Correlational Relationships Between the Hippocampus and Medial Septal Area and Their Changes During Epileptogenesis

Harangozó

Pedraza

et al. 2021

Brain

Temporal lobe epilepsy with distributed hippocampal seizure foci is often intractable and its secondary generalization might lead to sudden death. Early termination through spatially extensive hippocampal intervention is not feasible directly, because of the large size and irregular shape of the hippocampus. In contrast, the medial septum is a promising target to govern hippocampal oscillations through its divergent connections to both hippocampi. Combining this ‘proxy intervention’ concept and precisely timed stimulation, we report here that closed-loop medial septum electrical stimulation can quickly terminate intrahippocampal seizures and suppress secondary generalization in a rat kindling model. Precise stimulus timing governed by internal seizure rhythms was essential. Cell type-specific stimulation revealed that the precisely timed activation of medial septum GABAergic neurons underlaid the effects. Our concept of time-targeted proxy stimulation for intervening pathological oscillations can be extrapolated to other neurological and psychiatric disorders, and has potential for clinical translation.

Section: Introductionmentioning

confidence: 99%

Closed-loop stimulation of the medial septum terminates epileptic seizures

Harangozó

Pedraza

et al. 2021

Brain

“…The MS and HPC are highly coherent in both physiological and pathophysiological conditions. The electrical or optogenetical stimulation of the MS is transmitted to the bilateral HPC at exactly the same frequency that is applied within the delta to gamma-band range (Sinel'nikova et al, 2009;Zutshi et al, 2018). For human application, the thalamic stimulation for refractory epilepsy, the fornical stimulation for AD, and the medial forebrain bundle stimulation for depression all utilize this principle for DBS (Dandekar et al, 2018;Li and Cook, 2018;Mirzadeh et al, 2016).…”

Section: How To Effectively Introduce or Disturb Oscillatory Activitiesmentioning

confidence: 99%

Oscillotherapeutics – Time-targeted interventions in epilepsy and beyond

Berényi

2020

Neuroscience Research

Oscillatory brain activities support many physiological functions from motor control to cognition. Disruptions of the normal oscillatory brain activities are commonly observed in neurological and psychiatric disorders including epilepsy, Parkinson's disease, Alzheimer's disease, schizophrenia, anxiety/traumarelated disorders, major depressive disorders, and drug addiction. Therefore, these disorders can be considered as common oscillation defects despite having distinct behavioral manifestations and genetic causes. Recent technical advances of neuronal activity recording and analysis have allowed us to study the pathological oscillations of each disorder as a possible biomarker of symptoms. Furthermore, recent advances in brain stimulation technologies enable time-and space-targeted interventions of the pathological oscillations of both neurological disorders and psychiatric disorders as possible targets for regulating their symptoms.

“…In addition, the stimulation of the MS is effective to modulate oscillations in the limbic system. For example, studies showed that electrical and optogenetic stimulation of the MS is robustly transmitted to the HPC at the same frequency that is applied within the delta to gamma frequency bands (Sinel'nikova et al, 2009;Zutshi et al, 2018;Takeuchi et al, 2021). Earlier study of the MS stimulation in humans in 1950 reported a high complication rate, but it was likely related to the inexperience of the teams with depth electrode placement (Baumeister, 2000;Fisher, 2015).…”

Section: The Medial Septum As a Target For Deep Brain Stimulation For Epilepsy Control And Beyondmentioning

confidence: 99%

The Medial Septum as a Potential Target for Treating Brain Disorders Associated with Oscillopathies

Nagy

Barcsai

et al. 2021

Preprint

The medial septum (MS), as part of the basal forebrain, supports many physiological functions, from sensorimotor integration to cognition. With often reciprocal connections with a broad set of peers at all major divisions of the brain, the MS orchestrates oscillatory neuronal activities throughout the brain. These oscillations are critical in generating sensory and emotional salience, locomotion, maintaining mood, supporting innate anxiety, and governing learning and memory. Accumulating evidence points out that the physiological oscillations under septal influence are frequently disrupted or altered in pathological conditions. Therefore, the MS may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. Recent studies have revealed that the patterned stimulation of the MS alleviates symptoms of epilepsy. We discuss here that stimulus timing is a critical determinant of treatment efficacy on multiple time scales. On-demand stimulation may dramatically reduce side effects by not interfering with normal physiological functions. A precise pattern-matched stimulation through adaptive timing governed by the ongoing oscillations is essential to effectively terminate pathological oscillations. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders including Alzheimer’s disease, anxiety/fear, schizophrenia, and depression, as well as pain.