A Multicenter Matched Cohort Study of Processed Nerve Allograft and Conduit in Digital Nerve Reconstruction.

PURPOSE: Biomaterials used to restore digital nerve continuity after injury associated with a defect may influence ultimate outcomes. An evaluation of matched cohorts undergoing digital nerve gap reconstruction was conducted to compare processed nerve allograft (PNA) and conduits. Based on scientific evidence and historical controls, we hypothesized that outcomes of PNA would be better than for conduit reconstruction. METHODS: We identified matched cohorts based on patient characteristics, medical history, mechanism of injury, and time to repair for digital nerve injuries with gaps up to 25 mm. Data were stratified into 2 gap length groups: short gaps of 14 mm or less and long gaps of 15 to 25 mm. Meaningful sensory recovery was defined as a Medical Research Council scale of S3 or greater. Comparisons of meaningful recovery were made by repair method between and across the gap length groups. RESULTS: Eight institutions contributed matched data sets for 110 subjects with 162 injuries. Outcomes data were available in 113 PNA and 49 conduit repairs. Meaningful recovery was reported in 61% of the conduit group, compared with 88% in the PNA group. In the group with a 14-mm or less gap, conduit and PNA outcomes were 67% and 92% meaningful recovery, respectively. In the 15- to 25-mm gap length group, conduit and PNA outcomes were 45% and 85% meaningful recovery, respectively. There were no reported adverse events in either treatment group. CONCLUSIONS: Outcomes of digital nerve reconstruction in this study using PNA were consistent and significantly better than those of conduits across all groups. As gap lengths increased, the proportion of patients in the conduit group with meaningful recovery decreased. This study supports the use of PNA for nerve gap reconstruction in digital nerve reconstructions up to 25 mm. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Peripheral nerve repair throughout the body with processed nerve allografts: Results from a large multicenter study.

BACKGROUND: Peripheral nerve damage resulting in pain, loss of sensation, or motor function may necessitate a reconstruction with a bridging material. The RANGER® Registry was designed to evaluate outcomes following nerve repair with processed nerve allograft (Avance® Nerve Graft; Axogen; Alachua, FL). Here we report on the results from the largest peripheral nerve registry to-date. METHODS: This multicenter IRB-approved registry study collected data from patients repaired with processed nerve allograft (PNA). Sites followed their own standard of care for patient treatment and follow-up. Data were assessed for meaningful recovery, defined as ≥S3/M3 to remain consistent with previously published results, and comparisons were made to reference literature. RESULTS: The study included 385 subjects and 624 nerve repairs. Overall, 82% meaningful recovery (MR) was achieved across sensory, mixed, and motor nerve repairs up to gaps of 70 mm. No related adverse events were reported. There were no significant differences in MR across the nerve type, age, time-to-repair, and smoking status subgroups in the upper extremity (p > .05). Significant differences were noted by the mechanism of injury subgroups between complex injures (74%) as compared to lacerations (85%) or neuroma resections (94%) (p = .03) and by gap length between the <15 mm and 50-70 mm gap subgroups, 91 and 69% MR, respectively (p = .01). Results were comparable to historical literature for nerve autograft and exceed that of conduit. CONCLUSIONS: These findings provide clinical evidence to support the continued use of PNA up to 70 mm in sensory, mixed and motor nerve repair throughout the body and across a broad patient population.

Peripheral neuropathy: surgical approaches simplified for the imagers.

Peripheral nerves traverse through different soft tissue compartments in the upper and lower extremities via specific anatomical tunnels, where they are susceptible to entrapment. Common sites in the upper extremity include carpal tunnel, cubital tunnel and radial tunnel. Common sites in the lower extremity include piriformis, fibular neck, and tarsal tunnel. Compressive peripheral neuropathy can develop in these sites, and are amenable for surgical decompression.

Sarcomatoid carcinoma in head and neck: a review of 30 years of experience--clinical outcomes and reconstructive results.

PROBLEM PRESENTED: Sarcomatoid carcinoma (SaCa) is a rare variant of squamous cell carcinoma (SCC) with sarcomatoid features. This study investigated the clinical presentation and outcomes of head and neck SaCa. In addition, reconstructive outcome for a subset of patients was also evaluated. STUDIES UNDERTAKEN: Seventy-eight SaCa cases including 72 men and 6 women were identified from 13,777 head and neck SCC cases. Clinical outcomes were evaluated based on locoregional control, distant metastases, and multivariate analyses. Reconstructive outcome was evaluated by flap survival rate. RESULT: Of the 78 cases, 71% (55) of cases were located in the oral mucosa; 64% (50) of patients were classified as T3 or T4 at the time of diagnosis. The 5-year survival was only 16%. Multivariate analysis revealed better outcomes only when the patient had a history of previous SCC. Forty-five patients underwent flap reconstruction, with 98% flap survival rate but the functional result varied because of the inevitable adjuvant radiotherapy and advanced stage of tumor. CONCLUSIONS: Sarcomatoid carcinoma is a different entity from the conventional SCC of the head and neck. Sarcomatoid carcinoma carries a poorer prognosis despite aggressive surgical intervention and concurrent adjuvant therapies. It remains a great challenge for clinical oncologists, and the optimal treatment strategy requires further studies. Free flap is still preferred for defect reconstruction but the design should be simplified to avoid complications.

Targeted muscle reinnervation and regenerative peripheral nerve interfaces for pain prophylaxis and treatment: A systematic review.

OBJECTIVE: Nerve pain frequently develops following amputations and peripheral nerve injuries. Two innovative surgical techniques, targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI), are rapidly gaining popularity as alternatives to traditional nerve management, but their effectiveness is unclear. LITERATURE SURVEY: A review of literature pertaining to TMR and RPNI pain results was conducted. PubMed and MEDLINE electronic databases were queried. METHODOLOGY: Studies were included if pain outcomes were assessed after TMR or RPNI in the upper or lower extremity, both for prophylaxis performed at the time of amputation and for treatment of postamputation pain. Data were extracted for evaluation. SYNTHESIS: Seventeen studies were included, with 14 evaluating TMR (366 patients) and three evaluating RPNI (75 patients). Of these, one study was a randomized controlled trial. Nine studies had a mean follow-up time of at least 1 year (range 4-27.6 months). For pain treatment, TMR and RPNI improved neuroma pain in 75%-100% of patients and phantom limb pain in 45%-80% of patients, averaging a 2.4-6.2-point reduction in pain scores on the numeric rating scale postoperatively. When TMR or RPNI was performed prophylactically, many patients reported no neuroma pain (48%-100%) or phantom limb pain (45%-87%) at time of follow-up. Six TMR studies reported Patient-Reported Outcomes Measurement Information System (PROMIS) scores assessing pain intensity, behavior, and interference, which consistently showed a benefit for all measures. Complication rates ranged from 13% to 31%, most frequently delayed wound healing. CONCLUSIONS: Both TMR and RPNI may be beneficial for preventing and treating pain originating from peripheral nerve dysfunction compared to traditional techniques. Randomized trials with longer term follow-up are needed to directly compare the effectiveness of TMR and RPNI with traditional nerve management techniques.

Surgical Technique for Concurrent Endoscopic Carpal Tunnel Release and Distal Radius Fracture Fixation Using the Flexor Carpi Radialis Approach: A Case Series.

Purpose: Multiple prior studies have assessed the results of open approaches for concurrent carpal tunnel release with distal radius fracture fixation; however, less is known regarding the feasibility of endoscopic techniques, especially in the setting of high-energy trauma. In this study, we assessed the feasibility and results of concurrent endoscopic carpal tunnel release and distal radius fracture fixation using the flexor carpi radialis approach after high- and low-energy trauma. Methods: We performed a retrospective, single-surgeon study of 17 consecutive adult patients (aged >18 years) who underwent open reduction internal fixation of an acute distal radius fracture with concurrent endoscopic carpal tunnel release at a level 1 trauma center between April 2017 and October 2020. Recovery from median nerve dysfunction was assessed from patient charts at routinely scheduled postoperative follow-up visits (at 2 weeks, 4 weeks, 6 weeks, and 12 weeks). Results: The transverse carpal ligament could be visualized and released in all patients. All patients had a return of light touch sensibility with or without intermittent paresthesia by 12 weeks after surgery (the median time from surgery to recovery was 19 days [range, 12-82 days]). There were no patient reports or clinical examination evidence of palmar cutaneous branch, recurrent motor branch, or the third common digital nerve injury. Time to recovery was significantly different in the setting of high- versus low-energy trauma (26 days vs 18 days, respectively; P = .02). Conclusions: In this study, we demonstrated that concurrent endoscopic carpal tunnel release using the flexor carpi radialis approach for distal radius fracture fixation in the settings of high- and low-energy trauma is safe from major complications and effective at releasing the transverse carpal ligament. Type of study/level of evidence: Therapeutic IV.

Osteoplastic Thumb Reconstruction in the Immediate Setting: A Case Series.

Background: Traumatic thumb amputation can have devastating effects on residual hand function. When replantation is not possible, thumb reconstruction is often performed in a delayed manner and may require multiple stages. Furthermore, reconstruction techniques often require microsurgical skills and equipment, which are not readily available at all institutions. This case series illustrates our technique for immediate osteoplastic thumb reconstruction following traumatic amputation. Methods: This is a case series involving all patients who sustained unreplantable thumb amputations and underwent immediate osteoplastic thumb reconstruction with bone autograft and pedicled groin flap by the senior author from September 2016 through August 2018. Results: Five patients underwent immediate osteoplastic thumb reconstruction during the study period. Total operative time for the initial osteoplastic reconstruction averaged 158 minutes (range 96-290 minutes). In addition to flap division surgery, patients underwent an average of 1.2 revision procedures (range 0-2), primarily for debulking and hardware removal. Patients achieved an average gain in length of 3.3 cm compared with the maximum anticipated length with revision amputation at the time of injury, and had stable clinical outcomes for a minimum of 12 months. Conclusions: Osteoplastic thumb reconstruction is a useful technique for thumb reconstruction for select patients following traumatic thumb amputation. Advantages of this approach include shorter overall operative times and hospital length of stay, minimal donor site morbidity, and a straightforward, reproducible technique.

Surface Electromyography-Driven Therapeutic Gaming for Rehabilitation of Upper Extremity Weakness: A Pilot Study.

SUMMARY: In patients with severe upper extremity weakness that may result from peripheral nerve injuries, stroke, and spinal cord injuries, standard therapy in the earliest stages of recovery consists primarily of passive rather than active exercises. Adherence to prescribed therapy may be poor, which may contribute to suboptimal functional outcomes. The authors have developed and integrated a custom surface electromyography device with a video game to create an interactive, biofeedback-based therapeutic gaming platform. Sensitivity of the authors' custom surface electromyography device was evaluated with simultaneous needle electromyography recordings. Testing of this therapeutic gaming platform was conducted with a single 30-minute gameplay session in 19 patients with a history of peripheral nerve injury, stroke, spinal cord injury, and direct upper extremity trauma, including 11 patients who had undergone nerve and/or tendon transfers. The device was highly sensitive in detecting low levels of voluntary muscle activation and was used with 10 distinct muscles of the arm, forearm, and hand. Nerve and tendon transfer patients successfully activated the donor nerve/muscle and elicited the desired movement to engage in gameplay. On surveys of acceptability and usability, patients felt the system was enjoyable, motivating, fun, and easy to use, and their hand therapists expressed similar enthusiasm. Surface electromyography-based therapeutic gaming is a promising approach to rehabilitation that warrants further development and investigation to examine its potential efficacy, not only for building muscle strength and endurance but also for facilitating motor relearning after nerve and tendon transfer surgical procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Nonsurgical Approaches to Neuroma Management.

Symptomatic neuromas and chronic neuropathic pain are significant problems affecting patients' quality of life and independence that are challenging to treat. These symptoms are due to structural and functional changes that occur peripherally within neuromas, as well as alterations that occur centrally within the brain and spinal cord. A multimodal approach is most effective, with goals to minimize opioid use, to capitalize on the synergistic effects of nonopioid medications and to explore potential benefits of novel adjunctive treatments.

Targeted Peripheral Nerve Interface: Case Report with Literature Review.

Nerve transection injuries can result in painful neuromas that adversely affect patient recovery. This is especially significant following amputation surgeries in the setting of prosthetic wear and function. Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interface (RPNI) are 2 modern surgical techniques that provide neuromuscular targets for these transected nerve endings to reinnervate. These strategies have been previously shown to reduce phantom limb pain, residual limb pain, and neuroma-related pain.1,2,7,11 Two recent articles described technical adaptations of combining targeted muscle reinnervation and RPNI to create a hybrid procedure.3,12 In this article, we propose a different modification of targeted muscle reinnervation and RPNI, where the transected nerve stump is coapted to a recipient unit consisting of an intact distal nerve branch with its associated muscle graft. We called this recipient unit a targeted peripheral nerve interface because it contains a distal nerve branch for nerve coaptation and can guide axonal regeneration from the donor nerve to its target muscle graft. We theorize that targeted peripheral nerve interface may lead to more even distribution of regenerating axons with potentially less pain and stronger signals for prosthetic control when compared with standard RPNI.

Occult primary breast cancer presenting with brachial plexopathy: A case report.

Breast cancer affects about one in eight women over the course of her lifetime. Occult breast cancer, in which primary breast cancer is detected without evidence of disease in the breast itself, comprises up to 1% of new diagnoses; this is typically detected from abnormal axillary lymph nodes, and distant metastases are rare. Here, we present an unusual case of occult breast cancer presenting as upper extremity pain, edema, and weakness, with a metastatic mass to the brachial plexus being the only site of disease.

Brachial Plexus Desmoid Tumor: Care for Functional Preservation.

Desmoid tumors are a rare, locally invasive, non-metastasizing tumor of mesenchymal origin. Most of such tumors occur sporadically, but some arise as part of germline adenomatous polyposis coli mutations. They tend to aggregate in the abdomen, thorax, extremities, and the head and neck region. They are challenging to treat, with a high rate of recurrence even if achieving negative margins. We present the case of an 18-year-old woman with a desmoid tumor involving her brachial plexus. A non-oncological resection was performed, with a focus on functional preservation. Residual disease is being treated with ß-catenin inhibitor and monitored with serial MRI.

Planning Interventions to Treat Brachial Plexopathies.

This article reviews the electrodiagnosis of brachial plexus injury, factors that predict outcome, the utility electrodiagnostic evaluation of potential nerve donors, and commonly used surgical interventions. Electrodiagnostic evaluation begins with a detailed understanding of brachial plexus anatomy and uses a complement of motor and sensory nerve conduction studies and needle electromyography to determine the location of injury and predict severity. Several factors are used to predict prognosis. In injuries with poor prognosis, surgical intervention is indicated. Nerve transfers are increasingly employed to improve functional outcomes. Electrodiagnosis is key to evaluating the viability of potential nerve donors.

Simultaneous reconstruction of extensor mechanism in the free transfer of vascularized proximal interphalangeal joint.

From a recent systemic review, vascularized toe proximal interphalangeal joint (PIPJ) transfer achieved an average arc of motion (AOM) of merely 37 degrees for finger PIPJ reconstruction. Despite the technical refinement over the past 3 decades, the resulting active motion of the reconstructed joint remains unpredictable and often fraught with extension lag. The technique for vascularized toe PIPJ transfer at our institute has evolved over the years to its current state, with simultaneous extensor mechanism reconstruction being a major component. During the transfer, the quality of extensor tendons on the recipient finger and donor toe are carefully evaluated. If the central slip of finger extensor is destroyed but the quality of lateral bands is adequate, centralization of lateral bands overlying the transferred PIPJ is performed. If there is acceptable central slip remnant at the proximal phalanx level, modified Stack procedure is performed for central slip reconstruction while leaving the lateral bands in continuity. If both lateral bands are poor, modified Stack procedure is performed unless the central tendon of the toe is strong enough to extend the PIPJ. From November 2008 to October 2010, 7 joints were transferred with this modified technique. The average follow-up was 18.2 months. The average active AOM of the transferred PIPJ was 56.4 degrees. The average extension lag of the toe PIPJ was 10.7 and 16.4 degrees before and after the transfer, respectively. Simultaneous reconstruction of extensor mechanism decreases the extension lag without sacrificing AOM of the transferred PIPJ.

The preventive effects of apolipoprotein mimetic D-4F from vibration injury-experiment in rats.

Hand-arm vibration syndrome (HAVS) is a debilitating sequela of neurological and vascular injuries caused by prolonged occupational exposure to hand-transmitted vibration. Our previous study demonstrated that short-term exposure to vibration can induce vasoconstriction and endothelial cell damage in the ventral artery of the rat's tail. The present study investigated whether pretreatment with D-4F, an apolipoprotein A-1 mimetic with known anti-oxidant and vasodilatory properties, prevents vibration-induced vasoconstriction, endothelial cell injury, and protein nitration. Rats were injected intraperitoneally with 3 mg/kg D-4F at 1 h before vibration of the tails for 4 h/day at 60 Hz, 49 m/s(2) r.m.s. acceleration for either 1 or 3 days. Vibration-induced endothelial cell damage was examined by light microscopy and nitrotyrosine immunoreactivity (a marker for free radical production). One and 3-day vibration produced vasoconstriction and increased nitrotyrosine. Preemptive treatment with D-4F prevented these negative changes. These findings suggest that D-4F may be useful in the prevention of HAVS.

Peroneal nerve compression by lateral gastrocnemius flap.

Lateral gastrocnemius muscle flaps are reliable flaps routinely used to cover defects in the lower thigh, the knee, and the upper third of the tibia. Peroneal neuropathy following lateral gastrocnemius flap has been described previously and mostly attributed to intraoperative nerve injury. However, compression of the nerve by the flap itself has not been reported. A 56-year-old female developed right common peroneal nerve palsy 10 months after a lateral gastrocnemius flap rotation for knee prosthesis coverage. Surgical exploration found a common peroneal nerve neuroma under a compressive band formed by the lateral fascial edge of the rotated gastrocnemius muscle. The motor nerve of the flap was not denervated. When stimulated, muscle contracted and compressed the common peroneal nerve underneath. Excision of the lateral fascia and selective motor denervation were performed. Postoperatively, the patient's symptoms improved. To prevent compressive common peroneal neuropathy from lateral gastrocnemius rotational flaps, we recommend fascial excision from the lateral aspect of the muscle and selective motor denervation.

Serological tests for diagnosis and staging of hand-arm vibration syndrome (HAVS).

The current gold standard for the diagnosis and staging of hand-arm vibration syndrome (HAVS) is the Stockholm workshop scale, which is subjective and relies on the patient's recalling ability and honesty. Therefore, great potentials exist for diagnostic and staging errors. The purpose of this study is to determine if objective serum tests, such as levels of soluble thrombomodulin (sTM) and soluble intercellular adhesion molecule-1 (sICAM-1), may be used in the diagnosis and staging of HAVS. Twenty two nonsmokers were divided into a control group (n = 11) and a vibration group (n = 11). The control group included subjects without history of frequent vibrating tool use. The vibration group included construction workers with average vibrating tool use of 12.2 years. All were classified according to the Stockholm workshop scale (SN, sensorineural symptoms; V, vascular symptoms. SN0, no numbness; SN1, intermittent numbness; SN2, reduced sensory perception; SN3, reduced tactile discrimination; V0, no vasospasmic attacks; V1, intermittent vasospasm involving distal phalanges; V2, intermittent vasospasm extending to middle phalanges; V3, intermittent vasospasm extending to proximal phalanges; V4, skin atrophy/necrosis). All control subjects were SN0 V0. Seven out of 11 vibration subjects were SN1 V1, and 4 out of 11 were SN1 V2. A 10-cm(3) sample of venous blood was collected from each subject. The sTM and sICAM-1 levels were determined by enzyme-linked immunosorbent assay. The mean plasma sTM levels were as follows: control group = 2.93 +/- 0.47 ng/ml, and vibration group = 3.61 +/- 0.24 ng/ml. The mean plasma sICAM-1 levels were as follows: control group = 218.8 +/- 54.1 ng/ml, and vibration group = 300.3 +/- 53.2 ng/ml. The sTM and sICAM-1 differences between control and vibration groups were statistically significant (p < 0.0002 and p < 0.001, respectively). When reference ranges provided by Hemostasis Reference Lab were used as cut-off values, all sTM and sICAM-1 levels were within range, except three vibration individuals (27%) who had sICAM-1 levels greater than the reference range. This was not statistically significant (p = 0.08). When subjects were compared based on the Stockholm workshop scale, mean plasma sTM levels were SN0 V0 group = 2.93 +/- 0.47 ng/ml, SN1 V1 group = 3.59 +/- 0.25 ng/ml, and SN1 V2 group = 3.65 +/- 0.27 ng/ml, and mean plasma sICAM-1 levels were SN0 V0 = 219 +/- 54.1 ng/ml, SN1 V1 = 275 +/- 33.5 ng/ml, and SN1 V2 = 345 +/- 54.6 ng/ml. The difference in sTM level among the three groups was statistically significant (p < 0.001). The difference in sICAM-1 level among the three groups was also statistically significant (p < 0.002). The sTM and sICAM-1 levels are statistically higher in subjects with HAVS, with levels proportional to the disease severity. However, large population studies are needed to determine the "real-life" standard reference ranges for sTM and sICAM-1.

Empiric antibiotic therapy for seawater injuries: a four-seasonal analysis.

BACKGROUND: Previous seawater studies found Vibrio species associated with morbidity, suggesting that seawater-contaminated wounds should be treated early. The purpose of this study was to identify common seawater pathogens and antibiotic sensitivities to provide empiric antibiotic therapy until patient-specific culture results are available. METHODS: Seasonal samples were collected from 25 Galveston beach locations and cultured. Colonies were identified and sensitivities were performed using MicroScan Positive and Negative Breakpoint Combo Panels. RESULTS: In the fall (28.3 degrees C), of 15 species isolated, the three most common isolates were Escherichia coli, Enterococcus faecium, and Klebsiella pneumoniae. Gram-negative isolates were sensitive to levofloxacin, lomefloxacin, and cefepime. Gram-positive isolates were sensitive to penicillin and ampicillin. In the winter (11.1 degrees C), of 14 species isolated, the three most common isolates were Enterobacter agglomerans, E. faecium, and E. coli. Gram-negative isolates were sensitive to levofloxacin, lomefloxacin, and cefepime. Most Gram-positive isolates were sensitive to vancomycin, levofloxacin, penicillin, and ampicillin. In the spring (26.6 degrees C), of 14 species isolated, the three most common isolates were E. coli, Bacillus species, and E. faecium. Gram-negative isolates were sensitive to levofloxacin, lomefloxacin, and cefepime. Most Gram-positive isolates were sensitive to penicillin, ampicillin, vancomycin, and levofloxacin. In the summer (29.7 degrees C), of 17 bacterial species isolated, the three most common isolates were Bacillus species, Enterobacter cloacae, and K. pneumoniae. Gram-negative isolates were sensitive to cefepime, lomefloxacin, and levofloxacin. Gram-positive isolates were sensitive to penicillin, ampicillin, vancomycin, levofloxacin, and chloramphenicol. CONCLUSIONS: Cultured pathogens were sensitive to penicillin, ampicillin, or levofloxacin. The authors recommend a combination of penicillin or ampicillin with levofloxacin for empiric antibiotic coverage for seawater-contaminated injuries.

Resting-state functional connectivity of the rat brain.

Regional-specific average time courses of spontaneous fluctuations in blood oxygen level dependent (BOLD) MRI contrast at 9.4T in lightly anesthetized resting rat brain are formed, and correlation coefficients between time course pairs are interpreted as measures of connectivity. A hierarchy of regional pairwise correlation coefficients (RPCCs) is observed, with the highest values found in the thalamus and cortex, both intra- and interhemisphere, and lower values between the cortex and thalamus. Independent sensory networks are distinguished by two methods: data driven, where task activation defines regions of interest (ROI), and hypothesis driven, where regions are defined by the rat histological atlas. Success in these studies is attributed in part to the use of medetomidine hydrochloride (Domitor) for anesthesia. Consistent results in two different rat-brain systems, the sensorimotor and visual, strongly support the hypothesis that resting-state BOLD fluctuations are conserved across mammalian species and can be used to map brain systems.

Modeling of region-specific fMRI BOLD neurovascular response functions in rat brain reveals residual differences that correlate with the differences in regional evoked potentials.

The response of the rat visual system to flashes of blue light has been studied by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The BOLD temporal response is dependent on the number of flashes presented and demonstrates a refractory period that depends on flash frequency. Activated brain regions included the primary and secondary visual cortex, superior colliculus (SC), dorsal lateral geniculate (DLG), and lateral posterior nucleus (LP), which were found to exhibit differing temporal responses. To explain these differences, the BOLD neurovascular response function was modeled. A second-order differential equation was developed and solved numerically to arrive at region-specific response functions. Included in the model are the light input from the diode (duty cycle), a refractory period, a transient response following onset and cessation of stimulus, and a slow adjustment to changes in the average level of the signal. Constants in the differential equation were evaluated for each region by fitting the model to the experimental BOLD response from a single flash, and the equation was then solved for multiple flashes. The simulation mimics the major features of the data; however, remaining differences in the frequency dependence of the response between the cortical and subcortical regions were unexplained. We hypothesized that these discrepancies were due to regional-specific differences in neuronal response to flash frequency. To test this hypothesis, cortical visual evoked potentials (VEPs) were recorded using the same stimulation protocol as the fMRI. Cortical VEPs were more suppressed than subcortical VEPs as flash frequency increased, supporting our hypothesis. This is the first report that regional differences in neuronal activation to the same stimulus lead to differential BOLD activation.