A speech planning network for interactive language use.

During conversation, people take turns speaking by rapidly responding to their partners while simultaneously avoiding interruption1,2. Such interactions display a remarkable degree of coordination, as gaps between turns are typically about 200 milliseconds3-approximately the duration of an eyeblink4. These latencies are considerably shorter than those observed in simple word-production tasks, which indicates that speakers often plan their responses while listening to their partners2. Although a distributed network of brain regions has been implicated in speech planning5-9, the neural dynamics underlying the specific preparatory processes that enable rapid turn-taking are poorly understood. Here we use intracranial electrocorticography to precisely measure neural activity as participants perform interactive tasks, and we observe a functionally and anatomically distinct class of planning-related cortical dynamics. We localize these responses to a frontotemporal circuit centred on the language-critical caudal inferior frontal cortex10 (Broca's region) and the caudal middle frontal gyrus-a region not normally implicated in speech planning11-13. Using a series of motor tasks, we then show that this planning network is more active when preparing speech as opposed to non-linguistic actions. Finally, we delineate planning-related circuitry during natural conversation that is nearly identical to the network mapped with our interactive tasks, and we find this circuit to be most active before participant speech during unconstrained turn-taking. Therefore, we have identified a speech planning network that is central to natural language generation during social interaction.

The human subthalamic nucleus transiently inhibits active attentional processes.

The subthalamic nucleus (STN) of the basal ganglia is key to the inhibitory control of movement. Consequently, it is a primary target for the neurosurgical treatment of movement disorders like Parkinson's Disease, where modulating the STN via deep-brain stimulation (DBS) can release excess inhibition of thalamo-cortical motor circuits. However, the STN is also anatomically connected to other thalamo-cortical circuits, including those underlying cognitive processes like attention. Notably, STN-DBS can also affect these processes. This suggests that the STN may also contribute to the inhibition of non-motor activity, and that STN-DBS may cause changes to this inhibition. We here tested this hypothesis in humans. We used a novel, wireless outpatient method to record intracranial local field potentials (LFP) from STN DBS implants during a visual attention task (Experiment 1, N=12). These outpatient measurements allowed the simultaneous recording of high-density EEG, which we used to derive the steady-state visual evoked potential (SSVEP), a well-established neural index of visual attentional engagement. By relating STN activity to this neural marker of attention (instead of overt behavior), we avoided possible confounds resulting from STN's motor role. We aimed to test whether the STN contributes to the momentary inhibition of the SSVEP caused by unexpected, distracting sounds. Furthermore, we causally tested this association in a second experiment, where we modulated STN via DBS across two sessions of the task, spaced at least one week apart (N=21, no sample overlap with Experiment 1). The LFP recordings in Experiment 1 showed that reductions of the SSVEP after distracting sounds were preceded by sound-related γ-frequency (>60Hz) activity in the STN. Trial-to-trial modeling further showed that this STN activity statistically mediated the sounds' suppressive effect on the SSVEP. In Experiment 2, modulating STN activity via DBS significantly reduced these sound-related SSVEP reductions. This provides causal evidence for the role of the STN in the surprise-related inhibition of attention. These findings suggest that the human STN contributes to the inhibition of attention, a non-motor process. This supports a domain-general view of the inhibitory role of the STN. Furthermore, these findings also suggest a potential mechanism underlying some of the known cognitive side-effects of STN-DBS treatment, especially on attentional processes. Finally, our newly-established outpatient LFP recording technique facilitates the testing of the role of subcortical nuclei in complex cognitive tasks, alongside recordings from the rest of the brain, and in much shorter time than perisurgical recordings.

A Pilot Study of Ex Vivo Human Prefrontal RNA Transcriptomics in Parkinson's Disease.

Parkinson's disease (PD) can dramatically change cortical neurophysiology. The molecular basis for PD-related cortical changes is unclear because gene expression data are usually derived from postmortem tissue collected at the end of a complex disease and they profoundly change in the minutes after death. Here, we studied cortical changes in tissue from the prefrontal cortex of living PD patients undergoing deep-brain stimulation implantation surgery. We examined 780 genes using the NanoString nCounter platform and found that 40 genes were differentially expressed between PD (n = 12) and essential tremor (ET; n = 9) patients. One of these 40 genes, STAT1, correlated with intraoperative 4-Hz rhythms and intraoperative performance of an oddball reaction-time task. Using a pre-designed custom panel of 780 targets, we compared these intraoperative data with those from a separate cohort of fresh-frozen tissue from the same frontal region in postmortem human PD donors (n = 6) and age-matched neurotypical controls (n = 6). This cohort revealed 279 differentially expressed genes. Fifteen of the 40 intraoperative PD-specific genes overlapped with postmortem PD-specific genes, including CALB2 and FOXP2. Transcriptomic analyses identified pathway changes in PD that had not been previously observed in postmortem cases. These molecular signatures of cortical function and dysfunction may help us better understand cognitive and neuropsychiatric aspects of PD.

Endoscopic extrasellar skull base reconstruction using bioabsorbable plates.

BACKGROUND: Many techniques have been utilized for reconstruction of the anterior skull base. Each method has advantages and disadvantages with respect to effectiveness, morbidity, strength, and cost. Rigid reconstruction may provide advantages in certain patients. OBJECTIVE: We evaluated all patients who had placement of rigid absorbable reconstruction plates in the anterior skull base in a variety of extrasellar locations and describe results and complications compared with other published techniques. METHODS: A retrospective review was conducted of consecutive patients at a tertiary referral institution who underwent endoscopic extrasellar skull base reconstruction, 2012-2019, using resorbable poly (D,L) lactic acid plates (Resorb-X Sellar Wall Plate; KLS Martin; Jacksonville, FL). Data reviewed included demographic information, indication for surgery, location and size of defect, pathology, peri-operative use of cerebrospinal fluid (CSF) diversion, postoperative complications, post-operative CSF leak, adjuvant therapy, and length of follow-up. RESULTS: Twenty-four subjects and 25 operative procedures met inclusion criteria. Mean age was 53 years (range 11-77). Average BMI was 34 kg/m2. Mean follow-up time was 30 months (range 1-78). Indications for surgery were CSF rhinorrhea (spontaneous, post-traumatic, or iatrogenic) or reconstruction after tumor resection. Four cases were revision procedures. Twenty patients had lumbar drains placed intraoperatively. Only two nasoseptal flaps and two free mucosal grafts were used. None of the patients had a postoperative CSF leak. There was no mortality or morbidity related to the skull base reconstruction or implanted material. CONCLUSION: The Resorb-X resorbable rigid plate provides an effective, customizable, bioabsorbable option that is easily manipulated for skull base reconstruction of defects of a variety of sizes in diverse locations. Reconstruction incorporating this plate provides an effective alternative to other previously described techniques.

Neural Correlates of Vocal Production and Motor Control in Human Heschl's Gyrus.

The present study investigated how pitch frequency, a perceptually relevant aspect of periodicity in natural human vocalizations, is encoded in Heschl's gyrus (HG), and how this information may be used to influence vocal pitch motor control. We recorded local field potentials from multicontact depth electrodes implanted in HG of 14 neurosurgical epilepsy patients as they vocalized vowel sounds and received brief (200 ms) pitch perturbations at 100 Cents in their auditory feedback. Event-related band power responses to vocalizations showed sustained frequency following responses that tracked voice fundamental frequency (F0) and were significantly enhanced in posteromedial HG during speaking compared with when subjects listened to the playback of their own voice. In addition to frequency following responses, a transient response component within the high gamma frequency band (75-150 Hz) was identified. When this response followed the onset of vocalization, the magnitude of the response was the same for the speaking and playback conditions. In contrast, when this response followed a pitch shift, its magnitude was significantly enhanced during speaking compared with playback. We also observed that, in anterolateral HG, the power of high gamma responses to pitch shifts correlated with the magnitude of compensatory vocal responses. These findings demonstrate a functional parcellation of HG with neural activity that encodes pitch in natural human voice, distinguishes between self-generated and passively heard vocalizations, detects discrepancies between the intended and heard vocalization, and contains information about the resulting behavioral vocal compensations in response to auditory feedback pitch perturbations. SIGNIFICANCE STATEMENT: The present study is a significant contribution to our understanding of sensor-motor mechanisms of vocal production and motor control. The findings demonstrate distinct functional parcellation of core and noncore areas within human auditory cortex on Heschl's gyrus that process natural human vocalizations and pitch perturbations in the auditory feedback. In addition, our data provide evidence for distinct roles of high gamma neural oscillations and frequency following responses for processing periodicity in human vocalizations during vocal production and motor control.

Sensory-motor networks involved in speech production and motor control: an fMRI study.

Speaking is one of the most complex motor behaviors developed to facilitate human communication. The underlying neural mechanisms of speech involve sensory-motor interactions that incorporate feedback information for online monitoring and control of produced speech sounds. In the present study, we adopted an auditory feedback pitch perturbation paradigm and combined it with functional magnetic resonance imaging (fMRI) recordings in order to identify brain areas involved in speech production and motor control. Subjects underwent fMRI scanning while they produced a steady vowel sound /a/ (speaking) or listened to the playback of their own vowel production (playback). During each condition, the auditory feedback from vowel production was either normal (no perturbation) or perturbed by an upward (+600 cents) pitch-shift stimulus randomly. Analysis of BOLD responses during speaking (with and without shift) vs. rest revealed activation of a complex network including bilateral superior temporal gyrus (STG), Heschl's gyrus, precentral gyrus, supplementary motor area (SMA), Rolandic operculum, postcentral gyrus and right inferior frontal gyrus (IFG). Performance correlation analysis showed that the subjects produced compensatory vocal responses that significantly correlated with BOLD response increases in bilateral STG and left precentral gyrus. However, during playback, the activation network was limited to cortical auditory areas including bilateral STG and Heschl's gyrus. Moreover, the contrast between speaking vs. playback highlighted a distinct functional network that included bilateral precentral gyrus, SMA, IFG, postcentral gyrus and insula. These findings suggest that speech motor control involves feedback error detection in sensory (e.g. auditory) cortices that subsequently activate motor-related areas for the adjustment of speech parameters during speaking.

Metastatic involvement of the pituitary gland: a systematic review with pooled individual patient data analysis.

PURPOSE: To report a rare case of pituitary metastasis (PM) from hepatocellular carcinoma (HCC) and help better understand the incidence of PM and its most common presenting symptoms through a pooled individual patient data analysis. METHODS: Literature regarding PM was systematically reviewed with a pooled individual patient data analysis conducted. Pooled individual data analysis result is also compared with the result in a most recent systematic review. RESULTS: Our results demonstrate that the incidence of PM among all intracranial metastases is 0.87% (95% CI 0.56, 1.18); it is 1.9% (95% CI 1.46, 2.34) among all autopsied cancer cases; it is 11.56% (95% CI 7.08, 16.04) among all breast cancer patients who had hypophysectomies and 12.83% (95% CI 10.5, 15.16) among all autopsied breast cancer patients. The fixed effect model showed that the incidence of PM in breast cancer patients group is significantly higher (p < 0.001) with an odds ratio of 6.71 (95% CI 4.24, 10.61). Breast and lung cancer are the most common primary cancer of PM with a percentage of 37.2 and 24.2 respectively. The next most common primary sites are prostate and kidney respectively, although the percentages for each are only about 5. Diabetes insipidus (DI) remains the most common symptom among all reported PM cases with a pooled incidence of 42.34% (95% CI 36.15, 48.53). Although not significant (χ(2) = 2.846, df = 1, p = 0.061), it is less common in the most recent reported cases which has a pooled incidence of 32.76% (95% CI 20.31, 45.21). DI is extremely rare in the reported PM cases from HCC (none of the eight cases presented with DI). The symptoms of anterior hypopituitarism (23.68 vs 39.66%, p = 0.015), visual deterioration (27.89 vs 41.38%, p = 0.039), cranial nerve palsies (21.58 vs 41.38%, p = 0.003) and headaches (15.79 vs 32.76%, p = 0.005) were reported significantly higher than previously described in the literature. CONCLUSIONS: Pituitary metastasis is rare in patients with cancer, and the pituitary gland is an uncommonly involved location in patients with intracranial metastases. With advanced diagnostic imaging techniques and increased awareness about the manifestation of sellar lesions, the incidence of cranial nerve palsies and anterior pituitarism are higher than reported. This information may allow earlier diagnosis of PM.

Sellar Reconstruction With a Bioabsorbable Plate After Endoscopic Transsphenoidal Pituitary Adenoma Resection: Safe and Efficacious.

OBJECTIVE: To report outcomes of a large cohort of patients who underwent endoscopic endonasal transsphenoidal surgery (EETS) for resection of a pituitary adenoma with subsequent Resorb-X plate (RXP) sellar reconstruction. METHODS: A retrospective review of 620 EETS operations performed at a single academic center between 2005 and 2020 was conducted. RESULTS: A total of 215 EETS operations of 208 patients were identified between 2012 and 2020 who underwent reconstruction with the RXP after EETS for pituitary tumor resection with a final pathologic diagnosis of pituitary adenoma. Analysis of pooled data revealed a mean preoperative tumor volume of 6.8 cm3 (range: 0.038-51.03 cm3). Postoperative cerebrospinal fluid leak occurred in 2 patients (0.93%). Postoperative meningitis occurred in 1 patient (0.47%). There were no cases of RXP extrusion. CONCLUSIONS: The rate of postoperative CSF leak and meningitis after use of the RXP for sellar reconstruction compares favorably to other methods, including use of autologous grafts and flaps. Use of RXP during EETS is a safe and efficacious method of sellar reconstruction and may obviate the need for autologous tissue reconstruction after pituitary adenoma resection.

Stimulation of caudal inferior and middle frontal gyri disrupts planning during spoken interaction.

Turn-taking is a central feature of conversation across languages and cultures.1,2,3,4 This key social behavior requires numerous sensorimotor and cognitive operations1,5,6 that can be organized into three general phases: comprehension of a partner's turn, preparation of a speaker's own turn, and execution of that turn. Using intracranial electrocorticography, we recently demonstrated that neural activity related to these phases is functionally distinct during turn-taking.7 In particular, networks active during the perceptual and articulatory stages of turn-taking consisted of structures known to be important for speech-related sensory and motor processing,8,9,10,11,12,13,14,15,16,17 while putative planning dynamics were most regularly observed in the caudal inferior frontal gyrus (cIFG) and the middle frontal gyrus (cMFG). To test if these structures are necessary for planning during spoken interaction, we used direct electrical stimulation (DES) to transiently perturb cortical function in neurosurgical patient-volunteers performing a question-answer task.7,18,19 We found that stimulating the cIFG and cMFG led to various response errors9,13,20,21 but not gross articulatory deficits, which instead resulted from DES of structures involved in motor control8,13,20,22 (e.g., the precentral gyrus). Furthermore, perturbation of the cIFG and cMFG delayed inter-speaker timing-consistent with slowed planning-while faster responses could result from stimulation of sites located in other areas. Taken together, our findings suggest that the cIFG and cMFG contain critical preparatory circuits that are relevant for interactive language use.

Intraventricular Pilocytic Astrocytoma in Adults: A 25-year Single-Center Case Series and Systematic Review of the Literature.

BACKGROUND: Pilocytic astrocytomas (PA) are the most common gliomas in children/adolescents but are less common and poorly studied in adults. Here, we describe the clinical presentation, surgical management, and outcomes of surgically treated adult patients with intraventricular (IV) PA and review the literature. METHODS: Consecutive adult patients treated for IV brain tumors at a tertiary academic center over 25 years (1997-2023) were identified. Clinical data were reviewed retrospectively for adult IV PA patients. A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Eight patients with IV PA were included. Median age was 25 years (range, 18-69 years), and 4 (50%) were female. The most common tumor location was the lateral ventricle (5, 63%), followed by the fourth ventricle (3, 37%). Subtotal and near total resection were the most common surgical outcomes (6 patients, 75%), followed by gross total resection in 2 (25%). Progression or recurrence occurred in 3 patients (37%), requiring repeat resection in 2 patients. The 5-year overall survival and progression-free survival were 67% and 40%, respectively. In addition, 42 cases were identified in the literature. CONCLUSIONS: PAs in adults are rare and an IV location is even more uncommon. The findings demonstrate the challenges in caring for these patients, with overall- and progression-free survival outcomes being poorer than the general adult PA population. Findings support the employment of surgical techniques and approaches that favor gross total resection when possible. Further studies are needed to better characterize this unique presentation.

No differential effects of subthalamic nucleus vs. globus pallidus deep brain stimulation in Parkinson's disease: Speech acoustic and perceptual findings.

Background: Deep Brain Stimulation (DBS) in the Subthalamic Nucleus (STN) or the Globus Pallidus Interna (GPI) is well-established as a surgical technique for improving global motor function in patients with idiopathic Parkinson's Disease (PD). Previous research has indicated speech deterioration in more than 30% of patients after STN-DBS implantation, whilst speech outcomes following GPI-DBS have received far less attention. Research comparing speech outcomes for patients with PD receiving STN-DBS and GPI-DBS can inform pre-surgical counseling and assist with clinician and patient decision-making when considering the neural targets selected for DBS-implantation. The aims of this pilot study were (1) to compare perceptual and acoustic speech outcomes for a group of patients with PD receiving bilateral DBS in the STN or the GPI with DBS stimulation both ON and OFF, and (2) examine associations between acoustic and perceptual speech measures and clinical characteristics. Methods: Ten individuals with PD receiving STN-DBS and eight individuals receiving GPI-DBS were audio-recorded reading a passage. Three listeners blinded to neural target and stimulation condition provided perceptual judgments of intelligibility and overall speech severity. Speech acoustic measures were obtained from the recordings. Acoustic and perceptual measures and clinical characteristics were compared for the two neural targets and stimulation conditions. Results: Intelligibility and speech severity were not significantly different across neural target or stimulation conditions. Generally, acoustic measures were also not statistically different for the two neural targets or stimulation conditions. Acoustic measures reflecting more varied speech prosody were associated with improved intelligibility and lessened severity. Convergent correlations were found between UPDRS-III speech scores and perceptual measures of intelligibility and severity. Conclusion: This study reports a systematic comparison of perceptual and acoustic speech outcomes following STN-DBS and GPI-DBS. Statistically significant differences in acoustic measures for the two neural targets were small in magnitude and did not yield group differences in perceptual measures. The absence of robust differences in speech outcomes for the two neural targets has implications for pre-surgical counseling. Results provide preliminary support for reliance on considerations other than speech when selecting the target for DBS in patients with PD.

Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM.

PURPOSE: Pharmacologic ascorbate (P-AscH-) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH- with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomarker in T2* mapping to predict GBM response to P-AscH- in humans. PATIENTS AND METHODS: The single-arm phase II clinical trial (NCT02344355) enrolled 55 subjects, with analysis performed 12 months following the completion of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared across patient subgroups with log-rank tests. Forty-nine of 55 subjects were evaluated using T2*-based MRI to assess its utility as an Fe-dependent biomarker. RESULTS: Median OS was estimated to be 19.6 months [90% confidence interval (CI), 15.7-26.5 months], a statistically significant increase compared with historic control patients (14.6 months). Subjects with initial T2* relaxation < 50 ms were associated with a significant increase in PFS compared with T2*-high subjects (11.2 months vs. 5.7 months, P < 0.05) and a trend toward increased OS (26.5 months vs. 17.5 months). These results were validated in preclinical in vitro and in vivo model systems. CONCLUSIONS: P-AscH- combined with temozolomide and radiotherapy has the potential to significantly enhance GBM survival. T2*-based MRI assessment of tumor iron content is a prognostic biomarker for GBM clinical outcomes. See related commentary by Nabavizadeh and Bagley, p. 255.

Intraarterial encephalography from an acutely implanted aneurysm embolization device in awake humans.

OBJECTIVE: Endovascular electroencephalography (evEEG) uses the cerebrovascular system to record electrical activity from adjacent neural structures. The safety, feasibility, and efficacy of using the Woven EndoBridge Aneurysm Embolization System (WEB) for evEEG has not been investigated. METHODS: Seventeen participants undergoing awake WEB endovascular treatment of unruptured cerebral aneurysms were included. After WEB deployment and before detachment, its distal deployment wire was connected to an EEG receiver, and participants performed a decision-making task for 10 minutes. WEB and scalp recordings were captured. RESULTS: All patients underwent successful embolization and evEEG with no complications. Event-related potentials were detected on scalp EEG in 9/17 (53%) patients. Of these 9 patients, a task-related low-gamma (30-70 Hz) response on WEB channels was captured in 8/9 (89%) cases. In these 8 patients, the WEB was deployed in 2 middle cerebral arteries, 3 anterior communicating arteries, the terminal internal carotid artery, and 2 basilar tip aneurysms. Electrocardiogram artifact on WEB channels was present in 12/17 cases. CONCLUSIONS: The WEB implanted within cerebral aneurysms of awake patients is capable of capturing task-specific brain electrical activities. Future studies are warranted to establish the efficacy of and support for evEEG as a tool for brain recording, brain stimulation, and brain-machine interface applications.

Human subthalamic nucleus neurons differentially encode speech and limb movement.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN), which consistently improves limb motor functions, shows mixed effects on speech functions in Parkinson's disease (PD). One possible explanation for this discrepancy is that STN neurons may differentially encode speech and limb movement. However, this hypothesis has not yet been tested. We examined how STN is modulated by limb movement and speech by recording 69 single- and multi-unit neuronal clusters in 12 intraoperative PD patients. Our findings indicated: (1) diverse patterns of modulation in neuronal firing rates in STN for speech and limb movement; (2) a higher number of STN neurons were modulated by speech vs. limb movement; (3) an overall increase in neuronal firing rates for speech vs. limb movement; and (4) participants with longer disease duration had higher firing rates. These data provide new insights into the role of STN neurons in speech and limb movement.

Lateralization and Time-Course of Cortical Phonological Representations during Syllable Production.

Spoken language contains information at a broad range of timescales, from phonetic distinctions on the order of milliseconds to semantic contexts which shift over seconds to minutes. It is not well understood how the brain's speech production systems combine features at these timescales into a coherent vocal output. We investigated the spatial and temporal representations in cerebral cortex of three phonological units with different durations: consonants, vowels, and syllables. Electrocorticography (ECoG) recordings were obtained from five participants while speaking single syllables. We developed a novel clustering and Kalman filter-based trend analysis procedure to sort electrodes into temporal response profiles. A linear discriminant classifier was used to determine how strongly each electrode's response encoded phonological features. We found distinct time-courses of encoding phonological units depending on their duration: consonants were represented more during speech preparation, vowels were represented evenly throughout trials, and syllables during production. Locations of strongly speech-encoding electrodes (the top 30% of electrodes) likewise depended on phonological element duration, with consonant-encoding electrodes left-lateralized, vowel-encoding hemispherically balanced, and syllable-encoding right-lateralized. The lateralization of speech-encoding electrodes depended on onset time, with electrodes active before or after speech production favoring left hemisphere and those active during speech favoring the right. Single-electrode speech classification revealed cortical areas with preferential encoding of particular phonemic elements, including consonant encoding in the left precentral and postcentral gyri and syllable encoding in the right middle frontal gyrus. Our findings support neurolinguistic theories of left hemisphere specialization for processing short-timescale linguistic units and right hemisphere processing of longer-duration units.

Endoscopic Reconstruction of the Anterior Skull Base Following Tumor Resection: Application of a Novel Bioabsorbable Plate.

OBJECTIVE: Endoscopic repair of skull base defects is required following resection of intracranial pathology via the endoscopic endonasal approach (EEA). Many closure techniques have been described, but choosing between techniques remains controversial. We report outcomes of 560 EEA procedures of skull base reconstruction performed on 508 patients over a 15-year-period. Halfway through this period, we adopted the use of a rigid, bioabsorbable extrasellar plate for reconstruction, enabling a comparison between this technique and those used previously. METHODS: All patients undergoing EEA from 2005 to 2019 at our institution were retrospectively reviewed. Demographic information, surgical pathology, tumor dimensions and radiographic features, reconstructive technique, and patient-related outcomes were collected and analyzed with univariate and multivariate statistical modeling. RESULTS: Five-hundred sixty procedures were performed on 508 patients. The series complication rate was 8.2%. Overall, cerebrospinal fluid (CSF) leak rate was 5.0% but varied significantly across closure techniques (p < 0.001). Critically, the CSF leak rate in the 272 cases prior to our 2013 adoption of the Resorb-X Plate (RXP) was 8.5%, whereas leak rate in the subsequent 288 cases was 1.7%. RXP was protective against CSF leak (p = 0.001), whereas gross total resection (GTR) correlated with increased leak rate (p = 0.001). Patient BMI was significantly associated with risk of leak (p = 0.047). Other variables did not impact leak risk. CONCLUSION: Reconstructive technique, extent of resection, and patient BMI significantly contributed to CSF leak rate. GTR was associated with increased leak risk while the RXP was protective. The bioabsorbable RXP is an effective option for rigid skull base repair with comparatively few complications. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1092-1098, 2023.

Preservation of spinal instrumentation after development of postoperative bacterial infections in patients undergoing spinal arthrodesis.

STUDY DESIGN: This is a retrospective review. OBJECTIVE: The purpose of this study is to evaluate the efficacy of medical and surgical management of postoperative infections after the placement of spinal instrumentation in the context of retaining the instrumentation. SUMMARY OF BACKGROUND DATA: The implementation of spinal instrumentation for the treatment of various spinal conditions is associated with a risk of developing a postoperative wound infection. An aggressive medical and surgical approach is necessary for eradication of subfascial infections and treatment is often performed with the guidance of infectious diseases consultants. These medical specialists frequently recommend removal of the implanted spinal instrumentation due to the concern for the potential of persistent microbial infection resulting from the formation of bacteria harboring biofilm on the indwelling spinal hardware. METHODS: Of 854 consecutive patients who had undergone spinal instrumentation by the senior author, 17 patients were identified who developed postoperative infections, 16 of which were treated by the senior author. RESULTS: All patients underwent surgical debridement and received antimicrobial therapy in consultation with the infectious diseases consultants. Spinal instrumentation was preserved in all cases. Two patients had clinical and radiologic evidence of nonunion and later underwent a staged instrumentation revision procedure. Eradication of the infection was successful in all patients. The mean follow-up period was 2.1 years (range, 12 mo to 4.5 y). CONCLUSIONS: A combination of aggressive surgical debridement with microbial-guided pharmacotherapy enabled infection cure in all patients with postoperative bacterial infections after spinal instrumentation. Adjunct measures including the use of wound vacuum devices and long-term suppressive antimicrobial therapy were also used in high-risk patients. These results show that postoperative bacterial infections in the setting of spinal instrumentation can be successfully treated without removing titanium alloy instrumentation.

A causal role for the human subthalamic nucleus in non-selective cortico-motor inhibition.

Common cortico-basal ganglia models of motor control suggest a key role for the subthalamic nucleus (STN) in motor inhibition.1-3 In particular, when already-initiated actions have to be suddenly stopped, the STN is purportedly recruited via a hyperdirect pathway to net inhibit the cortico-motor system in a broad, non-selective fashion.4 Indeed, the suppression of cortico-spinal excitability (CSE) during rapid action stopping extends beyond the stopped muscle and affects even task-irrelevant motor representations.5,6 Although such non-selective CSE suppression has long been attributed to the broad inhibitory influence of STN on the motor system, causal evidence for this association is hitherto lacking. Here, 20 Parkinson's disease patients treated with STN deep-brain stimulation (DBS) and 20 matched healthy controls performed a verbal stop-signal task while CSE was measured from a task-unrelated hand muscle. DBS allowed a causal manipulation of STN, while CSE was measured using transcranial magnetic stimulation (TMS) over primary motor cortex and concurrent electromyography. In patients OFF-DBS and controls, the CSE of the hand was non-selectively suppressed when the verbal response was successfully stopped. Crucially, this effect disappeared when STN was disrupted via DBS in the patient group. Using this unique combination of DBS and TMS during human behavior, the current study provides first causal evidence that STN is likely involved in non-selectively suppressing the physiological excitability of the cortico-motor system during action stopping. This confirms a core prediction of long-held cortico-basal ganglia circuit models of movement. The absence of cortico-motor inhibition during STN-DBS may also provide potential insights into the common side effects of STN-DBS, such as increased impulsivity.7-11.

Endoscopic pituitary surgery: National database review.

BACKGROUND: Pituitary tumors surgery is increasingly performed via endoscopic transsphenoidal approach (TSP). This study describes outcomes of TSP surgery in the United States. METHODS: A retrospective cross-sectional analysis of adult patients with pituitary adenoma was performed using the Nationwide Readmissions Database, 2010-2015. RESULTS: A total of 5891 patients were identified. The average age was 51.29 ± 0.29 years. The risk of postoperative epistaxis, diabetes insipidus, cerebrospinal fluid (CSF) leak, and other general postoperative complications was 0.71%, 10.20%, 8.35%, and 2.37%, respectively. Independent risk factors of CSF leak included: age <65-year, male, body mass index ≥25, and multiple comorbidities (p < 0.001 each). The prevalence of CSF leak was not associated with hospital TSP volume and teaching status. CONCLUSION: This study provides a national epidemiological perspective on TSP in the United States. The risk of postoperative CSF leak appears to be associated with intrinsic patient factors rather than resource and expertise availability.

Minimally Invasive Approaches to Anterior Skull Base Meningiomas.

Objective Anterior skull base meningiomas include olfactory groove, planum sphenoidale, and tuberculum sellae lesions. Traditionally, standard craniotomy approaches have been used to access meningiomas in these locations. More recently, minimally invasive techniques including supraorbital and endonasal endoscopic approaches have gained favor; however there are limited published series comparing the use of these two techniques for these meningiomas. Using our patent database, we identified patients who underwent these two approaches, and conducted a retrospective chart review to compare outcomes between these two techniques. Methods A total of 32 patients who underwent minimally invasive approaches were identified: 20 supraorbital and 11 endoscopic endonasal. Radiographic images, presenting complaints and outcomes, were analyzed retrospectively. The safety of each approach was evaluated. Results The mean extent of resection through a supraorbital approach was significantly greater than that of the endoscopic endonasal approach, 88.1 vs. 57.9%, respectively ( p = 0.016). Overall, preoperative visual acuity and anopsia deficits were more frequent in the endonasal group that persisted postoperatively (visual acuity: p = 0.004; anopsia: p = 0.011). No major complications including cerebrospinal fluid (CSF) leaks or wound-related complications were identified in the supraorbital craniotomy group, while the endonasal group had two CSF leaks requiring lumbar drain placement. Length of stay was shorter in the supraorbital group (3.4 vs. 6.1 days, p < 0.001). Conclusion Anterior skull base meningiomas can be successfully managed by both supraorbital and endoscopic endonasal approaches. Both approaches provide excellent direct access to tumor in carefully selected patients and are safe and efficient, but patient factors and symptoms should dictate the approach selected.