Navigating spatial environments is foundational to human behavior, critically involving familiarity and recollection processes. The extent to which these cognitive processes are affected by encoding manipulations is poorly understood, though, as most research examining encoding manipulation effects on recognition has implemented standard word list-learning paradigms. The current study examined how encoding manipulations impacted recognition memory by having participants tour dynamic scenes under different encoding conditions (passively viewing scenes while listening to pre-generated names, self-generating descriptive names to describe the scenes, or judging whether scenes took place in an indoor or outdoor setting), then tour novel test scenes that were either configurally similar or dissimilar to studied scenes. Results indicated that, compared to passive viewing, orienting participants toward perceptual aspects (i.e., requiring indoor/outdoor judgments) boosted familiarity-based discrimination and decreased recollection. Conversely, elaborative, semantic encoding (i.e., self-generating study scene names) increased recollection but not familiarity-based discrimination compared to passive viewing. These results fit with the broader verbal learning literature, suggesting that familiarity is sensitive to perceptual manipulations, whereas recollection is sensitive to elaborative processing, while also demonstrating encoding manipulation effects on scene memory. We propose that the relevance of encoded features is impactful on subsequent memory performance, as orienting participants to perceptual scene properties boosts familiarity, while elaborative task-relevant processing boosts recollection.

Highly Superior Autobiographical Memory (HSAM) is the rare ability to recollect nearly all of one's past personal experiences with great detail and accuracy. When given a date, a person with HSAM can recall verifiable details about what they experienced that day. People with HSAM do not tend to stand out on standard neuropsychological assessments, common laboratory tasks, or other measures that assess intentional forms of memory. Some clues suggest that the superior autobiographical remembering of people with HSAM occurs involuntarily. In a newly identified case of a person with HSAM, we found evidence using the Involuntary Autobiographical Memory Inventory (IAMI) that the person's involuntary memory indeed stands out. This person's past-oriented Involuntary Autobiographical Memory (IAM) frequency was two standard deviations above the mean reported in previous research. while, in line with past research, her performance on standard neuropsychological batteries and laboratory tasks was unremarkable. We propose that these intrusive recollections facilitate the consolidation of memory for past events.

People with epilepsy (PWE), including adults with epilepsy (AWE) and children with epilepsy (CWE), may experience problems with attention and memory. We hypothesized that epilepsy and sleep disturbances are associated with subjective memory and executive dysfunction. Using cross-sectional investigation of two nationally-representative U.S. surveys, the 2021-2023 National Health Interview Survey (NHIS) and the 2016-2023 National Survey of Children's Health (NSCH), we tested if subjective concentration or memory difficulty differed between children or adults with (n = 2675 children; n = 1570 adults) and without (n = 217,579 children; n = 84,763 adults) epilepsy. Analyses examined epilepsy (comparisons of no epilepsy, inactive epilepsy, and active epilepsy) as a predictor of memory, concentration, or decision-making difficulties. Data were analyzed in survey-weighted adjusted logistic regression models. Exploratory analyses evaluated seizure frequency, sleep health, physical activity, depression, and anxiety, as well as socialization in children. CWE had > 7 times higher odds of subjective memory, concentration, or decision-making difficulty compared to children without epilepsy (ORadj = 7.3; 95%CI: 6.21, 8.56; p < 0.001), and AWE had > 3.5 times higher odds of memory or concentration difficulty compared to people without epilepsy (ORadj = 3.7; 95%CI: 3.2, 4.2; p < 0.001). Odds were higher for PWE with active epilepsy. Reported memory or concentration difficulty were associated with worse sleep health in both AWE and CWE (p < 0.05). This large epidemiological study evaluated the prevalence of memory and executive dysfunction among 4,245 PWE, highlighting the ubiquity of memory and attention complaints, regardless of age or disease status. Memory and attention difficulties, particularly among CWE, may be an important factor in epilepsy-related disparities.

PURPOSE:These American Clinical Neurophysiology Society technical standards suggest best practices for electrical stimulation mapping (ESM) with subdural and stereotactic depth electrodes for seizure induction and mapping of brain function. METHODS:A working group was convened from American Clinical Neurophysiology Society membership with expertise in ESM. PubMed searches were performed to identify pertinent peer-reviewed literature. Recurrent meetings reviewed progress, built consensus by discussion, and developed evidence-based recommendations to the extent possible. RECOMMENDATIONS:Stimulators used for ESM should have sufficient dynamic range, ability to interrupt a stimulus train, and ictal disrupt mechanism(s). Charge density should be calculated for the specific electrodes and ESM settings, the maximum safe limits being 52 to 57 μC/cm 2 /phase for subdural electrodes and not established for stereotactic depth electrodes. Subdural ESM for functional mapping is typically performed at 50-Hz pulse frequency, 200- to 300-µs pulse width, 2- to 8-s train duration, and 1- to 20-mA current strength. Stereo ESM is commonly performed using 2 different pulse frequencies: 1 Hz (300-500 µs pulse width, train duration up to 30 s, and often a constant current of 3-5 mA), and 50 Hz (100-500 µs pulse width, train duration 2-8 s, and 0.5-10 mA current intensity). CONCLUSIONS:This guideline provides technical standards for the performance of ESM, which will likely evolve over time with advances in technology and additional evidence (also see Graphical Abstract).

Introduction Medication-refractory focal epilepsy creates a significant clinical challenge, with approximately 30% of patients deemed ineligible for surgery due to involvement of eloquent cortical regions within the epileptogenic network. For these patients, electrical neuromodulation represents a promising alternative therapy. We investigated the potential of non-invasive temporal interference (TI) electrical stimulation in reducing epileptic biomarkers in patients with mesiotemporal epilepsy (MTLE) Material and Method Thirteen patients implanted with stereoelectroencephalography (sEEG) depth electrodes received TI stimulation with an amplitude modulation (AM) frequency of 130 Hz (Δf), delivered through either low-frequency (1 kHz + 1.13 kHz) or high-frequency (9 kHz + 9.13 kHz) carrier waves, specifically targeting the hippocampus—a common epileptic focus in MTLE. Intracerebral recordings before, during, and after TI stimulation were compared to recordings during sham stimulation at varying high-frequency (HF) carrier frequencies (1, 2, 5, and 9 kHz). Results TI stimulation resulted in a statistically significant decrease in interictal epileptiform discharges (IEDs) and pathological high-frequency oscillations (HFOs), particularly fast-ripples (FR), with prominent suppression observed in the hippocampal focus and reduced propagation brain-wide. In contrast, HF sham stimulation at 1 kHz frequency partially reduced cortical IED rates without effectively reaching the hippocampal focus. This cortical impact diminished progressively at higher sham frequencies (2, 5, and 9 kHz), exhibiting depth-dependent attenuation—a phenomenon not observed with TI stimulation, irrespective of carrier frequency. Additionally, TI stimulation demonstrated a significant carry-over effect, suppressing epileptic biomarkers beyond the stimulation period, which was not evident following kHz sham stimulation. Conclusion Our findings underscore the therapeutic potential of TI as a non-invasive brain stimulation modality for epilepsy, offering significant suppression of epileptic biomarkers through subthreshold modulation of the epileptogenic zone. Furthermore, this study highlights distinct biophysical differences between kilohertz-frequency stimulation and focal amplitude-modulated stimulation, supporting TI’s unique utility in neuromodulation research.

ABSTRACT We estimated the statistical power of studies predicting seizure freedom after epilepsy surgery. We extracted data from a Cochrane meta‐analysis. The median power across all studies was 14%. Studies with a median sample size or less ( n ≤ 56) and a statistically significant result exaggerated the true effect size by a factor of 5.4, while the Bayesian estimate of the odds ratio only exaggerated the true effect size by a factor of 1.6. We conclude that Bayesian estimation of odds ratios attenuates the exaggeration of significant effect sizes in underpowered studies. This result could improve interpretation of studies with small sample sizes.

Visual memory relies on synchronized interactions and rhythms between the medial temporal lobes and neocortical brain regions. Non-invasive manipulation of memory-related brain regions, specifically deeper temporal lobe regions, has been limited by the lack of precision of non-invasive neuromodulation - when targeting deeper structures, the cortex is always stimulated, never deeper structures in isolation. Temporal Interference (TI) stimulation, a novel non-invasive technique, uses high-frequency carrier fields to deliver targeted, physiologically relevant neuromodulation via amplitude-modulated envelopes at specific brain regions. Here, we investigate TI's impact on figure memory encoding in 70 healthy participants using the Rey-Osterrieth and Taylor Complex Figure tasks, with TI applied in several brain regions independently and simultaneously - allowing investigation of combinations of medial temporal lobe and neocortical brain regions. Interestingly, higher frequency TI envelopes (130 Hz offset) targeting bilateral hippocampi and temporal cortices significantly impair recall (p = 6.54e-04), while lower frequency TI envelopes (5 Hz offset) targeting only the bilateral hippocampi significantly enhance recall (p = 0.0447). Stimulation using other combinations of medial temporal lobe and neocortical regions showed no effect, underscoring the critical role of frequency and focality of non-invasive brain stimulation and correct target selection. Finally, functional MRI reveals strong differences between the effects of 130 Hz and 5 Hz envelopes, specifically in hippocampal BOLD signals, brain connectivity, default mode, and attentional networks. These findings demonstrate TI's ability to bidirectionally modulate memory encoding through precise frequency and target tuning, offering a powerful tool for cognitive neuroscience and potential therapeutic applications for memory disorders.

Independent automated scoring of sleep-wake and seizures have recently been achieved; however, the combined scoring of both states has yet to be reported. Mouse models of epilepsy typically demonstrate an abnormal electroencephalographic (EEG) background with significant variability between mice, making combined scoring a more difficult classification problem for manual and automated scoring. Given the extensive EEG variability between epileptic mice, large group sizes are needed for most studies. As large datasets are unwieldy and impractical to score manually, automatic seizure and sleep-wake classification are warranted. To this end, we developed an accurate automated classifier of sleep-wake states, seizures, and the post-ictal state. Our benchmark was a classification accuracy at or above the 93% level of human inter-rater agreement. Given the failure of parametric scoring in the setting of altered baseline EEGs, we adopted a machine-learning approach. We created several multi-layer neural network architectures that were trained on human-scored training data from an extensive repository of continuous recordings of electrocorticogram (ECoG), left and right hippocampal local field potential (HPC-L and HPC-R), and electromyogram (EMG) in the murine intra-amygdala kainic acid model of medial temporal lobe epilepsy. We then compared different network models, finding a bidirectional long short-term memory (BiLSTM) design to show the best performance with validation and test portions of the dataset. The SWISC (sleep-wake and the ictal state classifier) achieved >93% scoring accuracy in all categories for epileptic and non-epileptic mice. Classification performance was principally dependent on hippocampal signals and performed well without EMG. Additionally, performance is within desirable limits for recording montages featuring only ECoG channels, expanding its potential scope. This accurate classifier will allow for rapid combined sleep-wake and seizure scoring in mouse models of epilepsy and other neurologic diseases with varying EEG abnormalities, thereby facilitating rigorous experiments with larger numbers of mice.

Sleep-wake states bidirectionally interact with epilepsy and seizures, but the mechanisms are unknown. A barrier to comprehensive characterization and the study of mechanisms has been the difficulty of annotating large chronic recording datasets. To overcome this barrier, we sought to develop an automated method of classifying sleep-wake states, seizures, and the postictal state in mice ranging from controls to mice with severe epilepsy with accompanying background electroencephalographic (EEG) abnormalities. We utilized a large dataset of recordings, including electromyogram, EEG, and hippocampal local field potentials, from control and intra-amygdala kainic acid-treated mice. We found that an existing sleep-wake classifier performed poorly, even after retraining. A support vector machine, relying on typically used scoring parameters, also performed below our benchmark. We then trained and evaluated several multilayer neural network architectures and found that a bidirectional long short-term memory-based model performed best. This "Sleep-Wake and Ictal State Classifier" (SWISC) showed high agreement between ground-truth and classifier scores for all sleep and seizure states in an unseen and unlearned epileptic dataset (average agreement 96.41%+/- SD 3.80%) and saline animals (97.77 +/- 1.40%). Channel dropping showed that SWISC was primarily dependent on hippocampal signals yet still maintained good performance (similar to 90% agreement) with EEG alone, thereby expanding the classifier's applicability to other epilepsy datasets. SWISC enables the efficient combined scoring of sleep-wake and seizure states in mouse models of epilepsy and healthy controls, facilitating comprehensive and mechanistic studies of sleep-wake and biological rhythms in epilepsy.

In cognitive psychology, research on attention is shifting from focusing primarily on how people orient toward stimuli in the environment toward instead examining how people orient internally toward memory representations. With this new shift the question arises: What factors in the environment send attention inward? A recent proposal is that one factor is cue familiarity-detection (Cleary, Irving & Mills, Cognitive Science, 47, e13274, 2023). Within this theoretical framework, we reinterpret a decades-old empirical pattern-a primacy effect in memory for repetitions-in a novel way. The effect is the finding that altered repetitions of an image were remembered as re-occurrences of the first presentation despite having a changed left-right orientation; participants better retained the first orientation while incorrectly remembering changed instantiations as repetitions of the first orientation (DiGirolamo & Hintzman, Psychonomic Bulletin & Review, 4, 121-124, 1997). We argue that this pattern, which has never been fully explained, is an existing empirical test of the newly proposed mechanism of cue familiarity-detection flipping attention inward toward memory. Specifically, an image's first appearance is novel so draws attention outward toward encoding the stimulus' attributes like orientation; subsequent mirror-reversed appearances are detected as familiar so flip attention inward toward memory search, which leads to 1) inattentional blindness for the changed orientation due to the familiarity-driven shift of attention inward and 2) memory retrieval of the first instance and its orientation, thereby enhancing memory for the first instance and its previously encoded attributes like orientation.

Many studies have investigated brain network dynamics involved in language, but most have done so from the scalp and focused on discrete components of language. Functional mapping using stereoelectroencephalography (SEEG) offers a unique opportunity to directly examine eloquent cortex supporting language. Picture naming is the most common task used during SEEG to map language but may not adequately capture neural network dynamics involved in “natural” language used in everyday conversation. In this exploratory case report, we used SEEG to examine high-frequency activity (HFA) and phase-amplitude coupling (PAC) in a 20-year-old patient with drug-resistant epilepsy, comparing spontaneous conversation with a picture naming task. Examination of HFA and PAC during the conversation showed a broad neural activation network that included canonical language regions and regions believed to be important for reasoning, monitoring behavior, and decision-making (i.e., bilateral frontal, temporal, and parietal activation). In comparison, HFA and PAC during picture naming were limited to the left temporal region and right superior frontal gyrus. Findings suggest natural language is supported by a broader network than is captured using an elemental, single-domain language task. While additional research is needed to substantiate these results, our findings suggest it may be possible to explore more complex (network-based) features of language processing using SEEG.

Low power is a problem in many fields, as underpowered studies that find a statistically significant result will exaggerate the magnitude of the observed effect size. We quantified the statistical power and magnitude error of studies of epilepsy surgery outcomes. The median power across all studies was 14%. Studies with a median sample size or less (n<=56) and a statistically significant result exaggerated the true effect size by a factor of 5.4 (median odds ratio 9.3 vs. median true odds ratio 1.7), while the Bayesian estimate of the odds ratio only exaggerated the true effect size by a factor of 1.6 (2.7 vs. 1.7). We conclude that Bayesian estimation of odds ratio attenuates the exaggeration of significant effect sizes in underpowered studies. This approach could help improve patient counseling about the chance of seizure freedom after epilepsy surgery.

The purpose of this study was to systematically examine three different surgical approaches in treating left medial temporal lobe epilepsy (mTLE) (viz., subtemporal selective amygdalohippocampectomy [subSAH], stereotactic laser amygdalohippocampotomy [SLAH], and anterior temporal lobectomy [ATL]), to determine which procedures are most favorable in terms of visual confrontation naming and seizure relief outcome. This was a retrospective study of 33 adults with intractable mTLE who underwent left temporal lobe surgery at three different epilepsy surgery centers who also underwent pre-, and at least 6-month post-surgical neuropsychological testing. Measures included the Boston Naming Test (BNT) and the Engel Epilepsy Surgery Outcome Scale. Fisher’s exact tests revealed a statistically significant decline in naming in ATLs compared to SLAHs, but no other significant group differences. 82% of ATL and 36% of subSAH patients showed a significant naming decline whereas no SLAH patient (0%) had a significant naming decline. Significant postoperative naming improvement was seen in 36% of SLAH patients in contrast to 9% improvement in subSAH patients and 0% improvement in ATLs. Finally, there were no statistically significant differences between surgical approaches with regard to seizure freedom outcome, although there was a trend towards better seizure relief outcome among the ATL patients. Results support a possible benefit of SLAH in preserving visual confrontation naming after left TLE surgery. While result interpretation is limited by the small sample size, findings suggest outcome is likely to differ by surgical approach, and that further research on cognitive and seizure freedom outcomes is needed to inform patients and providers of potential risks and benefits with each.

The effects of electromagnetic interference have been hiding in plain sight for millennia and are now being applied to the non-invasive stimulation of deep tissues. In the article by Missey et al., the effect of non-invasive stimulation of the hypoglossal nerve by an interference envelope of interfering carrier waves is examined in mice and participants with sleep apnea. This stimulation is capable of activating the nerve and reducing apnea-hypopnea events. Temporally interfering electric fields have potential applications far beyond hypoglossal stimulation and may represent a revolutionary new approach to treating illness and understanding the functional organization of the nervous system.

The conventional intracarotid amobarbital (Wada) test has been used to assess memory function in patients being considered for temporal lobe epilepsy (TLE) surgery. Minimally invasive approaches that target the medial temporal lobe (MTL) and spare neocortex are increasingly used, but a knowledge gap remains in how to assess memory and language risk from these procedures. We retrospectively compared results of two versions of the Wada test, the intracarotid artery (ICA-Wada) and posterior cerebral artery (PCA-Wada) approaches, with respect to predicting subsequent memory and language outcomes, particularly after stereotactic laser amygdalohippocampotomy (SLAH). We included all patients being considered for SLAH who underwent both ICA-Wada and PCA-Wada at a single institution. Memory and confrontation naming assessments were conducted using standardized neuropsychological tests to assess pre- to post-surgical changes in cognitive performance. Of 13 patients who initially failed the ICA-Wada, only one patient subsequently failed the PCA-Wada (p=0.003, two-sided binomial test with p 0 =0.5) demonstrating that these tests assess different brain regions or networks. PCA-Wada had a high negative predictive value for the safety of SLAH, compared to ICA-Wada, as none of the patients who underwent SLAH after passing the PCA-Wada experienced catastrophic memory decline (0 of 9 subjects, p <.004, two-sided binomial test with p 0 =0.5), and all experienced a good cognitive outcome. In contrast, the single patient who received a left anterior temporal lobectomy after failed ICA- and passed PCA-Wada experienced a persistent, near catastrophic memory decline. On confrontation naming, few patients exhibited disturbance during the PCA-Wada. Following surgery, SLAH patients showed no naming decline, while open resection patients, whose surgeries all included ipsilateral temporal lobe neocortex, experienced significant naming difficulties (Fisher's exact test, p <.05). These findings demonstrate that (1) failing the ICA-Wada falsely predicts memory decline following SLAH, (2) PCA-Wada better predicts good memory outcomes of SLAH for MTLE, and (3) the MTL brain structures affected by both PCA-Wada and SLAH are not directly involved in language processing.

The piriform cortex is recognized as highly epileptogenic in rodents, yet its electrophysiological role in human epilepsy remains understudied. Recent surgical outcomes have suggested potential benefits in resecting the piriform cortex for cases of medial temporal lobe epilepsy. However, little is known about its electrophysiological activity in human epilepsy. This case-series study aimed to explore the electrophysiological role of the piriform cortex within the epileptogenic network among patients with suspected temporal lobe epilepsy. Participants were recruited from Emory University Hospital or Children's Healthcare of Atlanta, with non-lesional frontotemporal or temporal lobe hypotheses, undergoing stereoelectroencephalographic studies. Specifically, focus was placed on patients with one or more electrode contacts in the piriform cortex. Primary objectives included determining piriform cortex involvement within the electrophysiologically defined epileptogenic network and assessing the effects of electrical stimulation. Twenty-two patients were included in the study. Notably, only one patient exhibited piriform cortex involvement at seizure onset, associated with an olfactory aura. Two patients showed early piriform cortex involvement, while others displayed late or no involvement. Electrical stimulation of the piriform cortex induced after-discharges in three patients and replicated a habitual seizure in one. These findings present a contrast to surgical outcome studies, suggesting that the piriform cortex may not typically play a significant role in the epileptogenic network among patients with non-lesional temporal lobe epilepsy.

Background With 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.Methods Eighty-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)).Results Preoperatively, 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).Conclusions Asymmetry 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.

Episodic memory may essentially be memory for one’s place within a temporally unfolding scene from a first-person perspective. Given this, pervasively used static stimuli may only capture one small part of episodic memory. A promising approach for advancing the study of episodic memory is immersing participants within varying scenes from a first-person perspective. We present a pool of distinct scene stimuli for use in virtual environments and a paradigm that is implementable across varying levels of immersion on multiple virtual reality (VR) platforms and adaptable to studying various aspects of scene and episodic memory. In our task, participants are placed within a series of virtual environments from a first-person perspective and guided through a virtual tour of scenes during a study phase and a test phase. In the test phase, some scenes share a spatial layout with studied scenes; others are completely novel. In three experiments with varying degrees of immersion, we measure scene recall, scene familiarity-detection during recall failure, the subjective experience of déjà vu, the ability to predict the next turn on a tour, the subjective sense of being able to predict the next turn on a tour, and the factors that influence memory search and the inclination to generate candidate recollective information. The level of first-person immersion mattered to multiple facets of episodic memory. The paradigm presents a useful means of advancing mechanistic understanding of how memory operates in realistic dynamic scene environments, including in combination with cognitive neuroscience methods such as functional magnetic resonance imaging and electrophysiology.

Objective:Hippocampal pathology is a consistent feature in persons with temporal lobe epilepsy (TLE) and a strong biomarker of memory impairment. Histopathological studies have identified selective patterns of cell loss across hippocampal subfields in TLE, the most common being cellular loss in the cornu ammonis 1 (CA1) and dentage gyrus (DG). Structural neuroimaging provides a non-invasive method to understand hippocampal pathology, but traditionally only at a whole-hippocampal level. However, recent methodological advances have enabled the non-invasive quantification of subfield pathology in patients, enabling potential integration into clinical workflow. In this study, we characterize patterns of hippocampal subfield atrophy in patients with TLE and examine the associations between subfield atrophy and clinical characteristics.Participants and Methods:High-resolution T2 and T1-weighted MRI were collected from 31 participants (14 left TLE; 6 right TLE; 11 healthy controls [HC], aged 18-61 years). Reconstructions of hippocampal subfields and estimates of their volumes were derived using the Automated Segmentation of Hippocampal Subfields (ASHS) pipeline. Total hippocampal volume was calculated by combining estimates of the subfields CA1-3, DG, and subiculum. To control for variations in head size, all volume estimates were divided by estimates of total brain volume. To assess disease effects on hippocampal atrophy, hippocampi were recoded as either ipsilateral or contralateral to the side of seizure focus. Two sample t-tests at a whole-hippocampus level were used to test for ipsilateral and contralateral volume loss in patients relative to HC. To assess whether we replicated the selective histopathological patterns of subfield atrophy, we carried out mixed-effects ANOVA, coding for an interaction between diagnostic group and hippocampal subfield. Finally, to assess effects of disease load, non-parametric correlations were performed between subfield volume and age of first seizure and duration of illness.Results:Patients had significantly smaller total ipsilateral hippocampal volume compared with HC (d=1.23, pConclusions:Histopathological characterization after surgery has revealed important associations between hippocampal subfield cell loss and memory impairments in patients with TLE. Here we demonstrate that non-invasive neuroimaging can detect a pattern of subfield atrophy in TLE (i.e., CA1/DG) that matches the most common form of histopathologically-observed hippocampal sclerosis in TLE (HS Type 1) and has been linked directly to both verbal and visuospatial memory impairment. Finally, we found evidence that longer disease duration is associated with larger contralateral hippocampal volume, driven by increases in CA1 and DG. This may reflect subfield-specific functional reorganization to the unaffected brain tissue, a compensatory effect which may have important implications for patient function and successful treatment outcomes.