The use of Functional transcranial Doppler ultrasound and repetitive Transcranial Magnetic Stimulation for the assessment of language lateralization. A comparison with functional MRI

Functional Magnetic Resonance Imaging (fMRI), is the current standard for
non-invasive language lateralization determination. However, the use of fMRI
has some restrictions. It is an outstanding technique for individual
investigations or small subjects groups, but does not lend itself easily for
detection of language lateralization in larger groups of subjects. Recently,
functional Transcranial Doppler Ultrasound (fTCD) has been shown an alternative
to non-invasively detecting cerebral language lateralization. The technique has
no known side-effects or contra-indications, although it cannot be used in
approximately 5% of subjects for lack of a temporal bone window. Another
technique that allows for non-invasive determination of language lateralization
is repetitive Transcranial Magnetic Stimulation (rTMS). RTMS can be applied for
determination of language dominance, because it can induce a temporary speech
arrest when applied over the dominant hemisphere. Both methods have been shown
to correlate highly with fMRI measurements of language lateralizationof
language lateralization.

1) To compare fTCD with fMRI, in order to reproduce the previously shown high
correlate between the two techniques. 2) to compare rTMS with fMRI and
subsequently with fTCD.

Subjects participate in 5 steps: 1) fill out a 20-item questionnaire on
handedness (Edinburgh Handedness Inventory, EHI). 2) Functional derivates of
language lateralization will be measured using a word production test and a
modified test of remote association or semantic distance. Both tests measure
right hemisphere function and will be presented on a laptop. 3) Determination
of language lateralization with fMRI. A functional scan of cerebral activation
is obtained while subjects are engaged in a language task, wherein they
silently generate words beginning with a prompted letter (paced letter
fluency). The task will be projected on a screen. 4) Determination of language
lateralization by fTCD. This device measures changes in flow velocity in the
right and left medial cerebral arteries. Subjects will perform the same
language task, which causes language areas of the dominant hemisphere to be
activated to a higher degree than the contralateral areas 5) determination of
language lateralization by repetitive Transcranial Magnetic Stimulation. A type
of task differing from the previous experiments will be used. Subjects will
speak out (e.g. counting up and down). During recitation speech will be
disturbed by influencing cortical activity by inducting a low current by means
of the pulsating magnetic field. Lateralization will be measured as a function
of speech disruption during magnetic stimulation of left or right hemisphere
motor language areas.

FTCD is a non-invasive Doppler technique that has been used extensively and has
no known associated risks. People wear a headset to which the Doppler-probes
are attached. When this causes distress it can easily be adjusted or taken of.
MRI has been used as a diagnostic, clinical tool for over 20 years. There are
no associated risks. In previous studies performed at the UMCU, all subjects
tolerated a similar MRI procedure well. When subjects become anxious in the
restricted space, anxiety vanishes after leaving the scanner. The main concern
when using rTMS is its potential to induce a seizure. World-wide, this has
occurred in only 6 healthy subjects. This has not been reported anymore since
implementation of safety guidelines by Wassermann (1998). Other potential
adverse effects of rTMS include induction of a muscle tension headache or a
neck ache in. These are generally mild discomforts that respond promptly to a
common analgesic.