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ObjectiveRefractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive–compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016.DesignHere we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses.ConclusionInterest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

Traditional strategies to develop new indications in functional neurosurgery include the translation of lesioning targets and the development of model-based approaches. These strategies have yielded some success, but the overall progress of neuromodulation has been limited by a few significant challenges. In particular, optimal clinical trial duration and device programming algorithms are questions that remain largely unanswered. New strategies are emerging that will attempt to address these hurdles and move the field of neuromodulation forward. By studying lessons from the past, we can identify a conceptual framework that organizes conditions in neuromodulation terms. It is then possible to deliberately align recent discoveries and technological advances toward the development of new applications.

Introduction: The amygdala is known to play a role in mediating emotion and possibly addiction. We used probabilistic tractography (PT) to evaluate whether structural connectivity of the amygdala to the brain reward network is associated with impulsive choice and tobacco smoking. Methods: Diffusion and structural MRI scans were obtained from 197 healthy subjects (45 with a history of tobacco smoking) randomly sampled from the Human Connectome database. PT was performed to assess amygdala connectivity with several brain regions. Seed masks were generated, and statistical maps of amygdala connectivity were derived. Connectivity results were correlated with a subject performance both on a delayed discounting task and whether they met specified criteria for difficulty quitting smoking. Results: Amygdala connectivity was spatially segregated, with the strongest connectivity to the hippocampus, orbitofrontal cortex (OFC), and brainstem. Connectivity with the hippocampus was associated with preference for larger delayed rewards, whereas connectivity with the OFC, rostral anterior cingulate cortex (rACC), and insula were associated with preference for smaller immediate rewards. Greater nicotine dependence with difficulty quitting was associated with less hippocampal and greater brainstem connectivity. Scores on the Fagerstrom Test for Nicotine Dependence (FTND) correlated with rACC connectivity. Discussion: These findings highlight the importance of the amygdala-hippocampal-ACC network in the valuation of future rewards and substance dependence. These results will help to identify potential targets for neuromodulatory therapies for addiction and related disorders.

Deep brain stimulation has been successful in treating Parkinson disease and essential tremor and is now reducing PTSD symptoms in the first patient enrolled in an early-phase safety trial.

Deep brain stimulation, a technique whereby electrodes are implanted into specific brain regions to modulate their activity, has been mainly used to treat movement disorders. More recently this technique has been proposed for the treatment of drug addiction, posttraumatic stress disorder (PTSD), and dementia. The nucleus accumbens, amygdala, and hippocampus, central nuclei within the limbic system, have been studied as potential targets for neuromodulation for the treatment of drug addiction, PTSD, and dementia, respectively. As the scope of neuromodulation grows to include disorders of mood and thought, new ethical and philosophic challenges that require multidisciplinary discussion and cooperation are emerging.

Background: Posttraumatic stress disorder (PTSD) is a very debilitating disease refractory to current treatment with selective serotonin reuptake inhibitors (SSRIs) in up to 30 percent of patients, illustrating the need for new treatments of PTSD. Neuroimaging studies have shown increased activity of the amygdala of patients with PTSD. Objective/hypothesis: To investigate amygdala deep brain stimulation (DBS) as a possible novel treatment for PTSD and compare it to current treatment with a commonly used SSRI, paroxetine, in a rat PTSD model. Methods: A PTSD model was created by subjecting rats to inescapable foot shocks in the presence of a conspicuous ball. Response to treatment was measured as a decreased burying behavior when presented with the same ball 1 and 2 weeks after the shocks. Rats were treated with either daily intraperitoneal paroxetine injections or amygdala DBS via an electrode implanted 1 week prior to shocks. Generalized anxiety was assessed using an elevated plus maze. Results: Animals treated with amygdala DBS showed less ball burying at 2 weeks relative to the animals treated with paroxetine. The animals treated with paroxetine, however, had a lower general anxiety level compared to the DBS-treated group. Conclusions: In this PTSD model, paroxetine was found to decrease the measured general anxiety level of rats that underwent the PTSD protocol, but did not counteract shock-induced hyper-vigilance toward the trauma-associated object (ball). Amygdala DBS, however, did decrease shock-induced hyper-vigilance as measured by a lower burying time, but had no effect on general anxiety assessed in the elevated plus maze. By attenuating amygdala function, DBS may act to treat the cause of PTSD, hyperactive amygdala function, and may be a promising novel alternative in cases of PTSD refractory to current pharmacological treatments.

The amygdala plays a critical role in emotion regulation. It could prove to be an effective neuromodulation target in the treatment of psychiatric conditions characterized by failure of extinction. We aim to describe our targeting technique, and intra-operative and post-operative electrodiagnostic findings associated with the placement of deep brain stimulation (DBS) electrodes in the amygdala. We used a transfrontal approach to implant DBS electrodes in the basolateral nucleus of the amygdala (BLn) of a patient suffering from severe post-traumatic stress disorder. We used microelectrode recording (MER) and awake intra-operative neurostimulation to assist with the placement. Post-operatively, the patient underwent monthly surveillance electroencephalograms (EEG). MER predicted the trajectory of the electrode through the amygdala. The right BLn showed a higher spike frequency than the left BLn. Intra-operative neurostimulation of the BLn elicited pleasant memories. The monthly EEG showed the presence of more sleep patterns over time with DBS. BLn DBS electrodes can be placed using a transfrontal approach. MER can predict the trajectory of the electrode in the amygdala and it may reflect the BLn neuronal activity underlying post-traumatic stress disorder PTSD. The EEG findings may underscore the reduction in anxiety.

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.

We report an unusual finding of bilateral facial and corporeal diaphoresis and sensation of heat during deep brain stimulation in two patients. Stimulation of the hypothalamospinal tract located medial to the subthalamic nucleus is likely to be responsible for this side effect.

Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by a life-threatening event causing intense fear. Recently, functional neuroimaging studies have suggested that amygdala hyperactivity is responsible for the symptoms of PTSD. Deep brain stimulation (DBS) can functionally reduce the activity of a cerebral target by delivering an electrical signal through an electrode. We tested whether DBS of the amygdala could be used to treat PTSD symptoms. Rats traumatized by inescapable shocks, in the presence of an unfamiliar object, develop the tendency to bury the object when re-exposed to it several days later. This behavior mimics the symptoms of PTSD. 10 Sprague-Dawley rats underwent the placement of an electrode in the right basolateral nucleus of the amygdala (BLn). The rats were then subjected to a session of inescapable shocks while being exposed to a conspicuous object (a ball). Five rats received DBS treatment while the other 5 rats did not. After 7 days of treatment, the rats were re-exposed to the ball and the time spent burying it under the bedding was recorded. Rats treated with BLn DBS spent on average 13 times less time burying the ball than the sham control rats. The treated rats also spent 18 times more time exploring the ball than the sham control rats. In conclusion, the behavior of treated rats in this PTSD model was nearly normalized. We argue that these results have direct implications for patients suffering from treatment-resistant PTSD by offering a new therapeutic strategy.

Background Waldenstrom's macroglobulinemia is a low-grade B-cell lymphoma characterized by monoclonal synthesis and secretion of IgM antibodies [3] . The classic symptoms of WM result from blood hyperviscosity. Neurologic symptoms, such as fatigue, dizziness, and blurred vision, are common. The metastatic spread to the CNS, which rarely has been reported, can occur either diffusely or in the form of a mass lesion. Case Description We present the case of a 73-year-old woman with intracerebral large B-cell lymphoma and concurrent WM. Conclusion This case illustrates the importance of histopathologic diagnosis by brain biopsy despite an existing diagnosis of systemic neoplasm.

Post-traumatic stress disorder (PTSD) is a serious psychiatric consequence of trauma that occurs in a proportion of individuals exposed to life-threatening events. Trauma-focused psychotherapy is often recommended as first choice for those who do not recover spontaneously. But many individuals require medications. In the US, only paroxetine (PRX) and sertraline (SRT) are FDA approved for PTSD. But response and remission rates with these medications are low, so numerous other pharmacologic interventions have been tried. To date, there has not been a systematic review of the data on what are the best next-step pharmacologic strategies for individuals who fail standard treatments. To that end, we review 168 published trials of medications other than PRX or SRT and provide a detailed analysis of the 88/168 studies that describe alternative pharmacologic interventions in patients refractory to other treatment. We also review clinical factors relevant to treatment-refractory PTSD; the neurobiology of extinction, as well as evidence-based psychotherapy and neuromodulation strategies for this condition.

Background Combat post-traumatic stress disorder (PTSD) involves significant suffering, impairments in social and occupational functioning, substance use and medical comorbidity, and increased mortality from suicide and other causes. Many veterans continue to suffer despite current treatments. Deep brain stimulation (DBS) has shown promise in refractory movement disorders, depression and obsessive-compulsive disorder, with deep brain targets chosen by integration of clinical and neuroimaging literature. The basolateral amygdala (BLn) is an optimal target for high-frequency DBS in PTSD based on neurocircuitry findings from a variety of perspectives. DBS of the BLn was validated in a rat model of PTSD by our group, and limited data from humans support the potential safety and effectiveness of BLn DBS. Methods/Design We describe the protocol design for a first-ever Phase I pilot study of bilateral BLn high-frequency DBS for six severely ill, functionally impaired combat veterans with PTSD refractory to conventional treatments. After implantation, patients are monitored for a month with stimulators off. An electroencephalographic (EEG) telemetry session will test safety of stimulation before randomization to staggered-onset, double-blind sham versus active stimulation for two months. Thereafter, patients will undergo an open-label stimulation for a total of 24 months. Primary efficacy outcome is a 30% decrease in the Clinician Administered PTSD Scale (CAPS) total score. Safety outcomes include extensive assessments of psychiatric and neurologic symptoms, psychosocial function, amygdala-specific and general neuropsychological functions, and EEG changes. The protocol requires the veteran to have a cohabiting significant other who is willing to assist in monitoring safety and effect on social functioning. At baseline and after approximately one year of stimulation, trauma script-provoked 18FDG PET metabolic changes in limbic circuitry will also be evaluated. Discussion While the rationale for studying DBS for PTSD is ethically and scientifically justified, the importance of the amygdaloid complex and its connections for a myriad of emotional, perceptual, behavioral, and vegetative functions requires a complex trial design in terms of outcome measures. Knowledge generated from this pilot trial can be used to design future studies to determine the potential of DBS to benefit both veterans and nonveterans suffering from treatment-refractory PTSD. Trial registration PCC121657, 19 March 2014. Electronic supplementary material The online version of this article (doi:10.1186/1745-6215-15-356) contains supplementary material, which is available to authorized users.

We report a patient with eyelid apraxia following deep brain stimulation of the periaqueductal gray area. Based on the position of our electrode, we argue that the phenomenon is linked to inhibition of the nearby central caudal nucleus of the oculomotor nucleus by high frequency stimulation.

The aim of this study was to examine a possible relation between the speed of information processing, as measured by simple and choice visual RT, and problem-solving, as measured by the Tower of Hanoi test. For 20 normal teenagers, performing all tests, significant correlations were found between choice RT and both measures of performance on the Tower of Hanoi, number of disk moves, and time taken to complete the task. Simple RT was correlated with Completion time but not with the number of moves, while the reverse pattern was discerned for decision time. Choice movement time was also associated with both measures, but simple movement time was not. These results are consistent with the hypothesis of a common neurobiological basis to information-processing speed and executive functions.

The amygdala was a popular target during the era of psychosurgery, specifically for the treatment of intractable aggression. This mesiotemporal structure was thought to primarily mediate fear and anger. However, recent evidence suggests that the amygdala is part of a complex network that mediates the formation of a larger repertoire of positive and negative emotions. Dysfunctions within the network or the amygdala itself can lead to various mental illnesses. In those cases, deep brain stimulation (DBS) applied focally may treat the symptoms. This review presents data supporting the potential therapeutic role of DBS of the amygdala in the treatment of anxiety disorders, addiction, and mood disorders. The success of DBS for psychiatric conditions will likely depend on our ability to precisely determine the optimal target for a specific case.

BACKGROUND: Recent work-hour restrictions and the constantly evolving body of knowledge are challenging the current ways of teaching neurosurgery residents. OBJECTIVE: To develop a curriculum-based digital library of multimedia content to face the challenges in neurosurgery education. METHOD: We used the residency program curriculum developed by the Congress of Neurological Surgeons to structure the library and Microsoft Sharepoint as the user interface. RESULTS: This project led to the creation of a user-friendly and searchable digital library that could be accessed remotely and throughout the hospital, including the operating rooms. CONCLUSION: The electronic format allows standardization of the content and transformation of the operating room into a classroom. This in turn facilitates the implementation of a curriculum within the training program and improves teaching efficiency. Future work will focus on evaluating the efficacy of the library as a teaching tool for residents.

Background: The long-term safety of deep brain stimulation (DBS) is an important issue because new applications are being investigated for a variety of disorders. Studying instances where DBS was inadvertently implanted in patients without a movement disorder may provide information about the safety of the therapy. We report the case of a patient with a psychogenic movement disorder treated with deep brain stimulation (DBS). Case Description: The patient presented at our clinic after 5 years of chronic DBS of the subthalamic nucleus (STN) for presumed Parkinson's disease. A dopamine transporter (DAT) scan (DaTscan) showed normal DAT distribution in the striatum. A positron emission tomography (PET) scan showed no abnormal metabolic patterns. Further psychiatric and neurological evaluations revealed that the patient was suffering from a psychogenic movement disorder. The patient displayed no sign or symptom from the stimulation, and DBS did not lead to any benefits or side effects for this patient. Conclusion: We argue that the absence of side effects, the normal DaTscan, and PET scan after 5 years of chronic stimulation illustrate the safety of DBS on neural tissue.