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.

Intracranial Mapping of Response Latencies and Task Effects for Spoken Syllable Processing in the Human Brain.

Prior lesion, noninvasive-imaging, and intracranial-electroencephalography (iEEG) studies have documented hierarchical, parallel, and distributed characteristics of human speech processing. Yet, there have not been direct, intracranial observations of the latency with which regions outside the temporal lobe respond to speech, or how these responses are impacted by task demands. We leveraged human intracranial recordings via stereo-EEG to measure responses from diverse forebrain sites during (i) passive listening to /bi/ and /pi/ syllables, and (ii) active listening requiring /bi/-versus-/pi/ categorization. We find that neural response latency increases from a few tens of ms in Heschl's gyrus (HG) to several tens of ms in superior temporal gyrus (STG), superior temporal sulcus (STS), and early parietal areas, and hundreds of ms in later parietal areas, insula, frontal cortex, hippocampus, and amygdala. These data also suggest parallel flow of speech information dorsally and ventrally, from HG to parietal areas and from HG to STG and STS, respectively. Latency data also reveal areas in parietal cortex, frontal cortex, hippocampus, and amygdala that are not responsive to the stimuli during passive listening but are responsive during categorization. Furthermore, multiple regions-spanning auditory, parietal, frontal, and insular cortices, and hippocampus and amygdala-show greater neural response amplitudes during active versus passive listening (a task-related effect). Overall, these results are consistent with hierarchical processing of speech at a macro level and parallel streams of information flow in temporal and parietal regions. These data also reveal regions where the speech code is stimulus-faithful and those that encode task-relevant representations.

Unveiling the development of human voice perception: Neurobiological mechanisms and pathophysiology.

The human voice is a critical stimulus for the auditory system that promotes social connection, informs the listener about identity and emotion, and acts as the carrier for spoken language. Research on voice processing in adults has informed our understanding of the unique status of the human voice in the mature auditory cortex and provided potential explanations for mechanisms that underly voice selectivity and identity processing. There is evidence that voice perception undergoes developmental change starting in infancy and extending through early adolescence. While even young infants recognize the voice of their mother, there is an apparent protracted course of development to reach adult-like selectivity for human voice over other sound categories and recognition of other talkers by voice. Gaps in the literature do not allow for an exact mapping of this trajectory or an adequate description of how voice processing and its neural underpinnings abilities evolve. This review provides a comprehensive account of developmental voice processing research published to date and discusses how this evidence fits with and contributes to current theoretical models proposed in the adult literature. We discuss how factors such as cognitive development, neural plasticity, perceptual narrowing, and language acquisition may contribute to the development of voice processing and its investigation in children. We also review evidence of voice processing abilities in premature birth, autism spectrum disorder, and phonagnosia to examine where and how deviations from the typical trajectory of development may manifest.

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.

Functional outcomes of pediatric hemispherotomy: Impairment, activity, and medical service utilization.

OBJECTIVE: The purpose of this study was to describe the functional outcomes of hemispherotomy in a pediatric cohort, including impairments, activity limitations, utilization of therapies and medical specialist services, and subsequent surgical intervention. METHODS: We conducted a retrospective review of patients who underwent hemispherotomy at UPMC Children's Hospital of Pittsburgh from 2001 to 2021. Data on impairments, activity limitations in mobility, self-care, and communication, and use of re/habilitative therapies and medical specialist services were collected pre-operatively and at 1, 5, 10, and 15 years postoperatively. Seizure outcomes were reported via Engel classification at the longest follow-up interval and subsequent surgical procedures were documented through the latest follow-up interval. RESULTS: A total of 28 patients who underwent hemispherotomy were assessed prior to surgery, 26 at 1 year post-op, 13 at 5 years, 9 at 10 years, and 5 at 15 years. Seizure outcomes at the longest follow-up interval showed that 84.6% of patients were seizure-free. Assessment of impairments to body structure & function from baseline to 1-year post-op revealed increased impairment in 73% of patients, while most patients saw no change in impairment at 5 years (69%), 10 years (100%), and 15 years (100%) post-op compared to the previous time point. Muscle tone abnormalities (100%), hemiparesis (92%), and visual field deficits (85%) were the most frequently observed impairments in the first year following surgery. Most patients saw no change in developmental or cognitive-affective impairments at 1 (65%), 5 (85%), 10 (89%), and 15 years (80%) post-op compared to the previous time point. The only qualitative reports of decreased ability occurred in 2/26 patients whose medical records indicated decreased mobility at the 1-year mark. All further qualitative reports of ability in mobility, self-care, and communication domains indicated increases or no change in ability for all patients at each of the subsequent follow-up intervals. Exploration of the utilization of re/habilitative therapy services shows that 84% of patients received at least one therapy service at baseline, 100% at1 year, 92% at 5 years, 100% at 10 years, and 80% at 15 years post-op. Patients were followed, on average (m), by multiple medical specialist services at baseline (m = 2.58) as well as the 1- (m = 1.70), 5- (m = 2.15), 10- (m = 3.00) and 15-year (m = 3.40) follow-up intervals. Following hemispherotomy, 15 (53.6%) patients required an average of 2.21 additional surgeries. Most often required was orthopedic surgical intervention (n = 16 procedures), followed by shunt placement (n = 7) and revision (n = 14) targeting hydrocephalus. SIGNIFICANCE: This retrospective study demonstrates expected increases in impairments such as hemiparesis and visual field deficits (i.e., homonymous hemianopia) in the context of increased activity and favorable seizure outcomes for 28 pediatric patients who underwent hemispherotomy for drug-resistant epilepsy. Most patients required rehabilitative therapies prior to surgery and continued to require these services post-operatively. Reported baseline functional status, the persistence of impairments following surgery, and comorbidities among this cohort underscore the medical complexity of this patient population and the importance of multidisciplinary care both pre-and post-operatively.

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.

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.

Subdural electrodes versus stereoelectroencephalography for pediatric epileptogenic zone localization: a retrospective cohort study.

OBJECTIVE: The objective of this study was to compare the relative safety and effectiveness of invasive monitoring with subdural electrodes (SDEs) and stereoelectroencephalography (sEEG) in pediatric patients with drug-resistant epilepsy. METHODS: A retrospective cohort study was performed in 176 patients who underwent invasive monitoring evaluations at UPMC Children's Hospital of Pittsburgh between January 2000 and September 2021. To examine differences between SDE and sEEG groups, independent-samples t-tests for continuous variables and Pearson chi-square tests for categorical variables were performed. A p value < 0.1 was considered statistically significant. RESULTS: There were 134 patients (76%) in the SDE group and 42 (24%) in the sEEG group. There was a difference in the proportion with complications (17.9% in the SDE group vs 7.1% in the sEEG group, p = 0.09) and resection (75.4% SDE vs 21.4% sEEG, p < 0.01) between SDE and sEEG patients. However, there was no observable difference in the rates of postresection seizure freedom at 1-year clinical follow-up (60.2% SDE vs 75.0% sEEG, p = 0.55). CONCLUSIONS: These findings reveal a difference in rates of surgical complications and resection between SDEs and sEEG. Larger prospective, multi-institutional pediatric comparative effectiveness studies may further explore these associations.

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.