G. Rees Cosgrove

Human anterior cingulate neurons and the integration of monetary reward with motor responses

Nat. Neurosci. 7, 1370–1375 (2004) A reference was deleted from this paper during the production process. It should have read as follows: 17. Botvinick, M., Nystrom, L.E., Fissell, K., Carter, C.S. & Cohen, J.D. Conflict monitoring versus selection-for-action in anterior cingulate cortex. Nature402, 179–181 (1999).

Deep brain stimulation of the anterior internal capsule for the treatment of Tourette syndrome: technical case report.

OBJECTIVE AND IMPORTANCE: Medical treatment of Tourette syndrome is often ineffective or is accompanied by debilitating side effects, therefore prompting the need to evaluate surgical therapies. CLINICAL PRESENTATION: We present the case of a 37-year-old woman with severe Tourette syndrome since the age of 10 years. Her symptoms included frequent vocalizations and severe head and arm jerks that resulted in unilateral blindness. Trials of more than 40 medications and other therapies had failed to relieve the tics. INTERVENTION: We implanted bilateral electrodes in the anterior limb of the internal capsule, terminating in the vicinity of the nucleus accumbens. At 18-month follow-up, optimal stimulation continued to lower her tic frequency and severity significantly. CONCLUSION: Our findings suggest that stimulation of the anterior internal capsule may be a safe and effective procedure for the treatment of Tourette syndrome.

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor

BACKGROUND Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder.

BACKGROUND As interventions for severe, treatment-refractory obsessive compulsive disorder (OCD), neurosurgical procedures are associated with only modest efficacy. The purpose of this study was to identify cerebral metabolic correlates as potential predictors of treatment response to anterior cingulotomy for OCD. METHODS Clinical data were analyzed in the context of a retrospective design. Subjects were 11 patients who underwent stereotactic anterior cingulotomy for OCD. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and at approximately 6 months postoperative. Preoperative F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) data were available. Statistical parametric mapping methods were used to identify loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in Y-BOCS scores. RESULTS One locus within right posterior cingulate cortex was identified, where preoperative metabolism was significantly correlated with improvement in OCD symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at that locus were associated with better postoperative outcome. CONCLUSIONS A possible predictor of treatment response was identified for patients with OCD undergoing anterior cingulotomy. Further research, utilizing a prospective design, is indicated to determine the validity and reliability of this finding. If confirmed, an index for noninvasively predicting response to cingulotomy for OCD would be of great value.

A Mobile Computed Tomographic Scanner with Intraoperative and Intensive Care Unit Applications

INTRODUCTION A mobile computed tomographic scanner has been developed in which the scan plane is selected by means of gantry translation, rather than by translation of the patient table. This permits computed tomographic scanning in situ of any patient who is positioned on a radiolucent surface that fits within the inner diameter of the gantry. We report the design of and initial experience with this scanner as used with adapters for intraoperative and bedside computed tomography (CT). METHODS The scanner is equipped with wheels, draws power from wall outlets (120 V, 20 A) in combination with batteries, and has a translating gantry. Preclinical studies of image quality were performed with phantoms. An operating table adapter was built for use with a radiolucent cranial fixation device. A bedside adapter was built that holds the head and shoulders of a patient in the intensive care unit. RESULTS The preclinical phantom studies showed satisfactory image spatial resolution (0.8 mm) and low-contrast resolution signal-to-noise relative standard deviation (0.37%). Experience to date with 12 patients has confirmed the feasibility of intraoperative CT on demand. Experience to date with 26 patients has confirmed the feasibility of routine bedside CT in the intensive care unit. CONCLUSION With these adaptations, mobile CT may increase the efficiency of intraoperative scanning by making it available to multiple operating rooms without committing it to any room for an entire operation and may increase the efficiency and safety of CT of critically ill patients who currently need to leave the intensive care unit to travel to a fixed CT installation and back.

Deficits in visual cognition and attention following bilateral anterior cingulotomy

A series of eight tests of visual cognitive abilities was used to examine pre- to post-operative performance changes in a patient receiving bilateral anterior cingulotomy. Compared with a set of eight matched control participants, post-operatively, the patient exhibited deficits in (a) the ability to sequence novel cognitive operations required to generate multipart images or rotate perceptual stimuli; (b) the ability to search for, select, and compare images of objects when the instructions did not specify precisely which objects should be visualized; and, (c) the ability to select a controlled and unpracticed response over an automatic one. Other imagery and cognitive tasks were not affected. Results are consistent with the hypothesis that anterior cingulate cortex is a component of an executive control system. One of the anterior cingulates roles may be to monitor on-line processing and signal the motivational significance of current actions or cognitions.

Visually Guided Movements Suppress Subthalamic Oscillations in Parkinson's Disease Patients

There is considerable evidence that abnormal oscillatory activity in the basal ganglia contributes to the pathogenesis of Parkinsons disease. However, little is known regarding the relationship of oscillations to volitional movements. Our goal was to evaluate the dynamics of oscillatory activity at rest and during movement. We performed microelectrode recordings from the subthalamic nucleus (STN) of patients undergoing deep brain stimulation surgery. During recordings, the patients used a joystick to guide a cursor to one of four targets on a monitor. We recorded 184 cells and 47 pairs of cells in 11 patients. At rest, 26 cells (14%) demonstrated significant oscillatory activity, with a mean frequency of 18 Hz. During movement, this oscillatory activity was either reduced or completely abolished in all of the cells. At rest, 18 pairs (38%) of cells in five patients exhibited synchronized oscillatory activity, with a mean frequency of 15 Hz. In 17 of the 18 pairs, both of the cells exhibited oscillations, and, in one pair, only one of the cells was oscillatory. These synchronized oscillations were also significantly decreased with movement. There was a strong inverse correlation between firing rates and oscillatory activity. As the firing rates increased with movement, there was a decrease in oscillatory activity. These findings suggest that visually guided movements are associated with a dampening and desynchronization of oscillatory activity in STN neurons. One possible explanation for these observations is that the increased cortical drive associated with movement preparation and execution leads to a transient dampening of STN oscillations, hence facilitating movement.

Magnetic Resonance Imaging-guided Stereotactic Limbic Leukotomy for Treatment of Intractable Psychiatric Disease

OBJECTIVE To assess the efficacy and complication rates of magnetic resonance imaging-guided stereotactic limbic leukotomy for the treatment of intractable major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). METHODS We conducted preoperative evaluations and postoperative follow-up assessments of efficacy and complications for 21 patients who underwent limbic leukotomy. Efficacy was based on physician- and patient-rated global assessments of functioning, as well as evaluations using disease-specific rating scales commonly used in studies of MDD and OCD. RESULTS The mean time from limbic leukotomy to follow-up assessment was 26 months. On the basis of standard outcome measures, 36 to 50% of patients were considered to be treatment responders. Although permanent surgical morbidity was rare, there were reports of postoperative sequelae, including apathy, urinary incontinence, and memory complaints, which occurred in a substantial minority of cases. CONCLUSION For this cohort of 21 patients with chronic severe MDD or OCD, who had experienced failure with an exhaustive array of previous treatments, limbic leukotomy was associated with substantial benefit for 36 to 50%. This rate is comparable to those of previous studies of limbic system surgery and indicates that limbic leukotomy is a feasible treatment option for severe, treatment-refractory MDD or OCD. Adverse consequences associated with the procedure included affective, cognitive, and visceromotor sequelae, which were generally transient.

Neurosurgical treatment of tourette's syndrome: A critical review

Some patients with Tourettes syndrome (TS) remain disabled despite conventional treatment. Recently, neurosurgical procedures have been reported to be potentially effective interventions for such intractable cases. Clinicians are now being asked to make recommendations to patients about these candidate operations. This review explores the reported experience with neurosurgical treatment of TS to assess critically the evidence regarding risks and benefits. Toward that end, the rationale for the various procedures and the relevant neuroanatomy are outlined and recommendations for patient selection and management of future cases are discussed. We reviewed all available published reports on this subject and two unpublished cases, totaling 36 patients. Although a variety of operations have been used to treat TS, there is limited evidence pertaining to the risks or benefits of any surgical procedure. Neurosurgical treatment of TS remains experimental, since there is only anecdotal experience with these operations. Furthermore, there is no compelling evidence that any neurosurgical procedure is superior to all others. If these experimental neurosurgeries are to continue, guidelines should be developed regarding patient and operation selection, and interdisciplinary assessment committees should implement such guidelines at institutions where these operations are performed. Moreover, future cases should be prospectively studied using contemporary technologies to assess lesion placement and size and validated clinical instruments to characterize patients and assess outcome, including adverse effects.

Introducing navigated transcranial magnetic stimulation as a refined brain mapping methodology.

Abstract. A major intrinsic limitation of transcranial magnetic stimulation (TMS) to map the human brain lies in the unclear relationship between the position of the stimulating coil on the scalp and the underlying stimulated cortex. The relationship between structure and function as the major feature constituting a brain mapping modality can therefore not be established. Recent advances in image processing allowed us to refine TMS by combining magnetic resonance imaging (MRI) modalities with TMS using a neuronavigation system to measure the position of the stimulating coil and map this position onto a MRI data set. This technique has several advantages over recent TMS mapping strategies. The position of the coil on the scalp can be held constant as verified by real time visual guidance. When evaluating higher cortical functions, the relationship between underlying cortical anatomy and the scalp stimulation site can be accurately assessed. Cortical motor output maps can be easily obtained for preoperative planning and decision making for mass lesions near rolandic cortex in patients. In conclusion, navigated TMS is a reliable alternative for localizing cortical functions and therefore may be a useful adjunct or in selected patients even a helpful alternative to other functional neuroimaging methods.