Clinical and EEG phenotypes of epilepsy in the baboon (Papio hamadryas spp.)

Szabó, C. Ákos; Leland, M. Michelle; Knape, Koyle D.; Elliott, Joanne; Haines, Vicky; Williams, Jeff T.

doi:10.1016/j.eplepsyres.2005.05.003

Cited by 50 publications

(15 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…epilepsy) using electroencephalographic (EEG) techniques described by Szabó et al . 35 The anesthetized animal preparation—for optimized physiological stability and functional imaging responses—has been described in previous studies. 5,36 Briefly, for each imaging procedure (MRI and PET), each animal received an injection of intramuscular ketamine (5 mg/kg) to facilitate oral intubation and catheterization of a venous delivery line; intramuscular atropine (0.3 mg) was administered to reduce oropharyngeal secretions.…”

Section: Methodsmentioning

confidence: 99%

Repetitive Transcranial Magnetic Stimulation Elicits Rate-Dependent Brain Network Responses in Non-Human Primates

et al. 2013

View full text Add to dashboard Cite

Background Transcranial magnetic stimulation (TMS) has the potential to treat brain disorders by tonically modulating firing patterns in disease-specific neural circuits. The selection of treatment parameters for clinical repetitive transcranial magnetic stimulation (rTMS) trials has not been rule-based, likely contributing to the variability of observed outcomes. Objective To utilize our newly developed baboon (Papio hamadryas anubis) model of rTMS during position-emission tomography (PET) to quantify the brain’s rate-response functions in the motor system during rTMS. Methods We delivered image-guided, suprathreshold rTMS at 3 Hz, 5 Hz, 10 Hz, 15 Hz and rest (in separate randomized sessions) to the primary motor cortex (M1) of the lightly anesthetized baboon during PET imaging; we also administered a (reversible) paralytic to eliminate any somatosensory feedback due to rTMS-induced muscle contractions. Each rTMS/PET session was analyzed using normalized cerebral blood flow (CBF) measurements; statistical parametric images and the resulting areas of significance underwent post-hoc analysis to determine any rate-specific rTMS effects throughout the motor network.

show abstract

Section: Methodsmentioning

confidence: 99%

Repetitive Transcranial Magnetic Stimulation Elicits Rate-Dependent Brain Network Responses in Non-Human Primates

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The methods for the scalp EEG studies (Nihon-Kohden, Japan) were modified from our previous studies (Szabó et al, 2005; Szabó et al, 2013). The surface electrodes were placed according to the standard international 10–20 electrode placement system at FP1, FP2, T8, C4, Cz, C3, T7, O1, O2, A1 and A2 positions.…”

Section: Methodsmentioning

confidence: 99%

“…At these doses, ketamine can activate interictal and ictal epileptic discharges, with minimal effect on photosensitivity. Interictal epileptic discharges (IEDs) were classified are previously indicated, consisting of 4–6 Hz generalized spike-and-wave discharges (Szabó et al, 2005; Szabó et al, 2013). Seizures were classified as generalized myoclonic or tonic or bilateral tonic-clonic (Berg et al, 2010).…”

Section: Methodsmentioning

confidence: 99%

High-frequency burst vagal nerve simulation therapy in a natural primate model of genetic generalized epilepsy

Szabó

Salinas²,

Papanastassiou

et al. 2017

Epilepsy Research

View full text Add to dashboard Cite

Purpose Since the approval of Vagal Nerve Stimulation (VNS) Therapy for medically refractory focal epilepsies in 1997, it has been also reported to be effective for a wide range of generalized seizures types and epilepsy syndromes. Instead of conventional VNS Therapy delivered at 20–30 Hz signal frequencies, this study evaluates efficacy and tolerability of high-frequency burst VNS in a natural animal model for genetic generalized epilepsy (GGE), the epileptic baboon. Methods Two female baboons (B1 P.h. Hamadryas and B2 P.h. Anubis × Cynocephalus) were selected because of frequently witnessed generalized tonic-clonic seizures (GTCS) for VNS implantation. High-frequency burst VNS Therapy was initiated after a 4–5 week baseline; different VNS settings (0.25, 2 or 2.5 mA, 300 Hz, 4 vs 7 pulses, 0.5–2.5 sec interburst interval, and intermittent stimulation for 1–2 vs for 24 hours per day) were tested over the subsequent 19 weeks, which included a 4–6 week wash-out period. GTCS frequencies were quantified for each setting, while seizure duration and postictal recovery times were compared to baseline. Scalp EEG studies were performed at almost every setting, including intermittent light stimulation (ILS) to evaluate photosensitivity. Pre-ILS ictal and interictal discharge rates, as well as ILS responses were compared between trials. The Novel Object test was used to assess potential treatment effects on behavior. Results High-frequency burst VNS Therapy reduced GTCS frequencies at all treatment settings in both baboons, except when output currents were reduced (0.25 mA) or intermittent stimulation was restricted (to 1–2 hours/day). Seizure duration and postictal recovery times were unchanged. Scalp EEG studies did not demonstrate treatment-related decrease of ictal or interictal epileptic discharges or photosensitivity, but continuous treatment for 120–180 seconds during ILS appeared to reduce photoparoxysmal responses. High-frequency burst VNS Therapy was well-tolerated by both baboons, without cardiac or behavioral changes. Repetitive muscle contractions involving the neck and left shoulder girdle were observed intermittently, most commonly at 0.5 interburst intervals, but these were transient, resolving with a few cycles of stimulation and not noted in wakefulness. Conclusions This preclinical pilot study demonstrates efficacy and tolerability of high-frequency burst VNS Therapy in the baboon model of GGE. The muscle contractions may be due to aberrant propagation of the stimulus along the vagal nerve or to the ansa cervicalis, but can be reduced by minimal adjustment of current output or stimulus duration.

show abstract

“…11 The data acquired in these five animals was used in prior publications 8,9 ; the results from these prior publications were reanalyzed in this study to assess the effective connectivity of the baboon’s motor network. Each animal was pre-screened—using electroencephalography 12 —to ensure that only animals with no neurological deficits were enrolled in the study. The optimized anesthetized animal preparation has been described in previous studies.…”

Section: Methodsmentioning

confidence: 99%

Repetitive Transcranial Magnetic Stimulation Educes Frequency-Specific Causal Relationships in the Motor Network

et al. 2016

View full text Add to dashboard Cite

Background Repetitive transcranial magnetic stimulation (rTMS) has the potential to treat brain disorders by modulating the activity of disease-specific brain networks, yet the rTMS frequencies used are delivered in a binary fashion—excitatory (> 1 Hz) and inhibitory (≤1 Hz). Objective To assess the effective connectivity of the motor network at different rTMS stimulation rates during positron-emission tomography (PET) and confirm that not all excitatory rTMS frequencies act on the motor network in the same manner. Methods We delivered image-guided, supra-threshold rTMS at 3 Hz, 5 Hz, 10 Hz, 15 Hz and rest (in separate randomized sessions) to the primary motor cortex (M1) of the lightly anesthetized baboon during PET imaging. Each rTMS/PET session was analyzed using normalized cerebral blood flow (CBF) measurements. Path analysis—using structural equation modeling (SEM)—was employed to determine the effective connectivity of the motor network at all rTMS frequencies. Once determined, the final model of the motor network was used to assess any differences in effective connectivity at each rTMS frequency. Results The exploratory SEM produced a very well fitting final network model (χ2 = 18.04, df = 21, RMSEA = 0.000, p = 0.647, TLI = 1.12) using seven nodes of the motor network. 5 Hz rTMS produced the strongest path coefficients in four of the seven connections, suggesting that this frequency is the optimal rTMS frequency for stimulation the motor network (as a whole), however, the premotor → cerebellum connection was optimally stimulated at 10 Hz rTMS and the supplementary motor area → caudate connection was optimally driven at 15 Hz rTMS. Conclusion(s) We have demonstrated that 1) 5 Hz rTMS revealed the strongest path coefficients (i.e. causal influence) on the nodes of the motor network, 2) stimulation at “excitatory” rTMS frequencies did not produce increased CBF in all nodes of the motor network, 3) specific rTMS frequencies may be used to target specific none-to-node interactions in the stimulated brain network, and 4) more research needs to be performed to determine the optimum frequency for each brain circuit and/or node.

show abstract

Clinical and EEG phenotypes of epilepsy in the baboon (Papio hamadryas spp.)

Cited by 50 publications

References 17 publications

Repetitive Transcranial Magnetic Stimulation Elicits Rate-Dependent Brain Network Responses in Non-Human Primates

Repetitive Transcranial Magnetic Stimulation Elicits Rate-Dependent Brain Network Responses in Non-Human Primates

High-frequency burst vagal nerve simulation therapy in a natural primate model of genetic generalized epilepsy

Repetitive Transcranial Magnetic Stimulation Educes Frequency-Specific Causal Relationships in the Motor Network

Contact Info

Product

Resources

About