Thalamic Stimulation Improves Postictal Cortical Arousal and Behavior.

The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. Previous work in disorders of consciousness including the postictal state suggests that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) may improve level of arousal. We tested the effects of postictal thalamic CL DBS in a rat model of secondarily generalized seizures elicited by electrical hippocampal stimulation. Thalamic CL DBS was delivered at 100 Hz during the postictal period in 21 female rats while measuring cortical electrophysiology and behavior. The postictal period was characterized by frontal cortical slow waves, like other states of depressed consciousness. In addition, rats exhibited severely impaired responses on two different behavioral tasks in the postictal state. Thalamic CL stimulation prevented postictal cortical slow wave activity but produced only modest behavioral improvement on a spontaneous licking sucrose reward task. We therefore also tested responses using a lever-press shock escape/avoidance (E/A) task. Rats achieved high success rates responding to the sound warning on the E/A task even during natural slow wave sleep but were severely impaired in the postictal state. Unlike the spontaneous licking task, thalamic CL DBS during the E/A task produced a marked improvement in behavior, with significant increases in lever-press shock avoidance with DBS compared with sham controls. These findings support the idea that DBS of subcortical arousal structures may be a novel therapeutic strategy benefitting patients with medically and surgically refractory epilepsy.SIGNIFICANCE STATEMENT The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. For the first time, we developed two behavioral tasks and demonstrate that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) decreased cortical slow wave activity and improved task performance in the postictal period. Because preclinical task performance studies are crucial to explore the effectiveness and safety of DBS treatment, our work is clinically relevant as it could support and help set the foundations for a human neurostimulation trial to improve postictal responsiveness in patients with medically and surgically refractory epilepsy.

Detecting Seizures and Epileptiform Abnormalities in Acute Brain Injury.

PURPOSE OF REVIEW: Acute brain injury (ABI) is a broad category of pathologies, including traumatic brain injury, and is commonly complicated by seizures. Electroencephalogram (EEG) studies are used to detect seizures or other epileptiform patterns. This review seeks to clarify EEG findings relevant to ABI, explore practical barriers limiting EEG implementation, discuss strategies to leverage EEG monitoring in various clinical settings, and suggest an approach to utilize EEG for triage. RECENT FINDINGS: Current literature suggests there is an increased morbidity and mortality risk associated with seizures or patterns on the ictal-interictal continuum (IIC) due to ABI. Further, increased use of EEG is associated with better clinical outcomes. However, there are many logistical barriers to successful EEG implementation that prohibit its ubiquitous use. Solutions to these limitations include the use of rapid EEG systems, non-expert EEG analysis, machine learning algorithms, and the incorporation of EEG data into prognostic models.

Stereoelectroencephalography-Guided Radiofrequency Thermocoagulation: Diagnostic and Therapeutic Implications.

Despite recent medical therapeutic advances, approximately one third of patients do not attain seizure freedom with medications. This drug-resistant epilepsy population suffers from heightened morbidity and mortality. In appropriate patients, resective epilepsy surgery is far superior to continued medical therapy. Despite this efficacy, there remain drawbacks to traditional epilepsy surgery, such as the morbidity of open neurosurgical procedures as well as neuropsychological adverse effects. SEEG-guided Radiofrequency Thermocoagulation (SgRFTC) is a minimally invasive, electrophysiology-guided intervention with both diagnostic and therapeutic implications for drug-resistant epilepsy that offers a convenient adjunct or alternative to ablative and resective approaches. We review the international experience with this procedure, including methodologies, diagnostic benefit, therapeutic benefit, and safety considerations. We propose a framework in which SgRFTC may be incorporated into intracranial EEG evaluations alongside passive recording. Lastly, we discuss the potential role of SgRFTC in both delineating and reorganizing epilepsy networks.

Expression pattern for unc5b, an axon guidance gene in embryonic zebrafish development.

Branching processes such as nerves and vessels share molecular mechanisms of path determination. Our study focuses on unc5b, a member of the unc5 axon guidance gene family. Here, we have cloned the full-length zebrafish ortholog of unc5b, mapped its chromosome location in the zebrafish genome, and compared its expression patterns to robo4, another axon guidance family member. In situ show that unc5b is expressed predominantly in sensory structures such as the eye, ear, and brain. Both unc5b and robo4 show robust expression in all three compartments of the embryonic brain, namely forebrain, midbrain, and hindbrain. In particular, the hindbrain rhombomere expression displays interesting patterns in that robo4 is expressed in medial rhombomere cell clusters when compared to unc5b expressed in lateral rhombomere clusters. A similar medial-lateral theme is observed in other neural structures such as the neural tube. Our expression analysis provides a starting point for studying the role of axon guidance genes in embryonic hindbrain patterning.

A cerebellum-like circuit in the auditory system cancels responses to self-generated sounds.

The dorsal cochlear nucleus (DCN) integrates auditory nerve input with a diverse array of sensory and motor signals processed in circuitry similar to that of the cerebellum. Yet how the DCN contributes to early auditory processing has been a longstanding puzzle. Using electrophysiological recordings in mice during licking behavior, we show that DCN neurons are largely unaffected by self-generated sounds while remaining sensitive to external acoustic stimuli. Recordings in deafened mice, together with neural activity manipulations, indicate that self-generated sounds are cancelled by non-auditory signals conveyed by mossy fibers. In addition, DCN neurons exhibit gradual reductions in their responses to acoustic stimuli that are temporally correlated with licking. Together, these findings suggest that DCN may act as an adaptive filter for cancelling self-generated sounds. Adaptive filtering has been established previously for cerebellum-like sensory structures in fish, suggesting a conserved function for such structures across vertebrates.