Using a Robotic-Assisted Approach for Stereotactic Laser Ablation Corpus Callosotomy: A Technical Report.

BACKGROUND: Corpus callosotomy for medically intractable epilepsy is an effective ablative procedure traditionally achieved using either standard open craniotomy or with less-invasive approaches. Advances in robotic-assisted stereotactic guidance for neurosurgery can be applied for LITT for corpus callosotomy. CLINICAL PRESENTATIONS: Two patients were included in this study. One was a 25-year-old female patient with extensive bi-hemispheric malformations of cortical development and medically refractory epilepsy, and the other was an 18-year-old male with medically refractory epilepsy and atonic seizures, who underwent a complete corpus callosotomy using robotic-assisted stereotactic guidance for LITT. RESULTS: Both patients underwent successful intended corpus callosotomy with volumetric analysis demonstrating a length disconnection of 74% and a volume disconnection of 55% for patient 1 and a length disconnection of 83% and a volume disconnection of 33% for patient 2. Postoperatively, both patients had clinical reductions in seizure. CONCLUSION: Our experience demonstrates that robotic guidance systems can safely and effectively be adapted for minimally invasive LITT corpus callosotomy.

Deep Brain Stimulation for Obsessive-Compulsive Disorder: Real World Experience Post-FDA-Humanitarian Use Device Approval.

Background: While case series have established the efficacy of deep brain stimulation (DBS) in treating obsessive-compulsive disorder (OCD), it has been our experience that few OCD patients present without comorbidities that affect outcomes associated with DBS treatment. Here we present our experience with DBS therapy for OCD in patients who all have comorbid disease, together with the results of our programming strategies. Methods: For this case series, we assessed five patients who underwent ventral capsule/ventral striatum (VC/VS) DBS for OCD between 2015 and 2019 at the University of Colorado Hospital. Every patient in this cohort exhibited comorbidities, including substance use disorders, eating disorder, tic disorder, and autism spectrum disorder. We conducted an IRB-approved, retrospective study of programming modifications and treatment response over the course of DBS therapy. Results: In addition to patients' subjective reports of improvement, we observed significant improvement in the Yale-Brown Obsessive-Compulsive Scale (44%), the Montgomery-Asberg Depression Rating Scale (53%), the Quality of Life Enjoyment and Satisfaction Questionnaire (27%), and the Hamilton Anxiety Rating scales (34.9%) following DBS. With respect to co-morbid disease, there was a significant improvement in a patient with tic disorder's Total Tic Severity Score (TTSS) (p = 0.005). Conclusions: DBS remains an efficacious tool for the treatment of OCD, even in patients with significant comorbidities in whom DBS has not previously been investigated. Efficacious treatment results not only from the accurate placement of the electrodes by the surgeon but also from programming by the psychiatrist.

Social Perception and Academic Trends on Women in the Field of Neurosurgery: A Bibliometric Analysis.

BACKGROUND: The ongoing trend of societal evolution in contemporary civilization has allowed increased inclusion of heterogenous identity groups into fields, such as neurosurgery, where certain groups have traditionally been underrepresented. In regard to the field of neurosurgery, the increasing recognition of the disparities faced by women is illustrated by a growing body of academic literature. METHODS: We conducted a bibliometric analysis querying the PubMed, Web of Science, Scopus, and Embase databases for articles on women in neurosurgery using the MeSH terms "woman," "women," "gender," neurosurgery," neurological surgery," and "neurosurgeon." Articles were excluded if they did not concern societal impact of nonmale population in the context of neurosurgery. Total citations, mean citations per year, publishing journal information, and author demographics were abstracted from included reports. Associations between abstracted continuous variables were evaluated using the Pearson correlation coefficient. Derived P values < 0.05 were taken as significant. RESULTS: A total of 49 articles were included. Total numbers of citations per report were positively associated with mean citations per year (r = 0.7289, P = 0.0253), the latter of which was slightly negatively associated with the age of the report (r = -0.0413, P = 0.0009). Age of publication year was found to be negatively correlated with the number of reports published per year (r = -0.648, P = 0.0066). Total citations per reports were significantly correlated with increased numbers of citations during the last completed calendar year (2019: r = 0.8956, P = 0.0397). CONCLUSIONS: Recognition in societal evolutionary trends as evidenced by academic activity has shown increased focus on the explicit and intrinsic biases faced by women in neurosurgery. Recent years have seen significant increases in published reports concerning the subject, as well as rising academic impact per a given report. This phenomenon is speculated to continue, and understanding to broaden as societal perception continues to develop.

Effects of the COVID-19 Pandemic on Operative Volume and Residency Training at Two Academic Neurosurgery Centers in New Orleans.

BACKGROUND: Medical subspecialties including neurosurgery have seen a dramatic shift in operative volume in the wake of the coronavirus disease 2019 (COVID-19) pandemic. The goal of this study was to quantify the effects of the COVID-19 pandemic on operative volume at 2 academic neurosurgery centers in New Orleans, Louisiana, USA from equivalent periods before and during the COVID-19 pandemic. METHODS: A retrospective review was conducted analyzing neurosurgical case records for 2 tertiary academic centers from March to June 2020 and March to June 2019. The records were reviewed for variables including institution and physician coverage, operative volume by month and year, cases per subspecialty, patient demographics, mortality, and morbidity. RESULTS: Comparison of groups showed a 34% reduction in monthly neurosurgical volume per institution during the pandemic compared with earlier time points, including a 77% decrease during April 2020. There was no change in mortality and morbidity across institutions during the pandemic. CONCLUSIONS: The COVID-19 pandemic has had a significant impact on neurosurgical practice and will likely continue to have long-term effects on patients at a time when global gross domestic products decrease and relative health expenditures increase. Clinicians must anticipate and actively prepare for these impacts in the future.

Effects of Medical Comorbidities on the Surgical Outcomes of Deep Brain Stimulation for Parkinson Disease: A Retrospective, Single-Institution Study.

OBJECTIVE: Advancing age and greater number of medical comorbidities are well-known risk factors for higher rates of surgical complications and undesirable outcomes. We sought to determine the risk of increasing medical comorbidities on surgical outcomes for patients with Parkinson disease undergoing deep brain stimulation (DBS) surgery. METHODS: We retrospectively reviewed 107 consecutive patients who underwent DBS for Parkinson disease at Ochsner Medical Center in 2008-2018. Patients were stratified into 3 groups based on Elixhauser comorbidity index (ECI) at the time of surgery: 0, 1, or ≥2. Outcome measures were changes in Unified Parkinson's Disease Rating Scale III scores, changes in medications, and surgical complications. Analysis of variance, paired t test, and nonparametric equivalents were used for statistical analysis. RESULTS: Of patients, 31 (29.0%) had ECI score 0, 44 (41.1%) had ECI score 1, and 32 (29.9%) had ECI score ≥2. For all groups, Unified Parkinson's Disease Rating Scale III scores decreased significantly postoperatively (P = 0.0014, P < 0.0001, P < 0.0001). All groups had a reduction in mean levodopa equivalent daily dose after surgery; however, only the group with ≥2 comorbidities achieved statistical significance (P = 0.0026). The rate of postoperative complications was significantly correlated with comorbidity score on univariate logistic regression analysis (P = 0.0425). CONCLUSIONS: Our findings indicate that DBS is efficacious in patients with multiple medical comorbidities. However, patients with ≥1 medical comorbidities may be more likely to have complications. The most common observed complication was wound infection. Patients with medical comorbidities may still benefit significantly from DBS when performed at experienced centers.

RNS modifications to eliminate stimulation-triggered signs or symptoms (STS): Case series and practical guide.

Responsive neurostimulation (RNS) for intractable epilepsy involves placement of electrodes onto or into the brain that detect seizure activity and then deliver a current to abort a seizure before it spreads. Successful RNS treatment can deliver hundreds of stimulations per day, which are generally unnoticeable to patients. Uncommonly, RNS electrodes may result in stimulation of brain regions or peripheral structures that causes uncomfortable sensory or motor effects, a phenomenon we refer to as stimulation-triggered signs or symptoms (STS). Occurrence of STS may limit the ability to use RNS to full capacity to reduce seizures. In this case series, we describe STS in six out of 58 (10.3%) RNS patients at our institution. To eliminate or minimize STS, we developed a protocol for modification of RNS parameters. Modifying RNS stimulation was associated with reduced STS in all six patients, five had adjustment of stimulation settings, one of lead position. Five out of six patients were able to undergo further optimization of RNS for improved seizure control after reduction of symptoms. One patient had recurrent STS that prevented further increase of RNS stimulation current. This study may help other medical teams in identifying and reducing STS in patients with epilepsy receiving RNS devices.

Coronavirus 2019 (COVID-19)-Associated Encephalopathies and Cerebrovascular Disease: The New Orleans Experience.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic has had a dramatic impact on health care systems and a variable disease course. Emerging evidence demonstrates that severe acute respiratory syndrome coronavirus 2 is associated with central nervous system disease. We describe central nervous system manifestations in critical patients with COVID-19 at our tertiary center. METHODS: We conducted a single-center retrospective analysis of all actively critical patients with COVID-19 admitted to our tertiary care academic center in New Orleans, Louisiana, on April 22, 2020, with new onset of neurologic disease. Patients were grouped into 1 of 3 categories according to imaging and clinical features; encephalopathy, acute necrotizing encephalopathy, and vasculopathy. RESULTS: A total of 27 of 76 (35.5%) critical patients with COVID-19 met inclusion criteria. Twenty patients (74%) were designated with COVID-19-associated encephalopathy, 2 (7%) with COVID-19-associated acute necrotizing encephalopathy, and 5 (19%) with COVID-19-associated vasculopathy. Sixty-three percent of neurologic findings were demonstrated on computed tomography, 30% on magnetic resonance imaging, and 44% on electroencephalography. Findings most often included ischemic strokes, diffuse hypoattenuation, subcortical parenchymal hemorrhages, and focal hypodensities within deep structures. Magnetic resonance imaging findings included diffuse involvement of deep white matter, the corpus callosum, and the basal ganglia. For patients with large-territory ischemic stroke, all but one displayed irregular proximal focal stenosis of the supraclinoid internal carotid artery. CONCLUSIONS: Analysis of active critical COVID-19 admissions at our revealed a high percentage of patients with new neurologic disease. Although variable, presentations followed 1 of 3 broad categories. A better understanding of the neurologic sequalae and radiographic findings will help clinicians mitigate the impact of this disease.

Commentary: The Tulane University-Ochsner Clinic Foundation Neurosurgery Program: 75 Years of History, Including the Program's Rebirth After Katrina.

Neurosurgery training in New Orleans began when Dr Dean Echols became the head of Neurosurgery for the Ochnser Clinic and Charity Hospital in 1944. The oldest in Louisiana, the Tulane-Ochsner program has trained 63 board-certified neurosurgeons since its founding, including 5 chairmen. The program has a colorful history linked to New Orleans. Its residents have enjoyed training at Charity Hospital, Tulane Hospital and Clinics, Veterans Affairs Medical Center, and the Ochsner Clinic Foundation.

Long-term outcomes of deep brain stimulation in severe Parkinson's disease utilizing UPDRS III and modified Hoehn and Yahr as a severity scale.

OBJECTIVES: Deep brain stimulation (DBS) is the surgical treatment of choice for moderate to severe Parkinson's Disease (PD). However, few studies have assessed its efficacy in severe PD as defined by the modified Hoehn and Yahr scale (HY). This study evaluates long-term and medication outcomes of DBS in severe PD. PATIENTS AND METHODS: We retrospectively collected the data of 15 patients from 2008 to 2014 with severe PD treated with DBS. Retrospective assessment with the modified Hoehn and Yahr scale and motor subset of the Unified Parkinson's Disease Rating Scale (UPDRS III) were used to objectively track severity and motor function improvement, respectively. Levodopa equivalence daily doses (LEDD), number of anti-PD medications and number of daily medication doses were used to measure improvements in medication burden. Data was evaluated using univariate analyses, one sample paired t-test, two sample paired t-test, and Wilcoxon signed-rank test. RESULTS: The mean post-operative follow-up was 44.63 months, average age at diagnosis and the average age at time of DBS was 51.3 years and 61.5 years, respectively, and the time from diagnosis to treatment was 13.2 years. Significant decreases were seen in UPDRS III scores (pre-op = 44.533; post-op = 26.13; p = 0.0094), LEDD (pre-op = 1679.34 mg; post-op = 837.48 mg; p = 0.0049), and number of daily doses (pre-op = 21.266; post-op 12.2; p = 0.0046). No significant decrease was seen in the number of anti-PD medications (pre-op = 3.8; post-op = 3.2; p = 0.16). CONCLUSION: Following DBS, severe PD patients demonstrated significant improvements in motor function and medication burden during long-term follow-up. We believe our results prove that DBS is efficacious in the management of severe PD, and that further research should follow to expand DBS criteria to include severe disease.

The shifting burden of neurosurgical disease: Vietnam and the middle-income nations.

OBJECTIVE: The Global Burden of Disease (GBD) is an international collaboration and the largest comprehensive investigation of global health disease burden ever conducted. It has been particularly insightful for understanding disease demographics in middle-income nations undergoing rapid development, such as Vietnam, where 6 of the top 10 causes of death are relevant to the neurosurgeon. The burden of stroke-the number one cause of death in Vietnam-is particularly impressive. Likewise, road injuries, with a disproportionate rate of traumatic brain injury, continue to increase in Vietnam following economic development. Low-back and neck pain is the number one cause of disability. Simultaneously, more patients have access to care, and healthcare spending is increased. METHODS: It is imperative that neurosurgical capital and infrastructure keep pace with Vietnam's growth. The authors searched the existing literature for assessments of neurosurgical infrastructure or initiatives to address neurosurgical disease burden. Using GBD data, the authors also abstracted data for death by cause and prevalence of years of life lost due to disability (YLD) for common neurosurgical pathologies for Vietnam and comparison nations. RESULTS: Interventions aimed at primary prevention of risk factors for neurosurgical disease and focused on the transference of self-sustainable technical skills were found to be analogous to those that have been successful in other regions. Efforts toward stroke prevention have been focused on causal risk factors. Multiple investigators have found that interventions aimed at increasing helmet use were successful in preventing traumatic brain injury. Government-led reforms and equipment donation programs have improved technical capacity. Nevertheless, Vietnam lags behind other nations in neurosurgeons per capita; cause-attributable death and YLD attributable to neurosurgical disease are considerably higher in Vietnam and middle-income nations compared to both lower-income nations and upper-income nations. CONCLUSIONS: More than two-thirds of deaths attributable to neurosurgical pathologies in Vietnam and other middle-income nations were due to stroke, and one-fifth of both cause-attributable death and YLD was associated with neurosurgical pathologies. Vietnam and other middle-income nations continue to assume a global burden of disease profile that ever more closely resembles that of developed nations, with particular cerebrovascular, neurotrauma, and spinal disease burdens, leading to exponentially increased demand for neurosurgeons that threatens to outpace the training of neurosurgeons.

Comparison of elderly and young patient populations treated with deep brain stimulation for Parkinson's disease: long-term outcomes with up to 7 years of follow-up.

OBJECTIVE: Deep brain stimulation (DBS) is the procedure of choice for Parkinson's disease (PD). It has been used in PD patients younger than 70 years because of better perceived intra- and postoperative outcomes than in patients 70 years or older. However, previous studies with limited follow-up have demonstrated benefits associated with the treatment of elderly patients. This study aims to evaluate the long-term outcomes in elderly PD patients treated with DBS in comparison with a younger population. METHODS: PD patients treated with DBS at the authors' institution from 2008 to 2014 were divided into 2 groups: 1) elderly patients, defined as having an age at surgery ≥ 70 years, and 2) young patients, defined as those < 70 years at surgery. Functional and medical treatment outcomes were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS III), levodopa-equivalent daily dose (LEDD), number of daily doses, and number of anti-PD medications. Study outcomes were compared using univariate analyses, 1-sample paired t-tests, and 2-sample t-tests. RESULTS: A total of 151 patients were studied, of whom 24.5% were ≥ 70 years. The most common preoperative Hoehn and Yahr stages for both groups were 2 and 3. On average, elderly patients had more comorbidities at the time of surgery than their younger counterparts (1 vs 0, p = 0.0001) as well as a higher average LEDD (891 mg vs 665 mg, p = 0.008). Both groups experienced significant decreases in LEDD following surgery (elderly 331.38 mg, p = 0.0001; and young 108.6 mg, p = 0.0439), with a more significant decrease seen in elderly patients (young 108.6 mg vs elderly 331.38 mg, p = 0.0153). Elderly patients also experienced more significant reductions in daily doses (young 0.65 vs elderly 3.567, p = 0.0344). Both groups experienced significant improvements in motor function determined by reductions in UPDRS III scores (elderly 16.29 vs young 12.85, p < 0.0001); however, reductions in motor score between groups were not significant. Improvement in motor function was present for a mean follow-up of 3.383 years postsurgery for the young group and 3.51 years for the elderly group. The average follow-up was 40.6 months in the young group and 42.2 months in the elderly group. CONCLUSIONS: This study found long-term improvements in motor function and medication requirements in both elderly and young PD patients treated with DBS. These outcomes suggest that DBS can be successfully used in PD patients ≥ 70 years. Further studies will expand on these findings.

First Case of Autonomic Dysreflexia Following Elective Lower Thoracic Spinal Cord Transection in a Spina Bifida Adult.

BACKGROUND: Spinal cord transection is a radical but effective treatment for highly selective cases of symptomatic spinal retethering in paraplegic spina bifida patients. Autonomic dysreflexia (AD) is a potentially life-threatening syndrome involving a dysregulated sympathetic discharge reflex commonly seen following cervical and high thoracic spinal cord injury, leading to a disconnect between autonomic pathways above and below the lesion that can lead to severe complications including uncontrolled hypertension, bradycardia, stroke, and potentially death. Herein we present a case in which a paraplegic spina bifida patient presenting with symptomatic spinal retethering experienced autonomic dysreflexia following an elective spinal cord transection. CASE DESCRIPTION: A 51-year-old male with a history of complex spina bifida presented with an active cerebrospinal fluid leak. Physical examination revealed a thin covering of abnormal epidermis over the large placode. Magnetic resonance imaging revealed a large myelomeningocele defect with posterior element defects spanning from L2 to the sacrum with evidence of tethering. The patient underwent an intradural transection of the spinal cord with a "blind-pouch" closure of the dura at the level of T12/L1. Postoperatively, the patient developed intermittent episodes of hypertension, bradycardia, headaches, altered mental status, severe perspiration, and red flushing of the upper torso, face, and arms. The diagnosis of AD was made clinically and managed with a positive response to a combination of beta- and alpha-blockade along with patient education on avoidance of common AD triggers. At 5-year follow-up the patient has continued to do well on medication. CONCLUSION: This case highlights a potential major side effect from elective transection of the spinal cord. If unrecognized and untreated, AD can cause significant distress and morbidity. We hope this first case report serves to supplement existing data and aid in future surgical and medical decision-making.

Short- and Long-Term Outcomes of Deep Brain Stimulation in Patients 70 Years and Older with Parkinson Disease.

BACKGROUND: Parkinson disease (PD) is a common neurodegenerative disease in elderly patients that may be treated with deep brain stimulation (DBS). DBS is an accepted surgical treatment in PD patients <70 years that demonstrates marked improvement in disease symptomology. Patients ≥70 years historically have been excluded from DBS therapy. Our objective is to evaluate the short- and long-term outcomes in patients with PD ≥70 years who underwent DBS at our center. METHODS: In our single-center study, we retrospectively assessed a prospective registry of patients with PD treated with DBS who were ≥70 years old at the time of their procedure. Univariate analyses and 1-sample paired t test were used to evaluate data. Motor scores were evaluated with the Unified Parkinson's Disease Rating Scale III, and the effects on medication requirements were evaluated with levodopa equivalence daily doses (LEDD). RESULTS: Thirty-seven patients were followed for an average of 42.2 months post-DBS. The average ages at diagnosis and at the time of DBS surgery were 63.05 years and 72.45 years, respectively. Significant reductions in the average Unified Parkinson's Disease Rating Scale III score were observed (preoperative 31.8; postoperative 15.6; P < 0.0001). Significant reductions in the average LEDD (preoperative 891.94 mg; postoperative 559.6 mg; P = 0.0008) and medication doses per day (preoperative 11.54; postoperative 7.97; P = 0.0112) also were present. CONCLUSION: DBS is effective in treating elderly patients with PD. Patients experienced improvement in motor function, LEDD, and medication doses per day after DBS. Our results suggest that DBS is an effective treatment modality in elderly patients with PD.

Fetal surgery: the ochsner experience with in utero spina bifida repair.

BACKGROUND: Myelomeningocele is the most common form of congenital central nervous system defect that is compatible with life. Most patients with myelomeningocele have significant functional impairment of ambulation and bowel and bladder function, require permanent cerebrospinal fluid diversion with shunting, and have significant morbidity and mortality from hindbrain herniation (Chiari II malformation). The advent of intrauterine surgery has provided new opportunities to better address this lifelong debilitating disease. CASE REPORT: The patient was a 19-year-old gravida 2 para 1 at 22-6/7 weeks whose fetus was diagnosed with an open neural tube defect and further demonstrated to have ventriculomegaly and hindbrain herniation. Amniocentesis confirmed normal karyotype and the presence of acetylcholinesterase. After an intrauterine procedure, the patient underwent cesarean section at 35-5/7 weeks and delivered a male infant. His spinal incision was well healed at birth without any evidence of cerebrospinal fluid leakage, and his extremities were normal in appearance, range of motion, and movement. The infant also has maintained relatively normal, age-appropriate bowel and bladder function and has no obvious neurologic deficit. CONCLUSION: As the benefit of fetal surgery becomes more widely accepted, quality of care and patient safety must be at the forefront of any institution's effort to offer fetal surgery. Given the current prevalence of spina bifida and the amount of resources required to treat this disease effectively either in utero or postnatally, it is our opinion that the treatment of spina bifida should be regionalized to tertiary referral centers with the interdisciplinary expertise to offer comprehensive treatment for all aspects of the disease and all phases of care for the patients.

Medial prefrontal lesions in mice impair sustained attention but spare maintenance of information in working memory.

Working memory and attention are complex cognitive functions that are disrupted in several neuropsychiatric disorders. Mouse models of such human diseases are commonly subjected to maze-based tests that can neither distinguish between these cognitive functions nor isolate specific aspects of either function. Here, we have adapted a simple visual discrimination task, and by varying only the timing of events within the same task construct, we are able to measure independently the behavioral response to increasing attentional demand and increasing length of time that information must be maintained in working memory. We determined that mPFC lesions in mice impair attention but not working memory maintenance.

Disseminated germinoma in the brain and cervical spinal cord 10 years after radiographic resolution of pineal germinoma.

Intracranial germinoma, a radiosensitive tumor, is seldom recurrent following initial treatment. When it does recur, it is usually soon after initial treatment and secondary to inadequate radiation field coverage of the tumor. Rarely, there have been case reports of late recurrence many years after initial therapy. Patients with recurrent germinoma in the spine have a less favorable prognosis in terms of treatment response compared to the initial lesion. Thus, careful consideration of the initial lesion, its treatment, and serial imaging of the neural axis with close follow-up is important. We report a patient with a rare delayed recurrence in the brain and cervical spinal cord despite close follow-up with clinical examination and serial imaging.

Transient and selective overexpression of D2 receptors in the striatum causes persistent deficits in conditional associative learning.

Cognitive deficits in schizophrenia are thought to derive from a hypofunction of the prefrontal cortex (PFC), but the origin of the hypofunction is unclear. To explore the nature of this deficit, we genetically modified mice to model the increase in striatal dopamine D(2) receptors (D(2)Rs) observed in patients with schizophrenia. Previously, we reported deficits in spatial working memory tasks in these mice, congruent with the working memory deficits observed in schizophrenia. However, patients with schizophrenia suffer from deficits in many executive functions, including associative learning, planning, problem solving, and nonspatial working memory. We therefore developed operant tasks to assay two executive functions, conditional associative learning (CAL) and nonspatial working memory. Striatal D(2)R-overexpressing mice show a deficit in CAL because of perseverative behavior, caused by interference from the previous trial. D(2)R up-regulation during development was sufficient to cause this deficit, because switching off the transgene in adulthood did not rescue the phenotype. We validated prefrontal dependency of CAL by using neurotoxic lesions. Lesions of the medial PFC including the anterior cingulate, infralimbic, and prelimbic cortices impair CAL because of increased interference from previously rewarded trials, exactly as observed in D(2)R transgenic mice. In contrast, lesions restricted to the infralimbic and prelimbic cortices have no effect on CAL but impair performance in the nonspatial working memory task. These assays not only give us insight into how excess striatal D(2)Rs affect cognition but also provide tools for studying cognitive endophenotypes in mice.