Altered fronto-limbic-motor response to stress differs between functional and epileptic seizures in a TBI model.

BACKGROUND AND OBJECTIVES: Psychogenic nonepileptic (functional) seizures (FS) clinically resemble epileptic seizures (ES) with both often preceded by traumatic brain injury (TBI). FS and ES emergence and occurrence after TBI may be linked to aberrant neurobehavioral stress responses. We hypothesized that neural activity signatures in response to a psychosocial stress task would differ between TBI + FS and TBI + ES after controlling for TBI status (TBI-only). METHODS: In the current multicenter study, participants were recruited prospectively from Rhode Island Hospital, Providence Rhode Island Veterans Administration Medical Center, and the University of Alabama at Birmingham Medical Center. Previous diagnoses of TBI, ES, and FS were verified based on data collected from participants, medical chart and record review, and, where indicated, results of EEG and/or video-EEG confirmatory diagnosis. TBI + ES (N = 21) and TBI + FS (N = 21) were matched for age and sex and combined into an initial group (TBI + SZ; N = 42). A TBI-only group (N = 42) was age and sex matched to the TBI with seizures (TBI + SZ) group. All participants completed an fMRI control math task (CMT) and stress math task (SMT) based on the Montreal Imaging Stress Task (MIST). RESULTS: The TBI + SZ group (n = 24 female) did not differ in mood or anxiety severity compared to TBI-only group (n = 24 female). However, TBI + FS group (n = 11 female) reported greater severity of these symptoms compared to TBI + ES (n = 13 female). The linear mixed effects analysis identified neural responses that differed between TBI-only and TBI + SZ during math performance within the left premotor cortex and during auditory feedback within bilateral prefrontal cortex and hippocampus/amygdala regions. Additionally, neural responses differed between TBI + ES and TBI + FS during math performance within the right dorsolateral prefrontal cortex and bilateral amygdala during auditory feedback within the supplementary motor area. All tests comparing neural stress responses to psychiatric symptom severity failed to reach significance. DISCUSSION: Controlling for TBI and seizure status, these findings implicate specific nodes within frontal, limbic, and sensorimotor networks that may maintain functional neurological symptoms and possibly distinguish FS from ES. This study provides class II evidence of differences in neural responses to psychosocial stress between ES and FS after TBI.

The effects of racial and socioeconomic disparities on time to diagnosis and treatment of pediatric functional seizures in the United States.

PURPOSE: The present study sought to assess the effects of racial and socioeconomic status in the United States on time to treatment and diagnosis of pediatric functional seizures (FS). METHODS: Eighty adolescents and their parent/guardian completed a demographics questionnaire and reported date of FS onset, diagnosis, and treatment. Paired samples t-tests compared time between FS onset and diagnosis, onset and treatment, and diagnosis and treatment based on race (White vs racial minority), annual household income (≤$79,999 vs ≥$80,000), maternal and paternal education (≤Associate's Degree vs Bachelor's Degree), and combined parental education (≤Post-graduate training vs Graduate degree). RESULTS: Adolescents with lower annual household income began treatment >6 months later than adolescents with greater annual household income (p = 0.049). Adolescents with lower maternal and paternal education (≤Associate's Degree vs Bachelor's Degree) began treatment >4 and ∼8.5 months later than adolescents with greater maternal and paternal education (p = 0.04; p = 0.03), respectively. Adolescents with lower maternal education also received a diagnosis >5 months later (p = 0.03). Adolescents without a mother or father with a graduate degree received a diagnosis and began treatment∼3 and >11 months later (p = 0.03; p = 0.01) than adolescents whose mother or father received a graduate degree, respectively. No racial differences were found. CONCLUSIONS: Adolescents with lower annual household income and/or parental education experienced increased duration between FS onset and treatment and diagnosis. Research is needed to clarify the mechanisms underlying this relationship, and action is needed to reduce these disparities given FS duration is associated with poorer prognosis and greater effects on the brain.

Relationship between sleep, physical fitness, brain microstructure, and cognition in healthy older adults: A pilot study.

BACKGROUND: There is a critical need for neuroimaging markers of brain integrity to monitor effects of modifiable lifestyle factors on brain health. This observational, cross-sectional study assessed relationships between brain microstructure and sleep, physical fitness, and cognition in healthy older adults. METHODS: Twenty-three adults aged 60 and older underwent whole-brain multi-shell diffusion imaging, comprehensive cognitive testing, polysomnography, and exercise testing. Neurite Orientation Dispersion and Density Imaging (NODDI) was used to quantify neurite density (NDI) and orientation dispersion (ODI). Diffusion tensor imaging (DTI) was used to quantify axial diffusivity (AxD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD). Relationships between sleep efficiency (SE), time and percent in N3 sleep, cognitive function, physical fitness (VO2 peak) and the diffusion metrics in regions of interest and the whole brain were evaluated. RESULTS: Higher NDI in bilateral white and gray matter was associated with better executive functioning. NDI in the right anterior cingulate and adjacent white matter was positively associated with language skills. Higher NDI in the left posterior corona radiata was associated with faster processing speed. Physical fitness was positively associated with NDI in the left precentral gyrus and corticospinal tract. N3 % was positively associated with NDI in the left caudate and right pre- and postcentral gyri. Higher ODI in the left putamen and adjacent white matter was associated with better executive function. CONCLUSION: NDI and ODI derived from NODDI are potential neuroimaging markers for associations between brain microstructure and modifiable risk factors in aging. If these associations are observable in clinical samples, NODDI could be incorporated into clinical trials assessing the effects of modifiable risk factors on brain integrity in aging and neurodegenerative diseases.

Traumatic Brain Injury Outcomes After Recreational Cannabis Use.

Purpose: Basic science data indicate potential neuroprotective effects of cannabinoids in traumatic brain injury (TBI). We aimed to evaluate the effects of pre-TBI recreational cannabis use on TBI outcomes. Patients and Methods: We used i2b2 (a scalable informatics framework; www.i2b2.org) to identify all patients presenting with acute TBI between 1/1/2014 and 12/31/2016, then conducted a double-abstraction medical chart review to compile basic demographic, urine drug screen (UDS), Glasgow Coma Scale (GCS), and available outcomes data (mortality, modified Rankin Scale (mRS), duration of stay, disposition (home, skilled nursing facility, inpatient rehabilitation, other)) at discharge and at specific time points thereafter. We conducted multivariable nested ordinal and logistic regression analyses to estimate associations between cannabis use, other UDS results, demographic factors, and selected outcomes. Results: i2b2 identified 6396 patients who acutely presented to our emergency room with TBI. Of those, 3729 received UDS, with 22.2% of them testing positive for cannabis. Mortality was similar in patients who tested positive vs negative for cannabis (3.9% vs 4.8%; p = 0.3) despite more severe GCS on admission in the cannabis positive group (p = 0.045). Several discharge outcome measures favored the cannabis positive group who had a higher rate of discharge home vs other care settings (p < 0.001), lower discharge mRS (p < 0.001), and shorter duration of hospital stay (p < 0.001) than the UDS negative group. Multivariable analyses confirmed mostly independent associations between positive cannabis screen and these post-TBI short- and long-term outcomes. Conclusion: This study adds evidence about the potentially neuroprotective effects of recreational cannabis for short- and long-term post-TBI outcomes. These results need to be confirmed via prospective data collections.

Non-lesional epilepsy does not necessarily convey poor outcomes after invasive monitoring followed by resection or thermal ablation.

OBJECTIVE: We aimed to compare outcomes including seizure-free status at the last follow-up in adult patients with medically refractory focal epilepsy identified as lesional vs. non-lesional based on their magnetic resonance imaging (MRI) findings who underwent invasive evaluation followed by subsequent resection or thermal ablation (LiTT). METHODS: We identified 88 adult patients who underwent intracranial monitoring between 2014 and 2021. Of those, 40 received resection or LiTT, and they were dichotomized based on MRI findings, as lesional (N = 28) and non-lesional (N = 12). Patient demographics, seizure characteristics, non-invasive interventions, intracranial monitoring, and surgical variables were compared between the groups. Postsurgical seizure outcome at the last follow-up was rated according to the Engel classification, and postoperative seizure freedom was determined by Kaplan-Meyer survival analysis. Statistical analyses employed Fisher's exact test to compare categorical variables, while a t-test was used for continuous variables. RESULTS: There were no differences in baseline characteristics between groups except for more often noted PET abnormality in the lesional group (p = 0.0003). 64% of the lesional group and 57% of the non-lesional group received surgical resection or LiTT (p = 0.78). At the last follow-up, 78.5% of the patients with lesional MRI findings achieved Engel I outcomes compared to 66.7% of non-lesional patients (p = 0.45). Kaplan-Meier curves did not show a significant difference in seizure-free duration between both groups after surgical intervention (p = 0.49). SIGNIFICANCE: In our sample, the absence of lesion on brain MRI was not associated with worse seizure outcomes in adult patients who underwent invasive intracranial monitoring followed by resection or thermal ablation.

Reduced Subjective Cognitive Concerns With Neurobehavioral Therapy in Functional Seizures and Traumatic Brain Injury.

OBJECTIVE: Functional seizures are common among people with traumatic brain injury (TBI). Subjective cognitive concerns refer to a person's own perception of problems with cognitive functioning in everyday life. The authors investigated the presence and correlates of subjective cognitive concerns and the response to neurobehavioral therapy among adults with TBI and functional seizures (TBI+FS group). METHODS: In this observational study, participants in the TBI+FS group (N=47) completed a 12-session neurobehavioral therapy protocol for seizures, while participants in the comparison group (TBI without seizures) (N=50) received usual treatment. Subjective cognitive concerns, objective cognition, mental health, and quality of life were assessed before and after treatment. Data collection occurred from 2018 to 2022. RESULTS: Baseline subjective cognitive concerns were reported for 37 (79%) participants in the TBI+FS group and 20 (40%) participants in the comparison group. In a multivariable regression model in the TBI+FS group, baseline global mental health (ß=-0.97) and obsessive-compulsive symptoms (ß=-1.01) were associated with subjective cognitive concerns at baseline. The TBI+FS group had fewer subjective cognitive concerns after treatment (η2=0.09), whereas the TBI comparison group showed a nonsignificant increase in subjective cognitive concerns. CONCLUSIONS: Subjective cognitive concerns are common among people with TBI and functional seizures and may be related to general mental health and obsessive-compulsive symptoms. Evidence-based neurobehavioral therapy for functional seizures is a reasonable treatment option to address such concerns in this population, although additional studies in culturally diverse samples are needed. In addition, people with functional seizures would likely benefit from rehabilitation specifically targeted toward cognitive functioning.

Brain temperature and free water increases after mild COVID-19 infection.

The pathophysiology underlying the post-acute sequelae of COVID-19 remains understudied and poorly understood, particularly in healthy adults with a history of mild infection. Chronic neuroinflammation may underlie these enduring symptoms, but studying neuroinflammatory phenomena in vivo is challenging, especially without a comparable pre-COVID-19 dataset. In this study, we present a unique dataset of 10 otherwise healthy individuals scanned before and after experiencing mild COVID-19. Two emerging MR-based methods were used to map pre- to post-COVID-19 brain temperature and free water changes. Post-COVID-19 brain temperature and free water increases, which are indirect biomarkers of neuroinflammation, were found in structures functionally associated with olfactory, cognitive, and memory processing. The largest pre- to post-COVID brain temperature increase was observed in the left olfactory tubercle (p = 0.007, 95% CI [0.48, 3.01]), with a mean increase of 1.75 °C. Notably, the olfactory tubercle is also the region of the primary olfactory cortex where participants with chronic olfactory dysfunction showed the most pronounced increases as compared to those without lingering olfactory dysfunction (adjusted pFDR = 0.0189, 95% CI [1.42, 5.27]). These preliminary insights suggest a potential link between neuroinflammation and chronic cognitive and olfactory dysfunction following mild COVID-19, although further investigations are needed to improve our understanding of what underlies these phenomena.

Compatibility of Standard Vagus Nerve Stimulation and Investigational Microburst Vagus Nerve Stimulation Therapy with fMRI.

Vagus nerve stimulation devices are conditionally approved for MR imaging with stimulation turned off, and the requirement to modify the stimulation settings may be a barrier to scanning in some radiology practices. There is increasing interest in studying the effects of stimulation during MR imaging/fMRI. This study evaluated the safety of standard and investigational microburst vagus nerve stimulation therapies during MR imaging/fMRI. A prospective, multicenter study was conducted in patients with an investigational vagus nerve stimulation device that delivered either standard or investigational microburst vagus nerve stimulation. Thirty participants underwent sequential MR imaging and fMRI scans, encompassing 188 total hours of scan time (62.7 hours with standard vagus nerve stimulation and 125.3 hours with investigational microburst vagus nerve stimulation). No adverse events were reported with active stimulation during MR imaging or during 12 months of follow-up. Our results support the safety of standard and investigational microburst vagus nerve stimulation therapy during MR imaging and fMRI scans.

Feasibility study of microburst VNS therapy in drug-resistant focal and generalized epilepsy.

BACKGROUND: Vagus nerve stimulation (VNS) at low frequencies (≤30 Hz) has been an established treatment for drug-resistant epilepsy (DRE) for over 25 years. OBJECTIVE: To examine the initial safety and efficacy performance of an investigational, high-frequency (≥250 Hz) VNS paradigm herein called "Microburst VNS" (µVNS). µVNS consists of short, high-frequency bursts of electrical pulses believed to preferentially modulate certain brain regions. METHODS: Thirty-three (33) participants were enrolled into an exploratory feasibility study, 21 with focal-onset seizures and 12 with generalized-onset seizures. Participants were titrated to a personalized target dose of µVNS using an investigational fMRI protocol. Participants were then followed for up to 12 months, with visits every 3 months, and monitored for side-effects at all time points. This study was registered as NCT03446664 on February 27th, 2018. RESULTS: The device was well-tolerated. Reported adverse events were consistent with typical low frequency VNS outcomes and tended to diminish in severity over time, including dysphonia, cough, dyspnea, and implant site pain. After 12 months of µVNS, the mean seizure frequency reduction for all seizures was 61.3% (median reduction: 70.4%; 90% CI of median: 48.9%-83.3%). The 12-month responder rate (≥50% reduction) was 63.3% (90% CI: 46.7%-77.9%) and the super-responder rate (≥80% reduction) was 40% (90% CI: 25.0%-56.6%). Participants with focal-onset seizures appeared to benefit similarly to participants with generalized-onset seizures (mean reduction in seizures at 12 months: 62.6% focal [n = 19], versus 59.0% generalized [n = 11]). CONCLUSION: Overall, µVNS appears to be safe and potentially a promising therapeutic alternative to traditional VNS. It merits further investigation in randomized controlled trials which will help determine the impact of investigational variables and which patients are most suitable for this novel therapy.

Optimized microburst VNS elicits fMRI responses beyond thalamic-specific response from standard VNS.

OBJECTIVE: In parallel to standard vagus nerve stimulation (VNS), microburst stimulation delivery has been developed. We evaluated the fMRI-related signal changes associated with standard and optimized microburst stimulation in a proof-of-concept study (NCT03446664). METHODS: Twenty-nine drug-resistant epilepsy patients were prospectively implanted with VNS. Three 3T fMRI scans were collected 2 weeks postimplantation. The maximum tolerated VNS intensity was determined prior to each scan starting at 0.125 mA with 0.125 mA increments. FMRI scans were block-design with alternating 30 sec stimulation [ON] and 30 sec no stimulation [OFF]: Scan 1 utilized standard VNS and Scan 3 optimized microburst parameters to determine target settings. Semi-automated on-site fMRI data processing utilized ON-OFF block modeling to determine VNS-related fMRI activation per stimulation setting. Anatomical thalamic mask was used to derive highest mean thalamic t-value for determination of microburst stimulation parameters. Paired t-tests corrected at P < 0.05 examined differences in fMRI responses to each stimulation type. RESULTS: Standard and microburst stimulation intensities at Scans 1 and 3 were similar (P = 0.16). Thalamic fMRI responses were obtained in 28 participants (19 with focal; 9 with generalized seizures). Group activation maps showed standard VNS elicited thalamic activation while optimized microburst VNS showed widespread activation patterns including thalamus. Comparison of stimulation types revealed significantly greater cerebellar, midbrain, and parietal fMRI signal changes in microburst compared to standard VNS. These differences were not associated with seizure responses. INTERPRETATION: While standard and optimized microburst VNS elicited thalamic activation, microburst also engaged other brain regions. Relationship between these fMRI activation patterns and clinical response warrants further investigation. CLINICAL TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT03446664).

Effectiveness and tolerability of brivaracetam in patients with epilepsy stratified by comorbidities and etiology in the real world: 12-month subgroup data from the international EXPERIENCE pooled analysis.

OBJECTIVE: To assess the effectiveness and tolerability of brivaracetam (BRV) in adults with epilepsy by specific comorbidities and epilepsy etiologies. METHODS: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from several non-interventional studies of patients with epilepsy initiating BRV in clinical practice. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within prior 3 months), continuous seizure freedom (no seizures since baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Analyses were performed for all adult patients (≥ 16 years of age) and stratified by comorbidity and by etiology at baseline (patients with cognitive/learning disability [CLD], psychiatric comorbidity, post-stroke epilepsy, brain tumor-related epilepsy [BTRE], and traumatic brain injury-related epilepsy [TBIE]). RESULTS: At 12 months, ≥ 50% seizure reduction was achieved in 35.6% (n = 264), 38.7% (n = 310), 41.7% (n = 24), 34.1% (n = 41), and 50.0% (n = 28) of patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, respectively; and continuous seizure freedom was achieved in 5.7% (n = 318), 13.7% (n = 424), 29.4% (n = 34), 11.4% (n = 44), and 13.8% (n = 29), respectively. During the study follow-up, in patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, 37.1% (n = 403), 30.7% (n = 605), 33.3% (n = 51), 39.7% (n = 68), and 27.1% (n = 49) of patients discontinued BRV, respectively; and TEAEs since prior visit at 12 months were reported in 11.3% (n = 283), 10.0% (n = 410), 16.7% (n = 36), 12.5% (n = 48), and 3.0% (n = 33), respectively. CONCLUSIONS: BRV as prescribed in the real world is effective and well tolerated among patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE.

Brain network entropy, depression, and quality of life in people with traumatic brain injury and seizure disorders.

OBJECTIVE: Traumatic brain injury (TBI) often precedes the onset of epileptic (ES) or psychogenic nonepileptic seizures (PNES) with depression being a common comorbidity. The relationship between depression severity and quality of life (QOL) may be related to resting-state network complexity. We investigated these relationships in adults with TBI-only, TBI + ES, or TBI + PNES using Sample Entropy (SampEn), a measure of physiologic signals complexity. METHODS: Adults with TBI-only (n = 60), TBI + ES (n = 21), or TBI + PNES (n = 56) completed the Beck Depression Inventory-II (BDI-II; depression symptom severity) and QOL in Epilepsy (QOLIE-31) assessments and underwent resting-state functional magnetic resonance imaging (rs-fMRI). SampEn values derived from six resting state functional networks were calculated per participant. Effects of group, network, and group-by-network-interactions for SampEn were investigated with a mixed-effects model. We examined relationships between BDI-II, QOL, and SampEn of each of the networks. RESULTS: Groups did not differ in age, but there was a higher proportion of women with TBI + PNES (p = 0.040). TBI + ES and TBI-only groups did not differ in BDI-II or QOLIE-31 scores, while the TBI + PNES group scored worse on both measures. The fixed effects of the model revealed significant differences in SampEn values across networks (lower SampEn for the frontoparietal network compared to other networks). The likelihood ratio test for group-by-network-interactions was significant (p = 0.033). BDI-II was significantly negatively associated with Overall QOL scale scores in all groups, and significantly negatively associated with network SampEn values only in the TBI + PNES group. SIGNIFICANCE: Only TBI + PNES had significant relationships between depression symptom severity and network SampEn values indicating that the resting state network complexity is related to depression severity in this group but not in TBI + ES or TBI-only. PLAIN LANGUAGE SUMMARY: The brain has a complex network of internal connections. How well these connections work may be affected by TBI and seizures and may underlie mental health symptoms including depression; the worse the depression, the worse the quality of life. Our study compared brain organization in people with TBI, people with epilepsy after TBI, and people with nonepileptic seizures after TBI. Only people with nonepileptic seizures after TBI showed a relationship between how organized their brain connections were and how bad was their depression. We need to better understand these relationships to develop more impactful, effective treatments.

Decreased uncinate fasciculus integrity in functional seizures following traumatic brain injury.

OBJECTIVE: The uncinate fasciculus (UF) has been implicated previously in contributing to the pathophysiology of functional (nonepileptic) seizures (FS). FS are frequently preceded by adverse life events (ALEs) and present with comorbid psychiatric symptoms, yet neurobiological correlates of these factors remain unclear. To address this gap, using advanced diffusion magnetic resonance imaging (dMRI), UF tracts in a large cohort of patients with FS and pre-existing traumatic brain injury (TBI + FS) were compared to those in patients with TBI without FS (TBI-only). We hypothesized that dMRI measures in UF structural connectivity would reveal UF differences when controlling for TBI status. Partial correlation tests assessed the potential relationships with psychiatric symptom severity measures. METHODS: Participants with TBI-only (N = 46) and TBI + FS (N = 55) completed a series of symptom questionnaires and MRI scanning. Deterministic tractography via diffusion spectrum imaging (DSI) was implemented in DSI studio (https://dsi-studio.labsolver.org) with q-space diffeomorphic reconstruction (QSDR), streamline production, and manual segmentation to assess bilateral UF integrity. Fractional anisotropy (FA), radial diffusivity (RD), streamline counts, and their respective asymmetry indices (AIs) served as estimates of white matter integrity. RESULTS: Compared to TBI-only, TBI + FS participants demonstrated decreased left hemisphere FA and RD asymmetry index (AI) for UF tracts (both p < .05, false discovery rate [FDR] corrected). Additionally, TBI + FS reported higher symptom severity in depression, anxiety, and PTSD measures (all p < .01). Correlation tests comparing UF white matter integrity differences to psychiatric symptom severity failed to reach criteria for significance (all p > .05, FDR corrected). SIGNIFICANCE: In a large, well-characterized sample, participants with FS had decreased white matter health after controlling for the history of TBI. Planned follow-up analysis found no evidence to suggest that UF connectivity measures are a feature of group differences in mood or anxiety comorbidities for FS. These findings suggest that frontolimbic structural connectivity may play a role in FS symptomology, after accounting for prior ALEs and comorbid psychopathology severity.

The longitudinal effects of cannabidiol on brain temperature in patients with treatment-resistant epilepsy.

Neuroinflammation (NI) is a key pathophysiological contributor to treatment-resistant epilepsy (TRE) that remains challenging to observe in vivo. Magnetic resonance spectroscopic imaging and thermometry (MRSI-t) is an emerging technique that can be used to non-invasively map brain temperature, whereby brain temperature elevations serve as a surrogate for the cellular and biochemical processes associated with NI. In a previous multimodal imaging study of focal epilepsy patients, we observed MRSI-t-based brain temperature elevations ipsilateral to the seizure onset zone (SOZ) that were concordant with evidence of edema (Sharma et al., 2023). Despite its potential as tool, it is unclear if MRSI-t can monitor changes in brain temperature in response to treatment. We imaged 25 participants approximately 12-weeks apart. Eight patients with TRE were imaged before receiving highly-purified pharmaceutical grade cannabidiol (CBD; pre-CBD) and after 12-weeks of CBD (on-CBD) therapy. Seventeen healthy controls (HCs) were also imaged twice. Repeated measures t-tests computed changes in TRE patients' seizure symptoms, mood, and brain temperature within their respective SOZs. Repeated measures ANOVAs tested Group*Time changes in imaging data. Participants with TRE had abnormally high peak brain temperatures within their SOZs that decreased after CBD initiation (p < 0.0001). Seizure severity scores also improved after CBD initiation (p < 0.001). These findings provide insights into the possible neural effects of CBD, and further demonstrate MRSI-t's potential as a tool for delineating SOZ. Further investigations into MRSI-t as a longitudinal measure of therapy-induced changes in NI are warranted.

Phase synchronization during the processing of taxonomic and thematic relations.

Semantic relations include "taxonomic" relations based on shared features and "thematic" relations based on co-occurrence in events. The "dual-hub" account proposes that the anterior temporal lobe (ATL) is functionally specialized for taxonomic relations and the inferior parietal lobule (IPL) for thematic relations. This study examined this claim by analyzing the intra- and inter-region phase synchronization of intracranial EEG data from electrodes in the ATL, IPL, and two subregions of the semantic control network: left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG). Ten participants with epilepsy completed a semantic relatedness judgment task during intracranial EEG recording and had electrodes in at least one hub and at least one semantic control region. Theta band phase synchronization was partially consistent with the dual-hub account: synchronization between the ATL and IFG/pMTG increased when processing taxonomic relations, and synchronization within the IPL and between IPL and pMTG increased when processing thematic relations.

Neuromorphometric associations with mood, cognition, and self-reported exercise levels in epilepsy and healthy individuals.

Regular physical activity may promote beneficial neuroplasticity, e.g., increased hippocampus volume. However, it is unclear whether self-reported physical exercise in leisure (PEL) levels are associated with the brain structure features demonstrated by exercise interventions. This pilot study investigated the relationship between PEL, mood, cognition, and neuromorphometry in patients with idiopathic generalized epilepsy (IGEs) compared to healthy controls (HCs). Seventeen IGEs and 19 age- and sex-matched HCs underwent magnetic resonance imaging (MRI) at 3T. The Baecke Questionnaire of Habitual Physical Activity, Profile of Mood States, and Montreal Cognitive Assessment (MoCA) assessed PEL, mood, and cognition, respectively. Structural MRI data were analyzed by voxel- and surface-based morphometry. IGEs had significantly lower PEL (p < 0.001), poorer mood (p = 0.029), and lower MoCA scores (p = 0.027) than HCs. These group differences were associated with reduced volume, decreased gyrification, and altered surface topology (IGEs < HCs) in frontal, temporal and cerebellar regions involved in executive function, memory retrieval, and emotional regulation, respectively. These preliminary results support the notion that increased PEL may promote neuroplasticity in IGEs, thus emphasizing the role of physical activity in promoting brain health in people with epilepsy.

Peripheral and Central Nervous System Biomarkers of Inflammation in Functional Seizures: Assessment with Magnetic Resonance Spectroscopy.

Purpose: Inflammation may link trauma to clinical symptoms in functional seizures (FS). We compared brain temperature and metabolites in FS, psychiatric (PCs) and healthy controls (HCs) and quantified their associations with serum biomarkers of inflammation and clinical symptoms. Patients and Methods: Brain temperature and metabolites were measured with whole-brain magnetic resonance spectroscopic imaging (MRSI) and compared between groups in regions of interest and the whole brain. Relationships with inflammatory biomarkers and symptoms were assessed with Pearson correlations. Results: Brain temperature was higher in FS than HCs in the orbitofrontal cortex (OFC) and anterior cingulate gyrus (ACG) and lower in the occipital cortex and frontal lobe. PCs showed lower temperatures than HCs in the frontal lobe including precentral gyrus and in the cerebellum. Myo-inositol (MINO) was higher in FS than HCs in the precentral gyrus, posterior temporal gyrus, ACG and OFC, and choline (CHO) was higher in the occipital lobe. CHO was higher in PCs than HCs in the ACG and OFC, and N-acetylaspartate (NAA) was higher in the ACG. There were no significant correlations with the serum inflammatory biomarkers. In FS, brain temperature correlated with depression, quality of life, psychological symptoms, and disability, CHO correlated with disability, and MINO correlated with hostility, disability, and quality of life. Conclusion: Some of the previously identified neuroimaging abnormalities in FS may be related to comorbid psychiatric symptoms, while others, such as abnormalities in sensorimotor cortex, occipital regions, and the temporo-parietal junction may be specific to FS. Overlapping MINO and temperature increases in the ACG and OFC in FS suggest neuroinflammation.

Functional Magnetic Resonance Imaging Activation During Unscripted Discourse in People With Poststroke Aphasia.

PURPOSE: The purpose of this project was to determine the feasibility of employing a functional magnetic resonance imaging (fMRI) task that captured activation associated with overt, unscripted (or free) discourse of people with aphasia (PWA), using a continuous scan paradigm. METHOD: Seven participants (six females, ages 48-70 years) with chronic poststroke aphasia underwent two fMRI scanning sessions that included a discourse fMRI paradigm that consisted of five 1-min picture description tasks, using personally relevant photographs, interspersed with two 30-s control periods where participants looked at a fixation cross. Audio during the continuous fMRI scan was collected and marked with speaking times and coded for correct information units. Activation maps from the fMRI data were generated for the contrast between speaking and control conditions. In order to show the effects of the multi-echo data analysis, we compared it to a single-echo analysis by using only the middle echo (echo time of 30 ms). RESULTS: Through the implementation of the free discourse fMRI task, we were able to elicit activation that included bilateral regions in the planum polare, central opercular cortex, precentral gyrus, superior temporal gyrus, middle temporal gyrus, superior temporal gyrus, Crus I of the cerebellum, as well as bilateral occipital regions. CONCLUSIONS: We describe a new tool for assessing discourse recovery in PWA. By demonstrating the feasibility of a natural language paradigm in patients with chronic, poststroke aphasia, we open a new area for future research.

Do people with epilepsy want to participate in an exercise intervention randomized controlled trial? - Results of a brief survey and its preliminary application.

Our goal was to survey people with epilepsy (PWE) about their interest in and factors that may influence willingness and ability to participate in an exercise randomized controlled trial (RCT). A brief survey was administered to 100 PWE asking if they would take part in a hypothetical 6-week exercise intervention RCT. Follow-up questions queried reasons for and against participation and why participation would be difficult. Sixty-nine percent of respondents indicated willingness to participate. The top reason for participation was "to improve overall health with exercise" (n = 49). The top reason for why participation would be difficult was they "do not have a reliable source of transportation" (n = 27). The top reason for not participating was "not interested in research participation" (n = 19). Preliminary results were used to budget for transportation in a prospective RCT (NCT04959019). Of the first 27 PWE enrolled (63 % female; 44 % African American/Black), six (50 % female; 50 % African American/Black) have used the transportation service. The majority of PWE surveyed were interested in participating in an exercise RCT, but some indicated barriers. Accommodating transportation in an ongoing RCT has facilitated recruitment of PWE who would otherwise not be able to participate. Barriers to participation should be accounted for when designing studies.