KUH
Professor Hilkka Soininen, MD, PhD 
Department of Neurology 
Kuopio University Hospital 
P.O.Box 1777 
70211 Kuopio, Finland 
phone: +358 17 173012 
mobile phone: +358 40 5735749 
fax: +358 17 173019 
http://www.uku.fi/neuro 
http://www.uku.fi/mediteknia 
http://www.uku.fi/bru 
HiIkka.Soininen@uku.fi 
Hilkka.Soininen@kuh.fi

Neuroimaging. New imaging technique, Navigated Brain Stimulation (NBS), combined with high spatial-temporal resolution EEG will be used to probe and visualize cortical functionality and effective neuronal connections in MCI (Fig. 1). The method is optimal in the studies of exact localization of cortical activity, in characterization of excitation/inhibition balance of cortex, and in following the temporal sequence of the activity spreading through effective cortical connections.  The NBS system produced by Nexstim (see www.nexstim.com, European IST Prize winner 2005) provides precise stereotactic stimulation on the basis of individual anatomy (CT/MRI) and reproducible measurement of TMS-evoked EEG responses with high spatio-temporal resolution.

           10 ms                  24 ms                                10 ms                                28 ms  

Fig. 1

The concept that time- and possibly phase-locked oscillatory neuronal activation within widespread networks spanning both cortical and subcortical areas may mediate higher order cognitive function is provocative. Our aim is to combine expertise in the field of clinical sciences, electrophysiology and NBS to investigate transient evoked brain activity in MCI. We shall use NBS-EEG recordings in MCI to characterize the dynamics of distributed and possibly altered brain networks in two separate modes:

 1) We shall measure the local excitation-inhibition balance in motor cortex by using localized, dose-defined, paired stimulation pulses to M1 and by recording evoked electromyographic (EMG) activity from hand muscles. There is ample evidence that motor responses with different pulse intervals depend on specific neurotransmitters (e.g., diminished muscle response with 3 ms NBS pulse interval represents GABA -mediated cortical inhibition, REFs). The overall goal is to characterize the individual cortical reactivity profile in MCI.

2) NBS will be used to perturb ongoing brain dynamics in the human subjects during performance of cognitive and memory task. NBS will be applied to targets identified from the other imaging data in frontal, parietal and cerebellar cortex. The effect of NBS on network dynamics as recorded by scalp EEG will be compared to analogous data obtained from neuronal models. EEG recorded immediately before and after single-pulse TMS in the absence of task performance will be used to interrogate latency of propagation between network nodes and possible induction of phase-locked network activity.

Nexstim

SME Nexstim Ltd. is an innovative start-up company that manufactures Navigated Brain Stimulation systems that allow one 1) to direct  and manipulate magnetic stimulation pulses very accurately to desired targets on the basis of individual MRI and 2) to record the brain’s TMS-evoked EEG response. In the course of the present project the company develops diagnostic software and other tools, which will be clinically tested on MCI patients. If successful, this would be a break-through in clinical diagnosis, providing a first genuinely physiological test for MCI. Presently the diagnosis of both MCI and Alzheimer disease are mostly based on patient interviews and psychological tests. The market for such software would be very large, both within Europe and outside.  Nexstim is the inventor and first-in-the-world developer of these techniques.

Exploitation and dissemination plan

Nexstim’s aim is to develop the use of its noninvasive tool to measure the functional state of the cortex. Navigated Brain Stimulation (NBS) combined with EEG allows one to probe both excitatory and inhibitory cortical mechanisms and their sensitivity to disorders as well as pharmaceutical and other manipulations. This technique also allows one to obtain time-resolved measures of area-to-area connectivity, which is crucial in the study of cortical information processing in MCI.

The company’s strategy includes the promotion of applications of the technique to major neurophysiological and neurological problems. Preliminary results obtained with NBS/EEG by Soininen et al. show that cortical reactivity and inhibition-excitation balance dramatically changes in degenerative disorders. The present project is of vital importance in promoting the use of NBS/EEG and in opening major, potentially highly significant areas of clinical application.