Characterization of the DELPhI System in Assessing Brain's Functionality in Different Neurological Disorders

Brain network plasticity evaluation has been shown extensively essential for understanding and monitoring of brain functional changes and brain disorders. However, existing clinically used imaging methods are unable to robustly indicate plasticity or plasticity changes. Therefore, there is a great need for developing such an imaging tool for brain functional evaluation. In basic neuroscience research plasticity evaluation is performed by conducting electrophysiological measurements in vivo. By using EEG - combined with TMS stimulation this methodology can be transformed into clinically used plasticity and connectivity assessment for evaluation of functional brain status. This study may thus introduce a novel, non-invasive and efficient method for brain functional imaging. DELPhI evaluation will offer a true multimodality imaging by combining EEG and TMS that allows a quantative objective and direct identification of disease assessment. There is a real unmet need for an accurate and objective evaluation that together with the common clinical practice will provide neurologists and psychiatrists a more definite and personalized treatment prescription.

Studies integrating TMS with EEG (TMS-EEG) have shown that TMS produces waves of activity that reverberate throughout the cortex and that are reproducible and reliable thus providing direct information about cortical excitability and connectivity with excellent time resolution. By evaluating the propagation of evoked activity in different behavioral states and in different tasks, TMS-EEG has been used to causally probe the dynamic effective connectivity of human brain networks. When applying the TMS coil above the motor cortex, a cascade effect called the motor-evoked potential (MEP), is initiated. The MEP is measurable at peripheral muscles. The Motor cortex is a brain structure located between the frontal and parietal cortices. Pyramidal neurons in the motor cortex, upper motor neuron going through the brain stem, send signals to lower motor neuron in the spinal cord which stimulate muscle fibers. TMS stimulus to the Motor cortex evokes a brain response which propagates to different brain regions in addition to the peripheral limb muscles [20]. An important feature of TEP topography is that even though only one cortical hemisphere is stimulated, bihemispheric EEG evoked responses are evoked with different features. TMS-evoked activity propagates from the stimulation site ipsilaterally via association fibers and contralaterally via transcallosal fibers and to subcortical structures via projection fibers. These TMS-evoked cortical potentials (TEPs) last for up to 300 ms in both the vicinity of the stimulation as well as in remote interconnected brain areas reflect long term changes in cortical network excitation-inhibition balance refeed to as brain network plasticity. A single TMS pulse delivered over the primary motor cortex (M1) results in a sequence of positive and negative EEG peaks at specific latencies (i.e., P25, N45, P70, N100, and P180).

In this study a wide population of subjects will be recruited. this population will include different neurological conditions and healthy subjects, arriving to the Hyperbaric center at Asaf-Harophe hospital. Each subject will be tested once before treatment initiation and subsequent tests will be performed also after treatment termination or at follow up time points. Each evaluation will last up to 90 minutes and will include affixed stimulation protocol ranging Up to 1000 TMS pulses, with intensities between 60-130% of motor threshold (MT). Inter-stimuli frequency will change from 0.01 up to 20 Hz.Existing clinical data such as MRI scans, neurocognitive assessments and clinical evaluations will be collected out of patient files. EEG data recorded will be analyzed and corrolations to the clinical data will be tested.