A hierarchy of processing complexity and timescales for natural sounds in human auditory cortex.

Efficient behavior is supported by humans' ability to rapidly recognize acoustically distinct sounds as members of a common category. Within auditory cortex, there are critical unanswered questions regarding the organization and dynamics of sound categorization. Here, we performed intracerebral recordings in the context of epilepsy surgery as 20 patient-participants listened to natural sounds. We built encoding models to predict neural responses using features of these sounds extracted from different layers within a sound-categorization deep neural network (DNN). This approach yielded highly accurate models of neural responses throughout auditory cortex. The complexity of a cortical site's representation (measured by the depth of the DNN layer that produced the best model) was closely related to its anatomical location, with shallow, middle, and deep layers of the DNN associated with core (primary auditory cortex), lateral belt, and parabelt regions, respectively. Smoothly varying gradients of representational complexity also existed within these regions, with complexity increasing along a posteromedial-to-anterolateral direction in core and lateral belt, and along posterior-to-anterior and dorsal-to-ventral dimensions in parabelt. When we estimated the time window over which each recording site integrates information, we found shorter integration windows in core relative to lateral belt and parabelt. Lastly, we found a relationship between the length of the integration window and the complexity of information processing within core (but not lateral belt or parabelt). These findings suggest hierarchies of timescales and processing complexity, and their interrelationship, represent a functional organizational principle of the auditory stream that underlies our perception of complex, abstract auditory information.

Thalamic stereoelectroencephalography for neuromodulation target selection: Proof of concept and review of literature of pulvinar direct electrical stimulation.

In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, various thalamic nuclei, including the anterior, centromedian, and pulvinar nuclei, have been extensively investigated as targets for neuromodulation. However, the therapeutic effects of different targets for thalamic neuromodulation on various types of epilepsy are not well understood. Here, we present a 32-year-old patient with multifocal bilateral temporoparieto-occipital epilepsy and bilateral malformations of cortical development (MCDs) who underwent bilateral stereoelectroencephalographic (SEEG) recordings of the aforementioned three thalamic nuclei bilaterally. The change in the rate of interictal epileptiform discharges (IEDs) from baseline were compared in temporal, central, parietal, and occipital regions after direct electrical stimulation (DES) of each thalamic nucleus. A significant decrease in the rate of IEDs (33% from baseline) in the posterior quadrant regions was noted in the ipsilateral as well as contralateral hemisphere following DES of the pulvinar. A scoping review was also performed to better understand the current standpoint of pulvinar thalamic stimulation in the treatment of DRE. The therapeutic effect of neuromodulation can differ among thalamic nuclei targets and epileptogenic zones (EZs). In patients with multifocal EZs with extensive MCDs, personalized thalamic targeting could be achieved through DES with thalamic SEEG electrodes.

The changing landscape of palliative epilepsy surgery for Lennox Gastaut Syndrome.

Lennox Gastaut Syndrome (LGS) is characterized by drug-resistant epilepsy that typically leads to decreased quality of life and deleterious neurodevelopmental comorbidities from medically refractory seizures. In recent years there has been a dramatic increase in the development and availability of novel treatment strategies for Lennox Gastaut Syndrome patient to improve seizure. Recent advances in neuromodulation and minimally invasive magnetic resonance guided laser interstitial thermal therapy (MRgLITT) have paved the way for new treatments strategies including deep brain stimulation (DBS), responsive neurostimulation (RNS), and MRgLITT corpus callosum ablation. These new strategies offer hope for children with drug-resistant generalized epilepsies, but important questions remain about the safety and effectiveness of these new approaches. In this review, we describe the opportunities presented by these new strategies and how each treatment strategy is currently being employed. Next, we will critically assess available evidence for these new approaches compared to traditional palliative epilepsy surgery approaches, such as vagus nerve stimulation (VNS) and open microsurgical corpus callosotomy (CC). Finally, we will describe future directions that would help define which of the available strategies should be employed and when.

Characterization of low-grade epilepsy-associated tumor from implanted stereoelectroencephalography electrodes.

Low-grade epilepsy-associated tumors (LEATs) are a common cause of drug-resistant epilepsy in children. Herein, we demonstrate the feasibility of using tumor tissue derived from stereoelectroencephalography (sEEG) electrodes upon removal to molecularly characterize tumors and aid in diagnosis. An 18-year-old male with focal epilepsy and MRI suggestive of a dysembryoplastic neuroepithelial tumor (DNET) in the left posterior temporal lobe underwent implantation of seven peri-tumoral sEEG electrodes for peri-operative language mapping and demarcation of the peri-tumoral ictal zone prior to DNET resection. Using electrodes that passed through tumor tissue, we show successful isolation of tumor DNA and subsequent analysis using standard methods for tumor classification by DNA, including Glioseq targeted sequencing and DNA methylation array analysis. This study provides preliminary evidence for the feasibility of molecular diagnosis of LEATs or other lesions using a minimally invasive method with microscopic tissue volumes. The implications of sEEG electrodes in tumor characterization are broad but would aid in diagnosis and subsequent targeted therapeutic strategies.

Clinical outcomes of MR-guided laser interstitial thermal therapy corpus callosum ablation in drug-resistant epilepsy: a systematic review and meta-analysis.

OBJECTIVE: The goal of this systematic review and meta-analysis was to provide an updated analysis of studies investigating outcomes, morbidity, and mortality associated with MR-guided laser interstitial thermal therapy (MRgLITT) corpus callosum ablation (CCA). METHODS: Study inclusion criteria for screening required that studies report on human subjects only, including patients aged 1-52 years diagnosed with drug-resistant epilepsy who underwent CCA. Sixteen articles published between 2016 and 2023 were included for the systematic review and analysis, including 4 case reports, 11 case series, and 1 case-control study. Altogether, 85 pediatric and adult patients undergoing CCA were included in the systematic review (46 patients younger and 39 patients older than 21 years). The main outcome of seizure freedom was measured using the decrease in the frequency of atonic seizures following surgery, percentage of atonic seizure freedom following surgery, and percentage of overall seizure freedom following surgery. These measurements were made using data from the last follow-up for patients with at least 6 months of follow-up post-CCA. RESULTS: The extent of CCA differed across the pooled cohorts, including anterior two-thirds CCA (38.89%, n = 35) and posterior one-third CCA for completion of a prior partial CCA (22.22%, n = 20), complete CCA (27.78%, n = 25), or CCA of residual white matter in the case of subtotal initial ablation (5.56%, n = 5). Overall, 12.94% of the patients undergoing CCA experienced operational complications. The most common operative complications across 90 CCA operations were probe malpositioning (n = 6), hemorrhage (n = 5), off-target extension of splenium ablation to the thalamus (n = 1), infection (n = 1), and postoperative CSF leak (n = 1). Neurological deficits following CCA were reported as transient in 18.82% and permanent in 4.71% of patients across all studies. The most common neurological deficits were disconnection syndrome (n = 4) or transient hemiplegia (supplementary motor area-like syndrome; n = 4). The 6-month overall seizure freedom rate was 18.87% of 53 patients, and the atonic seizure freedom rate was 46.28% of 52 patients postoperatively. CCA resulted in an average decrease in atonic seizure rate from 8.30 to 1.65 atonic seizures per day (average decrease 80.12%). CONCLUSIONS: CCA is associated with an acceptable complication profile, and most patients experience a meaningful reduction in target seizure semiologies. Accurate MRgLITT probe placement is likely important for maximizing CCA while avoiding collateral damage. Avoidable complications of CCA include off-target ablation (and associated deficits), hemorrhage, and future surgery for residual CCA to palliate continued seizures.

Comparison of magnetic resonance-guided laser interstitial thermal therapy corpus callosum ablation to open microsurgical corpus callosotomy: A single-center retrospective cohort study.

OBJECTIVE: Corpus callosotomy (CC) is an important treatment for atonic seizures in patients with generalized or multifocal drug-resistant epilepsy (DRE). Traditionally, CC is performed via an open microsurgical approach, but more recently, MR-guided stereotactic laser interstitial thermal therapy (LITT) corpus callosum ablation (CCA) has been developed to leverage the safety and minimally invasive nature of LITT. Given the recent adoption of CCA at select centers, how CCA compares to CC is unknown. We aim to compare the clinical seizure outcomes of CCA and CC after extended follow-up. METHODS: We performed a retrospective cohort study to compare the effectiveness and safety of CC to CCA from 1994 to 2022. The primary outcome was a 50% reduction in target seizure. Secondary outcome measures were postoperative length of stay, adverse events, and other effectiveness metrics. Comparative statistics were executed using Stata. Normality for continuous variables was assessed, and parametric statistics were utilized as needed. Frequency was compared with chi-squared or Fischer's exact tests, when applicable. RESULTS: Data from 47 operations performed on 36 patients were included in this study, of which 13 (36%) patients underwent 17 CCA. Patients who received CCA had similar rates of meaningful reduction (>50%) of atonic seizures as their CC counterparts (55% vs 70% P = 0.15). Patients undergoing CCA had significantly shorter hospitalizations than those receiving CC (2.5 vs 6.0 days P < 0.001). There was no significant difference in rates of postoperative complications between the groups, although the magnitude of the complication rates was lower in the CCA cohort (12% vs 28%). SIGNIFICANCE: This early experience suggests CCA has similar outcomes to traditional CC, albeit with a shorter hospital stay. However, future studies are necessary to investigate the noninferiority between these two approaches. Large multicenter studies are necessary to investigate differences in adverse events and whether these findings generalize across other centers.

Relationship of cervical soft tissue injury and surgical predication following pediatric cervical spinal trauma and its sequelae on long-term neurologic outcome.

Within the sample of 181 patients with cervical CT, CT identified unstable injury with a sensitivity of 100% and specificity of 95%. CT identified operable injury at the CCJ with 86% sensitivity and 91% specificity. CT was considered the gold standard for identification of fractures. Together, the presence of CT imaging suggestive of unstable injury or persistent neurologic complaint had a 100% sensitivity and 81% specificity. Finally, across all patients MRI had 100% sensitivity and 89% specificity for detection of unstable injury requiring surgery.

Electrocorticography reveals the dynamics of famous voice responses in human fusiform gyrus.

Voice and face processing occur through convergent neural systems that facilitate speaker recognition. Neuroimaging studies suggest that familiar voice processing engages early visual cortex, including the bilateral fusiform gyrus (FG) on the basal temporal lobe. However, what role the FG plays in voice processing and whether it is driven by bottom-up or top-down mechanisms is unresolved. In this study we directly examined neural responses to famous voices and faces in human FG with direct cortical surface recordings (electrocorticography) in epilepsy surgery patients. We tested the hypothesis that neural populations in human FG respond to famous voices and investigated the temporal properties of voice responses in FG. Recordings were acquired from five adult participants during a person identification task using visual and auditory stimuli from famous speakers (U.S. Presidents Barack Obama, George W. Bush, and Bill Clinton). Patients were presented with images of presidents or clips of their voices and asked to identify the portrait/speaker. Our results demonstrate that a subset of face-responsive sites in and near FG also exhibit voice responses that are both lower in magnitude and delayed (300-600 ms) compared with visual responses. The dynamics of voice processing revealed by direct cortical recordings suggests a top-down feedback-mediated response to famous voices in FG that may facilitate speaker identification.NEW & NOTEWORTHY Interactions between auditory and visual cortices play an important role in person identification, but the dynamics of these interactions remain poorly understood. We performed direct brain recordings of fusiform face cortex in human epilepsy patients performing a famous voice naming task, revealing the dynamics of famous voice processing in human fusiform face cortex. The findings support a model of top-down interactions from auditory to visual cortex to facilitate famous voice recognition.

Cost-effectiveness of invasive monitoring strategies in epilepsy surgery.

OBJECTIVE: Drug-resistant epilepsy occurs in up to 40% of patients with epilepsy who may be considered for epilepsy surgery. For drug-resistant focal epilepsy, up to 50% of patients require invasive monitoring prior to surgery. Of the most common invasive monitoring strategies (subdural electrodes [SDEs] and stereo-electroencephalography [sEEG]), the most cost-effective strategy is unknown despite substantial differences in morbidity profiles. METHODS: Using data collected from an internationally representative sample published in available systematic reviews and meta-analyses, this economic evaluation study employs a decision analysis model to simulate the risks and benefits of SDE and sEEG invasive monitoring strategies. In this model, patients faced differing risks of morbidity, mortality, resection, and seizure freedom depending on which invasive monitoring strategy they underwent. A range of cost values was obtained from a recently published single-center cost-utility analysis. The model considers a base case simulation of a characteristic patient with drug-resistant epilepsy using clinical parameters obtained from systematic reviews of invasive monitoring available in the literature. The main outcome measure was the probability of a positive outcome after invasive monitoring, which was defined as improvement in seizures without a complication. Cost-effectiveness was measured using an incremental cost-effectiveness ratio (ICER). RESULTS: Invasive monitoring with sEEG had an increased cost of $274 and increased probability of effectiveness of 0.02 compared with SDEs, yielding an ICER of $12,630 per positive outcome obtained. Sensitivity analyses varied parameters widely and revealed consistent model results across the range of clinical parameters reported in the literature. One-way sensitivity analyses revealed that invasive monitoring strategy costs were the most influential parameter for model outcome. CONCLUSIONS: In this analysis, based on available observational data and estimates of complication costs, invasive monitoring with either SDEs or sEEG was nearly equivalent in terms of cost-effectiveness.

Responsive neurostimulation for pediatric patients with drug-resistant epilepsy: a case series and review of the literature.

OBJECTIVE: Responsive neurostimulation (RNS) is a promising treatment for pediatric patients with drug-resistant epilepsy for whom resective surgery is not an option. The relative indications and risk for pediatric patients undergoing RNS therapy require further investigation. Here, the authors report their experience with RNS implantation and therapy in pediatric patients. METHODS: The authors performed a retrospective chart review to identify patients implanted with RNS depth or strip electrodes for the treatment of drug-resistant epilepsy at their institution between 2020 and 2022. Patient demographics, surgical variables, and patient seizure outcomes (Engel class and International League Against Epilepsy [ILAE] reporting) were evaluated. RESULTS: The authors identified 20 pediatric patients ranging in age from 8 to 21 years (mean 15 [SD 4] years), who underwent RNS implantation, including depth electrodes (n = 15), strip electrodes (n = 2), or both (n = 3). Patient seizure semiology, onset, and implantation strategy were heterogeneous, including bilateral centromedian nucleus (n = 5), mesial temporal lobe (n = 4), motor cortex or supplementary motor area (n = 7), or within an extratemporal epileptogenic zone (n = 4). There were no acute complications of RNS implantation (hemorrhage or stroke) or device malfunctions. One patient required rehospitalization for postoperative infection. At the longest follow-up (mean 10 [SD 7] months), 13% patients had Engel class IIB, 38% had Engel class IIIA, 6% had Engel class IIIB, 19% had Engel class IVA, 19% had Engel class IVB, and 6% had Engel class IVC outcomes. Using ILAE metrics, 6% were ILAE class 3, 25% were ILAE class 4, and 69% were ILAE class 5. CONCLUSIONS: This case series supports current literature suggesting that RNS is a safe and potentially effective surgical intervention for pediatric patients with drug-resistant epilepsy. The authors report comparable rates of serious adverse events to current RNS literature in pediatric and adult populations. Seizure outcomes may continue to improve with follow-up as stimulation strategy is refined and the chronic neuromodulatory effect evolves, as previously described in patients with RNS. Further large-scale, multicenter case series of RNS in pediatric patients with drug-resistant epilepsy are required to determine long-term pediatric safety and effectiveness.

Neural responses in human superior temporal cortex support coding of voice representations.

The ability to recognize abstract features of voice during auditory perception is an intricate feat of human audition. For the listener, this occurs in near-automatic fashion to seamlessly extract complex cues from a highly variable auditory signal. Voice perception depends on specialized regions of auditory cortex, including superior temporal gyrus (STG) and superior temporal sulcus (STS). However, the nature of voice encoding at the cortical level remains poorly understood. We leverage intracerebral recordings across human auditory cortex during presentation of voice and nonvoice acoustic stimuli to examine voice encoding at the cortical level in 8 patient-participants undergoing epilepsy surgery evaluation. We show that voice selectivity increases along the auditory hierarchy from supratemporal plane (STP) to the STG and STS. Results show accurate decoding of vocalizations from human auditory cortical activity even in the complete absence of linguistic content. These findings show an early, less-selective temporal window of neural activity in the STG and STS followed by a sustained, strongly voice-selective window. Encoding models demonstrate divergence in the encoding of acoustic features along the auditory hierarchy, wherein STG/STS responses are best explained by voice category and acoustics, as opposed to acoustic features of voice stimuli alone. This is in contrast to neural activity recorded from STP, in which responses were accounted for by acoustic features. These findings support a model of voice perception that engages categorical encoding mechanisms within STG and STS to facilitate feature extraction.

Quantitative Sodium (23Na) MRI in Pediatric Gliomas: Initial Experience.

Background: 23Na MRI correlates with tumor proliferation, and studies in pediatric patients are lacking. The purpose of the study: (1) to compare total sodium concentration (TSC) between pediatric glioma and non-neoplastic brain tissue using 23Na MRI; (2) compare tissue conspicuity of bound sodium concentration (BSC) using 23Na MRI dual echo relative to TSC imaging. Methods: TSC was measured in: (1) non-neoplastic brain tissues and (2) three types of manually segmented gliomas (diffuse intrinsic brainstem glioma (DIPG), recurrent supratentorial low-grade glioma (LGG), and high-grade glioma (HGG)). In a subset of patients, serial changes in both TSC and BSC (dual echo 23Na MRI) were assessed. Results: Twenty-six pediatric patients with gliomas (median age of 12.0 years, range 4.9−23.3 years) were scanned with 23Na MRI. DIPG treated with RT demonstrated higher TSC values than the uninvolved infratentorial tissues (p < 0.001). Recurrent supratentorial LGG and HGG exhibited higher TSC values than the uninvolved white matter (WM) and gray matter (GM) (p < 0.002 for LGG, and p < 0.02 for HGG). The dual echo 23Na MRI suppressed the sodium signal within both CSF and necrotic foci. Conclusion: Quantitative 23Na MRI of pediatric gliomas demonstrates a range of values that are higher than non-neoplastic tissues. Dual echo 23Na MRI of BCS improves tissue conspicuity relative to TSC imaging.

Stereotactic laser interstitial thermal therapy for the treatment of pediatric drug-resistant epilepsy: indications, techniques, and safety.

BACKGROUND: MRI-guided laser interstitial thermal therapy (MRgLITT) is a promising alternative to open surgery for treatment of drug-resistant epilepsy, offering significant advantages over traditional approaches for candidate patients, including minimally invasive approach, shorter hospitalization, and decreased patient post-operative discomfort. LITT uses a stereotactically placed fiber optic laser probe to ablate tissue under real-time MR thermometry. METHODS: Retrospective chart review of intraoperative and perioperative characteristics was performed for 28 cases of MRgLITT in 25 pediatric patients, ages 4-21 years old, at our institution between 2019 and 2021. MRgLITT ablation of the mesial temporal lobe was performed in 8 cases, extratemporal epileptogenic foci in 9 cases, and for corpus callosotomy in 11 cases. RESULTS: At 1 year of follow-up, 53% of all patients experienced improvement in seizure frequency (Engel I or II) (class I: 38%, class II: 15%, class III: 17%, class IV: 31%), including 37% of MTL ablations and 80% extratemporal SOZ ablations. After MRgLITT corpus callosotomy, 71% of patients were free from atonic seizures at most recent follow-up. Median length of hospitalization was 2 days (1-3), including a median ICU stay of 1 day (1-2). CONCLUSION: This series demonstrates the safety of MRgLITT as an approach for seizure control in drug-resistant epilepsy. We provide additional evidence that MRgLITT is an effective procedure that is well-tolerated by pediatric patients and is accompanied by an acceptable rate of complications and relatively short hospital stay.

Stereotactic laser interstitial thermal therapy corpus callosotomy for the treatment of pediatric drug-resistant epilepsy.

OBJECTIVE: Corpus callosotomy is a safe and effective procedure for reducing the frequency of drop attacks. MR-guided laser interstitial thermal therapy (MRgLITT) offers a minimally invasive alternative to conventional open craniotomy for callosotomy. We hypothesized that MRgLITT callosotomy could be safely performed in pediatric patients with similar seizure control. METHODS: We present an institutional case series of 11 procedures in 10 patients for the treatment of drop attacks in drug-refractory primary generalized epilepsy. MRgLITT was used for complete callosotomy, anterior two-thirds, posterior, or ablation of residual callosal fibers following prior callosotomy (open or MRgLITT). We retrospectively reviewed clinical course, operative details, radiographic imaging, clinical outcomes, and complications. RESULTS: Operative time ranged from 4-8 hours, and median hospitalization was 2 days. No complications were encountered. Among the 7 patients with at least 3 months of follow-up, 71% experienced freedom from drop attacks at longest follow-up and 57% of cases showed improvement in their other seizure semiologies as well (Engel Class II: 28%, Class III: 28%, Class IV: 43%). SIGNIFICANCE: MR-guided LITT callosotomy is safe and effective modality in the management of pediatric patients with medically intractable epilepsy characterized by drop attacks. While this is among the largest pediatric series to date, further studies are required to delineate its safety and efficacy among such patients.

Developmental variation in regional brain iron and its relation to cognitive functions in childhood.

Non-heme iron is a vital metabolic cofactor for many core processes of brain development including myelination, dendritogenesis, and neurotransmitter synthesis, and accumulates in the brain with age. However, little is known about development-related differences in brain iron and its association with emerging cognitive abilities during formative years. In this study, we estimated brain iron via R2* relaxometry in children ages 7-16 (N = 57; 38 females) and examined its relation to age-related differences in cognitive ability. As we hypothesized, age correlated positively with iron content in the hippocampus and across subregions of the basal ganglia. The magnitude of age differences in iron content differed between regions such that the largest effects were observed in basal ganglia subregions: globus pallidus, substantia nigra, caudate nucleus, and putamen, as compared to values obtained for the hippocampus and red nucleus. We did not observe sex or hemispheric differences in iron content. Notably, greater brain iron content was associated with both faster processing speed and higher general intelligence, and shared 21.4% of the age-related improvement in processing speed and 12.5% of the improvement in general intelligence. These results suggest that non-heme iron plays a central neurobiological role in the development of critical cognitive abilities during childhood.