Signal transmission is a critical physiological process. For certain cells, this transmission is electrical in nature. Excitability is determined by how these cells regulate, generate, and conduct electrical stimuli. Excitability can be measured at a central (cortical excitability) or peripheral level (peripheral nerve and muscle excitability). A growing body of evidence suggests that abnormal excitability plays an important role in a wide variety of conditions including epilepsy, ALS, (neuropathic) pain, psychiatric disorders, polyneuropathy and muscle disorders. CHDR offers validated methods that can be used as biomarkers to measure excitability at all three levels: corticospinal, peripherical nerve and muscle excitability.
An overview of our excitability methods
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Transcranial magnetic stimulation (TMS) coupled with electromyography (EMG) and electroencephalography (EEG) can be used as a biomarker to study the clinical effects of drugs that are expected to affect cortical excitability. Both single-pulse and paired-pulse TMS stimulation protocols have been implemented at CHDR and can be customised according to study design. Abnormal cortical excitability is observed in various conditions including ALS, epilepsy and depression. Drug targets that would benefit from applying this biomarker include GABA, AMPA, glutamate and voltage-gated sodium channels.
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Muscle velocity recovery cycles (MVRC) is a technique used to assess the excitability of muscle cells, independent of neuromuscular transmission. Using a standardised and validated stimulation protocol, MVRC can be used to determine a range of muscle excitability properties, such as relative refractory period and the physiological depolarising afterpotentials (early and late supernormality). Abnormal muscle cell excitability can be detected in neuropathies, myotonias and channelopathies. Drug targets that would benefit from applying this biomarker include chloride and sodium channels.
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Nerve excitability threshold tracking (NETT) is a technique used to measure the excitability of the peripheral motor or sensory nerves. Using a standardised and validated stimulation protocol, it is possible to assess a range of nerve properties, such as resting membrane potential and sodium and potassium channel conductance. NETT also detects nerve excitability abnormalities in conditions such as ALS, neuropathic pain and polyneuropathy. Drug targets that could benefit from applying this biomarker include potassium channels and voltage-gated sodium channels.
Watch the following video to get an overview of TMS-EEG and EMG:
