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Posterior quadrant epilepsy surgery, involving the occipital lobe, parietal lobe, or the posterior border of the temporal lobe, accounts for a small percentage of focal resections for medically refractory epilepsy. Prior studies investigating seizure control from posterior quadrant epilepsy surgery are limited. In this study, a retrospective database of patients undergoing surgery for left sided posterior cortex epilepsy at a single large level 4 epilepsy center was analyzed between August 2008 to April 2021 in order to characterize seizure control outcomes. Nine patients presented with epileptogenic foci in the left posterior cortex with a malformation of cortical development deemed as the etiology of seizures for all but one patient. Absolute seizure freedom (Engel I) was achieved in 4 of 9 patients, with the remaining 5 patients achieving an improvement in the frequency of seizures (Engel II/III). Complete resection of the anatomic and physiologic abnormalities was performed in 3 of 4 patients with Engel 1 outcomes and 1 of 5 patients with Class II/III outcomes. Five patients developed new right sided visual field defects, all of which were expected based on the sub-lobar, occipital localization and were viewed as acceptable by the patients and did not interfere with activities of daily living. Overall, our study demonstrates the potential for surgical resection to yield excellent seizure-control outcomes with anticipated, tolerable neurological deficits. This information is important for patients with disabling seizures who may not benefit sufficiently from palliative procedures.
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In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate fine neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the cortical interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic neurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP) and manipulate (opto- or chemo-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.
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OBJECTIVE: To (a) examine whether the effect of the Choosing Wisely consumer questions on question-asking and shared decision-making (SDM) outcomes differs based on individuals' health literacy and (b) explore the relationship between health literacy, question-asking and other decision-making outcomes in the context of low value care. METHODS: Preplanned analysis of randomised trial data comparing: the Choosing Wisely questions, a SDM video, both interventions or control (no intervention). Randomisation was stratified by participant health literacy ('adequate' vs 'limited'), as assessed by the Newest Vital Sign. MAIN OUTCOME MEASURES: Self-efficacy to ask questions and be involved in decision-making, and intention to engage in SDM. PARTICIPANTS: 1439 Australian adults, recruited online. RESULTS: The effects of the Choosing Wisely questions and SDM video did not differ based on participants' health literacy for most primary or secondary outcomes (all two-way and three-way interactions p>0.05). Compared with individuals with 'adequate' health literacy, those with 'limited' health literacy had lower knowledge of SDM rights (82.1% vs 89.0%; 95% CI: 3.9% to 9.8%, p<0.001) and less positive attitudes towards SDM (48.3% vs 58.1%; 95% CI: 4.7% to 15.0%, p=0.0002). They were also more likely to indicate they would follow low-value treatment plans without further questioning (7.46/10 vs 6.94/10; 95% CI: 0.33 to 0.72, p<0.001) and generated fewer questions to ask a healthcare provider which aligned with the Choosing Wisely questions (χ2 (1)=73.79, p<.001). On average, 67.7% of participants with 'limited' health literacy indicated that they would use video interventions again compared with 55.7% of individuals with 'adequate' health literacy. CONCLUSION: Adults with limited health literacy continue to have lower scores on decision-making outcomes in the context of low value care. Ongoing work is needed to develop and test different intervention formats that support people with lower health literacy to engage in question asking and SDM.
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Purpose: The aim of this study was to examine demographic and surgical factors that influence patient-reported knee function in patients who undergo anterior crucial ligament reconstruction (ACLR) with concurrent bucket-handle meniscal tear (BHMT) procedures. We hypothesized that repair of BHMT in the setting of concomitant ACLR and shorter time from injury to surgery would lead to improved patient-reported outcomes. Methods: Forty-one patients (mean age: 28.0 ± 9.8 years, 72% male) with BHMT at the time of ACLR completed the International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) via online survey at an average of 15.2 months postop. Patient demographics and surgical characteristics, including time from injury to surgery, were compared between repair (n = 22) and meniscectomy (n = 19) groups using one-way analysis of variances; distributions of sex, graft source, BHMT compartment and zone were compared between groups using χ 2 tests. The association between IKDC-SKF score, demographics and surgical characteristics was evaluated using multivariable linear regression. A priori alpha level was p < 0.05. Results: Meniscal repair and meniscectomy groups differed based on graft source and BHMT zone but not IKDC-SKF score (p = 0.085). Patients undergoing ACLR with autograft (p = 0.003) and with red-red zone BHMT (p < 0.001) more often underwent meniscal repair. The regression model demonstrated longer time from injury to surgery (p = 0.049), red-red tear zone (p = 0.04) and meniscectomy (p = 0.008); these were predictive of poorer IKDC-SKF scores. Conclusion: BHMT repair was more likely performed in ACL autograft and on red-red zone tears. Longer time from injury to surgery is an indicator of poorer IKDC-SKF score, as this may increase the risk of concomitant pathologies. White-white zone BHMTs are associated with better IKDC-SKF scores than red-red zone BHMTs, which may be due to the smaller volume of tissue removed during meniscectomy of white-white zone tears and the avoidance of iatrogenic complications of meniscal repair. Level of Evidence: Level III, therapeutic study.
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Antebrazo , Colgajos Tisulares Libres , Calidad de Vida , Humanos , Colgajos Tisulares Libres/trasplante , Colgajos Tisulares Libres/efectos adversos , Antebrazo/cirugía , Cúbito/cirugía , Radio (Anatomía)/cirugía , Sitio Donante de Trasplante , Procedimientos de Cirugía Plástica/métodos , Procedimientos de Cirugía Plástica/efectos adversosAsunto(s)
Esclerosis Amiotrófica Lateral , Trastornos de la Articulación , Interfaces Cerebro-Computador , Humanos , Comunicación , Trastornos de la Articulación/etiología , Trastornos de la Articulación/rehabilitación , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/rehabilitaciónRESUMEN
Seizures in people with epilepsy were long thought to occur at random, but recent methods for seizure forecasting enable estimation of the likelihood of seizure occurrence over short horizons. These methods rely on days-long cyclical patterns of brain electrical activity and other physiological variables that determine seizure likelihood and that require measurement through long-term, multimodal recordings. In this retrospective cohort study of 15 adults with bitemporal epilepsy who had a device that provides chronic intracranial recordings, functional connectivity of hippocampal networks fluctuated in multiday cycles with patterns that mirrored cycles of seizure likelihood. A functional connectivity biomarker of seizure likelihood derived from 90-s recordings of background hippocampal activity generalized across individuals and forecasted 24-h seizure likelihood as accurately as cycle-based models requiring months-long baseline recordings. Larger, prospective studies are needed to validate this approach, but our results have the potential to make reliable seizure forecasts accessible to more people with epilepsy.
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Advances in large-scale single-unit human neurophysiology, single-cell RNA sequencing, spatial transcriptomics and long-term ex vivo tissue culture of surgically resected human brain tissue have provided an unprecedented opportunity to study human neuroscience. In this Perspective, we describe the development of these paradigms, including Neuropixels and recent brain-cell atlas efforts, and discuss how their convergence will further investigations into the cellular underpinnings of network-level activity in the human brain. Specifically, we introduce a workflow in which functionally mapped samples of human brain tissue resected during awake brain surgery can be cultured ex vivo for multi-modal cellular and functional profiling. We then explore how advances in human neuroscience will affect clinical practice, and conclude by discussing societal and ethical implications to consider. Potential findings from the field of human neuroscience will be vast, ranging from insights into human neurodiversity and evolution to providing cell-type-specific access to study and manipulate diseased circuits in pathology. This Perspective aims to provide a unifying framework for the field of human neuroscience as we welcome an exciting era for understanding the functional cytoarchitecture of the human brain.
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Encéfalo , Neurofisiología , Neurociencias , Análisis de la Célula Individual , Humanos , Encéfalo/citología , Encéfalo/fisiología , Neuropatología/métodos , Neuropatología/tendencias , Neurofisiología/métodos , Neurofisiología/tendencias , Neurociencias/métodos , Neurociencias/tendencias , Análisis de la Célula Individual/métodos , Análisis de la Célula Individual/tendencias , Análisis de Expresión Génica de una Sola Célula , Transcriptoma , Flujo de Trabajo , AnimalesRESUMEN
INTRODUCTION: Osteoradionecrosis (ORN) of the mandible is an unfortunate potential sequela of radiotherapy for head and neck cancer. In advanced cases of ORN, mandibulectomy, and free fibula flap reconstruction are required. We hypothesized that patients undergoing fibula free flap reconstruction and mandibulectomy for ORN pose unique challenges and experience more complications than patients undergoing fibula free flaps after oncologic mandibulectomy. METHODS: After IRB approval, we created a database of all free fibula flaps for mandible reconstruction from April 2005 through February 2019. Medical records were retrospectively reviewed for patient and surgical characteristics and postoperative outcomes. RESULTS: Four-hundred seventy-nine patients met the inclusion criteria (168 ORN vs. 311 non-ORN patients). Propensity-matching was performed based on age, BMI, smoking status, preoperative chemotherapy, and virtual surgery planning use, which yielded 159 patients in each group. ORN patients received more double-skin-island fibula flaps than non-OR patients (20.8% vs. 5.7%, p < 0.001). Recipient artery other than the facial artery was utilized more commonly in ORN patients (42.1% vs. 17.0%, p < 0.001). In the unmatched cohort, ORN patients had higher rates of delayed wound healing (26.2% vs. 16.8%, p = 0.01) and surgical site infections (21.4% vs. 13.2%, p = 0.02). Rates of flap loss, return to the operating room, hematoma, operative time, and length of stay were similar between the groups. On logistic regression analysis, osteoradionecrosis was an independent risk factor for delayed wound healing. CONCLUSION: Based on these data, mandibular reconstruction with fibula flaps for osteoradionecrosis appears more complicated than mandible reconstruction following de novo cancer resection. Surgeons should anticipate employing two skin islands for intraoral and extraoral resurfacing, utilizing unconventional recipient vessels, and managing the delayed wound healing that ensues more commonly than non-ORN patients.
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Background: Lower socioeconomic status and public insurance lead to a longer delay to surgery and a higher likelihood of concomitant pathology before undergoing anterior cruciate ligament reconstruction (ACLR). However, few studies have examined the influence of community deprivation on ACLR timing and outcomes. Purpose/Hypothesis: The primary aim of this study was to define the effect of the area deprivation index (ADI) and insurance classification on access to orthopaedic care after an ACL rupture, and the secondary aim was to determine whether these variables were associated with a second ACL injury after primary ACLR. It was hypothesized that patients with a greater national ADI percentile and Medicaid insurance would experience longer delays to care and an increased risk of reinjury after ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective study was performed to evaluate patients undergoing primary ACLR between 2016 and 2019. The national ADI percentile was obtained utilizing the Neighborhood Atlas website. The relationship between national ADI percentile and care characteristics (eg, time to specialized care) was investigated using the Spearman rho correlation coefficient (r). The association between patient and care characteristics and second ACL injury after the index procedure (ie, graft rerupture or contralateral ACL rupture) was investigated using binary logistic regression. Results: A total of 197 patients met the inclusion criteria. Longer times from injury to surgery (r = 0.238; P < .001) and from specialized care to surgery (r = 0.217; P = .002) were associated with a greater national ADI percentile. The second injury group reported significantly greater national ADI (P = .026) and included a greater percentage of patients with Medicaid insurance (31.3%) compared with the no second injury group. Patients experienced 5.1% greater odds of a second ACL injury for each additional month between evaluation and surgery. Conclusion: Greater national ADI percentile and Medicaid insurance status were associated with adverse ACLR timing and outcomes. Patients with a greater national ADI percentile took significantly longer to obtain surgery after ACL injury. Those who sustained a second ACL injury after ACLR had an overall higher mean national ADI percentile and included a greater proportion of patients with Medicaid compared with those who did not sustain a second ACL injury. Future studies should critically investigate the underlying factors of these associations to reach equity in orthopaedic care.
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Loss of speech after paralysis is devastating, but circumventing motor-pathway injury by directly decoding speech from intact cortical activity has the potential to restore natural communication and self-expression. Recent discoveries have defined how key features of speech production are facilitated by the coordinated activity of vocal-tract articulatory and motor-planning cortical representations. In this Review, we highlight such progress and how it has led to successful speech decoding, first in individuals implanted with intracranial electrodes for clinical epilepsy monitoring and subsequently in individuals with paralysis as part of early feasibility clinical trials to restore speech. We discuss high-spatiotemporal-resolution neural interfaces and the adaptation of state-of-the-art speech computational algorithms that have driven rapid and substantial progress in decoding neural activity into text, audible speech, and facial movements. Although restoring natural speech is a long-term goal, speech neuroprostheses already have performance levels that surpass communication rates offered by current assistive-communication technology. Given this accelerated rate of progress in the field, we propose key evaluation metrics for speed and accuracy, among others, to help standardize across studies. We finish by highlighting several directions to more fully explore the multidimensional feature space of speech and language, which will continue to accelerate progress towards a clinically viable speech neuroprosthesis.
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Interfaces Cerebro-Computador , Habla , Humanos , Habla/fisiología , Prótesis Neurales , AnimalesAsunto(s)
Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Reoperación , Humanos , Colgajos Tisulares Libres/trasplante , Procedimientos de Cirugía Plástica/métodos , Reoperación/métodos , Factores de Tiempo , Neoplasias de Cabeza y Cuello/cirugía , Insuficiencia del Tratamiento , Cuello/cirugíaRESUMEN
Advancements in decoding speech from brain activity have focused on decoding a single language. Hence, the extent to which bilingual speech production relies on unique or shared cortical activity across languages has remained unclear. Here, we leveraged electrocorticography, along with deep-learning and statistical natural-language models of English and Spanish, to record and decode activity from speech-motor cortex of a Spanish-English bilingual with vocal-tract and limb paralysis into sentences in either language. This was achieved without requiring the participant to manually specify the target language. Decoding models relied on shared vocal-tract articulatory representations across languages, which allowed us to build a syllable classifier that generalized across a shared set of English and Spanish syllables. Transfer learning expedited training of the bilingual decoder by enabling neural data recorded in one language to improve decoding in the other language. Overall, our findings suggest shared cortical articulatory representations that persist after paralysis and enable the decoding of multiple languages without the need to train separate language-specific decoders.
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Electrocorticografía , Multilingüismo , Habla , Humanos , Habla/fisiología , Electrocorticografía/métodos , Corteza Motora/fisiología , Masculino , Interfaces Cerebro-Computador , Lenguaje , Aprendizaje Profundo , Prótesis NeuralesRESUMEN
The field of microsurgical head and neck reconstruction has witnessed tremendous advancements in recent years. While the historic goals of reconstruction were simply to maximize flap survival, optimizing both aesthetic and functional outcomes has now become the priority. With an increased understanding of perforator anatomy, improved technology in instruments and microscopes, and high flap success rates, the reconstructive microsurgeon can push the envelope in harvesting and designing the ideal flap to aid patients following tumor extirpation. Furthermore, with improvements in cancer treatment leading to improved patient survival and prognosis, it becomes increasingly important to have a broader repertoire of donor sites. The present review aims to provide a review of newly emerging soft tissue flap options in head and neck reconstruction. While certainly a number of bony flap options also exist, the present review will focus on soft tissue flaps that can be harvested reliably from a variety of alternate donor sites. From the upper extremity, the ulnar forearm as well as the lateral arm, and from the lower extremity, the profunda artery perforator, medial sural artery perforator, and superficial circumflex iliac perforator flaps will be discussed, and we will provide details to aid reconstructive microsurgeons in incorporating these alternative flaps into their armamentarium.
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Models of speech perception are centered around a hierarchy in which auditory representations in the thalamus propagate to primary auditory cortex, then to the lateral temporal cortex, and finally through dorsal and ventral pathways to sites in the frontal lobe. However, evidence for short latency speech responses and low-level spectrotemporal representations in frontal cortex raises the question of whether speech-evoked activity in frontal cortex strictly reflects downstream processing from lateral temporal cortex or whether there are direct parallel pathways from the thalamus or primary auditory cortex to the frontal lobe that supplement the traditional hierarchical architecture. Here, we used high-density direct cortical recordings, high-resolution diffusion tractography, and hemodynamic functional connectivity to evaluate for evidence of direct parallel inputs to frontal cortex from low-level areas. We found that neural populations in the frontal lobe show speech-evoked responses that are synchronous or occur earlier than responses in the lateral temporal cortex. These short latency frontal lobe neural populations encode spectrotemporal speech content indistinguishable from spectrotemporal encoding patterns observed in the lateral temporal lobe, suggesting parallel auditory speech representations reaching temporal and frontal cortex simultaneously. This is further supported by white matter tractography and functional connectivity patterns that connect the auditory nucleus of the thalamus (medial geniculate body) and the primary auditory cortex to the frontal lobe. Together, these results support the existence of a robust pathway of parallel inputs from low-level auditory areas to frontal lobe targets and illustrate long-range parallel architecture that works alongside the classical hierarchical speech network model.
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OBJECTIVE: Brain areas implicated in semantic memory can be damaged in patients with epilepsy (PWE). However, it is challenging to delineate semantic processing deficits from acoustic, linguistic, and other verbal aspects in current neuropsychological assessments. We developed a new Visual-based Semantic Association Task (ViSAT) to evaluate nonverbal semantic processing in PWE. METHOD: The ViSAT was adapted from similar predecessors (Pyramids & Palm Trees test, PPT; Camels & Cactus Test, CCT) comprised of 100 unique trials using real-life color pictures that avoid demographic, cultural, and other potential confounds. We obtained performance data from 23 PWE participants and 24 control participants (Control), along with crowdsourced normative data from 54 Amazon Mechanical Turk (Mturk) workers. RESULTS: ViSAT reached a consensus >90% in 91.3% of trials compared to 83.6% in PPT and 82.9% in CCT. A deep learning model demonstrated that visual features of the stimulus images (color, shape; i.e., non-semantic) did not influence top answer choices (p = 0.577). The PWE group had lower accuracy than the Control group (p = 0.019). PWE had longer response times than the Control group in general and this was augmented for the semantic processing (trial answer) stage (both p < 0.001). CONCLUSIONS: This study demonstrated performance impairments in PWE that may reflect dysfunction of nonverbal semantic memory circuits, such as seizure onset zones overlapping with key semantic regions (e.g., anterior temporal lobe). The ViSAT paradigm avoids confounds, is repeatable/longitudinal, captures behavioral data, and is open-source, thus we propose it as a strong alternative for clinical and research assessment of nonverbal semantic memory.
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Biomarker-driven therapeutic clinical trials require the implementation of standardized, evidence-based practices for sample collection. In diffuse glioma, phosphatidylinositol 3 (PI3)-kinase/AKT/mTOR (PI3/AKT/mTOR) signaling is an attractive therapeutic target for which window-of-opportunity clinical trials could facilitate the identification of promising new agents. Yet, the relevant preanalytic variables and optimal tumor sampling methods necessary to measure pathway activity are unknown. To address this, we used a murine model for isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) and human tumor tissue, including IDH-wildtype GBM and IDH-mutant diffuse glioma. First, we determined the impact of delayed time-to-formalin fixation, or cold ischemia time (CIT), on the quantitative assessment of cellular expression of 6 phosphoproteins that are readouts of PI3K/AK/mTOR activity (phosphorylated-proline-rich Akt substrate of 40 kDa (p-PRAS40, T246), -mechanistic target of rapamycin (p-mTOR; S2448); -AKT (p-AKT, S473); -ribosomal protein S6 (p-RPS6, S240/244 and S235/236), and -eukaryotic initiation factor 4E-binding protein 1 (p-4EBP1, T37/46). With CITs ≥ 2 hours, typical of routine clinical handling, all had reduced or altered expression with p-RPS6 (S240/244) exhibiting relatively greater stability. A similar pattern was observed using patient tumor samples from the operating room with p-4EBP1 more sensitive to delayed fixation than p-RPS6 (S240/244). Many clinical trials utilize unstained slides for biomarker evaluation. Thus, we evaluated the impact of slide storage conditions on the detection of p-RPS6 (S240/244), p-4EBP1, and p-AKT. After 5 months, storage at -80°C was required to preserve the expression of p-4EBP1 and p-AKT, whereas p-RPS6 (240/244) expression was not stable regardless of storage temperature. Biomarker heterogeneity impacts optimal tumor sampling. Quantification of p-RPS6 (240/244) expression in multiple regionally distinct human tumor samples from 8 patients revealed significant intratumoral heterogeneity. Thus, the accurate assessment of PI3K/AKT/mTOR signaling in diffuse glioma must overcome intratumoral heterogeneity and multiple preanalytic factors, including time-to-formalin fixation, slide storage conditions, and phosphoprotein of interest.
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Neoplasias Encefálicas , Glioma , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Glioma/patología , Glioma/metabolismo , Glioma/genética , Ratones , Biomarcadores de Tumor/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Modelos Animales de Enfermedad , Manejo de Especímenes/métodosRESUMEN
Anxiety is a common symptom across psychiatric disorders, but the neurophysiological underpinnings of these symptoms remain unclear. This knowledge gap has prevented the development of circuit-based treatments that can target the neural substrates underlying anxiety. Here, we conducted an electrophysiological mapping study to identify neurophysiological activity associated with self-reported state anxiety in 17 subjects implanted with intracranial electrodes for seizure localization. Participants had baseline anxiety traits ranging from minimal to severe. Subjects volunteered to participate in an anxiety induction task in which they were temporarily exposed to the threat of unpredictable shock during intracranial recordings. We found that anterior insular beta oscillatory activity was selectively elevated during epochs when unpredictable aversive stimuli were being delivered, and this enhancement in insular beta was correlated with increases in self-reported anxiety. Beta oscillatory activity within the frontoinsular region was also evoked selectively by cues-predictive of threat, but not safety cues. Anterior insular gamma responses were less selective than gamma, strongly evoked by aversive stimuli and had weaker responses to salient threat and safety cues. On longer timescales, this gamma signal also correlated with increased skin conductance, a measure of autonomic state. Lastly, we found that direct electrical stimulation of the anterior insular cortex in a subset of subjects elicited self-reported increases in anxiety that were accompanied by enhanced frontoinsular beta oscillations. Together, these findings suggest that electrophysiologic representations of anxiety- related states and behaviors exist within anterior insular cortex. The findings also suggest the potential of reducing anterior insular beta activity as a therapeutic target for refractory anxiety-spectrum disorders.