The epileptic amygdala: Toward the development of a neural prosthesis by temporally coded electrical stimulation

Cota, Vinícius Rosa; Drabowski, Bruna Marcela Bacellar; Oliveira, Jasiara Carla de; Moraes, Márcio Flávio Dutra

doi:10.1002/jnr.23741

“…We speculate that the choice of coil type and stimulation area may be one of the reasons for the difference in study findings, and that the potential mechanism may be closely related to the amygdala. Recently, researchers have revealed that the amygdale pays a preponderant role in the pathogenesis of epilepsy (Cota et al, 2016). Although magnetic stimulation can cover the amygdala in our study, the circular coil has a disadvantage of poor targeting compared with a figure-of-eight coil.…”

Section: Discussionmentioning

confidence: 75%

Effects of low-frequency repetitive transcranial magnetic stimulation on depression- and anxiety-like behaviors in epileptic rats

Wang

¹

,

Mao

²

,

Yao

³

et al. 2019

Journal of Integrative Neuroscience

View full text Add to dashboard Cite

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been considered as a treatment option for depression and anxiety. However, its role in epilepsy comorbid with depression and anxiety is unclear. Therefore, we evaluated whether low-frequency rTMS can alleviate depression-and anxiety-like behavior in epileptic rats. Forty-eight adult rats were allocated at random to four groups: Control, Pentylenetetrazol (PTZ), PTZ-rTMS and PTZ-Sham. The control group received intraperitoneal injections of normal saline, while the other groups received intraperitoneal injections of pentylenetetrazol (35 mg/kg/d) once a day for 15 days. Low-frequency rTMS or sham stimulation were administered to the PTZ-rTMS and PTZ-Sham group, respectively, over the two-week period. The open-field test (OFT), elevated plus-maze test (EPM) and forced swimming test (FST) were carried out before the experiment, on the 8th and 15th day to assess depression-and anxiety-like behavior in the rats. Two weeks of low-frequency rTMS treatment could not impair the increases of seizure severity in epileptic rats. However, relative to the PTZ and PTZ-Sham group, the twoweek low-frequency rTMS treatment significantly reduced the immobility time in the forced swimming test and attenuated the progressive decrease in total distance traveled, frequency of rearing, velocity in the open-field test, number of entries in the open arms (%) and the time spent in the open arms (%) in the elevated plus-maze test of the PTZ-rTMS group. We proposed that low-frequency rTMS can benefit epileptic rats via amelioration of comorbid depression and anxiety, but it can not alleviate the seizure severity.

show abstract

“…We opted to use a slower stimulation frequency to ensure that the neuronal circuits are not entrained, preventing eventual pro-ictal effects due to the stimulus [72] (for a review on the pro or anticonvulsant effects of various stimulation parameters, see Ref. [73]).…”

Section: Methodsmentioning

confidence: 99%

Active probing to highlight approaching transitions to ictal states in coupled neural mass models

Carvalho

¹

,

Moraes

²

,

Cash

³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

The extraction of electrophysiological features that reliably forecast the occurrence of seizures is one of the most challenging goals in epilepsy research. Among possible approaches to tackle this problem is the use of active probing paradigms in which responses to stimuli are used to detect underlying system changes leading up to seizures. This work evaluates the theoretical and mechanistic underpinnings of this strategy using a well-studied seizure-generating neural mass model with two coupled populations. Different simulations are done by shifting parameters (excitability, slow inhibition, and coupling gains) towards ictal states while low-frequency probing stimuli are applied to either one or both populations. The correlation between the extracted features and the shifted parameter indicates if the impending transition to the ictal state may be identified in advance. Results show that not only can the response to the probing stimuli forecast seizures but this is true regardless of the altered ictogenic parameter. That is, similar feature changes are highlighted by probing stimuli responses in advance of the seizure including: increased response variance and lag-1 autocorrelation, decreased skewness, and increased mutual information between the outputs of both model subsets. These changes were restricted to the stimulated population, showing a local effect of this perturbational approach. The transition latencies from normal activity to sustained discharges of spikes were not affected, suggesting that stimuli had no pro-ictal effects. However, stimuli were found to elicit interictal-like spikes just before the transition to the ictal state. Furthermore, the observed feature changes highlighted by probing the neuronal populations may reflect the phenomenon of critical slowing down, where increased recovery times from perturbations may signal the loss of a systems’ resilience and are common hallmarks of an impending critical transition. These results provide more evidence that active probing approaches highlight information about underlying system changes involved in ictogenesis and may be able to play a role in assisting seizure forecasting methods which can be incorporated into early-warning systems that ultimately enable closing the loop for targeted seizure-controlling interventions.Author summaryEpilepsy is characterized by spontaneous and recurrent seizures. Developing a method to forecast the occurrence of these events would ease part of the burden to patients by providing warning systems and identifying critical periods for closed-loop seizure suppressing methods. However, this task is far from trivial and doing this in a clinical setting has been a challenge that is not yet solved. A possible way to achieve this is by using active probing paradigms, in which stimuli are used to highlight otherwise hidden changes in brain dynamics that may lead to seizures. In this work, this approach is tested in a computational model with two coupled neuronal populations. Active probing responses highlighted underlying model parameter changes that led neuronal activity closer to seizures, something that was not detected with the passive observation in most evaluated model settings. Observed feature changes revealed higher excitability, longer recovery times from stimuli, and increased synchrony between populations as the threshold to seizure-like activity approached. This indicates that low frequency stimuli may be used to reveal early-warning signs and assist in seizure forecasting methods.

show abstract

“…We opted to use a slower stimulation frequency to ensure that the neuronal circuits are not entrained, preventing eventual pro-ictal effects due to the stimulus [75] (for a review on the pro or anticonvulsant effects of various stimulation parameters, see Ref. [76]).…”

Section: Model Parameters and Modificationsmentioning

confidence: 99%

Active probing to highlight approaching transitions to ictal states in coupled neural mass models

Carvalho

¹

,

Moraes

²

,

Cash

³

et al. 2021

Self Cite

View full text Add to dashboard Cite

The extraction of electrophysiological features that reliably forecast the occurrence of seizures is one of the most challenging goals in epilepsy research. Among possible approaches to tackle this problem is the use of active probing paradigms in which responses to stimuli are used to detect underlying system changes leading up to seizures. This work evaluates the theoretical and mechanistic underpinnings of this strategy using two coupled populations of the well-studied Wendling neural mass model. Different model settings are evaluated, shifting parameters (excitability, slow inhibition, or inter-population coupling gains) from normal towards ictal states while probing stimuli are applied every 2 seconds to the input of either one or both populations. The correlation between the extracted features and the ictogenic parameter shifting indicates if the impending transition to the ictal state may be identified in advance. Results show that not only can the response to the probing stimuli forecast seizures but this is true regardless of the altered ictogenic parameter. That is, similar feature changes are highlighted by probing stimuli responses in advance of the seizure including: increased response variance and lag-1 autocorrelation, decreased skewness, and increased mutual information between the outputs of both model subsets. These changes were mostly restricted to the stimulated population, showing a local effect of this perturbational approach. The transition latencies from normal activity to sustained discharges of spikes were not affected, suggesting that stimuli had no pro-ictal effects. However, stimuli were found to elicit interictal-like spikes just before the transition to the ictal state. Furthermore, the observed feature changes highlighted by probing the neuronal populations may reflect the phenomenon of critical slowing down, where increased recovery times from perturbations may signal the loss of a systems’ resilience and are common hallmarks of an impending critical transition. These results provide more evidence that active probing approaches highlight information about underlying system changes involved in ictogenesis and may be able to play a role in assisting seizure forecasting methods which can be incorporated into early-warning systems that ultimately enable closing the loop for targeted seizure-controlling interventions.

show abstract

The epileptic amygdala: Toward the development of a neural prosthesis by temporally coded electrical stimulation

Cited by 30 publications

References 204 publications

Effects of low-frequency repetitive transcranial magnetic stimulation on depression- and anxiety-like behaviors in epileptic rats

Effects of low-frequency repetitive transcranial magnetic stimulation on depression- and anxiety-like behaviors in epileptic rats

Active probing to highlight approaching transitions to ictal states in coupled neural mass models

Active probing to highlight approaching transitions to ictal states in coupled neural mass models

Contact Info

Product

Resources

About