Matthew K. Mian

Human dorsal anterior cingulate cortex neurons mediate ongoing behavioural adaptation

The ability to optimize behavioural performance when confronted with continuously evolving environmental demands is a key element of human cognition. The dorsal anterior cingulate cortex (dACC), which lies on the medial surface of the frontal lobes, is important in regulating cognitive control. Hypotheses about its function include guiding reward-based decision making, monitoring for conflict between competing responses and predicting task difficulty. Precise mechanisms of dACC function remain unknown, however, because of the limited number of human neurophysiological studies. Here we use functional imaging and human single-neuron recordings to show that the firing of individual dACC neurons encodes current and recent cognitive load. We demonstrate that the modulation of current dACC activity by previous activity produces a behavioural adaptation that accelerates reactions to cues of similar difficulty to previous ones, and retards reactions to cues of different difficulty. Furthermore, this conflict adaptation, or Gratton effect, is abolished after surgically targeted ablation of the dACC. Our results demonstrate that the dACC provides a continuously updated prediction of expected cognitive demand to optimize future behavioural responses. In situations with stable cognitive demands, this signal promotes efficiency by hastening responses, but in situations with changing demands it engenders accuracy by delaying responses.

Deep brain stimulation for obsessive-compulsive disorder: past, present, and future

Obsessive-compulsive disorder (OCD) is a psychiatric illness that can lead to chronic functional impairment. Some patients with severe, chronic OCD have been treated with ablative neurosurgical techniques over the past 4 decades. More recently, deep brain stimulation (DBS) has been investigated as a therapy for refractory OCD, and the procedure was granted a limited humanitarian device exemption by the FDA in 2009. In this article, the authors review the development of DBS for OCD, describe the current understanding of the pathophysiological mechanisms of the disorder and how the underlying neural circuits might be modulated by DBS, and discuss the clinical studies that provide evidence for the use of this evolving therapy. The authors conclude with suggestions for how a combined basic science and translational research approach could drive the understanding of the neural mechanisms underlying OCD as well as the clinical effectiveness of DBS in the setting of recalcitrant disease.

Single-Neuron Responses in the Human Nucleus Accumbens during a Financial Decision-Making Task

Linking values to actions and evaluating expectations relative to outcomes are both central to reinforcement learning and are thought to underlie financial decision-making. However, neurophysiology studies of these processes in humans remain limited. Here, we recorded the activity of single human nucleus accumbens neurons while subjects performed a gambling task. We show that the nucleus accumbens encodes two signals related to subject behavior. First, we find that under relatively predictable conditions, single neuronal activity predicts future financial decisions on a trial-by-trial basis. Interestingly, we show that this activity continues to predict decisions even under conditions of uncertainty (e.g., when the probability of winning or losing is 50/50 and no particular financial choice predicts a rewarding outcome). Furthermore, we find that this activity occurs, on average, 2 s before the subjects physically manifest their decision. Second, we find that the nucleus accumbens encodes the difference between expected and realized outcomes, consistent with a prediction error signal. We show this activity occurs immediately after the subject has realized the outcome of the trial and is present on both the individual and population neuron levels. These results provide human single neuronal evidence that the nucleus accumbens is integral in making financial decisions.

Postoperative Intensive Care Unit Requirements After Elective Craniotomy

OBJECTIVE Commonly, patients undergoing craniotomy are admitted to an intensive care setting postoperatively to allow for close monitoring. We aim to determine the frequency with which patients who have undergone elective craniotomies require intensive care unit (ICU)-level interventions or experience significant complications during the postoperative period to identify a subset of patients for whom an alternative to ICU-level care may be appropriate. METHODS Following Institutional Review Board approval, a prospective, consecutive cohort of adult patients undergoing elective craniotomy was established at the Massachusetts General Hospital between the dates of April 2010 and March 2011. Inclusion criteria were intradural operations requiring craniotomy performed on adults (18 years of age or older). Exclusion criteria were cases of an urgent or emergent nature, patients who remained intubated postoperatively, and patients who had a ventriculostomy drain in place at the conclusion of the case. RESULTS Four hundred patients were analyzed. Univariate analysis revealed that patients with diabetes (P = 0.00047), those who required intraoperative blood product administration (P = 0.032), older patients (P < 0.0001), those with higher intraoperative blood losses (P = 0.041), and those who underwent longer surgical procedures (P = 0.021) were more likely to require ICU-level interventions or experience significant postoperative complications. Multivariate analysis only found diabetes (P = 0.0005) and age (P = 0.0091) to be predictive of a patients need for postoperative ICU admission. CONCLUSIONS Diabetes and older age predict the need for ICU-level intervention after elective craniotomy. Properly selected patients may not require postcraniotomy ICU monitoring. Further study of resource utilization is necessary to validate these preliminary findings, particularly in different hospital types.

Interfacility Helicopter Ambulance Transport of Neurosurgical Patients: Observations, Utilization, and Outcomes from a Quaternary Level Care Hospital

Background The clinical benefit of helicopter transport over ground transportation for interfacility transport is unproven. We sought to determine actual practice patterns, utilization, and outcomes of patients undergoing interfacility transport for neurosurgical conditions. Methodology/Principal Findings We retrospectively examined all interfacility helicopter transfers to a single trauma center during 2008. We restricted our analysis to those transfers leading either to admission to the neurosurgical service or to formal consultation upon arrival. Major exclusion criteria included transport from the scene, death during transport, and transport to any area of the hospital other than the emergency department. The primary outcome was time interval to invasive intervention. Secondary outcomes were estimated ground transportation times from the referring hospital, admitting disposition, and discharge disposition. Of 526 candidate interfacility helicopter transfers to our emergency department in 2008, we identified 167 meeting study criteria. Seventy-five (45%) of these patients underwent neurosurgical intervention. The median time to neurosurgical intervention ranged from 1.0 to 117.8 hours, varying depending on the diagnosis. For 101 (60%) of the patients, estimated driving time from the referring institution was less than one hour. Four patients (2%) expired in the emergency department, and 34 patients (20%) were admitted to a non-ICU setting. Six patients were discharged home within 24 hours. For those admitted, in-hospital mortality was 28%. Conclusions/Significance Many patients undergoing interfacility transfer for neurosurgical evaluation are inappropriately triaged to helicopter transport, as evidenced by actual times to intervention at the accepting institution and estimated ground transportation times from the referring institution. In a time when there is growing interest in health care cost containment, practitioners must exercise discretion in the selection of patients for air ambulance transport—particularly when it may not bear influence on clinical outcome. Neurosurgical evaluation via telemedicine may be one strategy for improving air transport triage.

Beneficial effect of subsequent lesion procedures after nonresponse to initial cingulotomy for severe, treatment-refractory obsessive-compulsive disorder.

BACKGROUND Anterior cingulotomy (AC) can be an effective therapy for patients with severe obsessive-compulsive disorder who are refractory to traditional medical therapy. For patients who do not respond to AC, the benefit of additional lesion procedures vs continued medical management remains unknown. OBJECTIVE To determine whether a second lesion procedure is beneficial after unsuccessful initial AC. METHODS In this retrospective cohort study, we reviewed the records of 31 patients who were nonresponders to initial AC. Full response was defined as at least a 35% decrease and partial response as a 25% to 34% decrease in Yale-Brown Obsessive-Compulsive Scale scores. Yale-Brown Obsessive-Compulsive Scale change was compared between patients who underwent additional surgery and those treated nonsurgically. In addition, for patients who underwent additional surgery, we compared the benefit of subcaudate tractotomy with repeat AC (extension of the initial lesion) as the second procedure. RESULTS Nineteen patients underwent a second surgery and 12 patients continued nonsurgical therapy. Fifty-three percent of patients who received additional surgery were full responders and 21% were partial responders at the most recent follow-up compared with 17% full responders and 25% partial responders among those who continued conventional therapy (P = .02). Of the patients who underwent an additional surgery, there were 64% full and 9% partial responders in the subcaudate tractotomy group compared with 38% full and 38% partial responders in the repeat AC group (P = .04). CONCLUSION Second lesion surgery can be a safe and effective therapy for patients who do not respond to initial AC. Subcaudate tractotomy may confer a higher response rate than repeat cingulotomy.

Utility of foramen ovale electrodes in mesial temporal lobe epilepsy.

To determine the ability of foramen ovale electrodes (FOEs) to localize epileptogenic foci after inconclusive noninvasive investigations in patients with suspected mesial temporal lobe epilepsy (MTLE).

Transsphenoidal surgery for cushing disease after nondiagnostic inferior petrosal sinus sampling.

BACKGROUND Inferior petrosal sinus sampling (IPSS) is a useful technique for confirming a pituitary source of adrenocorticotropic hormone (ACTH) overproduction in Cushing disease. Uncertainty remains regarding the appropriate course of therapy when an ectopic tumor is predicted by IPSS but none can be found and in circumstances when the procedure cannot be successfully completed owing to technical or anatomic limitations. OBJECTIVE To determine an appropriate course of action after nondiagnostic IPSS. METHODS We reviewed 288 IPSS procedures in 283 patients between 1986 and 2010 at our center. An IPS:peripheral ACTH ratio ≥ 2 at baseline or ≥ 3 after corticotrophin-releasing hormone was considered predictive of a pituitary source of ACTH. A procedure was considered nondiagnostic if the procedure was successfully performed and the results predicted an ectopic source but none could be found despite extensive imaging or if the IPS could not be bilaterally cannulated because of technical difficulties or anatomic variants. RESULTS The sensitivity, specificity, positive predictive value, and negative predictive value of IPSS for detecting a pituitary source in Cushing disease were 94%, 50%, 98%, and 29%, respectively. We identified 3 categories of nondiagnostic IPSS comprising 44 of the total procedures. These patients underwent exploratory transsphenoidal surgery, and in 42 of these patients (95%), a pituitary source was surgically proven, with a remission rate of 83%. CONCLUSION Transsphenoidal surgery should be considered in cases of ACTH-dependent Cushing disease and noncentralized or technically unsuccessful IPSS without evidence of ectopic tumor.

Studying task-related activity of individual neurons in the human brain

Single-neuronal studies remain the gold standard for studying brain function. Here we describe a protocol for studying task-related single-neuronal activity in human subjects during neurosurgical procedures involving microelectrode recordings. This protocol has two phases: a preoperative phase and an intraoperative phase. During the preoperative phase, we discuss informed consent, equipment setup and behavioral testing. During the intraoperative phase, we discuss the procedure for microelectrode recordings. Because patients are often awake during these procedures, this protocol can be performed in conjunction with behavioral tasks for studying a variety of cognitive functions. We describe the protocol in detail and provide two examples of expected results. In addition, we discuss the potential difficulties and pitfalls related to intraoperative studies. This protocol takes ∼1.5 h to complete.

Intraspinal migration of a clavicular Steinmann pin: case report and management strategy

Spine injury resulting from migration of previously implanted appendicular skeleton fixation hardware is rare. We present a 41-year-old man who had Steinmann fixation pins placed for a left clavicular fracture 2 years prior. He presented with a burning sensation over his biceps bilaterally and numbness over the left anterior chest and abdomen following a significant blunt traumatic injury. A CT scan revealed migration of a fractured Steinmann pin entering the left C8 neural foramen, traversing anterior to the spinal cord. The patient underwent a left C7 hemilaminectomy, foraminal decompression, and first rib resection to identify the extraforaminal portion of the pin and remove it under direct vision. He recovered uneventfully. We conclude that a principle of safe surgical removal includes adequate exposure to allow for direct visualization of the pin and neural structures. We review the evaluation and management strategies of this unusual condition.