WHICH BIOMARKER
FOR MY RESEARCH?

EEG Biomarkers provide objective measures
of Brain [dys]function. At the source.

Modified electrical activity in neuronal networks is symptomatic of a wide range of CNS disorders

Local Field Potentials (LFP) are recorded in vivo by EEG, in the brain of freely-moving, translational models. These oscillations offer a direct window on neuronal networks activity.

Disease-specific EEG signatures can be used as surrogate Biomarkers to assess your compounds effects in vivo, longitudinally.

Unique on the market, our EEG Biomarker approach delivers smooth human-rodent translation, high reproducibility levels and robust endpoints, particularly well-suited to evaluate your compounds effects with no bias.

SynapCell-Measures-at-the-source

What is Phase-amplitude coupling (PAC)?

Phase Amplitude Coupling reflects the interactions between oscillations in different bands and helps understand brain function. Involved in sensory integration, PAC is observed in rodents, monkeys, and in humans. The theta-gamma PAC could be a potential new biomarker of Parkinson's Disease.

Phase Amplitude Coupling

Exacerbated phase-amplitude coupling between beta-phase (13-30 Hz) and gamma-amplitude (50-200 Hz) has been characterized in the motor cortex of PD patients.

A strong coupling between the phase of theta (4-6Hz) and the amplitude of high gamma (90-160Hz) in the ipsilateral motor cortex of 6-OHDA lesioned rats.

Phase Amplitude Coupling

In addition, anti-parkinsonian drugs like L-Dopa, apomorphine or SKF-38393-2, significantly suppressed this theta-gamma PAC.

This theta-gamma PAC signature in an animal model of PD can be used as a new translational biomarker, thus providing a stable, quantifiable, reliable and objective endpoint for the development of new therapies against PD.

Parkinson's Disease
View communication at AD/PD2019
PAC was March Term of the Month


What are Event (evoked) related Potentials (ERP)?

In rodents, EEG responses evoked by auditory stimulation can be recorded in various brain areas and underlie the integration and processing of sensory information which are altered in a large number of neurological and psychiatric disorders.

We can distinguish two main types of auditory evoked responses, the auditory evoked related potentials (AERP) and the auditory steady state response (ASSR).

AERPs are composed of successive positive and negative deflections, which differ from their latencies and amplitudes and are well conserved throughout the evolution.

ERP protocols can be very useful to test a novel mecanism of action of a compound, measure how the brain integrates and processes new information: in a rodent model of psychiatric disorder (ex Ketamine modelisation and NMDA hypofunction in schizophrenia) or on a model of interest you wish to phenotype.

What is ASSR?

Sensory information Integration and processing by the brain are altered in several neurological and psychiatric disorders, especially in schizophrenia.
This integration of sensory information can be monitored using EEG in the auditory cortex. Several experimental protocols are commonly used in the clinic on human patients.
That includes the use of Auditory Event-Related Potential (AERP) protocols, which consists in stimulating the auditory cortex with one single short noise (a click) then recording the resulting cortical response, characterized by typical positive and negative deflections, well described in the clinical litterature.

Another type of auditory stimulation protocol is the Auditory Steady-State Response (ASSR).
ASSRs consist in cortical electrophysiological oscillations entrained to the frequency and phase of a periodic auditory stimulus presented at a rhythm in the gamma range (that is, 30-80Hz).
ASSR protocol consists in stimulating the auditory cortex by a train of clicks (usually for 0.5 to 2 s) with a fixed inter-click interval (Brenner et al., 2009). After an initial response lasting ~250 ms, the train rapidly entrains the cortical activity to the stimulation frequency and phase of the stimulus.

ASSRs are believed to reflect the interplay between cortical pyramidal neurons and parvalbuminergic interneurons. Consistent with the theory of imbalance between cortical excitation and inhibition in schizophrenia, patients show reduced power and phase locking, to stimulations presented at 40Hz.

evoked-response-and-train-SsynapCell

From the steady-state oscillation evoked by the ASSR stimulus, an entrainment power can be extracted, usually measured at the stimulation frequency (± 5 Hz) where the entrainment peaks. Two different calculations can be applied. The total power measures the total EEG power comprised in the frequency band. The evoked power measures the power of the activity that is phase-locked with the stimulation. Another calculation compares the inter-trial coherence (ITC), and was developed more recently to evaluate the phase-locking of the signal (Delorme and Makeig, 2004).

ASSR-vehicle-SynapCell

Testing with EEG the ability of the auditory cortex to follow a continuous stimulation provides a noninvasive method to determine the characteristic of its response to stimulus.
In particular, modulations of the ASSR has been studied in schizophrenia, in which auditory hallucinations and delusions is a diagnostic criterion. ASSR responses at 40 Hz have been shown to be reduced in power and phase-locking in schizophrenic patients (Kwon et al., 1999; O’Donnel et al., 2013; Sun et al., 2018).

zhou-et-al-ASSR

Additionally, multiple neurotransmitter receptors and other molecules are known to impact auditory information processing, allowing these measurements to be used as target engagement biomarkers, i.e. to assess whether experimental compounds are interacting with their target molecule.

ASSR-MAP6-SynapCell

At SynapCell, we have developed an ASSR protocol in rodents (example below shows reduced 40Hz ASSR power in the MAP6+/- mouse model of schizophrenia).
Our paradigm reproduces the clinical protocol by recording the EEG response to a train of clicks in the parietal auditory cortex and in the frontal associative cortex. Recording at these two brain levels allows evaluating the processing of auditory information at two different stages, which enables to evaluate the effect of drug candidates in a translational biomarker equivalent to a clinical protocol.

What are SWD?

Absence epilepsy is a particular form of epileptic syndrome where patients show generalized non-convulsive seizures characterized by a brief unresponsiveness to environmental stimuli and cessation of activity. In human, typical absence seizures are associated with bilateral, synchronous and regular spike and wave discharges (SWD) (Loiseau et al., 1995). These epileptiform patterns are characterized by the repetitive occurrence of a Spike followed by Slow Wave.

GAERS-SWD-explained-synapcell

This type of epilepsy presents a specific pharmacology different from the one observed in other types of epilepsies. Therefore, careful evaluation of new antiepileptic drugs in development is mandatory regarding a possible aggravation of SWD in idiopathic generalized epilepsies (Manning et al., 2003; Genton, 2000) and particularly absence epilepsy.

The genetic absence epilepsy rat from Strasbourg (GAERS) is a selectively inbred strain of Wistar rats displaying spontaneous SWD. For the past thirty years, the GAERS has become a reference model for absence epilepsy, since these rats were shown to present behavioral, electrophysiological, and pharmacological features of absence seizures (Depaulis et al., 2016).
Cortical EEG recording is characterized by SWD lasting 18-25 sec, with a recurrence of 45-60 seizures per hour. SWD start and end abruptly and are associated with a behavioral arrest lasting the time of the discharge (Vergnes et al., 1982).

SynapCell-Anti-and-Pro-epileptic-effect-GAERS-Pharmacology-synapcell

As in human patients, SWD in GAERS are suppressed by antiepileptic drugs (AED) such as valproate (Dedeurwaerdere et al., 2011), ethosuximide (Nehlig et al., 1993) and levetiracetam (Gower et al., 1995), whereas other AEDs have no efficacy (lacosamide, Higgins et al., 2010) or can even aggravate SWD, particularly carbamazepine (Wallengren et al., 2005), phenytoin (Gurbanova et al., 2006), and high doses (>200mg/kg) of pregabalin (Vartanian et al., 2006).

SynapCell-Anti-and-Pro-epileptic-effect-GAERS-synapcell

The use of SWD as a biomarker for absence epilepsy therefore offers very high predictivity level for identifying anti-absence as well as pro-epileptic effect for AED in development or other compounds acting on the CNS (Klitgaard et al., 2002; van Luijtelaar et al., 2002).

Generalized Absence Epilepsy

The GAERS on Wikipedia
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BetaPark is a translational and objective EEG Biomarker of Parkinson's disease. Found in both PD patients and in the 6-OHDA rat model of PD, BetaPark is stable over time and transiently lowered by dopamine agonists.

BetaPark will be August' Term of the Month!

In the meantime, please head to our Parkinson's page to learn more on BetaPark

Coming soon!

Stay tuned for monthly updates on our translational EEG biomarkers for drug discovery.

Coming soon!

Stay tuned for monthly updates on our translational EEG biomarkers for drug discovery.

Coming soon!

Stay tuned for monthly updates on our translational EEG biomarkers for drug discovery.

Coming soon!

Stay tuned for monthly updates on our translational EEG biomarkers for drug discovery.

GammaPark is a translational EEG Biomarker for L-DOPA induced Dyskinesia, in a Parkinson's context.

Dopamine agonists lower BetaPark and increase GammaPark expression at the same time.

Anti-PD strategies with EEG aim at lowering BetaPark (Parkinsonism signature), while silencing GammaPark, after L-DOPA priming.

Discover GammaPark and the data 

Coming soon!

Stay tuned for monthly updates on our translational EEG biomarkers for drug discovery.

What are HPD?

Mesio-Temporal Lobe Epilepsy represents a major challenge in the clinical management of seizures.

This form of epilepsy is often associated with severe cognitive and emotional impairments, and affects about 10% of the total epileptic population. In addition, MTLE becomes generally resistant to most pharmacological treatments (Engel et al., 1997).

mtle-modeling-clinical-features-synapcell

SynapCell has developed an animal model of MTLE in which, unlike most other models, dispersion of the dentate gyrus is observed (Bouilleret et al., 1999 and Riban et al., 2002). In this model, unilateral injection of a small dose of kainate (1 nmole) in the dorsal hippocampus of mice results in neuronal losses in CA1, CA3 areas and hilus as well as mossy fiber sprouting, in addition to an important dispersion and increase of granule cells of the dentate gyrus (Suzuki et al., 1995 and Mitsuya et al., 2009).

HPD-cell-loss-synapcell

Three weeks after kainate injection, spontaneous and recurrent hippocampal paroxysmal discharges (HPD), lasting about 15-20 s, can be recorded using electroencephalography (EEG), concomitantly with behavioral arrest and/or automatisms.

MTLE-HPD-explained-translational-synapcell

These focal seizures remain stable during the rest of the animal life and occur regularly (about 40/h) when the animals are in a state of quiet wakefulness (Riban et al., 2002 and Arabadzisz et al., 2005). During the first two weeks following kainate injection, before the occurrence of HPD, interictal spikes progressively occur by bursts of increasing duration

MTLE-HPD-epileptogenesis-synapcell

More importantly, this model is resistant to most classical antiepileptic drugs: valproate, carbamazepine and lamotrigine can suppress the hippocampal discharges upon acute treatment only at high doses and with side effects (Riban et al., 2002; Duveau et al., 2016). We have shown that HPD are dose-dependently suppressed by acute administration of diazepam. However, recently developed AEDs, such as pregabalin, levetiracetam or vigabatrin were shown to be active on this model with no side effects (Duveau et al., 2016).

HPD-MTLE-Pharmacology-synapcell

Altogether the histological, electrophysiological, behavioral and pharmacological features, in addition to a species-appropriate latent period following the initial insult, validate this model of pharmaco-resistant MTLE. Indeed, it fulfils most criteria recently proposed for an efficient preclinical development of antiepileptic and prophylactic therapeutic strategies for MTLE (White, 2003).

Focal Epilepsy

Epileptic disorders

View Abstract
Video on YouTube

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Stay tuned for monthly updates on our translational EEG biomarkers for drug discovery.

Coming soon!

Stay tuned for monthly updates on our translational EEG biomarkers for drug discovery.

MMN or Mismatch Negativity can be a significant biomarker in psychiatric disorders.

We carried out several R&D studies on MMN, but results did not match our validation criteria.

Our MMN program has therefore been stopped.

However, we'd be glad to exchange with you about it, so contact us!

Coming soon!

Stay tuned for monthly updates on our translational EEG biomarkers for drug discovery.

Coming soon!

Stay tuned for monthly updates on our translational EEG biomarkers for drug discovery.

Coming soon!

Stay tuned for monthly updates on our translational EEG biomarkers for drug discovery.

What is the ET band?

The Harmaline mouse model is reported to be one of the most relevant to modelize Essential Tremor.

A specific oscillatory frequency can be found in our harmaline mouse (30-55 Hz).
This band (ET Band) is lowered by today's treatments for Human patients and can be reversed by propranolol.

Check the ET page for more!

The Term of the Month, by SynapCell

Every month, we pick and explain one of the EEG Biomarkers we have developed for preclinical research. Your EEG biomarker of interest is not yet explained above? No worries, new content every month here, on YouTube, LinkedIn and Twitter, so stay tuned!

Let's talk about your next project