Dual Treatment of Refractory Focal Epilepsy and Obsessive-Compulsive Disorder With Intracranial Responsive Neurostimulation.

Purpose Of The Review: Intracranial neurostimulation is a well-established treatment of neurologic conditions such as drug-resistant epilepsy (DRE) and movement disorders, and there is emerging evidence for using deep brain stimulation to treat obsessive-compulsive disorder (OCD) and depression. Nearly all published reports of intracranial neurostimulation have focused on implanting a single device to treat a single condition. The purpose of this review was to educate neurology clinicians on the background literature informing dual treatment of 2 comorbid neuropsychiatric conditions epilepsy and OCD, discuss ethical and logistical challenges to dual neuropsychiatric treatment with a single device, and demonstrate the promise and pitfalls of this approach through discussion of the first-in-human closed-looped neurostimulator (RNS) implanted to treat both DRE (on-label) and OCD (off-label).

Responsive deep brain stimulation guided by ventral striatal electrophysiology of obsession durably ameliorates compulsion.

Treatment-resistant obsessive-compulsive disorder (OCD) occurs in approximately one-third of OCD patients. Obsessions may fluctuate over time but often occur or worsen in the presence of internal (emotional state and thoughts) and external (visual and tactile) triggering stimuli. Obsessive thoughts and related compulsive urges fluctuate (are episodic) and so may respond well to a time-locked brain stimulation strategy sensitive and responsive to these symptom fluctuations.

Accumbens connectivity during deep-brain stimulation differentiates loss of control from physiologic behavioral states.

Background: Loss of control (LOC) eating, the subjective sense that one cannot control what or how much one eats, characterizes binge-eating behaviors pervasive in obesity and related eating disorders. Closed-loop deep-brain stimulation (DBS) for binge eating should predict LOC and trigger an appropriately timed intervention.

Objective/hypothesis: This study aimed to identify a sensitive and specific biomarker to detect LOC onset for DBS.

Pilot study of responsive nucleus accumbens deep brain stimulation for loss-of-control eating.

Cravings that precede loss of control (LOC) over food consumption present an opportunity for intervention in patients with the binge eating disorder (BED). In this pilot study, we used responsive deep brain stimulation (DBS) to record nucleus accumbens (NAc) electrophysiology during food cravings preceding LOC eating in two patients with BED and severe obesity (trial registration no. NCT03868670).

Aberrant impulse control circuitry in obesity.

The ventromedial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) circuit has been implicated in impulsive reward-seeking. This disinhibition has been implicated in obesity and often manifests as binge eating, which is associated with worse treatment outcomes and comorbidities. It remains unclear whether the vmPFC-NAc circuit is perturbed in impulsive eaters with obesity.

Complex negative emotions induced by electrical stimulation of the human hypothalamus.

Background: Stimulation of the ventromedial hypothalamic region in animals has been reported to cause attack behavior labeled as sham-rage without offering information about the internal affective state of the animal being stimulated.

Objective: To examine the causal effect of electrical stimulation near the ventromedial region of the human hypothalamus on the human subjective experience and map the electrophysiological connectivity of the hypothalamus with other brain regions.

Methods: We examined a patient (Subject S20_150) with intracranial electrodes implanted across 170 brain regions, including the hypothalamus.

The insulo-opercular cortex encodes food-specific content under controlled and naturalistic conditions.

The insulo-opercular network functions critically not only in encoding taste, but also in guiding behavior based on anticipated food availability. However, there remains no direct measurement of insulo-opercular activity when humans anticipate taste. Here, we collect direct, intracranial recordings during a food task that elicits anticipatory and consummatory taste responses, and during ad libitum consumption of meals.

Neural recruitment by ephaptic coupling in epilepsy.

Objective: One of the challenges in treating patients with drug-resistant epilepsy is that the mechanisms of seizures are unknown. Most current interventions are based on the assumption that epileptic activity recruits neurons and progresses by synaptic transmission. However, several experimental studies have shown that neural activity in rodent hippocampi can propagate independently of synaptic transmission.

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies.

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field.

Self-propagating, non-synaptic epileptiform activity recruits neurons by endogenous electric fields.

It is well documented that synapses play a significant role in the transmission of information between neurons. However, in the absence of synaptic transmission, neural activity has been observed to continue to propagate. Previous studies have shown that propagation of epileptiform activity takes place in the absence of synaptic transmission and gap junctions and is outside the range of ionic diffusion and axonal conduction.

Slow periodic activity in the longitudinal hippocampal slice can self-propagate non-synaptically by a mechanism consistent with ephaptic coupling.

Key Points: Slow periodic activity can propagate with speeds around 0.1 m s and be modulated by weak electric fields. Slow periodic activity in the longitudinal hippocampal slice can propagate without chemical synaptic transmission or gap junctions, but can generate electric fields which in turn activate neighbouring cells.

Slow moving neural source in the epileptic hippocampus can mimic progression of human seizures.

Fast and slow neural waves have been observed to propagate in the human brain during seizures. Yet the nature of these waves is difficult to study in a surgical setting. Here, we report an observation of two different traveling waves propagating in the in-vitro epileptic hippocampus at speeds similar to those in the human brain.

Propagating Neural Source Revealed by Doppler Shift of Population Spiking Frequency.

Unlabelled: Electrical activity in the brain during normal and abnormal function is associated with propagating waves of various speeds and directions. It is unclear how both fast and slow traveling waves with sometime opposite directions can coexist in the same neural tissue. By recording population spikes simultaneously throughout the unfolded rodent hippocampus with a penetrating microelectrode array, we have shown that fast and slow waves are causally related, so a slowly moving neural source generates fast-propagating waves at ∼0.

Can Neural Activity Propagate by Endogenous Electrical Field?

It is widely accepted that synaptic transmissions and gap junctions are the major governing mechanisms for signal traveling in the neural system. Yet, a group of neural waves, either physiological or pathological, share the same speed of ∼0.1 m/s without synaptic transmission or gap junctions, and this speed is not consistent with axonal conduction or ionic diffusion.

Propagation of epileptiform activity can be independent of synaptic transmission, gap junctions, or diffusion and is consistent with electrical field transmission.

The propagation of activity in neural tissue is generally associated with synaptic transmission, but epileptiform activity in the hippocampus can propagate with or without synaptic transmission at a speed of ∼0.1 m/s. This suggests an underlying common nonsynaptic mechanism for propagation.