Frequency-dependent seizure-suppressing effects of optogenetic activation of septal inhibitory cells in mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) is characterized by recurring focal seizures that arise from limbic areas and are often refractory to pharmacological interventions. We have reported that optogenetic stimulation of PV-positive cells in the medial septum at 0.5 Hz exerts seizure-suppressive effects. Therefore, we compared here these results with those obtained by optogenetic stimulation of medial septum PV-positive neurons at 8 Hz in male PV-ChR2 mice (P60-P100) undergoing an initial, pilocarpine-induced status epilepticus (SE). Optogenetic stimulation (5 min ON, 10 min OFF) was performed from day 8 to day 12 after SE at a frequency of 8 Hz (n = 6 animals) or 0.5 Hz (n = 8 animals). Surprisingly, in both groups, no effects were observed on the occurrence of interictal spikes and interictal high frequency oscillations (HFOs). However, 0.5 Hz stimulation induced a significant decrease of seizure occurrence (p < 0.05). Such anti-ictogenic effect was not observed in the 8 Hz protocol that instead triggered seizures (p < 0.05); these seizures were significantly longer under optogenetic stimulation compared to when optogenetic stimulation was not implemented (p < 0.05). Analysis of ictal HFOs revealed that in the 0.5 Hz group, but not in the 8 Hz group, seizures occurring under optogenetic stimulation were associated with significantly lower rates of fast ripples compared to when optogenetic stimulation was not performed (p < 0.05). Our results indicate that activation of GABAergic PV-positive neurons in the medial septum exerts seizure-suppressing effects that are frequency-dependent and associated with low rates of fast ripples. Optogenetic activation of medial septum PV-positive neurons at 0.5 Hz is efficient in blocking seizures in the pilocarpine model of MTLE, an effect that did not occur with 8 Hz stimulation.

Epileptic activity on foramen ovale electrodes is associated with sleep and tau pathology in Alzheimer's disease.

Both sleep alterations and epileptiform activity are associated with the accumulation of amyloid-ß and tau pathology and are currently investigated for potential therapeutic interventions in Alzheimer's disease (AD). However, a bidirectional intertwining relation between sleep and neuronal hyperexcitability might modulate the effects of AD pathology on the corresponding associations. To investigate this, we performed multiple day simultaneous foramen ovale (FO) plus scalp EEG and polysomnography (PSG) recordings and acquired 18F-MK6240 tau PET-MR in three patients in the prodromal stage of AD and in two patients with mild and moderate dementia due to AD, respectively. As an eligibility criterion for the present study, subjects either had a history of a recent seizure (n = 2) or subclinical epileptiform activity (SEA) on a previous scalp EEG taken in a research context (n = 3). The 18F-MK6240 standard uptake value ratio (SUVR) and asymmetry index (AI) were calculated in a priori defined volumes of interest (VOIs). Linear mixed effects models were used to study associations between interictal epileptiform discharges (IEDs), PSG parameters and 18F-MK6240 SUVR. Epileptiform activity was bilateral but asymmetrically present on FO electrodes in all patients and ≥ 95% of IEDs were not visible on scalp EEG. In one patient two focal seizures were detected on FO electrodes, both without visual scalp EEG correlate. We observed lateralized periodic discharges, brief potentially ictal rhythmic discharges and lateralized rhythmic delta activity on FO electrodes in four patients. Unlike scalp EEG, intracranial electrodes showed a lateralization of epileptiform activity. Although the amount of IEDs on intracranial electrodes was not associated to the 18F-MK6240 SUVR binding in different VOIs, there was a congruent asymmetry of the 18F-MK6240 binding towards the most epileptic hemisphere for the mesial (P = 0.007) and lateral temporal cortex (P = 0.006). IEDs on intracranial electrodes were most abundant during slow wave sleep (SWS) (92/h) and N2 (81/h), followed by N1 (33/h) and least frequent during wakefulness (17/h) and REM sleep (9/h). The extent of IEDs during sleep was not reflected in the relative time in each sleep stage spent (REM% (P = 0.415), N1% (P = 0.668), N2% (P = 0.442), SWS% (P = 0.988)), and not associated with the arousal index (P = 0.317), apnea-hypopnea index (P = 0.846) or oxygen desaturation index (P = 0.746). Together, our observations suggest a multi-directional interaction between sleep, epileptiform activity and tau pathology in AD.

Verbal short term memory contribution to sentence comprehension decreases with increasing syntactic complexity in people with aphasia.

Sentence comprehension requires the integration of linguistic units presented in a temporal sequence based on a non-linear underlying syntactic structure. While it is uncontroversial that storage is mandatory for this process, there are opposing views regarding the relevance of general short-term-/working-memory capacities (STM/WM) versus language specific resources. Here we report results from 43 participants with an acquired brain lesion in the extended left hemispheric language network and resulting language deficits, who performed a sentence-to-picture matching task and an experimental task assessing phonological short-term memory. The sentence task systematically varied syntactic complexity (embedding depth and argument order) while lengths, number of propositions and plausibility were kept constant. Clinical data including digit-/ block-spans and lesion size and site were additionally used in the analyses. Correlational analyses confirm that performance on STM/WM-tasks (experimental task and digit-span) are the only two relevant predictors for correct sentence-picture-matching, while reaction times only depended on age and lesion size. Notably increasing syntactic complexity reduced the correlational strength speaking for the additional recruitment of language specific resources independent of more general verbal STM/WM capacities, when resolving complex syntactic structure. The complementary lesion-behaviour analysis yielded different lesion volumes correlating with either the sentence-task or the STM-task. Factoring out STM measures lesions in the anterior temporal lobe correlated a larger decrease in accuracy with increasing syntactic complexity. We conclude that overall sentence comprehension depends on STM/WM capacity, while increases in syntactic complexity tax another independent cognitive resource.

Socioemotional Dysfunction From Temporal Lobe Involvement in Frontotemporal Dementia: A Preliminary Report.

OBJECTIVE: Socioemotional changes, rather than cognitive impairments, are the feature that defines behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed the socioemotional changes in bvFTD and other dementias to frontal lobe dysfunction; however, recent work implies a further contribution from right anterior temporal disease. The authors evaluated relationships between regional brain atrophy and socioemotional changes in both bvFTD and early-onset Alzheimer's disease (EOAD). METHODS: This study explored the neuroanatomical correlations of performance on the Socioemotional Dysfunction Scale (SDS), an instrument previously shown to document socioemotional changes in bvFTD, among 13 patients with bvFTD not preselected for anterior temporal involvement and 16 age-matched patients with early-onset Alzheimer's disease (EOAD). SDS scores were correlated with volumes of regions of interest assessed with tensor-based morphometric analysis of MRI images. RESULTS: As expected, the bvFTD group had significantly higher SDS scores overall and smaller frontal regions compared with the EOAD group, which in turn had smaller volumes in temporoparietal regions. SDS scores significantly correlated with lateral anterior temporal lobe (ATL) atrophy, and a regression analysis that controlled for diagnosis indicated that SDS scores predicted lateral ATL volume. Within the bvFTD group, higher SDS scores were associated with smaller lateral and right ATL regions, as well as a smaller orbitofrontal cortex. Within the EOAD group, higher SDS scores were associated with a smaller right parietal cortex. CONCLUSIONS: This study confirms that, in addition to orbitofrontal disease, there is a prominent right and lateral ATL origin of socioemotional changes in bvFTD and further suggests that right parietal involvement contributes to socioemotional changes in EOAD.

Neuroprotective potential of topiramate, pregabalin and lacosamide combination in a rat model of acute SE and intractable epilepsy: Perspectives from electroencephalographic, neurobehavioral and regional degenerative analysis.

The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining. Results revealed that acute electrophysiological (EEG) profiling of the ASD cocktail markedly halted sharp ictogenic spikes as well as altered dynamics of brain wave oscillations thus validating the need for polytherapy vs. monotherapy. In TLE animals, pharmacological intervention for 6 weeks with topiramate 10 mg/kg in combination with PREG and LAC at the dose of 20 mg/kg exhibited marked protection from SRS incidence, improved body weight, offensive aggression, anxiety-like behavior, cognitive impairments, and depressive-like behavior (p < 0.05). Moreover, combination therapy impeded redox impairments as evidenced by decreased MDA and AchE levels and increased activity of antioxidant SOD, GSH enzymes. Furthermore, polytherapy rescued animals from SE-induced neurodegeneration with increased neuronal density in CA1, CA3c, CA3ab, hilus, and granular cell layer (GCL) of the dentate gyrus. In conclusion, early polytherapy with topiramate in combination with pregabalin and lacosamide prompted synergy and prevented epileptogenesis with associated psychological and neuropathologic alterations.

Anterior thalamic nucleus local field potentials during focal temporal lobe epileptic seizures.

Objective: To analyze the local field potentials (LFPs) in patients with focal drug-resistant epilepsy (DRE) from the anterior nucleus of the thalamus (ANT) during inter-ictal state and seizure state. Method: ANT stereotactic EEG (SEEG) recordings were studied in four patients with focal temporal lobe epilepsy. SEEG data was classified as inter-ictal and ictal state and sub-categorized into electrographic (ESz), focal aware seizure (FAS), focal with impaired awareness (FIA), or focal to bilateral tonic-clonic seizure (FBTC). LFP was analyzed at 4 Hz, 8 Hz, 16 Hz, 32 Hz, high gamma (100 Hz), and ripples (200 Hz) using spectrogram analysis and a statistical comparison of normalized power spectral density (PSD) averaged during seizures versus pre-ictal baseline segments. Result: The LFP recordings were analyzed for 162 seizures (127 ESz, 23 FAS, 6 FIA, and 6 FBTC). Based on time-frequency data (spectrogram), a broad band of activity, occurring between 2 and 6 Hz and centered at 4 Hz, and thin-band activity occurring specifically at 8 Hz on the frequency spectrogram were observed during the inter-ictal state. Statistically significant changes in LFP-PSD were seen for FAS, FIA, and FBTC. We observed a significant gain in LFP at the lower frequency band during FAS at 4 Hz, FIA, and FBTC at 4, 8, and 16 Hz while also observing increases at higher frequencies during FBTC at 100 and 200 Hz and a decrease during FAS seizures at 32 Hz. In contrast, no significant change in LFP power was seen for electrographic seizures. Interpretation: Our observations from a limited dataset indicate that all clinical seizure types, but not electrographic seizures, caused a change in ANT-LFP based on the magnitude of the associated power spectral density (PSD). Future work will be needed to validate the use of ANT-LFP at these frequencies as accurate measurements of seizure occurrence and severity. This work represents a first step toward understanding ANT thalamic LFP patterns during focal seizures and developing adaptive DBS strategies.

Altered correlation of concurrently recorded EEG-fMRI connectomes in temporal lobe epilepsy.

Whole-brain functional connectivity networks (connectomes) have been characterized at different scales in humans using EEG and fMRI. Multimodal epileptic networks have also been investigated, but the relationship between EEG and fMRI defined networks on a whole-brain scale is unclear. A unified multimodal connectome description, mapping healthy and pathological networks would close this knowledge gap. Here, we characterize the spatial correlation between the EEG and fMRI connectomes in right and left temporal lobe epilepsy (rTLE/lTLE). From two centers, we acquired resting-state concurrent EEG-fMRI of 35 healthy controls and 34 TLE patients. EEG-fMRI data was projected into the Desikan brain atlas, and functional connectomes from both modalities were correlated. EEG and fMRI connectomes were moderately correlated. This correlation was increased in rTLE when compared to controls for EEG-delta/theta/alpha/beta. Conversely, multimodal correlation in lTLE was decreased in respect to controls for EEG-beta. While the alteration was global in rTLE, in lTLE it was locally linked to the default mode network. The increased multimodal correlation in rTLE and decreased correlation in lTLE suggests a modality-specific lateralized differential reorganization in TLE, which needs to be considered when comparing results from different modalities. Each modality provides distinct information, highlighting the benefit of multimodal assessment in epilepsy.

The relationship between resting-state hemodynamic (fMRI) and electrophysiological (EEG) connectivity has been investigated in healthy subjects, but this relationship is unknown in patients with left and right temporal lobe epilepsies (l/rTLE). Does the magnitude of the relationship differ between healthy subjects and patients? What role does the laterality of the epileptic focus play? What are the spatial contributions to this relationship? Here we use concurrent EEG-fMRI recordings of 65 subjects from two centers (35 controls, 34 TLE patients), to assess the correlation between EEG and fMRI connectivity. For all datasets, frequency-specific changes in cross-modal correlation were seen in lTLE and rTLE. EEG and fMRI connectivities do not measure perfectly overlapping brain networks and provide distinct information on brain networks altered in TLE, highlighting the benefit of multimodal assessment to inform about normal and pathological brain function.

Theory of mind in epilepsy.

Epilepsy is characterized by recurrent, chronic, and unprovoked seizures. Epilepsy has a significant negative impact on a patient's quality of life even if seizures are well controlled. In addition to the distress caused by seizures, patients with epilepsy (PwE) may suffer from cognitive impairment with serious social consequences such as poor interpersonal relationships, loss of employment, and reduced social networks. Pathological changes and functional connectivity abnormalities observed in PwE can disrupt the neural network responsible for the theory of mind. Theory of mind is the ability to attribute mental states to other people (intentions, beliefs, and emotions). It is a complex aspect of social cognition and includes cognitive and affective constructs. In recent years, numerous studies have assessed the relationship between social cognition, including the theory of mind, in PwE, and suggested impairment in this domain. Interventions targeting the theory of mind can be potentially helpful in improving the quality of life of PwE.

Transient global amnesia after the right temporal epilepsy surgery: A case report.

Transient global amnesia (TGA) is characterized by sudden and temporary memory impairment, while transient epileptic amnesia (TEA) represents amnestic attacks as the main manifestation of focal epilepsy with presumed temporal origin. We present a 48-year-old patient who experienced transient amnesia 10 weeks after right selective amygdalo-hippocampectomy for right temporal lobe epilepsy. Despite TEA being a plausible explanation for amnesia in patients with temporal lobe epilepsy, no epileptiform discharges were found during the amnestic episode and key features indicative of TGA, including long duration, isolated occurrence, and dense anterograde amnesia of the episode, argued against a diagnosis of TEA in this case. Notably, the patient has remained seizure-free (now 4,5 years) and stopped taking antiseizure medication 32 months after surgery. Although TGA clinical criteria formally exclude patients with recent active epilepsy, neurologists should be aware that TGA can occur after epilepsy surgery in the temporal lobe. Therefore, we consider it of high clinical relevance to establish a careful differential diagnosis between TGA and epileptic amnestic attacks after epilepsy surgery to avoid unnecessary reintroduction or continuation of antiseizure medication. Additionally, this case presents the first comparison of detailed neuropsychological test results before and after a presumed TGA episode, revealing a complete recovery of anterograde memory functions within 1 day. PLAIN LANGUAGE SUMMARY: A 48-year-old patient experienced an episode of transient amnesia 10 weeks after epilepsy surgery. Given the patient's history, an epileptic origin of the episode initially seemed likely. However, tests revealed no seizure activity during the episode and the characteristics matched a condition called transient global amnesia. This case highlights the importance of correctly diagnosing memory impairments after epilepsy surgery to prevent unnecessary treatment.

Slow wave sleep is associated with forgetting in patients with temporal lobe epilepsy.

While time spent in slow wave sleep (SWS) after learning promotes memory consolidation in the healthy brain, it is unclear if the same benefit is obtained in patients with temporal lobe epilepsy (TLE). Interictal epileptiform discharges (IEDs) are potentiated during SWS and thus may disrupt memory consolidation processes thought to depend on hippocampal-neocortical interactions. Here, we explored the relationship between SWS, IEDs, and overnight forgetting in patients with TLE. Nineteen patients with TLE studied object-scene pairs and memory was tested across a day of wakefulness (6 hrs) and across a night of sleep (16 hrs) while undergoing continuous scalp EEG monitoring. We found that time spent in SWS after learning was related to greater forgetting overnight. Longer duration in SWS and number of IEDs were each associated with greater forgetting, although the number of IEDs did not mediate the relationship between SWS and memory. Further research, particularly with intracranial recordings, is required to identify the mechanisms by which SWS and IEDs can be pathological to sleep-dependent memory consolidation in patients with TLE.

Increased body mass index (BMI) associated with late epilepsy onset in patients with temporal encephaloceles: a systematic review and analysis of individual patient data.

OBJECTIVE: This study investigates the association of Body Mass Index (BMI) and age of epilepsy onset, in patients with epilepsy associated with temporal encephaloceles (TEs). METHODS: A comprehensive PubMed literature review was conducted using the keywords "temporal encephaloceles" and "epilepsy" for identifying articles for the analysis. Inclusion criteria encompassed all evidence levels reporting patients with TE-related epilepsy and documented BMI. Logistic regression analyses were performed to examine the effect of BMI on predicting epilepsy onset after the 25th year of age. Spearman's correlation assessed the relationship between BMI with epilepsy onset. Finally, the association between BMI and postsurgical outcomes, distinguishing between more favourable outcomes (Engel Class I and II) and less favourable outcomes (Engell Class III and IV) was explored. RESULTS: Of the initially identified 88 articles, nine were included in the analysis, involving 127 patients with TE-related epilepsy and reported BMI. The mean age of epilepsy onset was 24.9 years (SD = 14.8 years), with a mean BMI of 28.0 kg/m2 (SD = 7.4 kg/m2). A significant positive correlation was observed between BMI and age of epilepsy onset (rho = 0.448, p < 0.001). Female patients had higher BMI compared to male patients (30.1 kg/m2, SD = 8.7 kg/m2 and 26.5 kg/m2, SD = 5.3 kg/m2 respectively, p = 0.008). However, the epilepsy onset did not differ significantly between male and female patients (p = 0.26). The bivariate logistic regression showed that patients with increased BMI were more likely to have an epilepsy onset after the 25th year of age, adjusted for the confounder sex (OR = 1.133, 95%-CI [1.060, 1.211], p < 0.001). Finally, a potential trend indicated a higher average BMI among patients with more favourable postsurgical outcomes than less favourable postsurgical outcomes (27.3 kg/m2, SD = 7.7 kg/m2 and 24.8 kg/m2, SD = 2.2 kg/m2 respectively, p = 0.076).

Cisternal, vascular, and parenchymal landmarks in amygdalohippocampectomy for mesial temporal sclerosis: an index case with learnings from 820 resections.

Cortico-amygdalo-hippocampectomy is the most common epilepsy surgery resection in adults and offers excellent outcomes. Seizure outcome benefits range from 75% to 88% with a 2%-4% adverse event rate. The safety profile and outcomes could be enhanced further by clearly defining key surgical landmarks that could also aid tumoral resections in the mesial temporal lobe and selective mesial resections. The authors present their learnings of intraoperative landmarks (cisternal, parenchymal, and vascular) and surgical substeps through an index case of cortico-amygdalo-hippocampectomy with lessons from 820 resections. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2428.

Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study.

INTRODUCTION: Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS: Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS: Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION: This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. HIGHLIGHTS: This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

[Memory impairments in temporal lobe epilepsy].

Temporal lobe epilepsy is known to present with various cognitive impairments, among which memory deficits are frequently reported by patients. Memory deficits can be classified into two types: classical hippocampal amnesia, which is characterized by abnormalities detected in neuropsychological assessments, and atypical memory deficits, such as accelerated long-term amnesia and autobiographical memory impairment, which cannot be identified using standard testing methods. These deficits are believed to arise from a complex interplay among structural brain abnormalities, interictal epileptic discharges, pharmacological factors, and psychological states. While fundamental treatments are limited, there are opportunities for interventions such as environmental adjustments and rehabilitation. This review article aims to provide a comprehensive overview of the types, underlying pathophysiology, and intervention methods for memory disorders observed in patients with temporal lobe epilepsy.

Decoding frontotemporal and cell-type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs.

Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in 'fresh' human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients' brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.

Medial temporal lobe atrophy patterns in early- versus late-onset amnestic Alzheimer's disease.

Background: The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer's disease (EOAD). Yet, detailed examination of MTL subfield volumes and drivers of atrophy in amnestic EOAD is lacking. Methods: BioFINDER-2 participants with memory impairment, abnormal amyloid-ß status and tau-PET were included. Forty-one EOAD individuals aged ≤65 years and, as comparison, late-onset AD (LOAD, ≥70 years, n=154) and Aß-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured. Results: AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups, although LOAD showed thinner entorhinal cortices compared to EOAD. EOAD showed lower WMH compared to LOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity was found. Conclusions: We found in vivo evidence for MTL atrophy in amnestic EOAD and overall similar levels to LOAD of MTL tau pathology and co-pathologies.

Automatic segmentation of medial temporal lobe subregions in multi-scanner, multi-modality MRI of variable quality.

Background: Volumetry of subregions in the medial temporal lobe (MTL) computed from automatic segmentation in MRI can track neurodegeneration in Alzheimer's disease. However, image quality may vary in MRI. Poor quality MR images can lead to unreliable segmentation of MTL subregions. Considering that different MRI contrast mechanisms and field strengths (jointly referred to as "modalities" here) offer distinct advantages in imaging different parts of the MTL, we developed a muti-modality segmentation model using both 7 tesla (7T) and 3 tesla (3T) structural MRI to obtain robust segmentation in poor-quality images. Method: MRI modalities including 3T T1-weighted, 3T T2-weighted, 7T T1-weighted and 7T T2-weighted (7T-T2w) of 197 participants were collected from a longitudinal aging study at the Penn Alzheimer's Disease Research Center. Among them, 7T-T2w was used as the primary modality, and all other modalities were rigidly registered to the 7T-T2w. A model derived from nnU-Net took these registered modalities as input and outputted subregion segmentation in 7T-T2w space. 7T-T2w images most of which had high quality from 25 selected training participants were manually segmented to train the multi-modality model. Modality augmentation, which randomly replaced certain modalities with Gaussian noise, was applied during training to guide the model to extract information from all modalities. To compare our proposed model with a baseline single-modality model in the full dataset with mixed high/poor image quality, we evaluated the ability of derived volume/thickness measures to discriminate Amyloid+ mild cognitive impairment (A+MCI) and Amyloid- cognitively unimpaired (A-CU) groups, as well as the stability of these measurements in longitudinal data. Results: The multi-modality model delivered good performance regardless of 7T-T2w quality, while the single-modality model under-segmented subregions in poor-quality images. The multi-modality model generally demonstrated stronger discrimination of A+MCI versus A-CU. Intra-class correlation and Bland-Altman plots demonstrate that the multi-modality model had higher longitudinal segmentation consistency in all subregions while the single-modality model had low consistency in poor-quality images. Conclusion: The multi-modality MRI segmentation model provides an improved biomarker for neurodegeneration in the MTL that is robust to image quality. It also provides a framework for other studies which may benefit from multimodal imaging.

Age-related differences in the intrinsic connectivity of the hippocampus and ventral temporal lobe in autistic individuals.

Introduction: Although memory challenges in autistic individuals have been characterized recently, the functional connectivity of the hippocampus and ventral temporal lobe, two structures important for episodic and semantic memory functions, are poorly understood in autistic individuals. Moreover, age-related differences in the functional connectivity associated with these two memory networks are unrevealed. Methods: The current study investigated age-related differences in intrinsic connectivity of the hippocampal and ventral temporal lobe (vTL) memory networks in well-matched ASD (n = 73; age range: 10.23-55.40 years old) and Non-ASD groups (n = 74; age range: 10.46-56.20 years old) from the open dataset ABIDE-I. Both theory-driven ROI-to-ROI approach and exploratory seed-based whole-brain approach were used. Results and discussion: Our findings revealed reduced connectivity in ASD compared to Non-ASD peers, as well as an age-related reduction in the connectivity of hippocampal and vTL networks with triple networks, namely, the default mode network (DMN), the central executive network (CEN), and the salience network (SN), potentially underpinning their challenges in memory, language, and social functions. However, we did not observe reliable differences in age-related effects between the ASD and Non-ASD groups. Our study underscores the importance of understanding memory network dysfunctions in ASD across the lifespan to inform educational and clinical practices.

Late-onset temporal lobe epilepsy: insights from brain atrophy and Alzheimer's disease biomarkers.

Considering the growing age of the world population, the incidence of epilepsy in older adults is expected to increase significantly. It has been suggested that late-onset temporal lobe epilepsy (LO-TLE) may be neurodegenerative in origin and overlap with Alzheimer's Disease (AD). Herein, we aimed to characterize the pattern of cortical atrophy and cerebrospinal fluid (CSF) biomarkers of AD (total and phosphorylated tau, and ß-amyloid) in a selected population of LO-TLE of unknown origin. We prospectively enrolled individuals with temporal lobe epilepsy onset after the age of 50 and no cognitive impairment. They underwent a structural MRI scan and CSF biomarkers measurement. Imaging and biomarkers data were compared to three retrospectively collected groups: (i) age-sex-matched healthy controls, (ii) patients with Mild Cognitive Impairment (MCI) and abnormal CSF AD biomarkers (MCI-AD), and (iii) patients with MCI and normal CSF AD biomarkers (MCI-noAD). From a pool of 52 patients, twenty consecutive eligible LO-TLE patients with a mean disease duration of 1.8 years were recruited. As control populations, 25 patients with MCI-AD, 25 patients with MCI-noAD, and 25 healthy controls were enrolled. CSF biomarkers returned normal values in LO-TLE, significantly different from patients with MCI due to AD. There were no differences in cortico-subcortical atrophy between epilepsy patients and healthy controls, while patients with MCI demonstrated widespread injuries of cortico-subcortical structures. Individuals with a late-onset form of temporal lobe epilepsy, characterized by short disease duration and normal CSF ß-amyloid and tau protein levels, showed patterns of cortical thickness and subcortical volumes not significantly different from healthy controls, but highly different from patients with MCI, either due to Alzheimer's Disease or not.

Finding the limits of deep learning clinical sensitivity with fractional anisotropy (FA) microstructure maps.

Background: Quantitative maps obtained with diffusion weighted (DW) imaging, such as fractional anisotropy (FA) -calculated by fitting the diffusion tensor (DT) model to the data,-are very useful to study neurological diseases. To fit this map accurately, acquisition times of the order of several minutes are needed because many noncollinear DW volumes must be acquired to reduce directional biases. Deep learning (DL) can be used to reduce acquisition times by reducing the number of DW volumes. We already developed a DL network named "one-minute FA," which uses 10 DW volumes to obtain FA maps, maintaining the same characteristics and clinical sensitivity of the FA maps calculated with the standard method using more volumes. Recent publications have indicated that it is possible to train DL networks and obtain FA maps even with 4 DW input volumes, far less than the minimum number of directions for the mathematical estimation of the DT. Methods: Here we investigated the impact of reducing the number of DW input volumes to 4 or 7, and evaluated the performance and clinical sensitivity of the corresponding DL networks trained to calculate FA, while comparing results also with those using our one-minute FA. Each network training was performed on the human connectome project open-access dataset that has a high resolution and many DW volumes, used to fit a ground truth FA. To evaluate the generalizability of each network, they were tested on two external clinical datasets, not seen during training, and acquired on different scanners with different protocols, as previously done. Results: Using 4 or 7 DW volumes, it was possible to train DL networks to obtain FA maps with the same range of values as ground truth - map, only when using HCP test data; pathological sensitivity was lost when tested using the external clinical datasets: indeed in both cases, no consistent differences were found between patient groups. On the contrary, our "one-minute FA" did not suffer from the same problem. Conclusion: When developing DL networks for reduced acquisition times, the ability to generalize and to generate quantitative biomarkers that provide clinical sensitivity must be addressed.