Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for ...severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.
Measurements in phantoms are used to predict temperature changes that would occur in vivo for medical implants due to the radio frequency (RF) field in magnetic resonance imaging (MRI). In this ...study, the impact of concentration of the gelling agent in a saline-based phantom on the RF-induced temperature rise was measured using an apparatus that accurately reproduces the RF environment present in a 1.5-T whole-body MR system. The temperature was measured using fluoroptic thermometry at the electrode and other sites for a deep brain neurostimulation system. The average power deposition in the 30-kg phantom was about 1.5 W/kg. Four phantom formulations were evaluated, using different concentrations of polyacrylic acid (PAA) added to saline solution, with NaCl concentration adjusted to maintain an electrical conductivity near 0.24 S/m. The greatest temperature rises occurred at the electrode, ranging from 16.2/spl deg/C for greatest concentration of PAA to 2.9/spl deg/C for only saline solution. The temperature rise attained the maximal value for sufficient concentration of PAA. Similar behavior was observed in the temperature versus time relationship near a current-carrying resistor, immersed in gel and saline, which was used to model a localized heat source. The temperature rise for insufficient PAA concentration is reduced due to convection of phantom material. In conclusion, an appropriate gelling agent is required to accurately simulate the thermal properties of body tissues for measurements of RF-induced heating with medical implants.
Deep brain stimulation (DBS) of the ventral anterior internal capsule/ventral striatum (VC/VS) is under investigation as an alternative to anterior capsulotomy for severe obsessive-compulsive ...disorder (OCD). In neuroimaging studies of patients with OCD, dysfunction in the orbitofrontal and anterior cingulate cortex, striatum, and thalamus has been identified; and modulation of activity in this circuit has been observed following successful nonsurgical treatment. The purpose of the current study was to test hypotheses regarding changes in regional cerebral blood flow (rCBF) during acute DBS at the VC/VS target in patients with OCD who were participating in a clinical DBS trial.
Six patients enrolled in a DBS trial for OCD underwent positron emission tomography to measure rCBF; the rCBF measured during acute DBS at high frequency was then compared with those measured during DBS at low frequency and off (control) conditions. On the basis of neuroanatomical knowledge about the VC/VS and neuroimaging data on OCD, the authors predicted that acute DBS at this target would result in modulation of activity within the implicated frontal-basal ganglia-thalamic circuit. Data were analyzed using statistical parametric mapping. In a comparison of acute high-frequency DBS with control conditions, the authors found significant activation of the orbitofrontal cortex, anterior cingulate cortex, striatum, globus pallidus, and thalamus.
Acute DBS at the VC/VS target is associated with activation of the circuitry implicated in OCD. Further studies will be necessary to replicate these findings and to determine the neural effects associated with chronic VC/VS DBS. Moreover, additional data are needed to investigate whether pretreatment imaging profiles can be used to predict a patient's subsequent clinical response to chronic DBS.
Background We investigated the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) for treatment refractory depression. Methods Fifteen patients with chronic, severe, ...highly refractory depression received open-label DBS at three collaborating clinical sites. Electrodes were implanted bilaterally in the VC/VS region. Stimulation was titrated to therapeutic benefit and the absence of adverse effects. All patients received continuous stimulation and were followed for a minimum of 6 months to longer than 4 years. Outcome measures included the Hamilton Depression Rating Scale—24 item (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Global Assessment of Function Scale (GAF). Results Significant improvements in depressive symptoms were observed during DBS treatment. Mean HDRS scores declined from 33.1 at baseline to 17.5 at 6 months and 14.3 at last follow-up. Similar improvements were seen with the MADRS (34.8, 17.9, and 15.7, respectively) and the GAF (43.4, 55.5, and 61.8, respectively). Responder rates with the HDRS were 40% at 6 months and 53.3% at last follow-up (MADRS: 46.7% and 53.3%, respectively). Remission rates were 20% at 6 months and 40% at last follow-up with the HDRS (MADRS: 26.6% and 33.3%, respectively). The DBS was well-tolerated in this group. Conclusions Deep brain stimulation of the VC/VS offers promise for the treatment of refractory major depression.
Recent work has shown a potential for excessive heating of deep brain stimulation electrodes during MR imaging. This in vitro study investigates the relationship between electrode heating and the ...specific absorption rate (SAR) of several MR images.
In vitro testing was performed by using a 1.5-T MR imaging system and a head transmit-receive coil, with bilateral deep brain stimulation systems positioned in a gel saline-filled phantom, and temperature monitoring with a fluoroptic thermometry system. Standardized fast spin-echo sequences were performed over a range of high, medium, and low SAR values. Several additional, clinically important MR imaging techniques, including 3D magnetization prepared rapid acquisition gradient-echo imaging, echo-planar imaging, quantitative magnetization transfer imaging, and magnetization transfer-suppressed MR angiography, were also tested by using typical parameters.
A significant, highly linear relationship between SAR and electrode heating was found, with the temperature elevation being approximately 0.9 times the local SAR value. Minor temperature elevations, <1 degrees C, were found with the fast spin-echo, magnetization prepared rapid acquisition gradient-echo, and echo-planar clinical imaging sequences. The high dB/dt echo-planar imaging sequence had no significant heating independent of SAR considerations. Sequences with magnetization transfer pulses produced temperature elevations in the 1.0 to 2.0 degrees C range, which was less than theoretically predicted for the relatively high SAR values.
A potential exists for excessive MR imaging-related heating in patients with deep brain stimulation electrodes; however, the temperature increases are linearly related to SAR values. Clinical imaging sequences that are associated with tolerable temperature elevations in the <or=2.0 degrees C range at the electrode tips can be performed safely within an SAR range <2.4 W/kg local (0.9 W/kg whole body averaged).
The ototoxic effects of salicylates, reversible hearing loss and tinnitus, are well documented. However, the pharmacological mechanisms underlying these changes in cochlear function are not well ...understood. The studies reported here were an investigation of the site and mechanism of salicylate ototoxicity through an examination of its effects on ionic, neural and mechanical aspects of cochlear transduction. Salicylate administration produced an intensity dependent reduction of the AP and SP, with the predominant effects occurring at low stimulus levels. In direct contrast, a significant increase was observed for corresponding CM responses, independent of stimulus intensity. Salicylates also reduced the magnitude of efferent induced shifts in the AP, CM and EP. Cochlear mechanics were altered as evidenced by the reduction in two-tone distortion products, electrically evoked emissions, and electrophonic APs. These changes in cochlear function are attributed to a salicylate mediated increase in the membrane conductance of the outer hair cells. This change in membrane permeability interferes with the reverse transduction process, effectively reducing the gain of the cochlear amplifier. Results of single unit recordings suggest parallels between salicylate intoxication and noise trauma, which are discussed with regard to potential mechanisms of tinnitus generation.
Refractory 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.
Here 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.
Interest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.
Spatial maps of electrical excitation were constructed by comparing electrical threshold with acoustic CF for large populations of auditory nerve fibers in cats. Thresholds among fibers with the same ...CF varied by factors of 4 or more. Monopolar electrodes, both intracochlear and extracochlear, excited fibers throughout the cochlea without spatial selectivity. Stimulation with intracochlear bipolar electrodes produced a minimum in the threshold distribution adjacent to the electrodes. With longitudinally oriented pairs, the width, depth, and location of the minimum shifted with stimulus polarity; spread of excitation throughout the cochlea occurred with stimulus intensities 6.2 to 14 dB above the lowest threshold. With radially oriented pairs, minima were sharper and deeper; spread of excitation occurred at intensities 23.7 to 32.8 dB above the minimum threshold.
Single auditory nerve fibers exhibit firing synchronized to one or both phases of periodic AC stimulus currents. Responses to biphasic pulses depend on order and excitation sites of the two phases. ...Sine and triangle stimuli between 100 Hz and 500 Hz elicit similar response patterns. Responses to square waves are sometimes more synchronized and generally shifted in phase with respect to sine wave responses. Preferred firing phase(s): (1) are largely independent of stimulus intensity; (2) vary among fibers; (3) may shift continuously or discontinuously over several seconds before steady state is achieved. Responses to an unprocessed synthetic vowel stimulus were dominated by pitch period, first formant, and 'spurious' components.
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