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BackgroundMesial temporal sclerosis (MTS) is an important cause of intractable epilepsy. Early and accurate diagnosis of MTS is essential to providing curative and life-changing therapy but can be challenging in children in whom the impact of diagnosis is particularly high. Magnetic resonance imaging (MRI) plays an important role in the diagnosis of MTS, and image processing of MRI is a recently studied strategy to improve its accuracy.ObjectiveIn a retrospective case-control study, we assessed the performance of an image processing algorithm (Correlative Image Enhancement [CIE]) for detecting MTS-related hippocampal signal abnormality in children.Materials and methodsTwenty-seven pediatric MTS cases (9 males, 18 females; mean age: 16±standard deviation [SD] 6.7 years) were identified from a pathology database of amygdylo-hippocampectomies performed in children with epilepsy. Twenty-seven children with no seizure history (9 males, 18 females; mean age: 13.8±SD 2.8 years), and with normal brain MRI, were identified for the control group. Blinded investigators processed the MRI coronal FLAIR (fluid-attenuated inversion recovery) images with CIE, saved the processed images as a separate series, and made equivalent region of interest measurements on the processed and unprocessed series to calculate contrast-to-noise ratio. Six blinded reviewers then rated the randomized series for hippocampal signal abnormality and MTS disease status.ResultsCIE increased signal intensity and contrast-to-noise ratio in 26/27 hippocampi with pathologically confirmed MTS (96.3%) with the mean (SD) contrast-to-noise ratio of cases increasing from 14.9 (11.1) to 77.7 (58.7) after processing (P<0.001). Contrast-to-noise ratio increased in 1/54 normal control hippocampi (1.9%), with no significant change in the mean contrast-to-noise ratio of the control group after processing (P=0.57). Mean (SD) reader sensitivity for detecting abnormal signal intensity increased from 83.3% (14.2) to 94.8% (3.3) after processing. Mean specificity for abnormal signal intensity increased from 94.4% (7.3) to 96.3% (0). While sensitivity improved after processing for detection of MTS disease status in 4/6 readers, the mean reader sensitivity and specificity for MTS detection increased only minimally after processing, from 79.6% to 80.7% and from 95.7% to 96.3%, respectively.ConclusionThe CIE image processing algorithm selectively increased the contrast-to-noise ratio of hippocampi affected by MTS, improved reader performance in detecting MTS-related hippocampal signal abnormality and could have high impact on pediatric patients undergoing work-up for seizures.

BackgroundWith expanding neurosurgical options in epilepsy, it is important to characterise each options’ risk for postoperative cognitive decline. Here, we characterise how patients’ preoperative white matter (WM) networks relates to postoperative memory changes following different epilepsy surgeries.MethodsEighty-nine patients with temporal lobe epilepsy with T1-weighted and diffusion-weighted imaging as well as preoperative and postoperative verbal memory scores (prose recall) underwent either anterior temporal lobectomy (ATL: n=38) or stereotactic laser amygdalohippocampotomy (SLAH; n=51). We computed laterality indices (ie, asymmetry) for volume of the hippocampus and fractional anisotropy (FA) of two deep WM tracts (uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF)).ResultsPreoperatively, left-lateralised FA of the ILF was associated with higher prose recall (p<0.01). This pattern was not observed for the UF or hippocampus (ps>0.05). Postoperatively, right-lateralised FA of the UF was associated with less decline following left ATL (p<0.05) but not left SLAH (p>0.05), while right-lateralised hippocampal asymmetry was associated with less decline following both left ATL and SLAH (ps<0.05). After accounting for preoperative memory score, age of onset and hippocampal asymmetry, the association between UF and memory decline in left ATL remained significant (p<0.01).ConclusionsAsymmetry of the hippocampus is an important predictor of risk for memory decline following both surgeries. However, asymmetry of UF integrity, which is only severed during ATL, is an important predictor of memory decline after ATL only. As surgical procedures and pre-surgical mapping evolve, understanding the role of frontal-temporal WM in memory networks could help to guide more targeted surgical approaches to mitigate cognitive decline.

Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy in adults, yet few patients receive curative surgery due to diagnostic and prognostic uncertainty. In a multicenter cohort, we analyzed multimodal MRI and clinical data from 282 TLE patients, 298 healthy controls, and 45 disease controls. Patient-specific deviations from typical lifespan trajectories of intrinsic brain function were mapped using normative modeling. Regional functional alterations were heterogeneous but overlapped most in the mesiotemporal cortex. Connectome-based simulations revealed abnormality spread followed structural network architecture, highlighting the hippocampus as well as paralimbic and medial default-mode regions as epicenters. Multimodal integration implicated superficial white-matter microstructural alterations as a key contributor. Supervised models achieved AUCs of 0.77 for distinguishing TLE from disease controls, 0.74 for lateralizing seizure focus, and 0.64 for predicting postsurgical seizure freedom; greater contralateral temporal deviations predicted poorer outcomes. These findings support individualized functional biomarkers for precision presurgical care in focal epilepsy. Xie and colleagues show that MRI-based brain function maps can identify patient-specific abnormalities in temporal lobe epilepsy, track how they spread along brain networks, and help diagnose, lateralize seizure focus, and predict surgical outcomes.

ObjectiveThis study investigated alterations of resting-state networks (RSNs) in primary insomnia patients as well as relationships between these changes and clinical features.MethodsFifty-nine primary insomnia patients and 53 healthy control subjects underwent a resting-state fMRI scan (rs-fMRI). Ten RSNs were identified using independent component analysis of rs-fMRI data. To assess significant differences between the two groups, voxel-wise analysis of ten RSNs was conducted using dual regression with FSL randomised non-parametric permutation testing and a threshold-free cluster enhanced technique to control for multiple comparisons. Relationships between abnormal functional connectivity and clinical variables were then investigated with Pearson’s correlation analysis.ResultsPrimary insomnia patients showed decreased connectivity in regions of the right frontoparietal network (FPN), including the superior parietal lobule and superior frontal gyrus. Moreover, decreased connectivity in the right middle temporal gyrus and right lateral occipital cortex with the FPN showed significant positive correlations with disease duration and self-rated anxiety, respectively.ConclusionsOur study suggests that primary insomnia patients are characterised by abnormal organisation of the right FPN, and dysfunction of the FPN is correlated with disease duration and anxiety. The results enhance our understanding of neural substrates underlying symptoms of primary insomnia from the viewpoint of resting-state networks.Key Points• Primary insomnia patients showed altered functional connectivity in the right FPN.• Middle temporal gyrus FC with FPN was significantly correlated with disease duration.• Lateral occipital cortex FC with FPN was significantly correlated with SAS scores.

Temporal lobe epilepsy (TLE) frequently involves an intricate, extensive epileptic frontal‐temporal network. This study aimed to investigate the interactions between temporal and frontal regions and the dynamic patterns of the frontal‐temporal network in TLE patients with different disease durations. The magnetoencephalography data of 36 postoperative seizure‐free patients with long‐term follow‐up of at least 1 year, and 21 age‐ and sex‐matched healthy subjects were included in this study. Patients were initially divided into LONG‐TERM (n = 18, DURATION >10 years) and SHORT‐TERM (n = 18, DURATION ≤10 years) groups based on 10‐year disease duration. For reliability, supplementary analyses were conducted with alternative cutoffs, creating three groups: 0 < DURATION ≤7 years (n = 11), 7 < DURATION ≤14 years (n = 11), and DURATION >14 years (n = 14). This study examined the intraregional phase‐amplitude coupling (PAC) between theta phase and alpha amplitude across the whole brain. The interregional directed phase transfer entropy (dPTE) between frontal and temporal regions in the alpha and theta bands, and the interregional cross‐frequency directionality (CFD) between temporal and frontal regions from the theta phase to the alpha amplitude were further computed and compared among groups. Partial correlation analysis was conducted to investigate correlations between intraregional PAC, interregional dPTE connectivity, interregional CFD, and disease duration. Whole‐brain intraregional PAC analyses revealed enhanced theta phase‐alpha amplitude coupling within the ipsilateral temporal and frontal regions in TLE patients, and the ipsilateral temporal PAC was positively correlated with disease duration (r = 0.38, p <.05). Interregional dPTE analyses demonstrated a gradual increase in frontal‐to‐temporal connectivity within the alpha band, while the direction of theta‐band connectivity reversed from frontal‐to‐temporal to temporal‐to‐frontal as the disease duration increased. Interregional CFD analyses revealed that the inhibitory effect of frontal regions on temporal regions gradually increased with prolonged disease duration (r = −0.36, p <.05). This study clarified the intrinsic reciprocal connectivity between temporal and frontal regions with TLE duration. We propose a dynamically reorganized triple‐stage network that transitions from balanced networks to constrained networks and further develops into imbalanced networks as the disease duration increases. We propose the triple‐stage network theory to interpret the dynamic evolution of the frontal‐temporal network in TLE patients. The theory suggests that the frontal‐temporal network in TLE patients may undergo sequential changes in three different stages over the duration of the disease.

Objective The aim of this study was to explore the relation of language functional MRI (fMRI)-guided tractography with postsurgical naming decline in people with temporal lobe epilepsy (TLE). Methods Twenty patients with unilateral TLE (9 left) were studied with auditory and picture naming functional MRI tasks. Activation maxima in the left posterobasal temporal lobe were used as seed regions for whole-brain fibre tractography. Clinical naming performance was assessed preoperatively, 4 months, and 12 months following temporal lobe resection. Volumes of white matter language tracts in both hemispheres as well as tract volume laterality indices were explored as moderators of postoperative naming decline using Pearson correlations and multiple linear regression with other clinical variables. Results Larger volumes of white matter language tracts derived from auditory and picture naming maxima in the hemisphere of subsequent surgery as well as stronger lateralization of picture naming tract volumes to the side of surgery correlated with greater language decline, which was independent of fMRI lateralization status. Multiple regression for picture naming tract volumes was associated with a significant decline of naming function with 100% sensitivity and 93% specificity at both short-term and long-term follow-up. Interpretation Naming fMRI-guided white matter language tract volumes relate to postoperative naming decline after temporal lobe resection in people with TLE. This can assist stratification of surgical outcome and minimize risk of postoperative language deficits in TLE.

Mnemonic discrimination (MD), the ability to distinguish between similar but distinct memories, relies heavily on the integrity of key medial temporal lobe (MTL) regions. Aging is associated with declines in MD, but evidence suggests that cognitive training may help mitigate this decline. While prior research has shown that such training can improve MD performance, little is known about the relationship between these behavioral improvements and structural changes in specific brain regions. This study investigates whether an 8-week web-based MD training program enhances MD in older adults and examines whether these gains are linked to volumetric changes in MTL areas, including the A36 perirhinal area, a critical region for object and scene memory. A total of 151 older adults (age M = 69.71 years, SD = 4.17) participated in an 8-week web-based MD training program. Participants were divided into three groups: object stimuli training (OG), scene stimuli training (SG), and an active control group (AC). A subset of OG (n = 33) and AC (n = 28) participants underwent pre- and post-training 7T MRI scans (MP2RAGE 0.6 mm; T2w imaging: 0.4 x 0.4 x 1 mm along the hippocampal axis). The training required participants to differentiate between similar objects and scenes ('lures') and repeated items ('repeats') in a progressively challenging MD task. Pre- and post-training, participants completed a behavioral battery assessing MD and cognitive transfer effects. Volumetric changes in key MTL subregions, including the A36 perirhinal area, were assessed using the T2w ASHS algorithm for the MTL areas' segmentations. Behavioral results showed significant gains in MD in the OG and SG groups compared to the control group. Notably, within the object training but not the control group, volumetric increases in the left A36 perirhinal area were specifically linked to MD performance gains for scenes (ie. near transfer to scenes) but not objects. This suggests a robust link between structural plasticity and MD behavioral improvement. Our findings indicate that an 8-week MD training program enhances memory performance in older adults and induces structural changes in the A36 perirhinal area, highlighting the potential for cognitive training to support brain health during aging.

Abstract Background Lesions causing refractory epilepsy, often associated with temporal lobe epilepsy (TLE), can be undetectable on standard magnetic resonance imaging (MRI) in dogs. Automated brain volumetry, widely used in human medicine, can now be applied in veterinary medicine because of the availability of brain atlases. Objectives This study aimed to develop an automatic volumetry method, translate the outcomes into the assessment of temporal lobe volumes in dogs with idiopathic epilepsy, and correlate the results with the electroencephalography (EEG) data of epileptiform discharges (EDs). Animals Thirty-one dogs of various breeds with dominant temporal lobe discharge. Methods Retrospective, observational study. The MRI and EEG examination results of dogs referred for neurological diagnosis data between 2016 and 2021 were retrospectively analyzed. An automated volumetry method was developed, which allowed the evaluation of temporal lobe volumes of the dogs. The asymmetric ratio (AR) was then estimated, and the results were correlated with the EEG EDs. Results 12/31 (38%; 95% CI: 21.8%-57.8%) dogs had an asymmetric ratio >6%. Among them, reduction in temporal lobe volumes correlated with the side of the EEG EDs in 7 cases. There was no statistical correlation between temporal lobe volume changes and ED location. Conclusions and Clinical Importance Preliminary volumetric analysis of the temporal lobes indicates the presence of volume differences between the lobes in some dogs with idiopathic epilepsy. Diagnosis of TLE in dogs based on MRI volumetry in correlation with EEG examination, especially for dogs with drug-resistant epilepsy, can influence the development of new therapeutic options, such as surgery.

PurposeTemporal lobe epilepsy (TLE) is a common, polygenic epilepsy syndrome that involves glucose hypometabolism in the epileptogenic zone. However, the transcriptional and cellular signatures underlying the metabolism in TLE remain unclear.MethodsIn this retrospective study, 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) scans of TLE patients (n = 104) who underwent anterior temporal lobectomy were consecutively collected between 2016 and 2021. The transcriptional profiles of TLE risk genes across the brain were identified by the gene expression analyses from six TLE patients and twelve postmortem donors (six from the Allen Human Brain Atlas). Integrating the neuroimaging and transcriptomic data, we examined the relationship between the expression of TLE-associated genes and metabolic alterations in TLE. Furthermore, we performed functional enrichment analyses of the genes with higher weight in partial least squares regression using Metascape.ResultsA total of 104 patients with TLE (mean age 29 ± 9 years, 50% male) and 30 healthy controls (HCs) (mean age 31 ± 6 years, 53% male) were enrolled. Compared to that of HCs, patients with TLE showed hypometabolism in the temporal lobes and adjacent structures but hypermetabolism in the thalamus and basal ganglia. The cortical map of inter-group differences in cerebral metabolism was spatially correlated with the expression of a weighted combination of genes enriched in ontology terms and pathways related to neurovascular unit (NVU) integrity and synaptic plasticity.DiscussionOur findings, combined with the analysis of neuroimaging and transcriptional data, suggest that genes related to NVU integrity and synaptic plasticity may drive alterations to brain metabolism that mediate the genetic risk of TLE.

Approximately 40% of individuals undergoing anterior temporal lobe resection for temporal lobe epilepsy experience episodic memory decline. There has been a focus on early memory network changes; longer-term plasticity and its impact on memory function are unclear. Our study investigates neural mechanisms of memory recovery and network plasticity over nearly a decade post-surgery. We assess memory network changes, from 3–12 months to 10 years postoperatively, in 25 patients (12 left-sided resections) relative to 10 healthy matched controls, using longitudinal task-based functional MRI and standard neuropsychology assessments. We observe key adaptive changes in memory networks of a predominantly seizure-free cohort. Ongoing neuroplasticity in posterior medial temporal regions and contralesional cingulum or pallidum contribute to long-term verbal and visual memory recovery. Here, we show the potential for sustained cognitive improvement and importance of strategic approaches in epilepsy treatment, advocating for conservative surgeries and long-term use of cognitive rehabilitation for ongoing recovery. Using functional MRI, the authors tracked memory recovery over a decade after epilepsy surgery, revealing key brain changes in spared medial temporal structures and contralateral regions, highlighting neural mechanisms behind sustained improvement.