Passive Localization of the Central Sulcus during Sleep Based on Intracranial EEG

Abstract

We test the performance of a novel operator-independent EEG-based method for passive identification of the central sulcus (CS) and sensorimotor (SM) cortex. We studied seven patients with intractable epilepsy undergoing intracranial EEG (icEEG) monitoring, in whom CS localization was accomplished by standard methods. Our innovative approach takes advantage of intrinsic properties of the primary motor cortex (MC), which exhibits enhanced icEEG band-power and coherence across the CS. For each contact, we computed a composite power, coherence, and entropy values for activity in the high gamma band (80–115) Hz of 6–10 min of NREM sleep. Statistically transformed EEG data values that did not reach a threshold (th) were set to 0. We computed a metric M based on the transformed values and the mean Euclidian distance of each contact from contacts with Z-scores higher than 0. The last step was implemented to accentuate local network activity. The SM cortex exhibited higher EEG-band-power than non-SM cortex (P < 0.0002). There was no significant difference between the motor/premotor and sensory cortices (P < 0.47). CS was localized in all patients with 0.4 < th < 0.6. The primary hand and leg motor areas showed the highest metric values followed by the tongue motor area. Higher threshold values were specific (94%) for the anterior bank of the CS but not sensitive (42%). Intermediate threshold values achieved an acceptable trade-off (0.4: 89% specific and 70% sensitive).

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Brief history of electrical cortical stimulation: A journey in time from Volta to Penfield

By Isitan C, Yan Q, Spencer DD, Alkawadri R

Interesting to know that major advances in studying the brain were incentivized by parallel advances in electromagnetism and vice versa. Of interest, Aldini’s experiments shown below are not far in the outlook from what we’ve conducted here, the scope, questions, and means available are without a doubt different and probably ahead. A draft version of the full article can be found here.

  • The study of electromagnetism was incentivized by a debate between Volta and Galvani over the origin of electricity in the frog leg experiment. Aldini’s stimulation of bodies in defense of his uncle Galvani’s views is the first known electrical stimulation in humans.

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• Bravais, Todd, Jackson, and Broca’s contributions were based mainly on clinical observations rather than electrical cortical stimulation.

• Victory Horsley was the first to use electrical stimulation in the operating room to ascertain the localization of epileptic foci decades before the discovery of the EEG.

• Victor Horsley paved the way to mapping the first detailed homunculi by David Ferrier in animals, then by Harvey Cushing in humans, before Wilder Penfield introduced electrical cortical stimulation to the mainstream of surgical care.

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  • Parallel advances in instrumentation were made from the Leyden jars (1745) to present customizable current-controlled stimulators.

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In a pursuit of effective methods for reliable localization of the epileptic network: The connectivity index an effective metric for grading epileptogenicity

We proposed the connectivity index, that is based on the evoked potentials to single pulse stimulation. Unlike spontaneous seizures which require multi-day or multi-week of monitoring, this method can be resulted in real-time in matter of minutes, improving potentially on the safety/comfort profile for patients and length of hospital days. We are aware of challenges and we plan our phase III implementation for the very near future.

The full article can be found here

Connectivity index: Calculation

Connectivity Index

Calculation method

Generating a volume of the epileptic brain regions in under a minute: Typical standard of care employ multi-day or multi-week long evaluations.

Generating a volume of the epileptic brain regions in under a minute: Typical standard of care employ multi-day or multi-week long evaluations.

Restoration of Brain Circulation and Cellular Functions Hours post-Mortem:

Link to the full article click here

The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity. These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.

This is exciting indeed and though the brain continuously demonstrated isoelectric rhythms the viability as demonstrated otherwise by metabolic measures, histopathological slices and slice electrophysiology is fascinating, to say the least. 

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Just in case you missed breaking news this week. I am excited to share with you our article in Nature:

Restoration of brain circulation and cellular functions hours post-mortem

a.k.a op. The curious case of a dead brain.

Aside from media buzz and just to be clear this is no where close to be applied in human.

A real a tour de force and fun because

1. It has not been done before and provides a reliable platform for further investigation

2. It demonstrates viability is not binary rather gradable even in the sub-conscious state post-mortem.

3. It reminds of the importance of clinical knowledge/experience even in the most basic lab settings as some of the movements observed were spino-cephalic, medula-cephaic or simply neuromuscular excitability from the severed nerves.

4. I expect that the ethical aspects related to such experiment would motivate work to quantify/grade pain and discomfort based on electrophysiology.

5. It validates previous observations of drug induced isoelectric EEG not incompatible with recovery. It is another reminder why EEG is not a major criterion in evaluation of brain death.

6. Lastly, if familiar with the work of Giovani Aldini and the big Volta/Galvani’s debate - this work is a reminder of the what the humankind is capable of within a short time frame in history.

Hope you enjoy!

Brain–Computer Interface (BCI) Applications in Mapping of Epileptic Brain Networks Based on Intracranial-EEG: An Update

The full article now available at

Brain–Computer Interface (BCI) Applications in Mapping of Epileptic Brain Networks Based on Intracranial-EEG: An Update

Technology alone is not enough–it’s technology married with liberal arts, married with the humanities, that yields the results that make our heart sing.

Steve Jobs

See also our post previous post.

I wish to acknowledge research support by the American Epilepsy Society (award #412064) and CTSA Grant Number KL2TR000140 from the National Center for Advancing Translational Science (NCATS), a component of the National Institute of Health (NIH), the C.G. Swebilius Trust, and TUBITAK Grant Number 1059B191700801. Note, the contents of the manuscript is solely the responsibility of the author and do not necessarily represent the official view of the NIH.

Conflict of Interest Statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

The author wishes to thank Rebecca Khozein DOM, MS, REEG/EPT, RPSGT, RNCST, and Tamara Wing REEGT for assistance in EEG data acquisition.

Physiologic High Frequency Oscillations

Physiologic High Frequency Oscillations

Real-Time EEG amplifiers

Real-Time EEG amplifiers

Brain Computer Interface (BCI) Applications in Mapping of Epileptic Brain Networks based on Intracranial-EEG

By Rafeed Alkawadri

Update 3/27/2019: The full article in now available.

Read our recent article on breakthroughs in BCI applications in caring for patients with refractory epilepsy.

Read the full article at:

Brain Computer Interface (BCI) Applications in Mapping of Epileptic Brain Networks based on Intracranial-EEG

A quick look at a recent submission to the annual BCI society award and research trends available from the BCI community annual conference shows:

1. There is a steady increasing trend in BCI research with emphasis on epilepsy and movement disorders.

2. This constituted however, only 3.8% of the projects submitted. These numbers eclipsed by other uses.

There is a responsibility that falls on the shoulder of subspecialized funding agencies and supporting communities to augment research in this area which will continue to benefit patients with drug-resistant epilepsy, in the foreseen future, until, researchers identify less invasive, and more preemptive and efficient methods to treat epilepsy in the future.

In summary, icEEG data is the ideal medium for applications of artificial intelligence and machine learning in real-time. The applications within the domain of epilepsy surgery and seizure localization have lagged behind, however, the transformation is inevitable.

Assessment of the Utility of Ictal Magnetoencephalography in the Localization of the Epileptic Seizure Onset Zone.

Authors: Alkawadri R, Burgess RC, Kakisaka Y, Mosher JC, Alexopoulos AV.

To read the full article please visit JAMA Neurology website

Key Points

Question  What is the chance of recording a seizure and the localizing yield of seizures recorded during routine magnetoencephalography (MEG) studies?

Findings  In this medical record analysis of 44 patients, MEG provided unique and more focal localization information, including in some electroencephalography and interictal MEG silent cases and in some cases that were nonlocalizable otherwise. Extended-source localization was more suitable for analysis of ictal rhythms than commonly used single-point solutions.

Meaning  If feasible, ictal MEG should be sought and considered in presurgical evaluation of drug-resistant epilepsy.

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Averaging in time-frequency domain reveals the temporal and spatial extent of seizures recorded by scalp EEG.

Authors: Alkawadri R, Gaspard N

To read the full article refer to Epileptic Disorders

To demonstrate the importance of averaging in time-frequency space and the added localizing value in time and space in a case of cortical myoclonus. One hundred myoclonic jerks were averaged in time series and in spectral domain. For the latter, we chose 100 (10-second) segments from interictal background and used the unpaired t-test for the jerk-related and control spectral data to obtain the t value and corresponding p value at each pixel. We corrected for multiple comparisons using false discovery rate procedure. We generated maps of spectral significance per electrode. All insignificant t-values were converted to 0 for easier visual analysis. Standard back-averaging of 100 jerks disclosed a single spike preceding EMG activity by 19-27 milliseconds. No other definite ictal patterns were discernible in the time domain. Statistical analysis of the same 100 epochs in the time-frequency domain disclosed a greater temporal extent of the seizure, as well as a more detailed rendering of rhythms and frequencies involved. Valproate was added and led to substantial improvement. Averaging in the spectral domain may reveal frequency-specific changes that may not be otherwise appreciated in the time domain. Future studies may elucidate the effect on the sensitivity of diagnosis of simple partial seizures and auras.

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Impairment of consciousness induced by bilateral electrical stimulation of the frontal convexity

We report a case of impairment of consciousness (IOC) induced by electrical cortical stimulation (ECS) of homologous regions within the lateral frontal convexities in a patient with medically intractable epilepsy. The patient had mixed features of idiopathic generalized and focal epilepsy. On intracranial EEG recording, interictal and ictal discharges showed a high degree of synchrony across widespread bilateral fronto-parietal areas. We identified regions in the lateral frontal lobes that reliably and produced loss of consciousness by ECS.

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Propagation of seizures in a case of lesional mid-cingulate gyrus epilepsy studied by stereo-EEG.

Authors: Alkawadri R, Gonzalez-Martinez J, Gaspard N, Alexopoulos AV

Read the full article here
We present a case of lesional mid-cingulate epilepsy confirmed by stereotactically implanted intracranial depth electrodes and subsequent surgical resection. Hypermotor symptomatology was seen during the first seven seconds of seizure onset while the seizure was still confined to the mid-cingulate gyrus contacts.

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The spatial and signal characteristics of physiologic high frequency oscillations.

Authors: Alkawadri et al. 

To read the full article visit Epilepsia 

OBJECTIVES: 

To study the incidence, spatial distribution, and signal characteristics of high frequency oscillations (HFOs) outside the epileptic network.

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Cingulate epilepsy: report of 3 electroclinical subtypes with surgical outcomes

Authors: Alkawadri R, So NK, Van Ness PC, Alexopoulos AV

Please visit JAMA Neurology to read the full article

Abstract

Importance  The literature on cingulate gyrus epilepsy in the magnetic resonance imaging era is limited to case reports and small case series. To our knowledge, this is the largest study of surgically confirmed epilepsy arising from the anterior or posterior cingulate region.

Objective  To characterize the clinical and electrophysiological findings of epilepsies arising from the anterior and posterior cingulate gyrus.

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