB acquisitions. Images were analyzed by a voxel-wise and a VOI-based approach. Functional connectivity was studied from the R1 and glucose uptake images. OC had a significant reduction of R1 and glucose uptake compared to YC, predominantly at the dorsolateral and mesial frontal cortex. EOAD and LOAD vs. OC showed a decreased R1 and glucose uptake at the posterior parietal cortex, precuneus, and posterior cingulum. EOAD vs. LOAD showed a reduction in glucose uptake and R1 at the occipital and parietal cortex and an increased at the mesial frontal and temporal cortex. There was a mild increase in an amyloid deposition at the frontal cortex in LOAD vs. EOAD. YC presented higher connectivity than OC in R1 but lower connectivity considering glucose uptake. Moreover, EOAD and LOAD showed a decreased connectivity compared to controls that were more pronounced in glucose uptake than R1. Our results demonstrated differences in amyloid deposition and functional imaging between groups and a differential pattern of functional connectivity in R1 and glucose uptake in each clinical condition. These findings provide new insights into the pathophysiological processes of AD and may have an impact on patient diagnostic evaluation.

Case of Asperger's Syndrome and Lesion of the Right Amygdala: Deficits in Implicit and Explicit Fearful Face Recognition.

Introduction: Studies of brain-damaged patients revealed that amygdala lesions cause deficits in the processing and recognition of emotional faces. Patients with autism spectrum disorders (ASD) have similar deficits also related to dysfunctions of the limbic system including the amygdala.Methods: We investigated a male patient who had been diagnosed with Asperger's syndrome. He also presented with a lesion of the right mesial temporal cortex, including the amygdala. We used functional magnetic resonance imaging (fMRI) to investigate neuronal processing during a passive viewing task of implicit and explicit emotional faces. Clinical assessment included a facial emotion recognition task.Results: There was no amygdala activation on both sides during the presentation of masked emotional faces compared to the no-face control condition. Presentation of unmasked happy and angry faces activated the left amygdala compared to the no-face control condition. There was no amygdala activation in response to unmasked fearful faces on both sides. In the facial emotion recognition task, the patient biased positive and neutral expressions as negative.Conclusions: This case report describes a male patient with right amygdala damage and an ASD. He displayed a non-response of the amygdala to fearful faces and tended to misinterpret fearful expressions. Moreover, a non-reactivity of both amygdalae to emotional facial expressions at an implicit processing level was revealed. It is discussed whether the deficient implicit processing of facial emotional information and abnormalities in fear processing could contribute and aggravate the patient's impairments in social behavior and interaction.

Impact of prophylactic cranial irradiation and hippocampal sparing on 18F-FDG brain metabolism in small cell lung cancer patients

Background and purposeProphylactic cranial irradiation (PCI) in small-cell lung cancer (SCLC) patients improves survival. However, it is also associated with cognitive impairment, although the underlying mechanisms remain poorly understood. Our study aims to evaluate the impact of PCI and potential benefit of hippocampal sparing (HS) on brain metabolism assessed by 18F-Fluoro-Deoxy-Glucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT). Materials and methodsWe retrospectively included 22 SCLC patients. 50% had hippocampal-sparing (HS) PCI. 18F-FDG PET/CT was performed 144.5 ± 73 days before and 383 ± 451 days after PCI. Brain 18F-FDG PET scans were automatically segmented in 12 regions using Combined-AAL Atlas from MI-Neurology Software (Syngo.Via, Siemens Healthineers). For all atlas regions, we computed SUV Ratio using brainstem as a reference region (SUVR = SUVmean/Brainstem SUVmean) and compared SUVR before and after PCI, using a Wilcoxon test, with a level of significance of p < 0.05. ResultsWe found significant decreases in 18F-FDG brain metabolism after PCI in the basal ganglia (p = 0.004), central regions (p = 0.001), cingulate cortex (p < 0.001), corpus striata (p = 0.003), frontal cortex (p < 0.001), parietal cortex (p = 0.001), the occipital cortex (p = 0.002), precuneus (p = 0.001), lateral temporal cortex (p = 0.001) and cerebellum (p < 0.001). Conversely, there were no significant changes in the mesial temporal cortex (MTC) which includes the hippocampi (p = 0.089). The subgroup who received standard PCI showed a significant decrease in metabolism of the hippocampi (p = 0.033). Contrastingly, the subgroup of patients who underwent HS-PCI showed no significant variation in metabolism of the hippocampi (p = 0.783). ConclusionPCI induced a diffuse decrease in 18F-FDG brain metabolism. HS-PCI preserves metabolic activity of the hippocampi.

Glucose Metabolism Characteristics of Extra-Hypothalamic Cortex in Patients With Hypothalamic Hamartomas (HH) Undergoing Epilepsy Evaluation: A Retrospective Study of 16 Cases.

Purpose: There are few studies on the glucose metabolic characteristics of the extra-hypothalamic cortex in the hypothalamic hamartomas (HH). A comprehensive understanding of pathogenic progression of the disease is required from the perspective of cortical metabolism; therefore, we aimed to characterize metabolic characteristics of extra-hypothalamic in HH patients.Methods: We investigated the metabolic characteristics of 16 HH patients, all of whom underwent epilepsy evaluation at Xuan Wu Hospital between 2017 and 2019. The lateralization and cortical distribution pattern of hypometabolism was assessed and related to HH mass neuroanatomy on magnetic resonance imaging (MRI) as well as scalp-electroencephalogram (scalp-EEG) abnormalities. Furthermore, asymmetry measurements of region of interest (ROI) in the temporal cortex (hippocampal formation, amygdala, and lateral temporal neocortex) were quantitatively assessed based on the normalized average positron emission tomography (PET) voxel values. The surgery prognosis was assessed using the International League Against Epilepsy (ILAE) classification system.Results: The lateralization of hypometabolism in global visual ratings was consistent with the HH mass lateralization seen on MRI. Cortical hypometabolism showed three patterns depending whether the HH mass involved mammillary bodies, middle hypothalamus nucleus, or both. The three patterns were hypometabolism of the mesial temporal cortex with symptom of mesial temporal epilepsy (3/16, pattern I), lateral temporal, and extratemporal (frontal or parietal) cortex with symptom of neocortex temporal or frontal epilepsy (5/16, pattern II), and mesial and lateral temporal cortex and extratemporal (frontal or parietal) cortex with varied symptoms (8/16, pattern III), respectively. A significant difference in PET voxel values was found between bilateral hippocampal formation (P = 0.001) and lateral temporal neocortex in the third group (P = 0.005). We suggest that the hypometabolic characteristics of the extra-hypothalamic cortex in HH patients have three patterns. The final cortical hypometabolic pattern depends on the neuroanatomic location of the HH mass and was consistent with the main involved cortex of the interictal and ictal discharges. The third hypometabolic pattern with the most extensive cortical hypometabolism has a poorer prognosis.

Cross sex hormone treatment is linked with a reversal of cerebral patterns associated with gender dysphoria to the baseline of cisgender controls

Transgender persons experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), is frequently treated with cross-sex hormones. However, very little is known about how this treatment affects the brain of individuals with GD, nor do we know the neurobiology of GD. We recently suggested that disconnection of fronto-parietal networks involved in own-body self-referential processing could be a plausible mechanism, and that the anatomical correlate could be a thickening of the mesial prefrontal and precuneus cortex, which is unrelated to sex. Here, we investigate how cross-sex hormone treatment affects cerebral tissue in persons with GD, and how potential changes are related to self-body perception. Longitudinal MRI measurements of cortical thickness (Cth) were carried out in 40 transgender men (TrM), 24 transgender women (TrW) and 19 controls. Cth increased in the mesial temporal and insular cortices with testosterone treatment in TrM, whereas anti-androgen and oestrogen treatment in TrW caused widespread cortical thinning. However, after correction for treatment-related changes in total grey and white matter volumes (increase with testosterone; decrease with anti-androgen and oestrogen), significant Cth decreases were observed in the mesial prefrontal and parietal cortices, in both TrM and TrW (vs. controls) - regions showing greater pre-treatment Cth than in controls. The own body - self congruence ratings increased with treatment, and correlated with a left parietal cortical thinning. These data confirm our hypothesis that GD may be associated with specific anatomical features in own-body/self-processing circuits that reverse to the pattern of cisgender controls after cross-sex hormone treatment.

(+)-[18F]Flubatine as a novel \u03b14\u03b22 nicotinic acetylcholine receptor PET ligand\u2014results of the first-in-human brain imaging application in patients with \u03b2-amyloid PET-confirmed Alzheimer\u2019s disease and healthy controls

PurposesWe present the first in-human brain PET imaging data of the new α4β2 nicotinic acetylcholine receptor (nAChR)–targeting radioligand (+)-[18F]Flubatine. Aims were to develop a kinetic modeling-based approach to quantify (+)-[18F]Flubatine and compare the data of healthy controls (HCs) and patients with Alzheimer’s disease (AD); to investigate the partial volume effect (PVE) on regional (+)-[18F]Flubatine binding; and whether (+)-[18F]Flubatine binding and cognitive test data respective β-amyloid radiotracer accumulation were correlated.MethodsWe examined 11 HCs and 9 mild AD patients. All subjects underwent neuropsychological testing and [11C]PiB PET/MRI examination. (+)-[18F]Flubatine PET data were evaluated using full kinetic modeling and regional as well as voxel-based analyses.ResultsWith 270-min p.i., the unchanged parent compound amounted to 97 ± 2%. Adequate fits of the time-activity curves were obtained with the 1 tissue compartment model (1TCM). (+)-[18F]Flubatine distribution volume (binding) was significantly reduced in bilateral mesial temporal cortex in AD patients compared with HCs (right 10.6 ± 1.1 vs 11.6 ± 1.4, p = 0.049; left 11.0 ± 1.1 vs 12.2 ± 1.8, p = 0.046; one-sided t tests each). PVE correction increased not only (+)-[18F]Flubatine binding of approximately 15% but also standard deviation of 0.4–70%. Cognitive test data and (+)-[18F]Flubatine binding were significantly correlated in the left anterior cingulate, right posterior cingulate, and right parietal cortex (r > 0.5, p < 0.05 each). In AD patients, (+)-[18F]Flubatine binding and [11C]PiB standardized uptake value ratios were negatively correlated in several regions; whereas in HCs, a positive correlation between cortical (+)-[18F]Flubatine binding and [11C]PiB accumulation in the white matter was found. No adverse event related to (+)-[18F]Flubatine occurred.Conclusion(+)-[18F]Flubatine is a safe and stable PET ligand. Full kinetic modeling can be realized by 1TCM without metabolite correction. (+)-[18F]Flubatine binding affinity was high enough to detect group differences. Of interest, correlation between white matter β-amyloid PET uptake and (+)-[18F]Flubatine binding indicated an association between white matter integrity and availability of α4β2 nAChRs. Overall, (+)-[18F]Flubatine showed favorable characteristics and has therefore the potential to serve as α4β2 nAChR–targeting PET ligand in further clinical trials.

Cingulate cortex function and multi-modal connectivity mapped using intracranial stimulation

The cingulate cortex is part of the limbic system. Its function and connectivity are organized in a rostro-caudal and ventral-dorsal manner which was addressed by various other studies using rather coarse cortical parcellations. In this study, we aim at describing its function and connectivity using invasive recordings from patients explored for focal drug-resistant epilepsy.We included patients that underwent stereo-electroencephalographic recordings using intracranial electrodes in the University Emergency Hospital Bucharest between 2012 and 2019. We reviewed all high frequency stimulations (50 ​Hz) performed for functional mapping of the cingulate cortex. We used two methods to characterize brain connectivity. Effective connectivity was inferred based on the analysis of cortico-cortical potentials (CCEPs) evoked by single pulse electrical stimulation (SPES) (15 ​s inter-pulse interval). Functional connectivity was estimated using the non-linear regression method applied to 60 ​s spontaneous electrical brain signal intervals. The effective (stimulation-evoked) and functional (non-evoked) connectivity analyses highlight brain networks in a different way. While non-evoked connectivity evidences areas having related activity, often in close proximity to each other, evoked connectivity highlights spatially extended networks. To highlight in a comprehensive way the cingulate cortex’s network, we have performed a bi-modal connectivity analysis that combines the resting-state broadband h2 non-linear correlation with cortico-cortical evoked potentials. We co-registered the patient’s anatomy with the fsaverage FreeSurfer template to perform the automatic labeling based on HCP-MMP parcellation. At a group level, connectivity was estimated by averaging responses over stimulated/recorded or recorded sites in each pair of parcels. Finally, for multiple regions that evoked a clinical response during high frequency stimulation, we combined the connectivity of individual pairs using maximum intensity projection.Connectivity was assessed by applying SPES on 2094 contact pairs and recording CCEPs on 3580 contacts out of 8582 contacts of 660 electrodes implanted in 47 patients. Clinical responses elicited by high frequency stimulations in 107 sites (pairs of contacts) located in the cingulate cortex were divided in 10 groups: affective, motor behavior, motor elementary, versive, speech, vestibular, autonomic, somatosensory, visual and changes in body perception. Anterior cingulate cortex was shown to be connected to the mesial temporal, orbitofrontal and prefrontal cortex. In the middle cingulate cortex, we located affective, motor behavior in the anterior region, and elementary motor and somatosensory in the posterior part. This region is connected to the prefrontal, premotor and primary motor network. Finally, the posterior cingulate was shown to be connected with the visual areas, mesial and lateral parietal and temporal cortex.

Voxel-based analysis of gray matter relaxation rates shows different correlation patterns for cognitive impairment and physical disability in relapsing-remitting multiple sclerosis.

Regional analyses of markers of microstructural gray matter (GM) changes, including relaxation rates, have shown inconsistent correlations with physical and cognitive impairment in MS. To assess voxelwise the correlation of the R1 and R2 relaxation rates with the physical and cognitive impairment in MS. GM R1 and R2 relaxation rate maps were obtained in 241 relapsing-remitting MS patients by relaxometric segmentation of MRI studies. Correlations with the Expanded Disability Status Scale (EDSS) and the percentage of impaired cognitive test (Brief Repeatable Battery and Stroop Test, available in 186 patients) were assessed voxelwise, including voxel GM content as nuisance covariate to remove the effect of atrophy on the correlations. Extensive clusters of inverse correlation between EDSS and R2 were detected throughout the brain, while inverse correlations with R1 were mostly limited to perirolandic and supramarginal cortices. Cognitive impairment correlated negatively with R1, and to a lesser extent with R2, in the middle frontal, mesial temporal, midcingulate and medial parieto-occipital cortices. In relapsing-remitting MS patients, GM microstructural changes correlate diffusely with physical disability, independent of atrophy, with a preferential role of the sensorimotor cortices. Neuronal damage in the limbic system and dorsolateral prefrontal cortices correlates with cognitive dysfunction.