Faculty Bibliography

Sound structures such as phonemes and words have highly variable durations. Therefore, there is a fundamental difference between integrating across absolute time (for example, 100 ms) versus sound structure (for example, phonemes). Auditory and cognitive models have traditionally cast neural integration in terms of time and structure, respectively, but the extent to which cortical computations reflect time or structure remains unknown. Here, to answer this question, we rescaled the duration of all speech structures using time stretching and compression and measured integration windows in the human auditory cortex using a new experimental and computational method applied to spatiotemporally precise intracranial recordings. We observed slightly longer integration windows for stretched speech, but this lengthening was very small (~5%) relative to the change in structure durations, even in non-primary regions strongly implicated in speech-specific processing. These findings demonstrate that time-yoked computations dominate throughout the human auditory cortex, placing important constraints on neurocomputational models of structure processing.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of gray and white matter structures. Evidence supports a progressive condition, although the temporal evolution of TLE is poorly defined. In this ENIGMA-Epilepsy study, we aim to investigate structural alterations in gray and white matter across the adult lifespan in patients with TLE by charting both gray and white matter changes and explore the covariance of age-related alterations in both compartments. METHODS:scores of all patients. Covariance analyses examined the coupled correlations of gray and white matter lifespan curves for each region. RESULTS: DISCUSSION/CONCLUSIONS:This study highlights that patients with TLE exhibit more pronounced and widespread gray and white matter atrophy across the lifespan. The cross-sectional nature of our study limits definitive conclusions on whether the atrophy shown is progressive but emphasizes the importance of prompt diagnosis and intervention in patients. Collectively, our results motivate future longitudinal studies to clarify consequences of drug-resistant epilepsy.

OBJECTIVES/OBJECTIVE:To investigate the associations between total and individual potato intake and risk of type 2 diabetes (T2D), estimate the effect on T2D risk of replacing potatoes with whole grains and other major carbohydrate sources, and conduct a dose-response and substitution meta-analysis of prospective cohort studies. DESIGN/METHODS:Prospective cohort study and dose-response meta-analysis of prospective cohort studies. SETTING/METHODS:Individual participant data from Nurses' Health Study (1984-2020), Nurses' Health Study II (1991-2021), and Health Professionals Follow-up Study (1986-2018). PARTICIPANTS/METHODS:205 107 men and women free of diabetes, cardiovascular disease, or cancer at baseline. MAIN OUTCOME MEASURE/METHODS:Incident type 2 diabetes. RESULTS:During 5 175 501 person years of follow-up, T2D was documented in 22 299 participants. After adjustment for updated body mass index and other diabetes related risk factors, higher intakes of total potatoes and French fries were associated with increased risk of T2D. For every increment of three servings weekly of total potato, the rate for T2D increased by 5% (hazard ratio 1.05, 95% confidence interval (CI) 1.02 to 1.08) and for every increment of three servings weekly of French fries the rate increased by 20% (1.20, 1.12 to 1.28). Intake of combined baked, boiled, or mashed potatoes was not significantly associated with T2D risk (pooled hazard ratio 1.01, 95% CI 0.98 to 1.05). In substitution analyses, replacing three servings weekly of potatoes with whole grains was estimated to lower T2D rates by 8% (95% CI 5% to 11%) for total potatoes, 4% (1% to 8%) for baked, boiled, or mashed potatoes, and 19% (14% to 25%) for French fries. In contrast, replacing total potatoes or baked, boiled, or mashed potatoes with white rice was associated with an increased risk of T2D. In a meta-analysis of 13 cohorts (587 081 participants and 43 471 diagnoses of T2D), the pooled hazard ratio for risk of T2D with each increment of three servings weekly of total potato was 1.03 (95% CI 1.02 to 1.05) and of fried potatoes was 1.16 (1.09 to 1.23). In substitution meta-analyses, replacing three servings weekly of total, non-fried, and fried potatoes with whole grains was estimated to lower the risk of T2D by 7% (95% CI 5% to 9%), 5% (3% to 7%), and 17% (12% to 22%), respectively. CONCLUSIONS:Higher intake of French fries, but not combined baked, boiled, or mashed potatoes, was associated with a higher risk of T2D. The T2D risk linked to potato intake seemed to depend on the food being replaced: replacing potato with whole grains was associated with lower risk, whereas replacing with white rice was associated with increased risk.

BACKGROUND:Sudden Unexpected Death in Epilepsy (SUDEP) is a rare and tragic outcome in epilepsy, identified by those with the condition as their most serious concern. Although several clinical factors are associated with elevated SUDEP risk, mechanisms underlying SUDEP are poorly understood, making individual risk prediction challenging, especially early in the disease course. We hypothesised that common genetic variation contributes to SUDEP risk. METHODS:Genetic data from people who had succumbed to SUDEP was compared to data from people with epilepsy who had not succumbed to SUDEP and from healthy controls. Polygenic risk scores (PRSs) for longevity, intelligence and epilepsy were compared across cohorts. Reactome pathways and gene ontology terms implicated by the contributing single nucleotide polymorphisms (SNPs) were explored. In the subset of SUDEP cases with the necessary data available, a risk score was calculated using an existing risk prediction tool (SUDEP-3); the added value to this prediction of SNP-based genomic information was evaluated. FINDINGS/RESULTS:Only European-ancestry participants were included. 161 SUDEP cases were compared to 768 cases with epilepsy and 1153 healthy controls. PRS for longevity was significantly reduced in SUDEP cases compared to disease (P = 0·0096) and healthy controls (P = 0·0016), as was PRS for intelligence (SUDEP cases compared to disease (P = 0·0073) and healthy controls (P = 0·00024)). The PRS for epilepsy did not differ between SUDEP cases and disease controls (P = 0·76). SNP-determined pathway and gene ontology analysis highlighted those related to inter-neuronal communication as amongst the most enriched in SUDEP. Addition of PRS for longevity and intelligence to SUDEP-3 scores improved risk prediction in a subset of cases (38) and controls (703), raising the area-under-the-curve in a receiver-operator characteristic from 0·699 using SUDEP-3 alone to 0·913 when PRSs were added. INTERPRETATION/CONCLUSIONS:Common genetic variation contributes to SUDEP risk, offering new approaches to improve risk prediction and to understand underlying mechanisms. FUNDING/BACKGROUND:The Amelia Roberts Fund; CURE Epilepsy; Epilepsy Society, UK; Finding A Cure for Epilepsy and Seizures (FACES).

BACKGROUND AND OBJECTIVES/OBJECTIVE:-related disorders, although descriptions are limited. We aimed to determine trajectories and outcomes of development and adaptive function. METHODS:-containing 2q24.3 copy number variants (CNVs) were considered separately. We collected medical and developmental history from parents/caregivers and medical records. Adaptive function and behavior were characterized using functional classification system levels and Vineland Adaptive Behavior Scales-3 (VABS-3) Parent/Caregiver Form. We repeated analyses on individuals with variants known to result in gain-of-function (GOF, typically EO phenotypes) or loss-of-function (LOF, typically LO phenotypes). RESULTS:< 0.01). Analyses of individuals with confirmed GOF/LOF variants (n = 57) showed similar results to the EO/LO analyses. DISCUSSION/CONCLUSIONS:-related disorders is extremely broad. Phenotypic subgroups provide prognostic information and critically inform clinical trial design.

BACKGROUND:Febrile seizures occur in 3%-4% of US children aged six months to five years and are considered benign. However, sudden unexplained death in childhood is associated with 10 times increase in febrile seizures. We assessed the characteristics of children with febrile seizure and sudden death to identify factors that confer increased sudden death risk. METHODS:We conducted a case-control analysis of children with febrile seizure and subsequent sudden death versus living controls from December 2021 to June 2023 through an ∼10-minute anonymous online survey. We enrolled parents of children, living or deceased, whose child had experienced a febrile seizure from age six months to six years. Subjects were excluded if the child had an afebrile seizure or parents had not witnessed a febrile seizure. Demographic characteristics, parasomnias, and febrile seizure features were analyzed. RESULTS:A total of 381 completed surveys were received; 53 (14%) cases of febrile seizure with sudden death and 328 (86%) living controls. Cases reported febrile seizure onset >2 months earlier (P = 0.013) and reported developmental concerns (odds ratio [OR] = 2.32, 95% confidence interval [CI] [1.14, 4.71], P = 0.03), less frequent night awakenings (OR = 0.34, 95% CI [0.18, 0.65], P = 0.001), and less restless sleep (OR = 0.37, 95% CI [0.16, 0.85], P = 0.02). Cases were also less likely to drool (OR = 0.442, 95% CI [0.218, 0.900], P = 0.032) or be unresponsive for more than one minute (OR = 0.45, 95% CI [0.238, 0.854], P = 0.021). CONCLUSIONS:We report novel associations of febrile seizure and sudden death related to age, development, sleep, and observed ictal features. Anonymous survey methodology cannot exclude ascertainment bias and any related potential effect on results. Our findings suggest that impaired arousal mechanisms may increase risk of death in subjects with febrile seizure.

Humans primarily use vision to engage with and learn about the world. The hippocampus plays a crucial role in binding visual experiences of people, objects and contexts over time to create event memories. Thus, eye tracking could read out hippocampal dynamics in a precise and sensitive manner. Furthermore, eye tracking could potentially detect subjective memory decline reported by temporal lobe epilepsy patients that is missed by standardized cognitive testing. We asked whether eye movements could precisely and sensitively detect memory variability within trials and between subject cohorts. We predicted that (i) eye-tracking behaviour during visual retrieval could be validated against accuracy-based tests and that (ii) memory failures would be characterized by distinct spatiotemporal patterns of visual scanning. Fourteen healthy controls and 30 temporal lobe epilepsy patients participated in a visual object association task while eye movements and pupil size were recorded. We found a difference in accuracy during retrieval between healthy controls and temporal lobe epilepsy patients. Correct retrieval trials correlated with fewer saccades, early target preference, and a more organized search pattern. Eye-movement patterns could predict retrieval accuracy at the single trial level with outstanding performance, with percentage of gaze time on the target versus the lure as the most important features. Even during correct retrieval trials, temporal lobe epilepsy patients exhibited a more chaotic scanning pattern compared to healthy controls, suggesting a weaker memory trace. Healthy versus epilepsy diagnosis could be predicted with good performance, with trial entropy and pupillary changes as key predictive factors. Saccade patterns correlated with individual subjects' accuracy scores and performance on standardized cognitive tests but provided a greater range of performance. In summary, scanning behaviour provides a continuous measure of associative memory function that capture meaningful variability during trials, between trials, and between subjects. Thus, eye tracking could be a precise and sensitive method to detect subtle memory decline in temporal lobe epilepsy or other neuropsychiatric populations with memory impairment and may generate precise behavioural phenotyping in research settings.

Naturalistic electrocorticography (ECoG) data are a rare but essential resource for studying the brain's linguistic capabilities. ECoG offers high temporal resolution suitable for investigating processes at multiple temporal timescales and frequency bands. It also provides broad spatial coverage, often along critical language areas. Here, we share a dataset of nine ECoG participants with 1,330 electrodes listening to a 30-minute audio podcast. The richness of this naturalistic stimulus can be used for various research questions, from auditory perception to narrative integration. In addition to the neural data, we extracted linguistic features of the stimulus ranging from phonetic information to large language model word embeddings. We use these linguistic features in encoding models that relate stimulus properties to neural activity. Finally, we provide detailed tutorials for preprocessing raw data, extracting stimulus features, and running encoding analyses that can serve as a pedagogical resource or a springboard for new research.