Functional and anatomical connectivity predict brain stimulation's mnemonic effects.

Closed-loop direct brain stimulation is a promising tool for modulating neural activity and behavior. However, it remains unclear how to optimally target stimulation to modulate brain activity in particular brain networks that underlie particular cognitive functions. Here, we test the hypothesis that stimulation's behavioral and physiological effects depend on the stimulation target's anatomical and functional network properties. We delivered closed-loop stimulation as 47 neurosurgical patients studied and recalled word lists. Multivariate classifiers, trained to predict momentary lapses in memory function, triggered the stimulation of the lateral temporal cortex (LTC) during the study phase of the task. We found that LTC stimulation specifically improved memory when delivered to targets near white matter pathways. Memory improvement was largest for targets near white matter that also showed high functional connectivity to the brain's memory network. These targets also reduced low-frequency activity in this network, an established marker of successful memory encoding. These data reveal how anatomical and functional networks mediate stimulation's behavioral and physiological effects, provide further evidence that closed-loop LTC stimulation can improve episodic memory, and suggest a method for optimizing neuromodulation through improved stimulation targeting.

Electrophysiological Signatures of Spatial Boundaries in the Human Subiculum.

Environmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. Although studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. To address this gap in the literature, we analyzed intracranial recordings from the hippocampal formation of surgical epilepsy patients (of both sexes) while they performed a virtual spatial navigation task and compared the power in three frequency bands (1-4, 4-10, and 30-90 Hz) for target locations near and far from the environmental boundaries. Our results suggest that encoding locations near boundaries elicited stronger theta oscillations than for target locations near the center of the environment and that this difference cannot be explained by variables such as trial length, speed, movement, or performance. These findings provide direct evidence of boundary-dependent neural activity localized in humans to the subiculum, the homolog of the hippocampal subregion in which most boundary cells are found in rodents, and indicate that this system can represent attended locations that rather than the position of one's own body.SIGNIFICANCE STATEMENT Spatial computations using environmental boundaries are an integral part of the brain's spatial mapping system. In rodents, border/boundary cells in the subiculum and entorhinal cortex reveal boundary coding at the single-neuron level. Although there is good reason to believe that such representations also exist in humans, the evidence has thus far been limited to functional neuroimaging studies that broadly implicate the hippocampus in boundary-based navigation. By combining intracranial recordings with high-resolution imaging of hippocampal subregions, we identified a neural marker of boundary representation in the human subiculum.

Multicenter validation of automated trajectories for selective laser amygdalohippocampectomy.

OBJECTIVE: Laser interstitial thermal therapy (LITT) is a novel minimally invasive alternative to open mesial temporal resection in drug-resistant mesial temporal lobe epilepsy (MTLE). The safety and efficacy of the procedure are dependent on the preplanned trajectory and the extent of the planned ablation achieved. Ablation of the mesial hippocampal head has been suggested to be an independent predictor of seizure freedom, whereas sparing of collateral structures is thought to result in improved neuropsychological outcomes. We aim to validate an automated trajectory planning platform against manually planned trajectories to objectively standardize the process. METHODS: Using the EpiNav platform, we compare automated trajectory planning parameters derived from expert opinion and machine learning to undertake a multicenter validation against manually planned and implemented trajectories in 95 patients with MTLE. We estimate ablation volumes of regions of interest and quantify the size of the avascular corridor through the use of a risk score as a marker of safety. We also undertake blinded external expert feasibility and preference ratings. RESULTS: Automated trajectory planning employs complex algorithms to maximize ablation of the mesial hippocampal head and amygdala, while sparing the parahippocampal gyrus. Automated trajectories resulted in significantly lower calculated risk scores and greater amygdala ablation percentage, whereas overall hippocampal ablation percentage did not differ significantly. In addition, estimated damage to collateral structures was reduced. Blinded external expert raters were significantly more likely to prefer automated to manually planned trajectories. SIGNIFICANCE: Retrospective studies of automated trajectory planning show much promise in improving safety parameters and ablation volumes during LITT for MTLE. Multicenter validation provides evidence that the algorithm is robust, and blinded external expert ratings indicate that the trajectories are clinically feasible. Prospective validation studies are now required to determine if automated trajectories translate into improved seizure freedom rates and reduced neuropsychological deficits.

Utility of foramen ovale electrodes in mesial temporal lobe epilepsy.

OBJECTIVES: 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). METHODS: We identified patients with medically intractable epilepsy who had undergone FOE investigation for initial invasive monitoring at our institution between 2005 and 2012. Indications for initiating FOE investigation were grouped into four categories: (1) bilateral anterior temporal ictal activity on scalp electroencephalography (EEG), (2) unclear laterality of scalp EEG onset due to muscle artifact or significant delay following clinical manifestation, (3) discordance between ictal and interictal discharges, and (4) investigation of a specific anatomic abnormality or competing putative focus. The FOE investigation was classified as informative if it provided sufficient evidence to make a treatment decision. RESULTS: Forty-two consecutive patients underwent FOE investigation, which was informative in 38 patients (90.5%). Of these 38 patients, 24 were determined to be appropriate candidates for resective surgery. Five were localized sufficiently for surgery, but were considered high risk for verbal memory deficit, and nine were deemed poor surgical candidates because of bilateral ictal origins. The remaining 4 of 42 patients had inconclusive FOE studies and were referred for further invasive investigation. Of the 18 patients who underwent resective surgery, 13 (72%) were seizure-free (Engel class I) at last follow-up (mean 22.5 months). SIGNIFICANCE: More than 90% of our 42 FOE studies provided sufficient evidence to render treatment decisions. When undertaken with an appropriate hypothesis, FOE investigations are a minimally invasive and efficacious means for evaluating patients with suspected MTLE after an inconclusive noninvasive investigation.

Stereoelectroencephalography-Guided Radiofrequency Thermocoagulation: Diagnostic and Therapeutic Implications.

Despite recent medical therapeutic advances, approximately one third of patients do not attain seizure freedom with medications. This drug-resistant epilepsy population suffers from heightened morbidity and mortality. In appropriate patients, resective epilepsy surgery is far superior to continued medical therapy. Despite this efficacy, there remain drawbacks to traditional epilepsy surgery, such as the morbidity of open neurosurgical procedures as well as neuropsychological adverse effects. SEEG-guided Radiofrequency Thermocoagulation (SgRFTC) is a minimally invasive, electrophysiology-guided intervention with both diagnostic and therapeutic implications for drug-resistant epilepsy that offers a convenient adjunct or alternative to ablative and resective approaches. We review the international experience with this procedure, including methodologies, diagnostic benefit, therapeutic benefit, and safety considerations. We propose a framework in which SgRFTC may be incorporated into intracranial EEG evaluations alongside passive recording. Lastly, we discuss the potential role of SgRFTC in both delineating and reorganizing epilepsy networks.

Model-based image updating in deep brain stimulation with assimilation of deep brain sparse data.

BACKGROUND: Accuracy of electrode placement for deep brain stimulation (DBS) is critical to achieving desired surgical outcomes and impacts the efficacy of treating neurodegenerative diseases. Intraoperative brain shift degrades the accuracy of surgical navigation based on preoperative images. PURPOSE: We extended a model-based image updating scheme to address intraoperative brain shift in DBS surgery and improved its accuracy in deep brain. METHODS: We evaluated 10 patients, retrospectively, who underwent bilateral DBS surgery and classified them into groups of large and small deformation based on a 2 mm subsurface movement threshold and brain shift index of 5%. In each case, sparse brain deformation data were used to estimate whole brain displacements and deform preoperative CT (preCT) to generate updated CT (uCT). Accuracy of uCT was assessed using target registration errors (TREs) at the Anterior Commissure (AC), Posterior Commissure (PC), and four calcification points in the sub-ventricular area by comparing their locations in uCT with their ground truth counterparts in postoperative CT (postCT). RESULTS: In the large deformation group, TREs were reduced from 2.5 mm in preCT to 1.2 mm in uCT (53% compensation); in the small deformation group, errors were reduced from 1.25 to 0.74 mm (41%). Average reduction of TREs at AC, PC and pineal gland were significant, statistically (p ⩽ 0.01). CONCLUSIONS: With more rigorous validation of model results, this study confirms the feasibility of improving the accuracy of model-based image updating in compensating for intraoperative brain shift during DBS procedures by assimilating deep brain sparse data.

Functional and anatomical connectivity predict brain stimulation's mnemonic effects.

Closed-loop direct brain stimulation is a promising tool for modulating neural activity and behavior. However, it remains unclear how to optimally target stimulation to modulate brain activity in particular brain networks that underlie particular cognitive functions. Here, we test the hypothesis that stimulation's behavioral and physiological effects depend on the stimulation target's anatomical and functional network properties. We delivered closed-loop stimulation as 47 neurosurgical patients studied and recalled word lists. Multivariate classifiers, trained to predict momentary lapses in memory function, triggered stimulation of the lateral temporal cortex (LTC) during the study phase of the task. We found that LTC stimulation specifically improved memory when delivered to targets near white matter pathways. Memory improvement was largest for targets near white matter that also showed high functional connectivity to the brain's memory network. These targets also reduced low-frequency activity in this network, an established marker of successful memory encoding. These data reveal how anatomical and functional networks mediate stimulation's behavioral and physiological effects, provide further evidence that closed-loop LTC stimulation can improve episodic memory, and suggest a method for optimizing neuromodulation through improved stimulation targeting.

Phasic stimulation in the nucleus accumbens enhances learning after traumatic brain injury.

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Despite improvements in survival, treatments that improve functional outcome remain lacking. There is, therefore, a pressing need to develop novel treatments to improve functional recovery. Here, we investigated task-matched deep-brain stimulation of the nucleus accumbens (NAc) to augment reinforcement learning in a rodent model of TBI. We demonstrate that task-matched deep brain stimulation (DBS) of the NAc can enhance learning following TBI. We further demonstrate that animals receiving DBS exhibited greater behavioral improvement and enhanced neural proliferation. Treated animals recovered to an uninjured behavioral baseline and showed retention of improved performance even after stimulation was stopped. These results provide encouraging early evidence for the potential of NAc DBS to improve functional outcomes following TBI and that its effects may be broad, with alterations in neurogenesis and synaptogenesis.

Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice.

Drug targeting of adult stem cells has been proposed as a strategy for regenerative medicine, but very few drugs are known to target stem cell populations in vivo. Mesenchymal stem/progenitor cells (MSCs) are a multipotent population of cells that can differentiate into muscle, bone, fat, and other cell types in context-specific manners. Bortezomib (Bzb) is a clinically available proteasome inhibitor used in the treatment of multiple myeloma. Here, we show that Bzb induces MSCs to preferentially undergo osteoblastic differentiation, in part by modulation of the bone-specifying transcription factor runt-related transcription factor 2 (Runx-2) in mice. Mice implanted with MSCs showed increased ectopic ossicle and bone formation when recipients received low doses of Bzb. Furthermore, this treatment increased bone formation and rescued bone loss in a mouse model of osteoporosis. Thus, we show that a tissue-resident adult stem cell population in vivo can be pharmacologically modified to promote a regenerative function in adult animals.

Modulation of Emotion Perception via Amygdala Stimulation in Humans.

BACKGROUND: Multiple lines of evidence show that the human amygdala is part of a neural network important for perception of emotion from environmental stimuli, including for processing of intrinsic attractiveness/"goodness" or averseness/"badness," i.e., affective valence. OBJECTIVE/HYPOTHESIS: With this in mind, we investigated the effect of electrical brain stimulation of the human amygdala on perception of affective valence of images taken from the International Affective Picture Set (IAPS). METHODS: Using intracranial electrodes in patients with epilepsy, we first obtained event-related potentials (ERPs) in eight patients as they viewed IAPS images of varying affective valence. Next, in a further cohort of 10 patients (five female and five male), we measured the effect of 50 Hz electrical stimulation of the left amygdala on perception of affective valence from IAPS images. RESULTS: We recorded distinct ERPs from the left amygdala and found significant differences in the responses between positively and negatively valenced stimuli (p = 0.002), and between neutral and negatively valenced stimuli (p = 0.017) 300-500 ms after stimulus onset. Next, we found that amygdala stimulation did not significantly affect how patients perceived valence for neutral images (p = 0.58), whereas stimulation induced patients to report both positively (p = 0.05) and negatively (< 0.01) valenced images as more neutral. CONCLUSION: These results render further evidence that the left amygdala participates in a neural network for perception of emotion from environmental stimuli. These findings support the idea that electrical stimulation disrupts this network and leads to partial disruption of perception of emotion. Harnessing this effect may have clinical implications in treatment of certain neuropsychiatric disorders using deep brain stimulation (DBS) and neuromodulation.

Stereoencephalography Electrode Placement Accuracy and Utility Using a Frameless Insertion Platform Without a Rigid Cannula.

BACKGROUND: Implantation of depth electrodes to localize epileptogenic foci in patients with drug-resistant epilepsy can be accomplished using traditional rigid frame-based, custom frameless, and robotic stereotactic systems. OBJECTIVE: To evaluate the accuracy of electrode implantation using the FHC microTargeting platform, a custom frameless platform, without a rigid insertion cannula. METHODS: A total of 182 depth electrodes were implanted in 13 consecutive patients who underwent stereoelectroencephalography (SEEG) for drug-resistant epilepsy using the microTargeting platform and depth electrodes without a rigid guide cannula. MATLAB was utilized to evaluate targeting accuracy. Three manual coordinate measurements with high inter-rater reliability were averaged. RESULTS: Patients were predominantly male (77%) with average age 35.62 (SD 11.0, range 21-57) and average age of epilepsy onset at 13.4 (SD 7.2, range 3-26). A mean of 14 electrodes were implanted (range 10-18). Mean operative time was 144 min (range 104-176). Implantation of 3 out of 182 electrodes resulted in nonoperative hemorrhage (2 small subdural hematomas and one small subarachnoid hemorrhage). Putative location of onset was identified in all patients. We demonstrated a median lateral target point localization error (LTPLE) of 3.95 mm (IQR 2.18-6.23), a lateral entry point localization error (LEPLE) of 1.98 mm (IQR 1.2-2.85), a target depth error of 1.71 mm (IQR 1.03-2.33), and total target point localization error (TPLE) of 4.95 mm (IQR 2.98-6.85). CONCLUSION: Utilization of the FHC microTargeting platform without the use of insertion cannulae is safe, effective, and accurate. Localization of seizure foci was accomplished in all patients and accuracy of depth electrode placement was satisfactory.

Model-Based Image Updating for Brain Shift in Deep Brain Stimulation Electrode Placement Surgery.

OBJECTIVE: The efficacy of deep brain stimulation (DBS) depends on accurate placement of electrodes. Although stereotactic frames enable co-registration of image-based surgical planning and the operative field, the accuracy of electrode placement can be degraded by intra-operative brain shift. In this study, we adapted a biomechanical model to estimate whole brain displacements from which we deformed preoperative CT (preCT) to generate an updated CT (uCT) that compensates for brain shift. METHODS: We drove the deformation model using displacement data derived from deformation in the frontal cortical surface that occurred during the DBS intervention. We evaluated 15 patients, retrospectively, who underwent bilateral DBS surgery, and assessed the accuracy of uCT in terms of target registration error (TRE) relative to a CT acquired post-placement (postCT). We further divided subjects into large (Group L) and small (Group S) deformation groups based on a TRE threshold of 1.6mm. Anterior commissure (AC), posterior commissure (PC) and pineal gland (PG) were identified on preCT and postCT and used to quantify TREs in preCT and uCT. RESULTS: In the group of large brain deformation, average TREs for uCT were 1.11 ± 0.13 and 1.07 ± 0.38 mm at AC and PC, respectively, compared to 1.85 ± 0.17 and 0.92 ± 0.52 mm for preCT. The model updating approach improved AC localization but did not alter TREs at PC. CONCLUSION: This preliminary study suggests that our image updating method may compensate for brain shift around surgical targets of importance during DBS surgery, although further investigation is warranted before conclusive evidence will be available. SIGNIFICANCE: With further development and evaluation, our model-based image updating method using intraoperative sparse data may compensate for brain shift in DBS surgery efficiently, and have utility in updating targeting coordinates.

Deep Brain Stimulation for Memory Modulation: A New Frontier.

BACKGROUND: In the coming years the number of patients with cognitive disorders, such as Alzheimer disease and traumatic brain injury, is expected to dramatically increase, leading to an ever-increasing societal cost. Unfortunately, few medical and pharmacologic treatments have shown tangible benefit in the treatment of these diseases. Deep brain stimulation (DBS) is an established surgical technique to address multiple conditions, including Parkinson disease and essential tremor. Data from patients being treated with DBS, as well as those being monitored for seizures with depth electrodes, have suggested improvement in memory with electrical neuromodulation. METHODS: MEDLINE was searched from inception through March 2018 using the keywords "DBS," "Deep Brain Stimulation," "Memory," "Memory Modulation," and "Cognition." Studies evaluating the effect of DBS on memory and learning were shortlisted and reviewed. RESULTS: Efforts to stimulate various nodes within the memory circuitry suggest that the variable effects may result from different mechanisms, including alteration of neural firing patterns, increased activity across several regions, and amplification of neural plasticity. Some of these targets, such as the entorhinal cortex, hippocampus, and nucleus basalis of Meynert, have shown promising results with regards to modulation of memory. CONCLUSIONS: Given the aging population and increasing numbers of patients with memory impairment from neurodegenerative diseases, interest in neuromodulation for memory enhancement will likely expand. Further work should employ more sophisticated responsive stimulation parameters and precise spatial targeting that may lead to an effective stimulation strategy for memory enhancement.

Cognitive tasks and human ambulatory electrocorticography using the RNS System.

BACKGROUND: Electrocorticography studies are typically conducted in patients undergoing video EEG monitoring, but these studies are subject to confounds such as the effects of pain, recent anesthesia, analgesics, drug changes, antibiotics, and implant effects. NEW METHOD: Techniques were developed to obtain electrocorticographic (ECoG) data from freely moving subjects performing navigational tasks using the RNS® System (NeuroPace, Inc., Mountain View, CA), a brain-responsive neurostimulation medical device used to treat focal onset epilepsy, and to align data from the RNS System with cognitive task events with high precision. These subjects had not had recent surgery, and were therefore not confounded by the perioperative variables that affect video EEG studies. RESULTS: Task synchronization using the synchronization marker technique provides a quantitative measure of clock uncertainty, and can align data to task events with less than 4 ms of uncertainty. Hippocampal ECoG activity was found to change immediately before an incorrect response to a math problem compared to hippocampal activity before a correct response. In addition, subjects were found to have variable but significant changes in theta band power in the hippocampus during navigation compared to when subjects were not navigating. We found that there is theta-gamma phase-amplitude coupling in the right hippocampus while subjects stand still during a navigation task. COMPARISON WITH EXISTING METHODS: An alignment technique described in this study improves the upper bound on task-ECoG alignment uncertainty from approximately 30 ms to under 4 ms. The RNS System is one of the first platforms capable of providing untethered ambulatory ECoG recording in humans, allowing for the study of real world instead of virtual navigation. Compared to intracranial video EEG studies, studies using the RNS System platform are not subject to confounds caused by the drugs and recent surgery inherent to the perioperative environment. Furthermore, these subjects provide the opportunity to record from the same electrodes over the course of many years. CONCLUSIONS: The RNS System enables us to study human navigation with unprecedented clarity. While RNS System patients have fewer electrodes implanted than video EEG patients, the lack of external artifact and confounds from recent surgery make this system a useful tool to further human electrophysiology research.

Vagus Nerve Stimulation in Rodent Models: An Overview of Technical Considerations.

Over the last several decades, vagus nerve stimulation (VNS) has evolved from a treatment for select neuropsychiatric disorders to one that holds promise in treating numerous inflammatory conditions. Growing interest has focused on the use of VNS for other indications, such as heart failure, rheumatoid arthritis, inflammatory bowel disease, ischemic stroke, and traumatic brain injury. As pre-clinical research often guides expansion into new clinical avenues, animal models of VNS have also increased in recent years. To advance this promising treatment, however, there are a number of experimental parameters that must be considered when planning a study, such as physiology of the vagus nerve, electrical stimulation parameters, electrode design, stimulation equipment, and microsurgical technique. In this review, we discuss these important considerations and how a combination of clinically relevant stimulation parameters can be used to achieve beneficial therapeutic results in pre-clinical studies of sub-acute to chronic VNS, and provide a practical guide for performing this work in rodent models. Finally, by integrating clinical and pre-clinical research, we present indeterminate issues as opportunities for future research.

Anatomical Correlates of Uncontrollable Laughter With Unilateral Subthalamic Deep Brain Stimulation in Parkinson's Disease.

INTRODUCTION: Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for the management of motor complications in Parkinson's disease. Uncontrollable laughter has been reported as a rare side effect of STN stimulation. The precise mechanism responsible for this unique phenomenon remains unclear. We examined in detail the DBS electrode position and stimulation parameters in two patients with uncontrollable laughter during programming after STN-DBS surgery and illustrated the anatomical correlates of the acute mood changes with STN stimulation. CASE REPORT: Unilateral STN-DBS induced uncontrollable laughter with activation of the most ventral contacts in both patients. However, the location of the electrodes responsible for this adverse effect differed between the patients. In the first patient, the DBS lead was placed more inferiorly and medially within the STN. In the second patient, the DBS lead was implanted more anteriorly and inferiorly than initially planned at the level of the substantia nigra reticulata (SNr). CONCLUSION: Unilateral STN-DBS can induce acute uncontrollable laughter with activation of electrodes located more anterior, medial, and inferior in relationship with the standard stereotactic STN target. We suggest that simulation of ventral and medial STN, surrounding limbic structures or the SNr, is the most plausible anatomical substrate responsible for this acute mood and behavioral change. Our findings provide insight into the complex functional neuroanatomical relationship of the STN and adjacent structures important for mood and behavior. DBS programming with more dorsal and lateral contacts within the STN should be entertained to minimize the emotional side effects.

Thoracic exophytic ependymoma masquerading as a benign extra-axial tumor.

Spinal tumors are conventionally differentiated based on location in relation to the spinal cord. Benign spinal tumors such as schwannomas and meningiomas are typically extra-axial (intradural extramedullary) lesions, whereas more aggressive primary spinal tumors such as ependymomas are typically intramedullary masses. Rarely, ependymomas can have both intramedullary and extramedullary components (typically referred to as exophytic ependymomas). We report a case of a spinal exophytic ependymoma that radiographically masqueraded as a benign intradural extramedullary lesion causing cord compression and neurologic deficit in a 47-year-old man. The diagnosis of exophytic ependymoma was made intra-operatively, with resultant gross total resection of the extramedullary portion and subtotal resection of the intramedullary portion. Histopathological examination confirmed ependymoma with World Health Organization grade II/IV. Pre-operative suspicion of an exophytic ependymoma influences operative planning and clinical management. We review the literature and discuss clinical management strategies for these interesting spinal tumors.

Episodic ventriculomegaly due to hypernatremia mimicking shunt malfunction: case report.

Patients with shunted hydrocephalus presenting with altered mental status and ventriculomegaly are generally considered to be in shunt failure requiring surgical treatment. The authors describe a case of shunted hydrocephalus secondary to a disseminated neuroectodermal tumor in a pediatric patient in whom rapid fluctuations in sodium levels due to diabetes insipidus repeatedly led to significant changes in ventricle size, with invasively confirmed normal shunt function and low intracranial pressure. This clinical picture exactly mimics shunt malfunction, requires urgent nonsurgical therapy, and underscores the importance of considering serum osmolar abnormalities in the differential diagnosis for ventriculomegaly.

Neuromodulation for obsessive-compulsive disorder.

This article describes the basis for neuromodulation procedures for obsessive-compulsive disorder (OCD) and summarizes the literature on the efficacy of these interventions. Discussion includes neural circuitry underlying OCD pathology, the history and types of ablative procedures, the targets and modalities used for neuromodulation, and future therapeutic directions.

Treatment of Moyamoya disease in the adult population with pial synangiosis.

OBJECT: Surgical treatment of moyamoya disease in the adult population commonly uses direct revascularization, the superficial temporal artery (STA) to middle cerebral artery (MCA) bypass (STA-MCA). Pial synangiosis, a method of indirect revascularization, has been used in adult patients with moyamoya when STA-MCA bypass was not technically feasible. Although the effectiveness of pial synangiosis has been well described in children, only limited reports have examined its role in adult patients with moyamoya disease. In this study the authors report on their experience with pial synangiosis revascularization for this population. METHODS: The authors reviewed the clinical and radiographic records of all adult patients (≥ 18 years of age) with moyamoya disease who underwent cerebral revascularization surgery using pial synangiosis at a single institution. RESULTS: From 1985 to 2010, 66 procedures (6 unilateral, 30 bilateral) were performed on 36 adult patients with moyamoya disease. The mean age at surgery was 28.3 years, and 30 patients were female. Twenty-eight patients (77.8%) presented with transient ischemic attacks (TIAs), 24 (66.7%) with stroke, and 3 (8.3%) with hemorrhage. Preoperative Suzuki stage was III or higher in 50 hemispheres (75.8%) and 3 patients had undergone prior treatments to the affected hemisphere before pial synangiosis surgery. Clinical follow-up was available for an average of 5.8 years (range 0.6-14.1 years), with 26 patients (72.2%) followed for longer than 2 years. Postoperative angiography was available for 24 patients and 46 revascularized hemispheres, and 39 (84.8%) of the 46 hemispheres demonstrated good collateral formation (Matsushima Grade A or B). Postoperative complications included 3 strokes, 5 TIAs, and 2 seizures, and there was no hemorrhage during the follow-up period. One patient required additional revascularization surgery 8 months after pial synangiosis. CONCLUSIONS: Pial synangiosis is a safe and durable method of cerebral revascularization in adult patients with moyamoya and can be considered as a potential treatment option for moyamoya disease in adults.