Brainjacking: Implant Security Issues in Invasive Neuromodulation.

The security of medical devices is critical to good patient care, especially when the devices are implanted. In light of recent developments in information security, there is reason to be concerned that medical implants are vulnerable to attack. The ability of attackers to exert malicious control over brain implants ("brainjacking") has unique challenges that we address in this review, with particular focus on deep brain stimulation implants. To illustrate the potential severity of this risk, we identify several mechanisms through which attackers could manipulate patients if unauthorized access to an implant can be achieved. These include blind attacks in which the attacker requires no patient-specific knowledge and targeted attacks that require patient-specific information. Blind attacks include cessation of stimulation, draining implant batteries, inducing tissue damage, and information theft. Targeted attacks include impairment of motor function, alteration of impulse control, modification of emotions or affect, induction of pain, and modulation of the reward system. We also discuss the limitations inherent in designing implants and the trade-offs that must be made to balance device security with battery life and practicality. We conclude that researchers, clinicians, manufacturers, and regulatory bodies should cooperate to minimize the risk posed by brainjacking.

Injecting realism in surgical training-initial simulation experience with custom 3D models.

UNLABELLED: The traditionally accepted form of training is direct supervision by an expert; however, modern trends in medicine have made this progressively more difficult to achieve. A 3-dimensional printer makes it possible to convert patients imaging data into accurate models, thus allowing the possibility to reproduce models with pathology. This enables a large number of trainees to be trained simultaneously using realistic models simulating actual neurosurgical procedures. The aim of this study was to assess the usefulness of these models in training surgeons to perform standard procedures that require complex techniques and equipment. METHODS: Multiple models of the head of a patient with a deep-seated small thalamic lesion were created based on his computed tomography and magnetic resonance imaging data. A workshop was conducted using these models of the head as a teaching tool. The surgical trainees were assessed for successful performance of the procedure as well as the duration of time and number of attempts taken to learn them. FINDINGS: All surgical candidates were able to learn the basics of the surgical procedure taught in the workshop. The number of attempts and time taken reflected the seniority and previous experience of each candidate. DISCUSSION: Surgical trainees need multiple attempts to learn essential procedures. The use of these models for surgical-training simulation allows trainees to practice these procedures repetitively in a safe environment until they can master it. This would theoretically shorten the learning curve while standardizing teaching and assessment techniques of these trainees.

Utility of multimaterial 3D printers in creating models with pathological entities to enhance the training experience of neurosurgeons.

The advent of multimaterial 3D printers allows the creation of neurosurgical models of a more realistic nature, mimicking real tissues. The authors used the latest generation of 3D printer to create a model, with an inbuilt pathological entity, of varying consistency and density. Using this model the authors were able to take trainees through the basic steps, from navigation and planning of skin flap to performing initial steps in a craniotomy and simple tumor excision. As the technology advances, models of this nature may be able to supplement the training of neurosurgeons in a simulated operating theater environment, thus improving the training experience.

Human periventricular grey somatosensory evoked potentials suggest rostrocaudally inverted somatotopy.

BACKGROUND: Somatosensory homunculi have been demonstrated in primary somatosensory cortex and ventral posterior thalamus but not periaqueductal and periventricular grey matter (PAVG), a therapeutic target for deep brain stimulation (DBS) in chronic pain. AIMS: The study is an investigation of somatotopic representation in PAVG and assessment for a somatosensory homunculus. METHODS: Five human subjects were investigated using electrical somatosensory stimulation and deep brain macroelectrode recording. DBS were implanted in the contralateral PAVG. Cutaneous arm, leg and face regions were stimulated while event-related potentials were recorded from deep brain electrodes. Electrode contact positions were mapped using MRI and brain atlas information. RESULTS: Monopolar P1 somatosensory evoked potential amplitudes were highest and onset latencies shortest in contralateral caudal PAVG with facial stimulation and rostral with leg stimulation, in agreement with reported subjective sensation during intra-operative electrode advancement. CONCLUSIONS: A rostrocaudally inverted somatosensory homunculus exists in the human PAVG region. Objective human evidence of PAVG somatotopy increases understanding of a brainstem region important to pain and autonomic control that is a clinical target for both pharmacological and neurosurgical therapies. Such knowledge may assist DBS target localisation for neuropathic pain syndromes related to particular body regions like brachial plexopathies, anaesthesia dolorosa and phantom limb pain.

Contrasting connectivity of the ventralis intermedius and ventralis oralis posterior nuclei of the motor thalamus demonstrated by probabilistic tractography.

BACKGROUND: Targeting of the motor thalamus for the treatment of tremor has traditionally been achieved by a combination of anatomical atlases and neuroimaging, intraoperative clinical assessment, and physiological recordings. OBJECTIVE: To evaluate whether thalamic nuclei targeted in tremor surgery could be identified by virtue of their differing connections with noninvasive neuroimaging, thereby providing an extra factor to aid successful targeting. METHODS: Diffusion tensor tractography was performed in 17 healthy control subjects using diffusion data acquired at 1.5-T magnetic resonance imaging (60 directions, b value = 1000 s/mm, 2 × 2 × 2-mm³ voxels). The ventralis intermedius (Vim) and ventralis oralis posterior (Vop) nuclei were identified by a stereotactic neurosurgeon, and these sites were used as seeds for probabilistic tractography. The expected cortical connections of these nuclei, namely the primary motor cortex (M1) and contralateral cerebellum for the Vim and M1, the supplementary motor area, and dorsolateral prefrontal cortex for the Vop, were determined a priori from the literature. RESULTS: Tractogram signal intensity was highest in the dorsolateral prefrontal cortex and supplementary motor area after Vop seeding (P < .001, Wilcoxon signed-rank tests). High intensity was seen in M1 after seeding of both nuclei but was greater with Vim seeding (P < .001). Contralateral cerebellar signal was highest with Vim seeding (P < .001). CONCLUSION: Probabilistic tractography can depict differences in connectivity between intimate nuclei within the motor thalamus. These connections are consistent with published anatomical studies; therefore, tractography may provide an important adjunct in future targeting in tremor surgery.

Sing the mind electric - principles of deep brain stimulation.

The remarkable efficacy of deep brain stimulation (DBS) for a range of treatment-resistant disorders is still not matched by a comparable understanding of the underlying neural mechanisms. Some progress has been made using translational research with a range of neuroscientific techniques, and here we review the most promising emerging principles. On balance, DBS appears to work by restoring normal oscillatory activity between a network of key brain regions. Further research using this causal neuromodulatory tool may provide vital insights into fundamental brain function, as well as guide targets for future treatments. In particular, DBS could have an important role in restoring the balance of the brain's default network and thus repairing the malignant brain states associated with affective disorders, which give rise to serious disabling problems such as anhedonia, the lack of pleasure. At the same time, it is important to proceed with caution and not repeat the errors from the era of psychosurgery.

Maintained deep brain stimulation for severe dystonia despite infection by using externalized electrodes and an extracorporeal pulse generator.

Infection in the context of implant surgery is a dreaded complication, usually necessitating the removal of all affected hardware. Severe dystonia is a debilitating condition that can present as an emergency and can occasionally be life threatening. The authors present 2 cases of severe dystonia in which deep brain stimulation was maintained despite the presence of infection, using ongoing stimulation by externalization of electrode wires and an extracorporeal pulse generator. This allowed the infection to clear and wounds to heal while maintaining stimulation. This strategy is similar to that used in the management of infected cardiac pacemakers. The authors suggest that this prolonged extracorporeal stimulation should be considered by neurosurgeons in the face of this difficult clinical situation.

Deep brain stimulation for cluster headache.

Cluster headache is a severely debilitating disorder that can remain unrelieved by current pharmacotherapy. Alongside ablative neurosurgical procedures, neuromodulatory treatments of deep brain stimulation (DBS) and occipital nerve simulation have emerged in the last few years as effective treatments for medically refractory cluster headaches. Pioneers in the field have sought to publish guidelines for neurosurgical treatment; however, only small case series with limited long-term follow-up have been published. Controversy remains over which surgical treatments are best and in which circumstances to intervene. Here we review current data on neurosurgical interventions for chronic cluster headache focusing upon DBS and occipital nerve stimulation, and discuss the indications for and putative mechanisms of DBS including translational insights from functional neuroimaging, diffusion weighted tractography, magnetoencephalography and invasive neurophysiology.

Translational principles of deep brain stimulation.

Deep brain stimulation (DBS) has shown remarkable therapeutic benefits for patients with otherwise treatment-resistant movement and affective disorders. This technique is not only clinically useful, but it can also provide new insights into fundamental brain functions through direct manipulation of both local and distributed brain networks in many different species. In particular, DBS can be used in conjunction with non-invasive neuroimaging methods such as magnetoencephalography to map the fundamental mechanisms of normal and abnormal oscillatory synchronization that underlie human brain function. The precise mechanisms of action for DBS remain uncertain, but here we give an up-to-date overview of the principles of DBS, its neural mechanisms and its potential future applications.

Deep brain stimulation for chronic pain investigated with magnetoencephalography.

Deep brain stimulation has shown remarkable potential in alleviating otherwise treatment-resistant chronic pain, but little is currently known about the underlying neural mechanisms. Here for the first time, we used noninvasive neuroimaging by magnetoencephalography to map changes in neural activity induced by deep brain stimulation in a patient with severe phantom limb pain. When the stimulator was turned off, the patient reported significant increases in subjective pain. Corresponding significant changes in neural activity were found in a network including the mid-anterior orbitofrontal and subgenual cingulate cortices; these areas are known to be involved in pain relief. Hence, they could potentially serve as future surgical targets to relieve chronic pain.

Identifying cardiorespiratory neurocircuitry involved in central command during exercise in humans.

For almost one hundred years, the exact role of human brain structures controlling the cardiorespiratory response to exercise ('central command') has been sought. Animal experiments and functional imaging studies have provided clues, but the underlying electrophysiological activity of proposed relevant neural sites in humans has never been measured. In this study, local field potentials were directly recorded in a number of 'deep' brain nuclei during an exercise task designed to dissociate the exercise from peripheral feedback mechanisms. Several patient groups had electrodes implanted sterotaxically for the treatment of movement disorder or chronic pain. Fast Fourier transform analysis was applied to the neurograms to identify the power of fundamental spectral frequencies. Anticipation of exercise resulted in increases in heart rate, blood pressure and ventilation. The greatest neural changes were found in the periaqueductal grey area (PAG) where anticipation of exercise was accompanied by an increase of 43% in the power of the 12-25 Hz frequency band (P = 0.007). Exercise increased the activity by 87% compared to rest (P = 0.006). Changes were also seen in the 60-90 Hz band when anticipation or exercise increased power by 32% (P = 0.006) and 109% (P < 0.001), respectively. In the subthalamic nucleus there was a reduction in the power of the beta frequency during both anticipation (7.6 +/- 0.68% P = 0.001) and exercise (17.3 +/- 0.96% P < 0.001), whereas an increase was seen with exercise only at higher frequencies (93 +/- 1.8% P = 0.007). No significant changes were seen in the globus pallidus during anticipation of exercise. We provide direct electrophysiological evidence highlighting the PAG as an important subcortical area in the neural circuitry of the cardiorespiratory response to exercise, since stimulation of this structure is known to alter blood pressure in awake humans.

Stimulating the human midbrain to reveal the link between pain and blood pressure.

The periaqueductal grey area (PAG) in the midbrain is an important area for both cardiovascular control and modulation of pain. However, the precise relationship between pain and blood pressure is unknown. We prospectively studied 16 patients undergoing deep brain stimulation of the rostral PAG for chronic pain. Pre-operatively, post-operatively, and at 1 year, pain scores were assessed using both visual analogue scores and the McGill Pain Questionnaire. Patients were tested post-operatively to determine whether electrical stimulation of the PAG would modulate blood pressure. We found that the degree of analgesia induced by deep brain stimulation of the rostral PAG in man is related to the magnitude of reduction in arterial blood pressure. We found that this relationship is linear and is related to reduced activity of the sympathetic nervous system. Thus stimulation of the PAG may partly control pain by reducing sympathetic activity as predicted by William James over a century ago.

Controlling the heart via the brain: a potential new therapy for orthostatic hypotension.

OBJECTIVE: Electrical stimulation of the midbrain is known to influence blood pressure in animals. In humans, it is used for the treatment of chronic neuropathic pain. Our aim was to assess whether orthostatic hypotension can be successfully treated with deep brain stimulation of the periventricular/periaqueductal gray areas in humans. METHODS: We recruited 11 patients who had chronic neuropathic pain and who had undergone implantation of a deep brain stimulator in the periventricular/periaqueductal gray areas. Patients were divided into three groups depending on whether they had orthostatic hypotension (one patient), mild orthostatic intolerance (five patients), or no orthostatic intolerance (five patients). Postoperatively, we continuously recorded blood pressure and heart rate with stimulation off and on and in both sitting and standing positions. From these values, we derived the blood pressure changing rate. Using autoregressive modeling techniques, we calculated changes in low- and high-frequency power spectra of heart rate and baroreflex sensitivity. RESULTS: Electrical stimulation reduced the decrease in systolic blood pressure on standing from 28.2 to 11.1% in one patient with orthostatic hypotension (P < 0.001). In the mild orthostatic intolerance group, an initial drop in systolic blood pressure of 15.4% was completely reversed (P < 0.001). There were no side effects in the remaining group. These changes were accompanied by increases in the blood pressure changing rate, the baroreflex sensitivity, and the baseline (sitting) low-frequency power of the RR interval, but not the high-frequency power. CONCLUSION: Electrical stimulation of the human periventricular/periaqueductal gray areas can reverse orthostatic hypotension. The cause seems to be an increase in sympathetic outflow and in baroreflex sensitivity. This has important implications for future therapies.

Deep brain stimulation for the alleviation of post-stroke neuropathic pain.

Our aim was to asses the efficacy of deep brain stimulation in post-stroke neuropathic pain. Since 2000, 15 patients with post-stroke intractable neuropathic pain were treated with deep brain stimulation of the periventricular gray area (PVG), sensory thalamus (Ventroposterolateral nucleus-VPL) or both. Pain was assessed using both a visual analogue scale and the McGill's pain questionnaire. VAS scores show a mean improvement of 48.8% (SD 8.6%). However, there is a wide variation between patients. This study demonstrates that it is an effective treatment in 70% of such patients.

Deep brain stimulation for neuropathic pain.

Objectives. To determine whether deep brain stimulation is an effective treatment for neuropathic pain of varied etiology. Material and Methods. Thirty-four patients with intractable neuropathic pain were prospectively studied using visual analog scores, McGill Pain Questionnaire, and Quality of Life Questionnaires (EUROQOL EQ-5D VAS, and SF-36 v-2). Patients had either deep brain stimulation of either the periventricular gray or ventroposterolateral nucleus of the thalamus, or both. Results. Seventy-six percent of patients underwent permanent implantation. Overall reduction of pain intensity was 54%. The burning component of pain improved by 77%. Health-related quality of life improved by 38%. Conclusions. Deep brain stimulation is an effective treatment for neuropathic pain. The factors that influence outcome, including etiology and site of stimulation, are discussed.

Deep brain stimulation can regulate arterial blood pressure in awake humans.

The periaqueductal grey matter is known to play a role in cardiovascular control in animals. Cardiovascular responses to electrical stimulation of the periventricular/periaqueductal grey matter were measured in 15 awake human study participants following implantation of deep brain stimulating electrodes for treatment of chronic pain. We found that stimulation of the ventral periventricular/periaqueductal grey matter caused a mean reduction in systolic blood pressure of 14.2+/-3.6 mmHg in seven patients and stimulation of the dorsal periventricular/periaqueductal grey matter caused a mean increase of 16.7+/-5.9 mmHg in six patients. A comparison between ventral and dorsal electrodes demonstrated significant differences (P<0.05). These changes were accompanied by analogous changes in diastolic blood pressure, pulse pressure, maximum dP/dt but not in the time interval between each R wave on the electrocardiogram.