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The great majority of spinal cord injury (SCI) patients have debilitating chronic pain. Despite decades of research, these pain pathways of neuropathic pain (NP) are unknown. SCI patients have been shown to have abnormal brain pain pathways. We hypothesize that SCI NP patients' pain matrix is altered compared to SCI patients without NP. This study examines the functional connectivity (FC) in SCI patients with moderate-severe chronic NP compared to SCI patients with mild-no NP. These groups were compared to control subjects. The Neuropathic Pain Questionnaire and neurological evaluation based on the International Standard Neurological Classification of SCI were utilized to define the severity and level of injury. Of the 10 SCI patients, 7 (48.6???17.02 years old, 6 male and 1 female) indicated that they had NP and 3 did not have NP (39.33???8.08 years old, 2 male and 1 female). Ten uninjured neurologically intact participants were used as controls (24.8???4.61 years old, 5 male and 5 female). FC metrics were obtained from the comparisons of resting-state functional magnetic resonance imaging among our various groups (controls, SCI with NP, and SCI without NP). For each comparison, a region-of-interest (ROI)-to-ROI connectivity analysis was pursued, encompassing a total of 175 ROIs based on a customized atlas derived from the AAL3 atlas. The analysis accounted for covariates such as age and sex. To correct for multiple comparisons, a strict Bonferroni correction was applied with a significance level of p?0.05/NROIs. When comparing SCI patients with moderate-to-severe pain to those with mild-to-no pain, specific thalamic nuclei had altered connections. These nuclei included: medial pulvinar; lateral pulvinar; medial geniculate nucleus; lateral geniculate nucleus; and mediodorsal magnocellular nucleus. There was increased FC between the lateral geniculate nucleus and the anteroventral nucleus in NP post-SCI. Our analysis additionally highlights the relationships between the frontal lobe and temporal lobe with pain. This study successfully identifies thalamic neuroplastic changes that occur in patients with SCI who develop NP. It additionally underscores the pain matrix and involvement of the frontal and temporal lobes as well. Our findings complement that the development of NP post-SCI involves cognitive, emotional, and behavioral influences.

Activity trackers and wearables allow accurate determination of physical activity, basic vital parameters, and tracking of complex medical conditions. This review attempts to provide a roadmap for the development of these applications, outlining the basic tools available, how they can be combined, and what currently exists in the marketplace for spine patients.Various types of sensors currently exist to measure distinct aspects of user movement. These include the accelerometer, gyroscope, magnetometer, barometer, global positioning system (GPS), Bluetooth and Wi-Fi, and microphone. Integration of data from these sensors allows detailed tracking of location and vectors of motion, resulting in accurate mobility assessments. These assessments can have great value for a variety of healthcare specialties, but perhaps none more so than spine surgery. Patient-reported outcomes (PROMs) are subject to bias and are difficult to track frequently - a problem that is ripe for disruption with the continued development of mobility technology.Currently, multiple mobile applications exist as an extension of clinical care. These include Manage My Surgery (MMS), SOVINITY-e-Healthcare Services, eHealth System, Beiwe Smartphone Application, QS Access, 6WT, and the TUG app. These applications utilize sensor data to assess patient activity at baseline and postoperatively. The results are evaluated in conjunction with PROMs. However, these applications have not yet exploited the full potential of available sensors.There is a need to develop smartphone applications that can accurately track the functional status and activity of spine patients, allowing a more quantitative assessment of outcomes, in contrast to legacy PROMs.

IntroductionIt is now understood that in focal epilepsy, impacted neural regions are not limited to the epileptogenic zone. As such, further investigation into the underlying functional connectivity (FC) patterns in those enduring Temporal Lobe Epilepsy (TLE) with Mesial Temporal Sclerosis (MTS) is imperative to understanding the intricacies of the disease.MethodsThe rsfMRIs of 17 healthy participants, 10 left-sided TLE-MTS patients with a pre-operative history of focal impaired awareness seizures (FIA), and 13 left-sided TLE-MTS patients with a pre-operative history of focal aware seizures (FA) were compared to determine the existence of distinct FC patterns with respect to seizure types. Similarly, the rsfMRIs of the above-mentioned healthy participants, 16 left-sided TLE-MTS individuals who were seizure-free (SF) 12 months postoperatively, and 16 left-sided TLE-MTS persons without seizure freedom (nSF) were interrogated. The ROI-to-ROI connectivity analysis included a total of 175 regions of interest (ROIs) and accounted for both age and duration of epileptic activity. Significant correlations were determined via two-sample t-tests and Bonferroni correction (α = 0.05).ResultsComparisons of FA and FIA groups depicted significant correlations between the contralateral anterior cingulate gyrus, subgenual region, and the contralateral cerebellum, lobule III (p-value = 2.26e-4, mean z-score = −0.05 ± 0.28, T = −4.23). Comparisons of SF with nSF depicted two significantly paired-ROIs; the contralateral amygdala and the contralateral precuneus (p-value = 2.9e-5, mean z-score = −0.12 ± 0.19, T = 4.98), as well as the contralateral locus coeruleus and the ipsilateral intralaminar nucleus (p-value= 1.37e-4, mean z-score = 0.06 ± 0.17, T = −4.41).SignificanceFC analysis proves to be a lucrative modality for exploring unique signatures with respect to seizure types and postoperative outcomes. By furthering our understanding of the differences between epileptic phenotypes, we can achieve improvement in future treatment modalities not limited to targeting advancements.

Abstract Fast ripples (FR) are a biomarker of epileptogenic brain, but when larger portions of FR generating regions are resected seizure freedom is not always achieved. To evaluate and improve the diagnostic accuracy of FR resection for predicting seizure freedom we compared the FR resection ratio (RR) with FR network graph theoretical measures. In 23 patients FR were semi-automatically detected and quantified in stereo EEG recordings during sleep. MRI normalization and co-registration localized contacts and relation to resection margins. The number of FR, and graph theoretical measures, which were spatial (i.e., FR rate-distance radius) or temporal correlational (i.e., FR mutual information), were compared with the resection margins and with seizure outcome We found that the FR RR did not correlate with seizure-outcome (p > 0.05). In contrast, the FR rate-distance radius resected difference and the FR MI mean characteristic path length RR did correlate with seizure-outcome (p

We report the case of a 62-year-old man who presented with a progressive myelopathy secondary to spinal cord compression from an odontoid process fracture and subaxial central canal stenosis. The patient underwent a C1-T2 posterior decompression and instrumented fusion (PCDF) and did well immediately postoperatively. However, on POD1, he developed a right hypoglossal nerve (HN) palsy attributed to direct mechanical compression or injury from the C1 lateral mass screw (LMS), which improved following a revision and screw replacement. While HN injury is a known complication of high anterior and anterolateral cervical spine approaches as well as transcondylar screw fixation, this case aims to expand on the limited reports available regarding hypoglossal nerve injury following placement of bicortical C1 LMS. Furthermore, the use of fluoroscopic guidance in addition to anatomic landmarks and triggered electromyography of the tongue are offered as potential solutions to prevent HN injury intraoperatively.

Abstract In this study, we examined whether amplitude synchronization of medial (MTL) and lateral (LTL) temporal lobes can detect unique alterations in patients with MTL epilepsy (mTLE) with mesial temporal sclerosis (MTS). This was a retrospective study of preoperative resting-state fMRI (rsfMRI) data from 31 patients with mTLE with MTS (age 23–69) and 16 controls (age 21–35). fMRI data were preprocessed based on a multistep preprocessing pipeline and registered to a standard space. Using each subject’s T1-weighted scan, the MTL and LTL were automatically segmented, manually revised and then fit to a standard space using a symmetric normalization registration algorithm. Dual regression analysis was applied on preprocessed rsfMRI data to detect amplitude synchronization of medial and lateral temporal segments with the rest of the brain. We calculated the overlapped volume ratio of synchronized voxels within specific target regions including the thalamus (total and bilateral). A general linear model was used with Bonferroni correction for covariates of epilepsy duration and age of patient at scan to statistically compare synchronization in patients with mTLE with MTS and controls, as well as with respect to whether patients remained seizure-free (SF) or not (NSF) after receiving epilepsy surgery. We found increased ipsilateral positive connectivity between the LTLs and the thalamus and contralateral negative connectivity between the MTLs and the thalamus in patients with mTLE with MTS compared to controls. We also found increased asymmetry of functional connectivity between temporal lobe subregions and the thalamus in patients with mTLE with MTS, with increased positive connectivity between the LTL and the lesional-side thalamus as well as increased negative connectivity between the MTL and the nonlesional-side thalamus. This asymmetry was also seen in NSF patients but was not seen in SF patients and controls. Amplitude synchronization was an effective method to detect functional connectivity alterations in patients with mTLE with MTS. Patients with mTLE with MTS overall showed increased temporal-thalamic connectivity. There was increased functional involvement of the thalamus in MTS, underscoring its role in seizure spread. Increased functional thalamic asymmetry patterns in NSF patients may have a potential role in prognosticating patient response to surgery. Elucidating regions with altered functional connectivity to temporal regions can improve understanding of the involvement of different regions in the disease to potentially target for intervention or use for prognosis for surgery. Future studies are needed to examine the effectiveness of using patient-specific abnormalities in patterns to predict surgical outcome.

Purpose: Identifying relationships between clinical features and quantitative characteristics of the amygdala-hippocampal and thalamic subregions in mesial temporal lobe epilepsy (mTLE) may offer insights into pathophysiology and the basis for imaging prognostic markers of treatment outcome. Our aim was to ascertain different patterns of atrophy or hypertrophy in mesial temporal sclerosis (MTS) patients and their associations with post-surgical seizure outcomes. To assess this aim, this study is designed in 2 folds: (1) hemispheric changes within MTS group and (2) association with postsurgical seizure outcomes. Methods and materials: 27 mTLE subjects with mesial temporal sclerosis (MTS) were scanned for conventional 3D T1w MPRAGE images and T2w scans. With respect to 12 months post-surgical seizure outcomes, 15 subjects reported being seizure free (SF) and 12 reported continued seizures. Quantitative automated segmentation and cortical parcellation were performed using Freesurfer. Automatic labeling and volume estimation of hippocampal subfields, amygdala, and thalamic subnuclei were also performed. The volume ratio (VR) for each label was computed and compared between (1) between contralateral and ipsilateral MTS using Wilcoxon rank-sum test and (2) SF and not seizure free (NSF) groups using linear regression analysis. False Discovery rate (FDR) with significant level of 0.05 were used in both analyses to correct for multiple comparisons. Results: Amygdala: The medial nucleus of the amygdala was the most significantly reduced in patients with continued seizures when compared to patients who remained seizure free. Hippocampus: Comparison of ipsilateral and contralateral volumes with seizure outcomes showed volume loss was most evident in the mesial hippocampal regions such as CA4 and hippocampal fissure. Volume loss was also most explicit in the presubiculum body in patients with continued seizures at the time of their follow-up. Ipsilateral MTS compared to contralateral MTS analysis showed the heads of the ipsilateral subiculum, presubiculum, parasubiculum, dentate gyrus, CA4, and CA3 were more significantly affected than their respective bodies. Volume loss was most noted in mesial hippocampal regions. Thalamus: VPL and PuL were the most significantly reduced thalamic nuclei in NSF patients. In all statistically significant areas, volume reduction was observed in the NSF group. No significant volume reductions were noted in the thalamus and amygdala when comparing ipsilateral to contralateral sides in mTLE subjects. Conclusions: Varying degrees of volume loss were demonstrated in the hippocampus, thalamus, and amygdala subregions of MTS, especially between patients who remained seizure-free and those who did not. The results obtained can be used to further understand mTLE pathophysiology. Clinical relevance/application: In the future, we hope these results can be used to deepen the understanding of mTLE pathophysiology, leading to improved patient outcomes and treatments.

Background: Positive correlations between low- and high-frequency spectra from stereotactic electroencephalogram (SEEG) recordings have been implicated in pathological brain activity interictally and have been used for ictal detection in both focal and network models. Objective: We evaluated SEEG signals in patients who ultimately underwent temporal lobectomy to evaluate their utility in seizure localization and prediction of seizure freedom post-resection. Methods: We retrospectively analyzed cross-frequency correlations between beta and high gamma (HG) interictal SEEG signals from 22 patients. We compared signals based on temporal versus extra-temporal locations, seizure-free (SF) versus non-seizure-free (NSF) outcomes, and mesial (M) versus mesial temporal-plus (M+) onset. Results: Positive cross-correlations were increased in temporal areas. NSF patients showed a higher proportion of positive electrodes in temporal areas. SF patients had a greater proportion of significant channels in mesial versus lateral temporal areas. HG/Beta correlations in mesial versus lateral temporal areas predicted seizure freedom better than ictal SEEG seizure onset localization to M or M+ locations. Conclusions: We present preliminary data that local HG/Beta correlations may predict epilepsy focus and surgical outcome and may have utility as adjunct methods to conventional SEEG analysis. Further studies are needed to determine strategies for prospective studies and clinical use.

IntroductionEpilepsy is defined as non-lesional (NLE) when a lesion cannot be localized via standard neuroimaging. NLE is known to have a poor response to surgery. Stereotactic electroencephalography (sEEG) can detect functional connectivity (FC) between zones of seizure onset (OZ) and early (ESZ) and late (LSZ) spread. We examined whether resting-state fMRI (rsfMRI) can detect FC alterations in NLE to see whether noninvasive imaging techniques can localize areas of seizure propagation to potentially target for intervention.MethodsThis is a retrospective study of 8 patients with refractory NLE who underwent sEEG electrode implantation and 10 controls. The OZ, ESZ, and LSZ were identified by generating regions around sEEG contacts that recorded seizure activity. Amplitude synchronization analysis was used to detect the correlation of the OZ to the ESZ. This was also done using the OZ and ESZ of each NLE patient for each control. Patients with NLE were compared to controls individually using Wilcoxon tests and as a group using Mann-Whitney tests. Amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DoC), and voxel-mirrored homotopic connectivity (VMHC) were calculated as the difference between NLE and controls and compared between the OZ and ESZ and to zero. A general linear model was used with age as a covariate with Bonferroni correction for multiple comparisons.ResultsFive out of 8 patients with NLE showed decreased correlations from the OZ to the ESZ. Group analysis showed patients with NLE had lower connectivity with the ESZ. Patients with NLE showed higher fALFF and ReHo in the OZ but not the ESZ, and higher DoC in the OZ and ESZ. Our results indicate that patients with NLE show high levels of activity but dysfunctional connections in seizure-related areas.DiscussionrsfMRI analysis showed decreased connectivity directly between seizure-related areas, while FC metric analysis revealed increases in local and global connectivity in seizure-related areas. FC analysis of rsfMRI can detect functional disruption that may expose the pathophysiology underlying NLE.

Serruya et al. test in an N-of-1 trial whether a wearable, powered exoskeletal orthosis, driven by a percutaneous, implanted brain–computer interface can restore voluntary upper extremity function following chronic hemiparesis subsequent to a cerebral subcortical stroke. Using this approach, voluntary opening of the paralyzed hand is restored.

Epileptiform spikes are used to localize epileptogenic brain tissue. The mechanisms that spontaneously trigger epileptiform discharges are not yet elucidated. Pathological fast ripple (FR, 200–600 Hz) are biomarkers of epileptogenic brain, and we postulated that FR network interactions are involved in generating epileptiform spikes. Using macroelectrode stereo intracranial EEG (iEEG) recordings from a cohort of 46 patients we found that, in the seizure onset zone (SOZ), propagating FR were more often followed by an epileptiform spike, as compared with non-propagating FR (p

Abstract To see whether acute intraoperative recordings using stereo EEG (SEEG) electrodes can replace prolonged interictal intracranial EEG (iEEG) recording, making the process more efficient and safer, 10 min of iEEG were recorded following electrode implantation in 16 anesthetized patients, and 1–2 days later during non-rapid eye movement (REM) sleep. Ripples on oscillations (RonO, 80–250 Hz), ripples on spikes (RonS), sharp-spikes, fast RonO (fRonO, 250–600 Hz), and fast RonS (fRonS) were semi-automatically detected. HFO power and frequency were compared between the conditions using a generalized linear mixed-effects model. HFO rates were compared using a two-way repeated measures ANOVA with anesthesia type and SOZ as factors. A receiver-operating characteristic (ROC) curve analysis quantified seizure onset zone (SOZ) classification accuracy, and the scalar product was used to assess spatial reliability. Resection of contacts with the highest rate of events was compared with outcome. During sleep, all HFOs, except fRonO, were larger in amplitude compared to intraoperatively (p

Deep brain stimulation (DBS) has been used to modulate aberrant circuits associated with Parkinson's disease (PD) for decades and has shown robust therapeutic benefits. However, the mechanism of action of DBS remains incompletely understood. With technological advances, there is an emerging use of functional magnetic resonance imaging (fMRI) after DBS implantation to explore the effects of stimulation on brain networks in PD. This systematic review was designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to summarize peer-reviewed articles published within the past 10 years in which fMRI was employed on patients with PD-DBS. Search in PubMed database provided 353 references, and screenings resulted in a total of 19 studies for qualitative synthesis regarding study designs (fMRI scan timepoints and paradigm), methodology, and PD subtypes. This review concluded that fMRI may be used in patients with PD-DBS after proper safety test; resting-state and block-based fMRI designs have been employed to explore the effects of DBS on brain networks and the mechanism of action of the DBS, respectively. With further validation of safety use of fMRI and advances in imaging techniques, fMRI may play an increasingly important role in better understanding of the mechanism of stimulation as well as in improving clinical care to provide subject-specific neuromodulation treatments.

We show that the human hippocampus exhibits two distinct theta oscillations during spatial navigation with the faster oscillation in posterior regions showing movement modulation. This result suggests a distinct feature of the human hippocampus compared to rodents, which generally show a single 8 Hz rhythm.

Background: A clinical feasibility study was undertaken at a single center of long-term intra-cerebroventricular drug delivery of the anti-seizure medication valproic acid, into the cerebrospinal fluid (CSF) in order to treat drug resistant focal seizures, using an implantable infusion system. The primary objective was to establish the dose range of VPA administered in this manner. Secondarily, safety, pharmacokinetics (PK) and a preliminary estimate of effectiveness were evaluated. Methods: In this single arm study, five adult subjects, with 29–234 focal onset seizures per month from a seizure focus involving the mesial temporal lobe were implanted with the system (clinicaltrials.gov identifier NCT02899611). Oral valproic acid (VPA) had previously been ineffective in all subjects. Post-surgery, pharmacokinetic studies of CSF infused VPA were performed. Valproic acid doses were increased stepwise in a standardised protocol. Findings: The procedure and implantation were well-tolerated by all subjects. Four subjects responded with > 50% seizure reduction at the highest tested dose of 160 mg/day. Two subjects experienced extended periods of complete seizure freedom. All five subjects reported significant quality of life improvement. No clinical dose limiting side effects were encountered and there was no evidence of local periventricular toxicity in three subjects who were evaluated with imaging (T2 MRI). Side effects included nausea and appetite loss but were not dose-limiting. Mean CSF valproic acid levels were 45 μg per ml (range 20–120 μg per ml), with corresponding serum levels of 4–14 μg per ml. Subjects have received therapy for up to 2.5 years in total . The efficacy analysis presented focuses on the period of time with the current pump with a mean 12.5 months, range 11.5–15 months. Pump failure requiring reimplantation was a significant initial issue in all subjects but resolved with use of pumps suitably compatible with long-term exposure to valproic acid. Interpretation: The study demonstrated that chronic intraventricular administration of valproic acid is safe and effective in subjects with medically refractory epilepsy over many months. The procedure for implanting the infusion system is safe and well-tolerated. High CSF levels are achieved with corresponding low serum levels and this therapy is shown to be effective despite unsuccessful earlier use of oral valproate preparations. Drug side effects were minimal. Funding: The study was funded by Cerebral Therapeutics Inc., Suite 137 12635 East Montview Blvd Aurora CO 80045.

Ripple oscillations (80–200 Hz) in the normal hippocampus are involved in memory consolidation during rest and sleep. In the epileptic brain, increased ripple and fast ripple (200–600 Hz) rates serve as a biomarker of epileptogenic brain. We report that both ripples and fast ripples exhibit a preferred phase angle of coupling with the trough-peak (or On-Off) state transition of the sleep slow wave in the hippocampal seizure onset zone (SOZ). Ripples on slow waves in the hippocampal SOZ also had a lower power, greater spectral frequency, and shorter duration than those in the non-SOZ. Slow waves in the mesial temporal lobe modulated the baseline firing rate of excitatory neurons, but did not significantly influence the increased firing rate associated with ripples. In summary, pathological ripples and fast ripples occur preferentially during the On-Off state transition of the slow wave in the epileptogenic hippocampus, and ripples do not require the increased recruitment of excitatory neurons.

Background: Anterior two-thirds corpus callosotomy is an effective palliative neurosurgical procedure for drug-refractory epilepsy that is most commonly used to treat drop-attacks. Laser interstitial thermal therapy is a novel stereotactic ablative technique that has been utilised as a minimally invasive alternative to resective and disconnective open neurosurgery. Case series have reported success in performing laser anterior two-thirds corpus callosotomy. Computer-assisted planning algorithms may help to automate and optimise multi-trajectory planning for this procedure. Objective: To undertake a simulation-based feasibility study of computer-assisted corpus callostomy planning in comparison with expert manual plans in the same patients. Methods: Ten patients were selected from a prospectively maintained database. Patients had previously undergone diffusion-weighted imaging and digital subtraction angiography as part of routine SEEG care. Computer-assisted planning was performed using the EpiNav™ platform and compared to manually planned trajectories from two independent blinded experts. Estimated ablation cavities were used in conjunction with probabilistic tractography to simulate the expected extent of interhemispheric disconnection. Results: Computer-assisted planning resulted in significantly improved trajectory safety metrics (risk score and minimum distance to vasculature) compared to blinded external expert manual plans. Probabilistic tractography revealed residual interhemispheric connectivity in 1/10 cases following computer-assisted planning compared to 4/10 and 2/10 cases with manual planning. Conclusion: Computer-assisted planning successfully generates multi-trajectory plans capable of LITT anterior two-thirds corpus callosotomy. Computer-assisted planning may provide a means of standardising trajectory planning and serves as a potential new tool for optimising trajectories. A prospective validation study is now required to determine if this translates into improved patient outcomes. Keywords: Computer-assisted planning, Laser interstitial thermal therapy, Corpus Callosotomy

Theta oscillations are implicated in memory formation. Here, the authors show that low-theta oscillations in the hippocampus are differentially modulated between each hemisphere, with oscillations in the left increasing when successfully learning object–location pairs and in the right during spatial navigation.

Background: Electrode contact locations are important when planning tailored brain surgeries to identify pathological tissue targeted for resection and conversely avoid eloquent tissue. Current methods employ trained experts to use neuroimaging scans that are manually co-registered and localize contacts within ~2 mm. Yet, the state of the art is limited by either the expertise needed for each type of intracranial electrode or the inter-modality co-registration which increases error, reducing accuracy. Patients often have a variety of strips, grids and depths implanted; therefore, it is cumbersome and time-consuming to apply separate localization methods for each type of electrode, requiring expertise across different approaches. New method: To overcome these limitations, a computational method was developed by separately registering an implant magnetic resonance image (MRI) and implant computed tomography image (CT) to the pre-implant MRI, then calculating an iterative closest point transformation using the contact locations extracted from the signal voids as ground truth. Results: The implant MRI is robustly co-registered to the pre-implant MRI with a boundary-based registration algorithm. By extracting and utilizing ‘signal voids’ (the metal induced artifacts from the implant MRI) as electrode fiducials, the novel method is an all-in-one approach for all types of intracranial electrodes while eliminating inter-modality co-registration errors. Comparison with existing methods: The distance between each electrode centroid and the brain's surface was measured, for the proposed method as well as the state of the art method using two available software packages, SPM 12 and FSL 4.1. The method presented here achieves the smallest distances to the brain's surface for all strip and grid type electrodes, i.e. contacts designed to rest directly on the brain surface. Conclusion: We use one of the largest reported sample sizes in localization studies to validate this novel method for localizing different kinds of intracranial electrodes including grids, strips and depth electrodes. Keywords: MRI, ECoG, Epilepsy, Localization, Grid, Strip, Depth

Pre-surgical evaluation of patients with temporal lobe epilepsy (TLE) relies on information obtained from multiple neuroimaging modalities. The relationship between modalities and their combined power in predicting the seizure focus is currently unknown. We investigated asymmetries from three different modalities, PET (glucose metabolism), MRI (cortical thickness), and diffusion tensor imaging (DTI; white matter anisotropy) in 28 left and 30 right TLE patients (LTLE and RTLE). Stepwise logistic regression models were built from each modality separately and from all three combined, while bootstrapped methods and split-sample validation verified the robustness of predictions. Among all multimodal asymmetries, three PET asymmetries formed the best predictive model (100% success in full sample, >95% success in split-sample validation). The combinations of PET with other modalities did not perform better than PET alone. Probabilistic classifications were obtained for new clinical cases, which showed correct lateralization for 7/7 new TLE patients (100%) and for 4/5 operated patients with discordant or non-informative PET reports (80%). Metabolism showed closer relationship with white matter in LTLE and closer relationship with gray matter in RTLE. Our data suggest that metabolism is a powerful modality that can predict seizure laterality with high accuracy, and offers high value for automated predictive models. The side of epileptogenic focus can affect the relationship of metabolism with brain structure. The data and tools necessary to obtain classifications for new TLE patients are made publicly available.

Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre- and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates.

Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is necessary to produce reductions in episodic memory recall. The latter, in particular, demonstrates the complex structure/function interactions at work when trying to understand cognition in TLE, suggesting that subtle network effects can emerge bearing specific relationships to hemisphere and the type of pathology.

Anterior temporal lobectomy (ATL) is commonly adopted to control medically intractable temporal lobe epilepsy (TLE). Depending on the side of resection, the degree to which Wallerian degeneration and adaptive plasticity occur after ATL has important implications for understanding cognitive and clinical outcome. We obtained diffusion tensor imaging from 24 TLE patients (12 left) before and after surgery, and 12 matched controls at comparable time intervals. Voxel-based analyses were performed on fractional anisotropy (FA) before and after surgery. Areas with postoperative FA increase were further investigated to distinguish between genuine plasticity and processes related to the degeneration of crossing fibers. Before surgery, both patient groups showed bilateral reduced FA in numerous tracts, but left TLE patients showed more extensive effects, including language tracts in the contralateral hemisphere (superior longitudinal fasciculus and uncinate). After surgery, FA decreased ipsilaterally in both ATL groups, affecting the fornix, uncinate, stria terminalis, and corpus callosum. FA increased ipsilaterally along the superior corona radiata in both left and right ATL groups, exceeding normal FA values. In these clusters, the mode of anisotropy increased as well, confirming fiber degeneration in an area with crossing fibers. In left ATL patients, pre-existing low FA values in right superior longitudinal and uncinate fasciculi normalized after surgery, while MO values did not change. Preoperative verbal fluency correlated with FA values in all areas that later increased FA in left TLE patients, but postoperative verbal fluency correlated only with FA of the right superior longitudinal fasciculus. Our results demonstrate that genuine reorganization occurs in non-dominant language tracts after dominant hemisphere resection, a process that may help implement the inter-hemispheric shift of language activation found in fMRI studies. The results indicate that left TLE patients, despite showing more initial white matter damage, have the potential for greater adaptive changes postoperatively than right TLE patients.