Theta burst transcranial magnetic stimulation to induce seizures in an epilepsy monitoring unit

Udupa, Kaviraja; Tai, Peter; Saha, Utpal; Wennberg, Richard; Valiante, Taufik A.; Andrade, D. Ciampi De; McAndrews, Mary Pat; Chen, Robert

doi:10.1016/j.brs.2020.10.009

Cited by 5 publications

(5 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, our models and methodology may further serve to identify EEG biomarkers of altered cellular and circuit mechanism in other neurological diseases, such as epilepsy and schizophrenia [39,[80][81][82][83].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the computational models we have developed provide a powerful tool to identify the EEG biomarkers of novel therapeutic compounds and treatments for depression[17,79] via in-silico simulations to improve treatment monitoring. Finally, our models and methodology may further serve to identify EEG biomarkers of altered cellular and circuit mechanism in other neurological diseases, such as epilepsy and schizophrenia[39,80–83].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

EEG biomarkers of reduced inhibition in human cortical microcircuits in depression

Mazza

Griffiths

Hay

2021

Preprint

View full text Add to dashboard Cite

Major depressive disorder (depression) is a complex condition that involves multiple physiological mechanisms, spanning a range of spatial scales. Altered cortical inhibition is associated with treatment-resistant depression, and reduced dendritic inhibition by somatostatin-expressing (SST) interneurons has been strongly implicated in this aspect of the pathology. However, whether the effects of reduced SST inhibition on microcircuit activity have signatures detectible in electroencephalography (EEG) signals remains unknown. We used detailed models of human cortical layer 2/3 microcircuits with normal or reduced SST inhibition to simulate resting-state activity together with EEG signals in health and depression. We first show that the healthy microcircuit models exhibit emergent key features of resting-state EEG. We then simulated EEG from depression microcircuits and found a significant power increase in theta, alpha and low beta frequencies (4 - 15 Hz). Following spectral decomposition, we show that the power increase involved a combination of aperiodic broadband component, and a periodic theta and low beta components. Neuronal spiking showed a spike preference for the phase preceding the EEG trough, which did not differ between conditions. Our study thus used detailed computational models to identify EEG biomarkers of reduced SST inhibition in human cortical microcircuits in depression, which may serve to improve the diagnosis and stratification of depression subtypes, and in monitoring the effects of pharmacological modulation of inhibition for treating depression.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

EEG biomarkers of reduced inhibition in human cortical microcircuits in depression

Mazza

Griffiths

Hay

2021

Preprint

View full text Add to dashboard Cite

show abstract

“… Koc et al (2017) safely applied single cTBS trains over the motor and cerebellar cortex of 15 subjects with idiopathic generalized epilepsy. Udupa et al (2020) performed TBS in seven epilepsy patients admitted to an epilepsy monitoring unit in an attempt to induce habitual seizures to speed up the diagnostic and localizing process. They applied both an excitatory iTBS and an inhibitory cTBS train over the EF, but were unable to induce any seizure activity, thereby concluding that TBS can be safely applied in this population.…”

Section: Discussionmentioning

confidence: 99%

Continuous theta burst stimulation for drug-resistant epilepsy

et al. 2022

View full text Add to dashboard Cite

IntroductionRepetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients.Materials and methodsWe performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers.ResultsSeven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort.ConclusionWe report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).

show abstract

“…To date, these effects have been transient and reversible, supporting the safety profile of current sonication regimes (Lee et al, 2020;Legon et al, 2020). Nevertheless, with reports of other non-invasive brain stimulation modalities such as TMS (Lenoir et al, 2018;Udupa et al, 2020) and transcranial direct current stimulation (Ekici, 2015) eliciting unexpected seizure activity in human subjects (but see Rossi et al, (2021) for a comprehensive discussion), a careful assessment of participant demographics might be prudent when designing TUS experiments. On the other hand, rodent and non-human primate studies have shown that certain TUS parameters suppress seizure activity in acute epilepsy models (Hakimova et al, 2015;Zou et al, 2020), highlighting the importance of parameter selection, and future research into TUS mechanisms of actions on hyperexcitable neural networks and circuits.…”

Section: Safety Considerations For Tus Exposurementioning

confidence: 95%