Acute modulation of the limbic network with low and high-frequency stimulation of the human fornix

Chaitanya, Ganne; Tóth, Emília; Pizarro, Diana; Iasemidis, Leonidas D.; Murray, Teresa A.; Riley, Kristen; Pati, Sandipan

doi:10.1016/j.ebr.2020.100363

Cited by 8 publications

(12 citation statements)

References 27 publications

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“…Although diverse hypotheses exist to explain the therapeutic mechanisms of deep brain stimulation (DBS), most authors agree that DBS influences neuronal output and that frequency of stimulation is one of the crucial determinants of clinical outcome 17 . For example, clinical experience in epilepsy suggests that high frequency (> 140 Hz) stimulation reduces seizure frequency by decreasing neural excitability and desynchrony, while 50 Hz stimulation provokes seizures 18 – 20 . In Parkinson’s disease, stimulation below 50 Hz worsens symptoms, while temporally patterned stimulation like the theta-burst can improve memory 21 – 23 .…”

Section: Introductionmentioning

confidence: 99%

Novel microwire-based biosensor probe for simultaneous real-time measurement of glutamate and GABA dynamics in vitro and in vivo

Doughty

Hossain

Gong

et al. 2020

Sci Rep

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Glutamate (GLU) and γ-aminobutyric acid (GABA) are the major excitatory (E) and inhibitory (I) neurotransmitters in the brain, respectively. Dysregulation of the E/I ratio is associated with numerous neurological disorders. enzyme-based microelectrode array biosensors present the potential for improved biocompatibility, localized sample volumes, and much faster sampling rates over existing measurement methods. However, enzymes degrade over time. To overcome the time limitation of permanently implanted microbiosensors, we created a microwire-based biosensor that can be periodically inserted into a permanently implanted cannula. Biosensor coatings were based on our previously developed GLU and reagent-free GABA shank-type biosensor. In addition, the microwire biosensors were in the same geometric plane for the improved acquisition of signals in planar tissue including rodent brain slices, cultured cells, and brain regions with laminar structure. We measured real-time dynamics of GLU and GABA in rat hippocampal slices and observed a significant, nonlinear shift in the E/I ratio from excitatory to inhibitory dominance as electrical stimulation frequency increased from 10 to 140 Hz, suggesting that GABA release is a component of a homeostatic mechanism in the hippocampus to prevent excitotoxic damage. Additionally, we recorded from a freely moving rat over fourteen weeks, inserting fresh biosensors each time, thus demonstrating that the microwire biosensor overcomes the time limitation of permanently implanted biosensors and that the biosensors detect relevant changes in GLU and GABA levels that are consistent with various behaviors. Near real-time measurement of neurotransmitter levels in the brain is expected to reveal important clues to the underlying mechanisms of neurological disorders, such as epilepsy, addiction, motor control 1-3 , and secondary damage after stroke 4 and traumatic brain injury 5,6. Two important and ubiquitous neurotransmitters in the brain are l-glutamine (GLU) and γ-aminobutyric acid (GABA), which are the major excitatory and inhibitory neurotransmitters, respectively. A balance of excitatory (E) and inhibitory (I) electrical signaling in local networks (E/I ratio) is observed in awake states and in sleep, with the exception of slow-wave sleep in humans and monkeys 7. Dysregulation in E/I is closely linked to dysregulation of GLU and/or GABA dynamics 8. Prolonged, excessive GLU release often leads to excitotoxic neuronal cell death directly or through a cascade of secondary cellular injury 9,10. Furthermore, insufficient release of GABA is associated with seizures 6,11 and autism 12. Most studies so far have only looked at GLU and GABA in isolation 13,14. However, a more meaningful interpretation of the mechanisms of disease and secondary injury can be obtained by knowing the regional E/I balance 15. Furthermore,

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Section: Introductionmentioning

confidence: 99%

Novel microwire-based biosensor probe for simultaneous real-time measurement of glutamate and GABA dynamics in vitro and in vivo

Doughty

Hossain

Gong

et al. 2020

Sci Rep

Self Cite

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“…The benefit of LFS may be from increased stimulation time, lower stimulation frequency, or a combination of the two. Previous reports suggest that for some anatomical structures, LFS may provide a greater 6 or lesser 15 benefit than HFS, which suggests the ideal stimulation frequency may depend on stimulation location. Another possibility is that some patients benefit from lower stimulation frequencies due to characteristics of their epileptic networks 5,16 …”

Section: Discussionmentioning

confidence: 99%

“…Low‐frequency stimulation (LFS) has been studied in animals as a potential antiepileptic strategy specially in rodent kindling models. In humans, LFS has been studied in DRE patients through stimulation of a wide variety of targets including hippocampus, 5 fornix, 6 thalamus, 7 and cortex 8 . Regarding the latter, chronic subthreshold stimulation involves open‐loop, continuous electrical stimulation of seizure foci in focal DRE patients through LFS and may be particularly useful when stimulating eloquent cortex 9 .…”

Section: Introductionmentioning

confidence: 99%

Responsive neurostimulation with low‐frequency stimulation

et al. 2022

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Deep brain stimulation and responsive neurostimulation (RNS) use highfrequency stimulation (HFS) per the pivotal trials and manufacturerrecommended therapy protocols. However, not all patients respond to HFS. In this retrospective case series, 10 patients implanted with the RNS System were programmed with low-frequency stimulation (LFS) to treat their seizures; nine of these patients were previously treated with HFS (100 Hz or greater). LFS was defined as frequency < 10 Hz. Burst duration was increased to at least 1000 ms. With HFS, patients had a median seizure reduction (MSR) of 13% (interquartile range[IQR] = −67 to 54) after a median of 19 months (IQR = 8-49). In contrast, LFS was associated with a 67% MSR (IQR = 13-95) when compared to HFS and 76% MSR (IQR = 43-91) when compared to baseline prior to implantation. Charge delivered per hour and pulses per day were not significantly different between HFS and LFS, although time stimulated per day was longer for LFS (228 min) than for HFS (7 min). There were no LFS-specific adverse effects reported by any of the patients. LFS could represent an alternative, effective method for delivering stimulation in focal drug-resistant epilepsy patients treated with the RNS System.

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“…Electrical deep-brain stimulation of the fornix has revealed distinct spatiotemporal network activation patterns of the CCEP. 62 Such investigations can yield quantitative evidence that nodes with stimulation-induced cortical activation exhibit changes in poststimulation cortical excitability. They could lead to new therapeutic applications involving a stimulation-induced network activation paradigm for neurologic diseases with functional impairments.…”

Section: Prospects Of the Ccep And Network Mappingmentioning

confidence: 99%

New approach of using cortico-cortical evoked potential for functional brain evaluation

Jo¹,

Kim²,

Song³

et al. 2021

ACN

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Cortico-cortical evoked potential (CCEP) mapping is a rapidly developing method for visualizing the brain network and estimating cortical excitability. The CCEP comprises the early N1 component the occurs at 10-30 ms poststimulation, indicating anatomic connectivity, and the late N2 component that appears at < 200 ms poststimulation, suggesting long-lasting effective connectivity. A later component at 200-1,000 ms poststimulation can also appear as a delayed response in some studied areas. Such delayed responses occur in areas with changed excitability, such as an epileptogenic zone. CCEP mapping has been used to examine the brain connections causally in functional systems such as the language, auditory, and visual systems as well as in anatomic regions including the frontoparietal neocortices and hippocampal limbic areas. Task-based CCEPs can be used to measure behavior. In addition to evaluations of the brain connectome, single-pulse electrical stimulation (SPES) can reflect cortical excitability, and so it could be used to predict a seizure onset zone. CCEP brain mapping and SPES investigations could be applied both extraoperatively and intraoperatively. These underused electrophysiologic tools in basic and clinical neuroscience might be powerful methods for providing insight into measures of brain connectivity and dynamics. Analyses of CCEPs might enable us to identify causal relationships between brain areas during cortical processing, and to develop a new paradigm of effective therapeutic neuromodulation in the future.

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Acute modulation of the limbic network with low and high-frequency stimulation of the human fornix

Cited by 8 publications

References 27 publications

Novel microwire-based biosensor probe for simultaneous real-time measurement of glutamate and GABA dynamics in vitro and in vivo

Novel microwire-based biosensor probe for simultaneous real-time measurement of glutamate and GABA dynamics in vitro and in vivo

Responsive neurostimulation with low‐frequency stimulation

New approach of using cortico-cortical evoked potential for functional brain evaluation

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