Utility and lower limits of frequency detection in surface electrode stimulation for somatosensory brain-computer interface in humans.

OBJECTIVE: Stimulation of the primary somatosensory cortex (S1) has been successful in evoking artificial somatosensation in both humans and animals, but much is unknown about the optimal stimulation parameters needed to generate robust percepts of somatosensation. In this study, the authors investigated frequency as an adjustable stimulation parameter for artificial somatosensation in a closed-loop brain-computer interface (BCI) system. METHODS: Three epilepsy patients with subdural mini-electrocorticography grids over the hand area of S1 were asked to compare the percepts elicited with different stimulation frequencies. Amplitude, pulse width, and duration were held constant across all trials. In each trial, subjects experienced 2 stimuli and reported which they thought was given at a higher stimulation frequency. Two paradigms were used: first, 50 versus 100 Hz to establish the utility of comparing frequencies, and then 2, 5, 10, 20, 50, or 100 Hz were pseudorandomly compared. RESULTS: As the magnitude of the stimulation frequency was increased, subjects described percepts that were "more intense" or "faster." Cumulatively, the participants achieved 98.0% accuracy when comparing stimulation at 50 and 100 Hz. In the second paradigm, the corresponding overall accuracy was 73.3%. If both tested frequencies were less than or equal to 10 Hz, accuracy was 41.7% and increased to 79.4% when one frequency was greater than 10 Hz (p = 0.01). When both stimulation frequencies were 20 Hz or less, accuracy was 40.7% compared with 91.7% when one frequency was greater than 20 Hz (p < 0.001). Accuracy was 85% in trials in which 50 Hz was the higher stimulation frequency. Therefore, the lower limit of detection occurred at 20 Hz, and accuracy decreased significantly when lower frequencies were tested. In trials testing 10 Hz versus 20 Hz, accuracy was 16.7% compared with 85.7% in trials testing 20 Hz versus 50 Hz (p < 0.05). Accuracy was greater than chance at frequency differences greater than or equal to 30 Hz. CONCLUSIONS: Frequencies greater than 20 Hz may be used as an adjustable parameter to elicit distinguishable percepts. These findings may be useful in informing the settings and the degrees of freedom achievable in future BCI systems.

Gamma-band modulation in the human amygdala during reaching movements.

OBJECTIVE: Motor brain-computer interface (BCI) represents a new frontier in neurological surgery that could provide significant benefits for patients living with motor deficits. Both the primary motor cortex and posterior parietal cortex have successfully been used as a neural source for human motor BCI, leading to interest in exploring other brain areas involved in motor control. The amygdala is one area that has been shown to have functional connectivity to the motor system; however, its role in movement execution is not well studied. Gamma oscillations (30-200 Hz) are known to be prokinetic in the human cortex, but their role is poorly understood in subcortical structures. Here, the authors use direct electrophysiological recordings and the classic "center-out" direct-reach experiment to study amygdaloid gamma-band modulation in 8 patients with medically refractory epilepsy. METHODS: The study population consisted of 8 epilepsy patients (2 men; age range 21-62 years) who underwent implantation of micro-macro depth electrodes for seizure localization and EEG monitoring. Data from the macro contacts sampled at 2000 Hz were used for analysis. The classic center-out direct-reach experiment was used, which consists of an intertrial interval phase, a fixation phase, and a response phase. The authors assessed the statistical significance of neural modulation by inspecting for nonoverlapping areas in the 95% confidence intervals of spectral power for the response and fixation phases. RESULTS: In 5 of the 8 patients, power spectral analysis showed a statistically significant increase in power within regions of the gamma band during the response phase compared with the fixation phase. In these 5 patients, the 95% bootstrapped confidence intervals of trial-averaged power in contiguous frequencies of the gamma band during the response phase were above, and did not overlap with, the confidence intervals of trial-averaged power during the fixation phase. CONCLUSIONS: To the authors' knowledge, this is the first time that direct neural recordings have been used to show gamma-band modulation in the human amygdala during the execution of voluntary movement. This work indicates that gamma-band modulation in the amygdala could be a contributing source of neural signals for use in a motor BCI system.

Electrocorticographic changes in field potentials following natural somatosensory percepts in humans.

OBJECTIVE: Restoration of somatosensory deficits in humans requires a clear understanding of the neural representations of percepts. To characterize the cortical response to naturalistic somatosensation, we examined field potentials in the primary somatosensory cortex of humans. METHODS: Four patients with intractable epilepsy were implanted with subdural electrocorticography (ECoG) electrodes over the hand area of S1. Three types of stimuli were applied, soft-repetitive touch, light touch, and deep touch. Power in the alpha (8-15 Hz), beta (15-30 Hz), low-gamma (30-50 Hz), and high-gamma (50-125 Hz) frequency bands were evaluated for significance. RESULTS: Seventy-seven percent of electrodes over the hand area of somatosensory cortex exhibited changes in these bands. High-gamma band power increased for all stimuli, with concurrent alpha and beta band power decreases. Earlier activity was seen in these bands in deep touch and light touch compared to soft touch. CONCLUSIONS: These findings are consistent with prior literature and suggest a widespread response to focal touch, and a different encoding of deeper pressure touch than soft touch.

A Multi-Level Analysis of Individual and Neighborhood Factors Associated with Patient Portal Use among Adult Emergency Department Patients with Multimorbidity.

Background: Patient portals tethered to electronic health records (EHR) have become vital to patient engagement and better disease management, specifically among adults with multimorbidity. We determined individual and neighborhood factors associated with patient portal use (MyChart) among adult patients with multimorbidity seen in an Emergency Department (ED). Methods: This study adopted a cross-sectional study design and used a linked database of EHR from a single ED site to patients' neighborhood characteristics (i.e., zip code level) from the American Community Survey. The study population included all adults (age > 18 years), with at least one visit to an ED and multimorbidity between 1 January 2019 to 31 December 2020 (N = 40,544). Patient and neighborhood characteristics were compared among patients with and without MyChart use. Random-intercept multi-level logistic regressions were used to analyze the associations of patient and neighborhood factors with MyChart use. Results: Only 19% (N = 7757) of adults with multimorbidity used the patient portal. In the fully adjusted multi-level model, at the patient level, having a primary care physician (AOR = 5.55, 95% CI 5.07−6.07, p < 0.001) and health insurance coverage (AOR = 2.41, 95% CI 2.23−2.61, p < 0.001) were associated with MyChart use. At the neighborhood level, 4.73% of the variation in MyChart use was due to differences in neighborhood factors. However, significant heterogeneity existed in patient portal use when neighborhood characteristics were included in the model. Conclusions: Among ED patients with multimorbidity, one in five adults used patient portals. Patient-level factors, such as having primary care physicians and insurance, may promote patient portal use.

Using Machine Learning Algorithms to Predict Patient Portal Use Among Emergency Department Patients With Diabetes Mellitus.

Background: Different machine learning (ML) technologies have been applied in healthcare systems with diverse applications. We aimed to determine the model feasibility and accuracy of predicting patient portal use among diabetic patients by using six different ML algorithms. In addition, we also compared model performance accuracy with the use of only essential variables. Methods: This was a single-center retrospective observational study. From March 1, 2019 to February 28, 2020, we included all diabetic patients from the study emergency department (ED). The primary outcome was the status of patient portal use. A total of 18 variables consisting of patient sociodemographic characteristics, ED and clinic information, and patient medical conditions were included to predict patient portal use. Six ML algorithms (logistic regression, random forest (RF), deep forest, decision tree, multilayer perception, and support vector machine) were used for such predictions. During the initial step, ML predictions were performed with all variables. Then, the essential variables were chosen via feature selection. Patient portal use predictions were repeated with only essential variables. The performance accuracies (overall accuracy, sensitivity, specificity, and area under receiver operating characteristic curve (AUC)) of patient portal predictions were compared. Results: A total of 77,977 unique patients were placed in our final analysis. Among them, 23.4% (18,223) patients were diabetic mellitus (DM). Patient portal use was found in 26.9% of DM patients. Overall, the accuracy of predicting patient portal use was above 80% among five out of six ML algorithms. The RF outperformed the others when all variables were used for patient portal predictions (accuracy 0.9876, sensitivity 0.9454, specificity 0.9969, and AUC 0.9712). When only eight essential variables were chosen, RF still outperformed the others (accuracy 0.9876, sensitivity 0.9374, specificity 0.9932, and AUC 0.9769). Conclusion: It is possible to predict patient portal use outcomes when different ML algorithms are used with fair performance accuracy. However, with similar prediction accuracies, the use of feature selection techniques can improve the interpretability of the model by addressing the most relevant features.

Patient Portal Use Among Diabetic Patients With Different Races and Ethnicities.

Background: Patient portal (PP) use varies among different patient populations, specifically among those with diabetes mellitus (DM). In addition, it is still uncertain whether PP use could be linked to improved clinical outcomes. Therefore, the aim of this paper was to determine PP use status for patients, recognize factors promoting PP use, and further identify the association between PP use and clinical outcome among diabetic patients of different races and ethnicities. Methods: This was a single-center cross-section study. Patients were divided into non-Hispanic white (NHW), non-Hispanic black (NHB), and Hispanic/Latino groups. PP use was compared among these three groups. Multivariate logistic regressions were used to determine factors associated with PP use, serum glycemic control, and emergency department (ED) hospitalizations. Results: A total of 77,977 patients were analyzed. The rate of PP use among patients of NHW (24%) was higher than those of NHB (19%) and Hispanic/Latinos (18%, P < 0.0001). The adjusted odds ratio (AOR) of insurance coverage associated with PP use was 2.12 (2.02 - 2.23, P < 0.0001), and having a primary care physician (PCP) associated with PP use was 3.89 (3.71 - 4.07, P < 0.0001). In terms of clinical outcomes, the AOR of PP use associated with serum glycemic control was 0.98 (0.90 - 1.05, P = 0.547) and ED hospitalization was 0.79 (0.73 - 0.86, P < 0.0001). Conclusion: PP use disparity occurred among NHB and Hispanic/Latino patients in the ED. Having insurance coverage and PCPs seem to correlate with PP use. PP use did not seem to associate with serum glycemic control among DM patients present in the ED but could possibly reduce patient hospitalizations.

Mapping of primary somatosensory cortex of the hand area using a high-density electrocorticography grid for closed-loop brain computer interface.

Objective.The ideal modality for generating sensation in sensorimotor brain computer interfaces (BCI) has not been determined. Here we report the feasibility of using a high-density 'mini'-electrocorticography (mECoG) grid in a somatosensory BCI system.Approach.Thirteen subjects with intractable epilepsy underwent standard clinical implantation of subdural electrodes for the purpose of seizure localization. An additional high-density mECoG grid was placed (Adtech, 8 by 8, 1.2 mm exposed, 3 mm center-to-center spacing) over the hand area of primary somatosensory cortex. Following implantation, cortical mapping was performed with stimulation parameters of frequency: 50 Hz, pulse-width: 250µs, pulse duration: 4 s, polarity: alternating, and current that ranged from 0.5 mA to 12 mA at the discretion of the epileptologist. Location of the evoked sensory percepts was recorded along with a description of the sensation. The hand was partitioned into 48 distinct boxes. A box was included if sensation was felt anywhere within the box.Main results.The percentage of the hand covered was 63.9% (± 34.4%) (mean ± s.d.). Mean redundancy, measured as electrode pairs stimulating the same box, was 1.9 (± 2.2) electrodes per box; and mean resolution, measured as boxes included per electrode pair stimulation, was 11.4 (± 13.7) boxes with 8.1 (± 10.7) boxes in the digits and 3.4 (± 6.0) boxes in the palm. Functional utility of the system was assessed by quantifying usable percepts. Under the strictest classification, 'dermatomally exclusive' percepts, the mean was 2.8 usable percepts per grid. Allowing 'perceptually unique' percepts at the same anatomical location, the mean was 5.5 usable percepts per grid.Significance.Compared to the small area of coverage and redundancy of a microelectrode system, or the poor resolution of a standard ECoG grid, a mECoG is likely the best modality for a somatosensory BCI system with good coverage of the hand and minimal redundancy.

Comparison of Intraoperative 3-Dimensional Fluoroscopy With Standard Computed Tomography for Stereotactic Frame Registration.

BACKGROUND: Three-dimensional fluoroscopy via the O-arm (Medtronic, Dublin, Ireland) has been validated for intraoperative confirmation of successful lead placement in stereotactic electrode implantation. However, its role in registration and targeting has not yet been studied. After frame placement, many stereotactic neurosurgeons obtain a computed tomography (CT) scan and merge it with a preoperative magnetic resonance imaging (MRI) scan to generate planning coordinates; potential disadvantages of this practice include increased procedure time and limited scanner availability. OBJECTIVE: To evaluate whether the second-generation O-arm (O2) can be used in lieu of a traditional CT scan to obtain accurate frame-registration scans. METHODS: In 7 patients, a postframe placement CT scan was merged with preoperative MRI and used to generate lead implantation coordinates. After implantation, the fiducial box was again placed on the patient to obtain an O2 confirmation scan. Vector, scalar, and Euclidean differences between analogous X, Y, and Z coordinates from fused O2/MRI and CT/MRI scans were calculated for 33 electrode target coordinates across 7 patients. RESULTS: Marginal means of difference for vector (X = -0.079 ± 0.099 mm; Y = -0.076 ± 0.134 mm; Z = -0.267 ± 0.318 mm), scalar (X = -0.146 ± 0.160 mm; Y = -0.306 ± 0.106 mm; Z = 0.339 ± 0.407 mm), and Euclidean differences (0.886 ± 0.190 mm) remained within the predefined equivalence margin differences of -2 mm and 2 mm. CONCLUSION: This study demonstrates that O2 may emerge as a viable alternative to the traditional CT scanner for generating planning coordinates. Adopting the O2 as a perioperative tool may offer reduced transport risks, decreased anesthesia time, and greater surgical efficiency.

Beta-band power modulation in the human hippocampus during a reaching task.

OBJECTIVE: Characterize the role of the beta-band (13-30 Hz) in the human hippocampus during the execution of voluntary movement. APPROACH: We recorded electrophysiological activity in human hippocampus during a reach task using stereotactic electroencephalography (SEEG). SEEG has previously been utilized to study the theta band (3-8 Hz) in conflict processing and spatial navigation, but most studies of hippocampal activity during movement have used noninvasive measures such as fMRI. We analyzed modulation in the beta band (13-30 Hz), which is known to play a prominent role throughout the motor system including the cerebral cortex and basal ganglia. We conducted the classic 'center-out' direct-reach experiment with nine patients undergoing surgical treatment for medically refractory epilepsy. MAIN RESULTS: In seven of the nine patients, power spectral analysis showed a statistically significant decrease in power within the beta band (13-30 Hz) during the response phase, compared to the fixation phase, of the center-out direct-reach task using the Wilcoxon signed-rank hypothesis test (p < 0.05). SIGNIFICANCE: This finding is consistent with previous literature suggesting that the hippocampus may be involved in the execution of movement, and it is the first time that changes in beta-band power have been demonstrated in the hippocampus using human electrophysiology. Our findings suggest that beta-band modulation in the human hippocampus may play a role in the execution of voluntary movement.

A Phantom Study of the Spatial Precision and Accuracy of Stereotactic Localization Using Computed Tomography Imaging with the Leksell Stereotactic System.

BACKGROUND: Stereotactic localization of neurosurgical targets traditionally relies on computed tomography (CT), which is considered the optimal imaging modality for geometric accuracy. However, in-depth investigations that characterize the precision and accuracy of CT images are lacking. We used a CT phantom to examine interscanner precision and interprotocol accuracy in coordinate localization. METHODS: A polymethylacrylate phantom was scanned with Toshiba Aquilion 64 and GE Healthcare LightSpeed 16 CT scanners, using both helical and incremental single-slice (SS) image acquisition protocols. The X, Y, and Z coordinates of 94 points across 6 surfaces of the phantom were physically measured. The CT scan-derived coordinates were compared with the phantom coordinates and with each other to determine accuracy and precision, respectively. RESULTS: Using the SS imaging protocol, the mean (SD) interscanner disparity in localization was 0.93 (0.39) mm, given by the average Euclidean distance between the coordinates of the 2 scanners. This discrepancy significantly varied by axis and surface, with the greatest discrepancy in the Z-axis of 0.30 mm (95% confidence interval, 0.25-0.35; P = 0.05) and on the superior surface of 1.30 mm (95% confidence interval, 1.15-1.45; P = 0.05). SS acquisition was significantly more accurate than the helical protocol. CONCLUSIONS: We found evidence of clinically relevant inconsistency between 2 CT scanners used for stereotactic localization. SS image acquisition was superior to helical scanning with respect to localization accuracy. Interscanner consistency cannot be assumed. Institutions would benefit from identifying the errors inherent in their CT scanners.

Delayed Small Bowel Incarceration Within a Lumbar Burst Fracture After Posterior Spinal Fusion: A Case Report.

We present a case report of a patient who had delayed small bowel obstruction secondary to an incarcerated loop of small bowel within an acute lumbar spine fracture. The patient was involved in a rollover motor vehicle accident, resulting in lumbar spine fractures at L2-4. A comminuted fracture of the L3 vertebral body with likely disruption of the anterior longitudinal ligament (ALL) was noted. The patient underwent L1-4 posterior spinal fusion with the introduction of mild lumbar lordosis to prevent future complications of flatback syndrome. On postoperative Day 4, the patient was noted to have signs and symptoms of progressive small bowel obstruction. Conservative management was initiated with minimal improvement. The patient was taken to the operating room on postoperative Day 7 for an exploratory laparotomy. A necrotic loop of small bowel was noted to be entrapped in the ventral L3 vertebral body defect. This bowel was released and resected, with side-to-side anastomosis performed. No previous cases describe small bowel incarceration because of posterior spinal fusion for trauma. The introduction of increased lumbar lordosis is thought to have contributed to this risk of small bowel herniation, and care must be taken when determining appropriate spinopelvic parameters in these cases.

Technical considerations for generating somatosensation via cortical stimulation in a closed-loop sensory/motor brain-computer interface system in humans.

Somatosensory feedback is the next step in brain computer interface (BCI). Here, we compare three cortical stimulating array modalities for generating somatosensory percepts in BCI. We compared human subjects with either a 64-channel "mini"-electrocorticography grid (mECoG; 1.2-mm diameter exposed contacts with 3-mm spacing, N = 1) over the hand area of primary somatosensory cortex (S1), or a standard grid (sECoG; 1.5-mm diameter exposed contacts with 1-cm spacing, N = 1), to generate artificial somatosensation through direct electrical cortical stimulation. Finally, we reference data in the literature from a patient implanted with microelectrode arrays (MEA) placed in the S1 hand area. We compare stimulation results to assess coverage and specificity of the artificial percepts in the hand. Using the mECoG array, hand mapping revealed coverage of 41.7% of the hand area versus 100% for the sECoG array, and 18.8% for the MEA. On average, stimulation of a single electrode corresponded to sensation reported in 4.42 boxes (range 1-11 boxes) for the mECoG array, 19.11 boxes (range 4-48 boxes) for the sECoG grid, and 2.3 boxes (range 1-5 boxes) for the MEA. Sensation in any box, on average, corresponded to stimulation from 2.65 electrodes (range 1-5 electrodes) for the mECoG grid, 3.58 electrodes for the sECoG grid (range 2-4 electrodes), and 11.22 electrodes (range 2-17 electrodes) for the MEA. Based on these findings, we conclude that mECoG grids provide an excellent balance between spatial cortical coverage of the hand area of S1 and high-density resolution.

Brain-Computer Interfaces in Quadriplegic Patients.

Brain-computer interfaces (BCI) are implantable devices that interface directly with the nervous system. BCI for quadriplegic patients restore function by reading motor intent from the brain and use the signal to control physical, virtual, and native prosthetic effectors. Future closed-loop motor BCI will incorporate sensory feedback to provide patients with an effective and intuitive experience. Development of widely available BCI for patients with neurologic injury will depend on the successes of today's clinical BCI. BCI are an exciting next step in the frontier of neuromodulation.

Directional tuning during reach planning in the supramarginal gyrus using local field potentials.

Previous work in directional tuning for brain machine interfaces has primarily relied on algorithm sorted neuronal action potentials in primary motor cortex. However, local field potential has been utilized to show directional tuning in macaque studies, and inferior parietal cortex has shown increased neuronal activity in reaching tasks that relied on MRI imaging. In this study we utilized local field potential recordings from a human subject performing a delayed reach task and show that high frequency band (76-100 Hz) spectral power is directionally tuned to different reaching target locations during an active reach. We also show that during the delay phase of the task, directional tuning is present in areas of the inferior parietal cortex, in particular, the supramarginal gyrus.

Clinical neuroprosthetics: Today and tomorrow.

Implantable neurostimulation devices provide a direct therapeutic link to the nervous system and can be considered brain-computer interfaces (BCI). Under this definition, BCI are not simply science fiction, they are part of existing neurosurgical practice. Clinical BCI are standard of care for historically difficult to treat neurological disorders. These systems target the central and peripheral nervous system and include Vagus Nerve Stimulation, Responsive Neurostimulation, and Deep Brain Stimulation. Recent advances in clinical BCI have focused on creating "closed-loop" systems. These systems rely on biomarker feedback and promise individualized therapy with optimal stimulation delivery and minimal side effects. Success of clinical BCI has paralleled research efforts to create BCI that restore upper extremity motor and sensory function to patients. Efforts to develop closed loop motor/sensory BCI is linked to the successes of today's clinical BCI.

Functional Frequency Discrimination From Cortical Somatosensory Stimulation in Humans.

Recently, efforts to produce artificial sensation through cortical stimulation of primary somatosensory cortex (PSC) in humans have proven safe and reliable. Changes in stimulation parameters like frequency and amplitude have been shown to elicit different percepts, but without clearly defined psychometric profiles. This study investigates the functionally useful limits of frequency changes on the percepts felt by three epilepsy patients with subdural electrocorticography (ECoG) grids. Subjects performing a hidden target task were stimulated with parameters of constant amplitude, pulse-width, and pulse-duration, and a randomly selected set of two frequencies (20, 30, 40, 50, 60, and 100 Hz). They were asked to decide which target had the "higher" frequency. Objectively, an increase in frequency differences was associated with an increase in perceived intensity. Reliable detection of stimulation occurred at and above 40 Hz with a lower limit of detection around 20 Hz and a just-noticeable difference estimated at less than 10 Hz. These findings suggest that frequency can be used as a reliable, adjustable parameter and may be useful in establishing settings and thresholds of functionality in future BCI systems.

Dual responsive neurostimulation implants for epilepsy.

Closed-loop brain-responsive neurostimulation via the RNS System is a treatment option for adults with medically refractory focal epilepsy. Using a novel technique, 2 RNS Systems (2 neurostimulators and 4 leads) were successfully implanted in a single patient with bilateral parietal epileptogenic zones. In patients with multiple epileptogenic zones, this technique allows for additional treatment options. Implantation can be done successfully, without telemetry interference, using proper surgical planning and neurostimulator positioning.Trajectories for the depth leads were planned using neuronavigation with CT and MR imaging. Stereotactic frames were used for coordinate targeting. Each neurostimulator was positioned with maximal spacing to avoid telemetry interference while minimizing patient discomfort. A separate J-shaped incision was used for each neurostimulator to allow for compartmentalization in case of infection. In order to minimize surgical time and risk of infection, the neurostimulators were implanted in 2 separate surgeries, approximately 3 weeks apart.The neurostimulators and leads were successfully implanted without adverse surgical outcomes. The patient recovered uneventfully, and the early therapy settings over several months resulted in preliminary decreases in aura and seizure frequency. Stimulation by one of the neurostimulators did not result in stimulation artifacts detected by the contralateral neurostimulator.

Utilizing Light-field Imaging Technology in Neurosurgery.

Traditional still cameras can only focus on a single plane for each image while rendering everything outside of that plane out of focus. However, new light-field imaging technology makes it possible to adjust the focus plane after an image has already been captured. This technology allows the viewer to interactively explore an image with objects and anatomy at varying depths and clearly focus on any feature of interest by selecting that location during post-capture viewing. These images with adjustable focus can serve as valuable educational tools for neurosurgical residents. We explore the utility of light-field cameras and review their strengths and limitations compared to other conventional types of imaging. The strength of light-field images is the adjustable focus, as opposed to the fixed-focus of traditional photography and video. A light-field image also is interactive by nature, as it requires the viewer to select the plane of focus and helps with visualizing the three-dimensional anatomy of an image. Limitations include the relatively low resolution of light-field images compared to traditional photography and video. Although light-field imaging is still in its infancy, there are several potential uses for the technology to complement traditional still photography and videography in neurosurgical education.

A role for the mTOR pathway in surface expression of AMPA receptors.

Delivery of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptors (AMPARs) to the synapse is a critical factor controlling synaptic strength. It is now established that blockade of synaptic activity increases the surface expression of AMPARs. Factors modulating the delivery, insertion and expression of AMPARs are not completely known. Using immunohistochemical techniques, we first confirmed rapamycin-mediated inhibition of the mammalian target of rapamycin (mTOR) pathway in cortical neuronal culture. We then demonstrated that acute AMPAR activity blockade increased the synaptic expression of GluR2/3 subunits and rapamycin significantly reduced this expression. Our results suggest a role for the mTOR pathway in surface expression of AMPA receptors on cortical neurons.