Search Results (53)

Background: Amnestic mild cognitive impairment (aMCI) is considered a transitional state between normal aging and dementia, often without visible abnormalities on standard brain magnetic resonance (MR) images. The aim of the study was to analyze both microstructural and functional brain abnormalities using advanced MR techniques. Methods: The study included 27 patients with aMCI and an age-matched control group (CG) of 25 healthy subjects. All MR studies were performed on a 3T MR scanner (Philips, Ingenia) with a 32-channel head and neck coil using volumetric 3D T1 sequences, followed by a resting-state functional MRI (rs-fMRI) sequence. Volumetric analysis was performed using the Destrieux atlas to assess potential structural differences between groups. Seed-to-voxel functional connectivity analyses were conducted using the bilateral hippocampi and both anterior and posterior divisions of the parahippocampal gyri as seed regions. Results: Compared to healthy controls, reduced cortical thickness was observed in aMCI subjects in the temporal regions, frontal and orbitofrontal areas, limbic areas, parietal and sensorimotor cortices, as well as occipito-temporal regions. Additionally, significantly increased functional connectivity was observed between bilateral medial temporal lobe (MTL) regions and the right thalamus. Conclusions: Cortical thinning in various brain regions along with the increased functional connectivity between the MTL regions and the right thalamus may reflect potential compensatory mechanisms in response to initial subtle degenerative changes, emphasizing the importance of using both functional and structural imaging to detect early changes in aMCI patients. Full article

Mesial temporal lobe epilepsy (TLE) is the most common and severe form of focal epilepsy. This review examines the diverse mechanisms by which the GABAergic system contributes both to seizure generation and to protective processes that limit epileptogenesis and seizure progression in TLE. We focus on findings from established animal models of TLE as well as studies of surgically resected tissue from patients who had undergone therapeutic intervention. Experimental models include sustained electrical stimulation of the perforant path, as well as the kainic acid (KA) and Li-pilocarpine models. Although these paradigms induce status epilepticus (SE) through distinct mechanisms, they ultimately converge on prolonged excitation of hippocampal CA3 pyramidal neurons and interconnected regions of the hippocampus and broader limbic network. In response to epileptic seizures, GABA synthesis is enhanced, as evidenced by the marked upregulation of the GABA-synthesizing enzymes GAD65 and GAD67, along with their ectopic expression in glutamatergic mossy fibers of the hippocampus. Shortly after acute seizures, a transient expression of the embryonic GAD67 splice variant, GAD25, is observed, although its functional significance remains unclear. At the receptor level, animal models of TLE show upregulation of GABA_A receptor subunits α2, α4, β3, and γ2, accompanied by downregulation of α5 and δ subunits, suggesting reduced tonic inhibition. In contrast, hippocampal tissue from patients with TLE exhibits pronounced upregulation of α5 and δ subunits, indicative of enhanced extrasynaptic tonic inhibition. Similarly, whereas GABA_A receptor subunits are mildly downregulated in animal models, they are consistently upregulated across hippocampal subfields in human TLE, pointing toward strengthened GABAergic inhibition. Conversely, genetic variants of GABA_A receptor subunits and autoantibodies targeting these receptors can contribute to the etiology of epilepsy, often with onset in childhood. Moreover, degeneration or functional silencing of specific GABAergic interneuron populations—such as parvalbumin-positive neurons in the subiculum—can induce epilepsy in rodent models and is likewise associated with TLE in humans. Full article

Background: Brain MRI abnormalities in anti-NMDA receptor encephalitis (ANMDARE) are classically described in limbic structures, particularly the medial temporal lobe. Paralimbic, neocortical, and meningeal abnormalities have been less consistently reported. Objective: The objective was to evaluate the diagnostic value of brain MRI abnormalities in patients with definite ANMDARE. Methods: We conducted a case–control study including 115 patients with ANMDARE and 115 controls with primary psychotic disorders or antibody-negative autoimmune encephalitis. Structural MRI studies were systematically reviewed by an expert neuroradiologist blinded to clinical diagnosis. Results: ANMDARE patients were younger and more frequently presented with seizures, dyskinesia, severe neuropsychiatric disturbances, abnormal cerebrospinal fluid and EEG findings, and worse outcomes, including mortality. T2-T2-FLAIR abnormalities commonly involved medial temporal limbic structures, paralimbic regions (anterior cingulate and insular cortices), and neocortical areas (parieto-occipital cortices). Pachymeningeal enhancement was observed in 26.1% of patients. MRI findings clearly differentiated ANMDARE from primary psychotic disorders but largely overlapped with antibody-negative autoimmune encephalitis, except for limited parietal and occipital differences. Conclusions: T2-FLAIR MRI abnormalities involving medial temporal, paralimbic, and posterior neocortical regions are common in ANMDARE. Pachymeningeal enhancement is not rare. While useful for distinguishing ANMDARE from primary psychotic disorders, a substantial overlap with antibody-negative autoimmune encephalitis was observed. Full article

Religious experiences represent a universal and timeless phenomenon that has accompanied humanity since its origins. In recent decades, neuroscience has explored the relationship between temporal lobe epilepsy (TLE) and hyperreligiosity phenomena, describing sudden convictions, states of ecstasy, and spiritual conversions associated with epileptic seizures. This article offers a narrative review of the literature on the relationship between epilepsy and religion, including its clinical manifestations (ictal, postictal, and interictal) and the main neurobiological models proposed to explain it, such as the limbic marker hypothesis and theory of mind (ToM). The possible role of the uncinate fasciculus as an integrative pathway between temporal and limbic regions is also explored, based on recent neuroimaging studies. Finally, we present an illustrative clinical case of a patient with meningioma and TLE associated with episodes of intense religious conviction, in whom a structural alteration of the right uncinate fasciculus was observed. This case reinforces the relevance of considering both neuronal networks and white matter tracts in the study of religious experiences, while underscoring the need for broader and more systematic studies to confirm these findings. Full article

The hippocampus is a crucial component of the human brain. It is located on the medial side of the temporal lobe and is connected to the limbic system, influencing memory and cognitive function. The critical functions of the hippocampus have a profound impact on an individual’s overall ability to maintain daily life functioning. In adults, hippocampal damage impairs cognitive functions, including memory, learning, and emotional regulation. It is associated with conditions such as memory impairment, Alzheimer’s disease, various forms of dementia, depression, and stress-related disorders. Damage to the developing hippocampus can have broad and profound, leading to deficits in memory development, language acquisition, and behavioral and emotional regulation, thereby impairing the individual’s ability to maintain normal daily functioning. One of the major factors affecting hippocampal development is epilepsy. Therefore, identifying the mechanism underlying epilepsy-induced hippocampal damage and developing therapeutic strategies to reduce or prevent epileptic events that significantly impair hippocampal maturation are of critical importance. Numerous studies have been conducted in this regard, and given the challenges of directly studying the human brain, organoid-based research approaches have gained increasing attention and widespread application. In particular, hippocampal organoids have emerged as valuable models for investigating various hippocampal functions; however, definitive findings have yet to be established. Therefore, elucidating the structural characteristics and underlying mechanisms of epilepsy using hippocampal organoids, and exploring potential strategies to mitigate its effects remains an important direction for future research. Full article

The mammalian amygdala is located in the temporal lobe of the telencephalon and plays a key role in limbic processing. Recently, our group proposed a radial morphological model to understand the glutamatergic (pallial) part of this nuclear complex in terms of separate progenitor domains. This model explains the amygdala region as consisting of several adjacent developmental radial progenitor units, disposing their distinct periventricular, intermediate, and superficial strata from the ventricle to the pial surface. It was expected that cell populations belonging to specific progenitor domains would present greater molecular similarity to each other than to neighboring developmental units. In this work, we aim to corroborate the existence of several radial domains in the pallial amygdala at the transcriptomic level. snRNAseq experiments in the amygdala of adult mice of both sexes indicated that at low resolution, the whole pallial amygdala was found to divide into two super-radial domains distinguished by differential expression of Slc17a6 and Slc17a7; the former partly imitates molecularly the subpallial (output) amygdalar regions, whereas the rest of the pallial amygdala is molecularly more akin to the surrounding cortical areas. In addition, our snRNAseq transcriptomic analysis fully supports the postulated amygdalar radial model of four main radial domains. Full article

Background: Congenital anosmia (CA) is a rare condition characterized by a lifelong inability to perceive odors, which significantly affects daily life and may be linked to broader neurodevelopmental alterations. This study aimed to investigate structural brain differences in patients with CA using MRI, focusing on gray matter (GM) and white matter (WM) changes and their implications for neurodevelopment. Methods: This retrospective study included 28 patients with CA and 28 age- and gender-matched healthy controls. Patients with CA were diagnosed at a single medical center between 1 January 2001 and 30 August 2024. Controls were randomly selected from an imaging database and had no history of olfactory dysfunction. Brain Magnetic Resonance Imaging (MRI)was analyzed using volumetric analysis in SPM12.GM and WM volumes were quantified across 11 anatomical brain regions based on theWFU_PickAtlas toolbox, including frontal, temporal, parietal, occipital, limbic, sub-lobar, cerebellum (anterior/posterior), midbrain, the pons, and the frontal–temporal junction. Left–right hemispheric comparisons were also conducted. Results: Patients with CA exhibited significantly smaller GM volumes compared to healthy controls (560.6 ± 114.7 cc vs. 693.7 ± 96.3 cc, p < 0.001) but larger WM volumes (554.2 ± 75.4 cc vs. 491.1 ± 79.7 cc, p = 0.015). Regionally, GM reductions were observed in the frontal (131.9 ± 33.7 cc vs. 173.7 ± 27.0 cc, p < 0.001), temporal (81.1 ± 18.4 cc vs. 96.5 ± 14.1 cc, p = 0.001), parietal (52.4 ± 15.2 cc vs. 77.2 ± 12.4 cc, p < 0.001), sub-lobar (57.8 ± 9.7 cc vs. 68.2 ± 10.2 cc, p = 0.001), occipital (39.1 ± 13.0 cc vs. 57.8 ± 8.9 cc, p < 0.001), and midbrain (2.0 ± 0.5 cc vs. 2.3 ± 0.4 cc, p = 0.006) regions. Meanwhile, WM increases were notable in the frontal(152.0 ± 19.9 cc vs. 139.2 ± 24.0 cc, p = 0.027), temporal (71.5 ± 11.5 cc vs. 60.8 ± 9.5 cc, p = 0.001), parietal (75.8 ± 12.4 cc vs. 61.9 ± 11.5 cc, p < 0.001), and occipital (58.7 ± 10.3 cc vs. 41.9 ± 7.9 cc, p < 0.001) lobes. A separate analysis of the left and right hemispheres revealed similar patterns of reduced GM and increased WM volumes in patients with CA across both sides. An exception was noted in the right cerebellum-posterior, where patients with CA showed significantly greater WM volume (5.625 ± 1.667 cc vs. 4.666 ± 1.583 cc, p = 0.026). Conclusions: This study demonstrates widespread structural brain differences in individuals with CA, including reduced GM and increased WM volumes across multiple cortical and sub-lobar regions. These findings suggest that congenital olfactory deprivation may impact brain maturation beyond primary olfactory pathways, potentially reflecting altered synaptic pruning and increased myelination during early neurodevelopment. The involvement of the cerebellum further implies potential adaptations beyond motor functions. These structural differences may serve as potential neuroimaging markers for monitoring CA-associated cognitive or emotional comorbidities. Full article

Background/Objectives: T1-weighted magnetic resonance imaging (MRI) and the Montreal Cognitive Assessment are standard, efficient, and swift clinical and research tools used when interrogating cognitively impairing (CI) conditions, such as Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). However, the associations between gross cognitive impairment (CI) as compared to domain-specific functioning and underlying neuroanatomical correlates have not been investigated among individuals with early-onset Mild Cognitive Impairment (MCI) or Alzheimer’s disease (EOAD), who can benefit greatly from early diagnosis and intervention strategies. Methods: We analyzed T1-weighted MRIs and Montreal Cognitive Assessment (MoCA) scores from the ADNI database in individuals < 65 years old who were either cognitively normal (CN) or had MCI or EOAD. Gray matter volume (GMV) was estimated in voxel-based morphometry (VBM) and ROI-parcellation general linear models examining associations with individual MoCA scores after adjusting for demographic covariates. Results: Results from 120 subjects (44 CN, 62 MCI, and 14 EOAD), identified significant global but also individually distinct domain-specific topographical signatures spanning the temporal, parietal, limbic, occipital, frontal lobes, and cingulate gyri. Conclusions: The results highlight neural correlates of cognitive functioning in a sample of young patients representative of the AD continuum, in addition to studying the structural MRI and functional cognitive difference. Full article

Limbic encephalitis (LE) associated with anti-LGI1 antibodies is an autoimmune disorder characterized by memory decline, behavioral changes, and temporal lobe epilepsy. Faciobrachial dystonic seizures (FBDS) are a hallmark symptom, often preceding cognitive and psychiatric issues. This report presents an 80-year-old male with LGI1 encephalitis, initially manifesting as FBDS. A lung adenocarcinoma was diagnosed two months after the onset of neurological symptoms. Clinical and paraclinical data, including MRI and [18]FDG PET imaging, are described. The patient responded to immunotherapy, including steroids and plasma exchange, along with tumor resection. Following treatment, neurological symptoms resolved, except for mild anxiety and apathy. Further research is needed to determine whether LGI1 encephalitis may occasionally have a paraneoplastic origin, potentially influencing screening and management strategies. Full article

Background/Objectives: Temporal lobe epilepsy (TLE) responds well to surgical treatment, although a considerable percentage of patients experience seizure recurrence after resection. Relapse from the contralateral mesial temporal lobe, extratemporal lobe epilepsy mimicking TLE, or temporal plus epilepsy might account for surgical failures. Methods: We included patients with a pre-implantation hypothesis suggesting TLE, who underwent stereo-EEG (SEEG) evaluation at our institution and had an individual SEEG exploration paradigm with at least twelve stereo-electrodes placed to sixteen brain regions allowing exploration of limbic and paralimbic networks. We analyzed the prevalence of TLE subtypes based on ictal onset localization with SEEG and response to resective surgery. Results: Twenty-four subjects met the inclusion criteria. Seven patients had unilateral mesial temporal epilepsy (UMTE), five had bilateral mesial temporal epilepsy (BMTE), five had unilateral neocortical temporal epilepsy (UNTE), six had temporal-plus epilepsy (TPE), one had extratemporal epilepsy (ETE). The number of patients who underwent destructive surgeries and surgical outcomes are as follows: UMTE—all seven patients, Engel I; BMTE- three out of five, Engel I, III, and IV, respectively; UNTE—three out of five, Engel I; TLE mimic (ETE)—one, Engel I; TPE—all six patients, Engel I–three, Engel III–two, Engel IV—one. Conclusions: In our study, UMTE was the most frequent TLE subtype (29%), and all patients proceeded to resective surgery with good outcomes. TPE comprised a substantial component (25%) of this cohort with initially presumed TLE, who had a notable proportion of unfavorable outcomes. Larger studies are needed to create guidelines for rational counseling of patients with presumed TLE regarding surgical outcomes. Full article

Temporal lobe epilepsy (TLE) is considered a network disorder rather than a localized lesion, making it essential to study the network mechanisms underlying TLE. In this study, we constructed directed brain networks based on clinical MEG data using the Granger Causality Analysis (GCA) method, aiming to provide new insights into the network mechanisms of TLE. MEG data from 13 lTLE and 21 rTLE patients and 14 healthy controls (HCs) were analyzed. The preprocessed MEG data were used to construct directed brain networks using the GCA method and undirected brain networks using the Pearson Correlation Coefficient (PCC) method. Graph theoretical analysis extracted global and local topologies from the binary matrix, and SVM classified topologies with significant differences (p < 0.05). Comparative studies were performed on connectivity strengths, graph theory metrics, and SVM classifications between GCA and PCC, with an additional analysis of GCA-weighted network connectivity. The results show that TLE patients showed significantly increased functional connectivity based on GCA compared to the control group; similarities of the hub brain regions between lTLE and rTLE patients and the cortical–limbic–thalamic–cortical loop were identified; TLE patients exhibited a significant increase in GCA-based Global Clustering Coefficient (GCC) and Global Local Efficiency (GLE); most brain regions with abnormal local topological properties in TLE patients overlapped with their hub regions. The directionality of brain connectivity has played a significantly more pivotal role in research on TLE. GCA may be a potential tool in MEG analysis to distinguish TLE patients and HC effectively. Full article

Background/Objectives: In this study, a medical decision support system is presented to assist physicians in epileptic focus detection by correlating MRI and EEG data of temporal lobe epilepsy patients. Methods: By exploiting the asymmetry in the hippocampus in MRI images and using voxel-based morphometry analysis, gray matter reduction in the temporal and limbic lobes is detected, and epileptic focus prediction is realized. In addition, an epileptic focus is also determined by calculating the asymmetry score from EEG channels. Finally, epileptic focus detection was performed by associating MRI and EEG data with a decision tree. Results: The results obtained from the proposed algorithm provide 100% overlap with the physician’s finding on the EEG data. Conclusions: MRI and EEG correlation in epileptic focus detection was improved compared with physicians. The proposed algorithm can be used as a medical decision support system for epilepsy diagnosis, treatment, and surgery planning. Full article

Our study aimed to identify the mechanisms of stress-induced and post-stress recovery states by evaluating voxel type and the total number of voxels activated based on Perceived Stress Scale scores. Functional MRI (fMRI) was used to measure the brain activation patterns in participants grouped into moderate- and high-stress categories. The number of activation voxels in the parahippocampal gyrus of the limbic lobe was greater in the high-stress group than in the moderate-stress group. Moreover, only the high-stress group showed the characteristic activation of the left precuneus. The moderate-stress group showed a greater number of activation voxels than the high-stress group for the occipital, frontal, and limbic lobes, while the reverse was true for the parietal lobe. In the post-stress recovery phase, the left lingual, inferior frontal, and middle frontal gyri were activated, and the number of activation voxels in these areas was greater in the high-stress group than in the moderate-stress group. The characteristic activation of the declive in the left cerebellum was observed in the moderate-stress group, whereas the activation of the right cuneus was dominant in the high-stress group. Our findings suggest that perceived stress may play an important role in determining the neural mechanisms underlying stress and post-stress recovery, providing insights into the complex interplay between the psychological and neural processes occurring in response to stress. Full article

Neuroscience has revolved around brain structural changes, functional activity, and connectivity alteration in Parkinson’s Disease (PD); however, how the network topology organization becomes altered is still unclear, specifically in Parkinson’s patients with severe hyposmia. In this study, we have examined the functional network topological alteration in patients affected by Parkinson’s Disease with normal cognitive ability (ODN), Parkinson’s Disease with severe hyposmia (ODP), and healthy controls (HCs) using resting-state functional magnetic resonance imaging (rsfMRI) data. We have analyzed brain topological organization using popular graph measures such as network segregation (clustering coefficient, modularity), network integration (participation coefficient, path length), small-worldness, efficiency, centrality, and assortativity. Then, we used a feature ranking approach based on the diagonal adaptation of neighborhood component analysis, aiming to determine a graph measure that is sensitive enough to distinguish between these three different groups. We noted significantly lower segregation and local efficiency and small-worldness in ODP compared to ODN and HCs. On the contrary, we did not find differences in network integration in ODP compared to ODN and HCs, which indicates that the brain network becomes fragmented in ODP. At the brain network level, a progressive increase in the DMN (Default Mode Network) was observed from healthy controls to ODN to ODP, and a continuous decrease in the cingulo-opercular network was observed from healthy controls to ODN to ODP. Further, the feature ranking approach has shown that the whole-brain clustering coefficient and small-worldness are sensitive measures to classify ODP vs. ODN, as well as HCs. Looking at the brain regional network segregation, we have found that the cerebellum and limbic, fronto-parietal, and occipital lobes have higher ODP reductions than ODN and HCs. Our results suggest network topological measures, specifically whole-brain segregation and small-worldness decreases. At the network level, an increase in DMN and a decrease in the cingulo-opercular network could be used as biomarkers to characterize ODN and ODP. Full article

Craving is one of the most important symptoms of cocaine use disorder (CUD) since it contributes to the relapse and persistence of such disorder. This systematic review aimed to investigate which brain regions are modulated during cocaine craving. The articles were obtained through searches in the Google Scholar, Regional BVS Portal, PubMed, and Scielo databases. Overall, there was a selection of 36 studies with 1574 individuals, the majority being participants with CUD, whereby about 61.56% were individuals with CUD and 38.44% were controls (mean age = 40.4 years). Besides the methodological points, the neurobiological investigations comprised fMRI (58.34%) and PET (38.89%). The induction of cocaine craving was studied using different methods: exposure to cocaine cues (69.45%), stressful stimuli, food cues, and methylphenidate. Brain activations demonstrated widespread activity across the frontal, parietal, temporal, and occipital lobes, basal ganglia, diencephalon, brainstem, and the limbic system. In addition to abnormalities in prefrontal cortex activity, abnormalities in various other brain regions’ activity contribute to the elucidation of the neurobiology of cocaine craving. Abnormalities in brain activity are justified not only by the dysfunction of dopaminergic pathways but also of the glutamatergic and noradrenergic pathways, and distinct ways of inducing craving demonstrated the involvement of distinct brain circuits and regions. Full article