A survey of preferences and expectations for surgical interventions targeting atonic seizures in Lennox-Gastaut syndrome.

PURPOSE: To assess preferences and outcome expectations for vagus nerve stimulation (VNS) and corpus callosotomy (CC) surgeries in the treatment of atonic seizure in Lennox-Gastaut syndrome (LGS). METHODS: A total of 260 surveys were collected from patients are caregivers of LGS patients via Research Electronic Data Capture (REDCap). RESULTS: Respondents reported an average acceptable atonic seizure reduction rate of 55.9% following VNS and 74.7% following CC. 21.3% (n = 50) were willing to be randomized. Respondents reported low willingness for randomization and a higher seizure reduction expectation with CC. CONCLUSION: Our findings guide surgical approaches for clinicians to consider patient preference in order to design future studies comparing effectiveness between these two procedures.

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.

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.

Pediatric neuromodulation for drug-resistant epilepsy: Survey of current practices, techniques, and outcomes across US epilepsy centers.

Neuromodulation via Responsive Neurostimulation (RNS) or Deep Brain Stimulation (DBS) is an emerging treatment strategy for pediatric drug-resistant epilepsy (DRE). Knowledge gaps exist in patient selection, surgical technique, and perioperative care. Here, we use an expert survey to clarify practices. Thirty-two members of the Pediatric Epilepsy Research Consortium were surveyed using REDCap. Respondents were from 17 pediatric epilepsy centers (missing data in one): Four centers implant RNS only while 13 implant both RNS and DBS. Thirteen RNS programs commenced in or before 2020, and 10 of 12 DBS programs began thereafter. The busiest six centers implant 6-10 new RNS devices per year; all DBS programs implant <5 annually. The youngest RNS patient was 3 years old. Most centers (11/12) utilize MP2RAGE and/or FGATIR sequences for planning. Centromedian thalamic nuclei were the unanimous target for Lennox-Gastaut syndrome. Surgeon exposure to neuromodulation occurred mostly in clinical practice (14/17). Clinically significant hemorrhage (n = 2) or infection (n = 3) were rare. Meaningful seizure reduction (>50%) was reported by 81% (13/16) of centers. RNS and DBS are rapidly evolving treatment modalities for safe and effective treatment of pediatric DRE. There is increasing interest in multicenter collaboration to gain knowledge and facilitate dialogue. PLAIN LANGUAGE SUMMARY: We surveyed 32 pediatric epilepsy centers in USA to highlight current practices of intracranial neuromodulation. Of the 17 that replied, we found that most centers are implanting thalamic targets in pediatric drug-resistant epilepsy using the RNS device. DBS device is starting to be used in pediatric epilepsy, especially after 2020. Different strategies for target identification are enumerated. This study serves as a starting point for future collaborative research.

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.

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.

Protracted neuronal recruitment in the temporal lobes of young children.

The temporal lobe of the human brain contains the entorhinal cortex (EC). This region of the brain is a highly interconnected integrative hub for sensory and spatial information; it also has a key role in episodic memory formation and is the main source of cortical hippocampal inputs1-4. The human EC continues to develop during childhood5, but neurogenesis and neuronal migration to the EC are widely considered to be complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions, with a large tangential stream persisting until the age of around one year and radial dispersal continuing until around two to three years of age. By contrast, we found no equivalent postnatal migration in rhesus macaques (Macaca mulatta). Immunostaining and single-nucleus RNA sequencing of ganglionic eminence germinal zones, the EC stream and the postnatal EC revealed that most migrating cells in the EC stream are derived from the caudal ganglionic eminence and become LAMP5+RELN+ inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life, when children are actively interacting with their environment. The EC is one of the first regions of the brain to be affected in Alzheimer's disease, and previous work has linked cognitive decline to the loss of LAMP5+RELN+ cells6,7. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood.

An ERK5-PFKFB3 axis regulates glycolysis and represents a therapeutic vulnerability in pediatric diffuse midline glioma.

Metabolic reprogramming in pediatric diffuse midline glioma is driven by gene expression changes induced by the hallmark histone mutation H3K27M, which results in aberrantly permissive activation of oncogenic signaling pathways. Previous studies of diffuse midline glioma with altered H3K27 (DMG-H3K27a) have shown that the RAS pathway, specifically through its downstream kinase, extracellular-signal-related kinase 5 (ERK5), is critical for tumor growth. Further downstream effectors of ERK5 and their role in DMG-H3K27a metabolic reprogramming have not been explored. We establish that ERK5 is a critical regulator of cell proliferation and glycolysis in DMG-H3K27a. We demonstrate that ERK5 mediates glycolysis through activation of transcription factor MEF2A, which subsequently modulates expression of glycolytic enzyme PFKFB3. We show that in vitro and mouse models of DMG-H3K27a are sensitive to the loss of PFKFB3. Multi-targeted drug therapy against the ERK5-PFKFB3 axis, such as with small-molecule inhibitors, may represent a promising therapeutic approach in patients with pediatric diffuse midline glioma.

Socioeconomic status and healthcare utilization disparities among children with epilepsy in the United States: Results from a nationally representative sample.

Epilepsy affects 1% of the US population. Healthcare disparities are well-studied among adults with epilepsy but less so among children. We examined whether children with epilepsy (1) have lower income than or (2) utilize the emergency department (ED) differently from children without epilepsy, and (3) if income moderates ED utilization. Data from the 2016-2019 National Survey of Children's Health were used to identify children with active "epilepsy or seizure disorder". Children with versus without epilepsy were compared. Income and ED visits were modeled with logistic and Poisson regressions. This analysis included 131,326 children; 835 were diagnosed with epilepsy. Estimated population prevalence of epilepsy was 0.6%. Children from higher-income-households were less likely to have epilepsy (aOR: 0.7). Children with epilepsy were more likely to visit EDs (aOR = 10.2), see healthcare professionals (aOR: 2.7), and receive care from specialists (aOR: 10.3). Income moderated the relationship between having epilepsy and ED visits. 7.7% of children with epilepsy did not receive needed healthcare. Some barriers were acquiring appointments (aOR: 3.9) and transportation (aOR: 4.7). In conclusion, children with epilepsy were more likely than children without epilepsy to live in lower-income-households, visit EDs, see healthcare professionals, and not receive needed healthcare. Barrier-specific policy interventions may improve medical access for children with epilepsy.

Patterns in Follow-Up Imaging Usage for Pediatric Patients with Whiplash-Associated Disorder.

BACKGROUND: A clinical concern exists that pediatric patients with whiplash-associated disorder (WAD) might have missed structural injuries or, alternatively, subsequently develop structural injuries over time, despite initially negative imaging findings. The primary objective of this study is to assess follow-up imaging usage for pediatric patients presenting with WAD. METHODS: A retrospective review of 444 pediatric patients presenting to a level 1 pediatric trauma hospital from January 1, 2010 to December 31, 2019 was performed. Imaging was reviewed at the initial encounter and the 3- and 6-month follow-up appointments. RESULTS: At the initial evaluation, children aged <6 years were more likely to receive radiographs (P = 0.007) and magnetic resonance imaging (P = 0.048) than were children aged 6-11 and 12-18 years. At the 3- and 6-month follow-up appointments, persistent neck pain was rare, representing <15% of patients at either time. Regardless of pain persistence, 80.2% of patients seen at the 3-month follow-up and 100% of patients at the 6-month follow-up underwent additional imaging studies. At the 3-month follow-up, children with persistent neck pain were more likely to undergo magnetic resonance imaging than were patients without persistent pain (P < 0.001). Also, patients with persistent neck pain were also more likely to not undergo any imaging evaluation (P = 0.002). Follow-up imaging studies did not reveal new structural injuries at either time point. CONCLUSIONS: Follow-up imaging for pediatric patients with low-grade WAD did not identify new structural pathology-in patients with or without persistent neck pain.

The Utility of Responsive Neurostimulation for the Treatment of Pediatric Drug-Resistant Epilepsy.

Drug-resistant epilepsy (DRE) has a strongly negative impact on quality of life, as well as the development of pediatric patients. Surgical treatments have evolved over time, including more invasive craniotomies for resection or disconnection. More recently, neuromodulation techniques have been employed as a less invasive option for patients. Responsive neurostimulation (RNS) is the first closed-loop technology that allows for both treatment and device data collection, which allows for an internal assessment of the efficacy of treatment. This novel technology has been approved in adults and has been used off label in pediatrics. This review seeks to describe this technology, its history, and future directions.

Utility of minimally invasive endoscopic skull base approaches for the treatment of drug-resistant mesial temporal lobe epilepsy: a review of current techniques and trends.

Mesial temporal lobe epilepsy (mTLE) is an important cause of drug-resistant epilepsy (DRE) in adults and children. Traditionally, the surgical option of choice for mTLE includes a frontotemporal craniotomy and open resection of the anterior temporal cortex and mesial temporal structures. Although this technique is effective and durable, the neuropsychological morbidity resulting from temporal neocortical resections has resulted in the investigation of alternative approaches to resect the mesial temporal structures to achieve seizure freedom while minimizing postoperative cognitive deficits. Outcomes supporting the use of selective temporal resections have resulted in alternative approaches to directly access the mesial temporal structures via endoscopic approaches whose direct trajectory to the epileptogenic zone minimizes retraction, resection, and manipulation of surrounding cortex. The authors reviewed the utility of the endoscopic transmaxillary, endoscopic endonasal, endoscopic transorbital, and endoscopic supracerebellar transtentorial approaches for the treatment of drug-resistant mesial temporal lobe epilepsy. First, a review of the literature demonstrated the anatomical feasibility of each approach, including the limits of exposure provided by each trajectory. Next, clinical data assessing the safety and effectiveness of these techniques in the treatment of DRE were analyzed. An outline of the surgical techniques is provided to highlight the technical nuances of each approach. The direct access to mesial temporal structures and avoidance of lateral temporal manipulation makes endoscopic approaches promising alternatives to traditional methods for the treatment of DRE arising from the temporal pole and mesial temporal lobe. A dearth of literature outlining clinical outcomes, a need for qualified cosurgeons, and a lack of experience with endoscopic approaches remain major barriers to widespread application of the aforementioned techniques. Future studies are warranted to define the utility of these approaches moving forward.

Development of a clinical model to predict vagus nerve stimulation response in pediatric patients with drug-resistant epilepsy.

OBJECTIVE: Epilepsy impacts 470,000 children in the United States. For patients with drug-resistant epilepsy (DRE) and unresectable seizure foci, vagus nerve stimulation (VNS) is a treatment option. Predicting response to VNS has been historically challenging. The objective of this study was to create a clinical VNS prediction tool for use in an outpatient setting. METHODS: The authors performed an 11-year retrospective cohort analysis with 1-year follow-up. Patients < 21 years of age with DRE who underwent VNS (n = 365) were included. Logistic regressions were performed to assess clinical factors associated with VNS response (≥ 50% seizure frequency reduction after 1 year); 70% and 30% of the sample were used to train and validate the multivariable model, respectively. A prediction score was subsequently developed. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS: Variables associated with VNS response were < 4-year epilepsy duration before VNS (p = 0.008) and focal motor seizures (p = 0.037). The variables included in the clinical prediction score were epilepsy duration before VNS, age at seizure onset, number of pre-VNS antiseizure medications, if VNS was the patient's first therapeutic epilepsy surgery, and predominant seizure semiology. The final AUCs were 0.7013 for the "fitted" sample and 0.6159 for the "validation" sample. CONCLUSIONS: The authors developed a clinical model to predict VNS response in a large sample of pediatric patients treated with VNS. Despite the large sample size, clinical variables alone were not able to accurately predict VNS response. This score may be useful after further validation, although its predictive ability underscores the need for more robust biomarkers to predict treatment response.

Investigation of the effectiveness of vagus nerve stimulation for pediatric drug-resistant epilepsies secondary to nonaccidental trauma.

PURPOSE: Epilepsy following non-accidental trauma (NAT) occurs in 18% of pediatric patients. About 33% of patients with epilepsy develop drug-resistant epilepsy. For these patients, vagus nerve stimulation (VNS) is a palliative treatment option. We aimed to investigate the effectiveness of VNS among pediatric NAT-related epilepsy patients compared to those with non-NAT-related epilepsy. METHODS: We performed an 11-year retrospective analysis of VNS implantations for drug-resistant epilepsy at UPMC Children's Hospital of Pittsburgh. Patients were split into two groups: NAT vs. non-NAT. The primary outcome was the attainment of ≥ 50% seizure frequency reduction at 1-year post-VNS implantation. Fisher's exact tests and Wilcoxon rank-sum tests were used to compare groups. Significance was assessed at the alpha = 0.05 level. RESULTS: This analysis included data from 370 pediatric VNS patients, of whom 9 had NAT-related epilepsy. NAT patients had a significantly younger age of epilepsy onset than non-NAT patients (0.3 years vs. 3.3 years). Otherwise, there were no statistically significant baseline differences between groups, including patient sex and quantity of antiseizure medications pre-VNS. Overall, 71% of NAT patients experienced ≥ 50% seizure frequency reduction compared to 48% of non-NAT patients (p = 0.269). CONCLUSION: VNS may allow a higher proportion of pediatric patients with NAT-related epilepsy to achieve ≥ 50% seizure frequency reduction compared to other epilepsy etiologies. While the results of this study were not statistically significant, the effect size was large. Our results underscore the need for larger, multi-center studies to validate the effectiveness of VNS for this patient population.

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.

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.