Septohippocampal Neuromodulation Improves Cognition after Traumatic Brain Injury

Lee, Darrin J.; Gurkoff, Gene G.; Izadi, Ali; Seidl, Stacey E.; Echeverri, Angela; Melnik, Mikhail; Berman, Robert F.; Ekstrom, Arne D.; Muizelaar, J. Paul; Lyeth, Bruce G.; Shahlaie, Kiarash

doi:10.1089/neu.2014.3744

Cited by 62 publications

(103 citation statements)

References 72 publications

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“…Medial septal nucleus stimulation prior to a spatial working memory task increased hippocampal theta oscillations 58 and improved spatial working memory in a TBI rat model, but did not have a significant effect in control rats.…”

mentioning

confidence: 73%

“…14 Traumatic brain injury reduces theta-frequency firing, a neural firing frequency known to play an important role in memory, in rat hippocampus CA1, 57,58 as well as firing in other frequency ranges. TBI decreases broadband power as well as theta oscillations in the hippocampus, perhaps associated with a change in the level of neuronal correlation.…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

“…Theta-frequency activity dominates hippocampal neural firing patterns and is known to play an important role in memory. 16,57,58 Connections between the medial septal nucleus and hippocampus have an important role in regulating hippocampal theta oscillations, 111 with the medial septal nucleus acting as a pacemaker for the hippocampus. 58 As such, the medial septal nucleus is positioned to modulate hippocampal activity and memory function.…”

Section: Medial Septal Nucleusmentioning

confidence: 99%

“…Theta-frequency oscillations predominate hippocampal activity and play a vital role in memory, in part by contributing to the transfer of information between the hippocampus and other regions involved in memory. 58 Phase synchronization occurs when the oscillation patterns of 2 connected regions become coordinated, and plays an important role in communication between neural regions as well as neural plasticity. Because of its higher frequency, gamma-phase synchronization plays an important role in neural communication and long-term potentiation by providing a tight temporal regulation and coordination of neural signals.…”

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confidence: 99%

“…58 Medial septal nucleus stimulation therefore appears to augment hippocampal theta oscillations, and may improve memory encoding by strengthening this rhythm, with its known importance in memory.…”

mentioning

confidence: 99%

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Neuromodulation for restoring memory

Bick¹,

Eskandar²

2016

FOC

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Disorders of learning and memory have a large social and economic impact in today's society. Unfortunately, existing medical treatments have shown limited clinical efficacy or potential for modification of the disease course. Deep brain stimulation is a successful treatment for movement disorders and has shown promise in a variety of other diseases including psychiatric disorders. The authors review the potential of neuromodulation for the treatment of disorders of learning and memory. They briefly discuss learning circuitry and its involvement in Alzheimer disease and traumatic brain injury. They then review the literature supporting various targets for neuromodulation to improve memory in animals and humans. Multiple targets including entorhinal cortex, fornix, nucleus basalis of Meynert, basal ganglia, and pedunculopontine nucleus have shown a promising potential for improving dysfunctional memory by mechanisms such as altering firing patterns in neuronal networks underlying memory and increasing synaptic plasticity and neurogenesis. Significant work remains to be done to translate these findings into durable clinical therapies.

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mentioning

confidence: 73%

Section: Traumatic Brain Injurymentioning

confidence: 99%

Section: Medial Septal Nucleusmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Neuromodulation for restoring memory

Bick¹,

Eskandar²

2016

FOC

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Clinically indicated electrical stimulation strategies to treat patients with medically refractory epilepsy

et al. 2018

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SummaryFocal epilepsies represent approximately half of all diagnoses, and more than one‐third of these patients are refractory to pharmacologic treatment. Although resection can result in seizure freedom, many patients do not meet surgical criteria, as seizures may be multifocal in origin or have a focus in an eloquent region of the brain. For these individuals, several U.S. Food and Drug Administration (FDA)–approved electrical stimulation paradigms serve as alternative options, including vagus nerve stimulation, responsive neurostimulation, and stimulation of the anterior nucleus of the thalamus. All of these are safe, flexible, and lead to progressive seizure control over time when used as an adjunctive therapy to antiepileptic drugs. Focal epilepsies frequently involve significant comorbidities such as cognitive decline. Similar to antiepilepsy medications and surgical resection, current stimulation targets and parameters have yet to address cognitive impairments directly, with patients reporting persistent comorbidities associated with focal epilepsy despite a significant reduction in the number of their seizures. Although low‐frequency theta oscillations of the septohippocampal network are critical for modulating cellular activity and, in turn, cognitive processing, the coordination of neural excitability is also imperative for preventing seizures. In this review, we summarize current FDA‐approved electrical stimulation paradigms and propose that theta oscillations of the medial septal nucleus represent a novel neuromodulation target for concurrent seizure reduction and cognitive improvement in epilepsy. Ultimately, further advancements in clinical neurostimulation strategies will allow for the efficient treatment of both seizures and comorbidities, thereby improving overall quality of life for patients with epilepsy.

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Plasticity impairment exposes CA3 vulnerability in a hippocampal network model of mild traumatic brain injury

2022

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Proper function of the hippocampus is critical for executing cognitive tasks such as learning and memory. Traumatic brain injury (TBI) and other neurological disorders are commonly associated with cognitive deficits and hippocampal dysfunction.Although there are many existing models of individual subregions of the hippocampus, few models attempt to integrate the primary areas into one system. In this work, we developed a computational model of the hippocampus, including the dentate gyrus, CA3, and CA1. The subregions are represented as an interconnected neuronal network, incorporating well-characterized ex vivo slice electrophysiology into the functional neuron models and well-documented anatomical connections into the network structure. In addition, since plasticity is foundational to the role of the hippocampus in learning and memory as well as necessary for studying adaptation to injury, we implemented spike-timing-dependent plasticity among the synaptic connections. Our model mimics key features of hippocampal activity, including signal frequencies in the theta and gamma bands and phase-amplitude coupling in area CA1.We also studied the effects of spike-timing-dependent plasticity impairment, a potential consequence of TBI, in our model and found that impairment decreases broadband power in CA3 and CA1 and reduces phase coherence between these two subregions, yet phase-amplitude coupling in CA1 remains intact. Altogether, our work demonstrates characteristic hippocampal activity with a scaled network model of spiking neurons and reveals the sensitive balance of plasticity mechanisms in the circuit through one manifestation of mild traumatic injury.

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Septohippocampal Neuromodulation Improves Cognition after Traumatic Brain Injury

Cited by 62 publications

References 72 publications

Neuromodulation for restoring memory

Neuromodulation for restoring memory

Clinically indicated electrical stimulation strategies to treat patients with medically refractory epilepsy

Plasticity impairment exposes CA3 vulnerability in a hippocampal network model of mild traumatic brain injury

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