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diagnostic ultrasound investigation of the brain in Parkinson’s disease. In

focused ultrasound therapy non-invasive stereotactic brain surgery is

performed during simultaneous thermosensitive MRI imaging.

Similarly, within the area of functional imaging, fMRI by using the BOLD

and other techniques provides a most promising link to brain physiology

on a systems level. Though primarily a neuroradiological tool, it can be

used simultaneously or in series with EEG to provide complementary

information about brain structure and function.

Stimulation

Deep brain stimulation (DBS) is now a routine method approved in the

EU for improving symptoms in movement disorders such as Parkinson’s

disease, dystonia and epilepsy. In DBS, electrodes are implanted into

nuclei such as the thalamus, subthalamic nucleus or other basal ganglia

regions. Currently, new targets in the brain and novel stimulation

protocols are being tested to treat other frequent diseases, such as

epilepsy, intractable pain and a variety of psychiatric disorders. Future

challenges encompass improvement of stimulation parameters,

introduction of closed-loop stimulation, discharge for interruption of

epileptic activity and seizure prevention by patterned brain stimulation,

directional sensitive electrodes and others.

Transcranial magnetic stimulation (TMS) can be used for the investigation

of the functional properties of the nervous system. Direct continuous

electrical stimulation of the brain by either weak alternating or direct

current or pulsed short duration stimulation mediated by TMS allows the

manipulation of brain function non-invasively for research, for clinical

diagnosis, and for the purpose of treating neurological and psychiatric

diseases. Repetitive TMS is now a standard treatment for depression

(and is reimbursed by insurance in the USA). It will be a main research

task to further develop and refine these stimulation methods for

treatment of other neurological diseases such as epilepsy, stroke

sequelae, and others.

Elsewhere, many integrative multimodal assessment techniques can be

combined for more power, including brain imaging in conjunction with

electrophysiological techniques and clinical or behavioural measures,

whilst brain-computer interface (BCI) enables those with profound

paralysis, e.g. locked-in syndrome, and some tetraplegics to

communicate and/or control external manipulanda.

Finally, clinical neurophysiology in the context of recordings during

epilepsy research or deep brain stimulation is important because it allows

reducing the need of animal experiments. In particular, when compared

to non-human cognitive primate research, it allows the design of much

more complex experimental paradigms. In general, this research provides

fundamental information on how the human brain works on levels from

systems to cells.

Promising future research topics

Using invasive recordings in humans during epilepsy monitoring or deep

brain stimulation for acquisition of neurophysiological data holds a lot of

potential for future research. The implantation of invasive electrodes in

patients with epilepsy or movement disorders provides a unique

horn cell, peripheral nerve, neuromuscular

junction or muscle disorders and to determine

the extent and severity of such conditions.

Reflexes are of paramount importance for

research as well as for evaluations of clinical

conditions including muscle tone abnormalities.

Quantitative motor unit studies such as

motor unit number estimates (MUNE) are

valuable endpoints in clinical trials on motor

neuron diseases and motor neuropathies.

Channelopathies can be diagnosed by

excitability testing with threshold tracking

providing information about the activity of a

variety of ion channels, energy-dependent

pumps and ion exchange processes activated

during the process of impulse conduction in

the nerve.

Neurophysiological techniques are used to

record various parameters associated with

autonomic disturbances including heart rate

variability, postural blood pressure and

cutaneous blood flow useful in the assessment

of small fibre nerve damage, which can occur

in diabetes and other conditions. Specialised

techniques, (contact heat evoked potentials and

laser evoked potentials) can assess the

pathways from skin to brain involved in the

perception of pain.

Signal plus imaging methods in

clinical neurophysiology

Within the area of structural imaging, MRI in

clinical neurophysiology provides high resolution

data of the brain for many functional purposes

(such as guidance of electrode position for deep

brain stimulation, dipole source calculation of

multichannel EEG data and identification of

epileptic foci). Ultrasound plays an increasing role

in diagnostics of peripheral nerve and muscle

disease, supplementary to MRI imaging and

electrodiagnostics. Further new fields include the

www.paneuropeannetworks.com

Pan European Networks: Science & Technology

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Co-Registration and

Data Fusion to define

the Epileptic Focus

(Courtesy of JM

Fernandes, UA-Portugal)

THE HUMAN BRAIN