Search

The success of deep brain stimulation (DBS) for treating Parkinsons disease has led to its application to several other disorders, including treatment-resistant depression. Results with DBS for treatment-resistant depression have been heterogeneous, with inconsistencies largely driven by incomplete understanding of the brain networks regulating mood, especially on an individual basis. We report results from the first subject treated with DBS for treatment-resistant depression using an approach that incorporates intracranial recordings to personalize understanding of network behavior and its response to stimulation. These recordings enabled calculation of individually optimized DBS stimulation parameters using a novel inverse solution approach. In the ensuing double-blind, randomized phase incorporating these bespoke parameter sets, DBS led to remission of symptoms and dramatic improvement in quality of life. Results from this initial case demonstrate the feasibility of this personalized platform, which may be used to improve surgical neuromodulation for a vast array of neurologic and psychiatric disorders.

Objective.Therapeutic efficacy of deep brain stimulation (DBS) in both established and emerging indications, is highly dependent on accurate lead placement and optimized clinical programming. The latter relies on clinicians experience to search among available sets of stimulation parameters and can be limited by the time constraints of clinical practice. Recent innovations in device technology have expanded the number of possible electrode configurations and parameter sets available to clinicians, amplifying the challenge of time constraints. We hypothesize that patient specific neuroimaging data can effectively assist the clinical programming using automated algorithms.Approach.This paper introduces the DBS Illumina 3D algorithm as a tool which uses patient-specific imaging to find stimulation settings that optimizes activating a target area while minimizing the stimulation of areas outside the target that could result in unknown or undesired side effects. This approach utilizes preoperative neuroimaging data paired with the postoperative reconstruction of the lead trajectory to search the available stimulation space and identify optimized stimulation parameters. We describe the application of this algorithm in three patients with treatment-resistant depression who underwent bilateral implantation of DBS in subcallosal cingulate cortex and ventral capsule/ventral striatum using tractography optimized targeting with an imaging defined target previously described.Main results.Compared to the stimulation settings selected by the clinicians (informed by anatomy), stimulation settings produced by the algorithm that achieved similar or greater target coverage, produced a significantly smaller stimulation area that spilled outside the target (P= 0.002).Significance. The DBS Illumina 3D algorithm is seamlessly integrated with the clinician programmer software and effectively and rapidly assists clinicians with the analysis of image based anatomy, and provides a starting point to search the highly complex stimulation parameter space and arrive at the stimulation settings that optimize activating a target area.

BackgroundThe efficacy of psychiatric DBS is thought to be driven by the connectivity of stimulation targets with mood-relevant fronto-temporal networks, which is typically evaluated using diffusion-weighted tractography.ObjectiveLeverage intracranial electrophysiology recordings to better predict the circuit-wide effects of neuromodulation to white matter targets. We hypothesize strong convergence between tractography-predicted structural connectivity and stimulation-induced electrophysiological responses.MethodsEvoked potentials were elicited by single-pulse stimulation to two common DBS targets for treatment-resistant depression - the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VCVS) - in two patients undergoing DBS with stereo-electroencephalographic (sEEG) monitoring. Evoked potentials were compared with predicted structural connectivity between DBS leads and sEEG contacts using probabilistic, patient-specific diffusion-weighted tractography.ResultsEvoked potentials and tractography showed strong convergence in both patients in orbitofrontal, ventromedial prefrontal, and lateral prefrontal cortices for both SCC and VCVS stimulation targets. Low convergence was found in anterior cingulate (ACC), where tractography predicted structural connectivity from SCC targets but produced no evoked potentials during SCC stimulation. Further, tractography predicted no connectivity to ACC from VCVS targets, but VCVS stimulation produced robust evoked potentials.ConclusionThe two connectivity methods showed significant convergence, but important differences emerged with respect to the ability of tractography to predict electrophysiological connectivity between SCC and VCVS to regions of the mood-related network. This multimodal approach raises intriguing implications for the use of tractography in surgical targeting and provides new data to enhance our understanding of the network-wide effects of neuromodulation.

In this issue of the JCI, the dream of restoring useful vision to blind individuals with neurotechnology moves one step closer to realization. Fernandez et al. implanted an electrode array with 96 penetrating electrodes in the visual cortex of a blind patient who had been without light perception for 16 years due to optic neuropathy. Remarkably, the patient was able to perceive visual patterns created by passing current through array electrodes. The use of a penetrating electrode array meant that action potentials from single neurons could be recorded to study the neural response to stimulation. Compared with electrodes resting on the cortical surface, penetrating electrodes require one-tenth the current to create a visual percept. However, patterned electrical stimulation often fails to produce the expected percept for penetrating and surface electrode arrays, highlighting the need for further research to untangle the relationship between stimulus and perception., Electrical stimulation of the visual cortex Neurosurgeons probing the brains of awake patients in the operating room discovered that electrical stimulation of early visual cortex produces the perception of a [...]

Prefrontal circuits in the human brain play an important role in cognitive and affective processing. Neuromodulation therapies delivered to certain key hubs within these circuits are being used with increasing frequency to treat a host of neuropsychiatric disorders. However, the detailed neurophysiological effects of stimulation to these hubs are largely unknown. Here, we performed intracranial recordings across prefrontal networks while delivering electrical stimulation to two well-established white matter hubs involved in cognitive regulation and depression: the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VC/VS). We demonstrate a shared frontotemporal circuit consisting of the ventromedial prefrontal cortex, amygdala, and lateral orbitofrontal cortex where gamma oscillations are differentially modulated by stimulation target. Additionally, we found participant-specific responses to stimulation in the dorsal anterior cingulate cortex and demonstrate the capacity for further tuning of neural activity using current-steered stimulation. Our findings indicate a potential neurophysiological mechanism for the dissociable therapeutic effects seen across the SCC and VC/VS targets for psychiatric neuromodulation and our results lay the groundwork for personalized, network-guided neurostimulation therapy. [ABSTRACT FROM AUTHOR]