Influence of prolonged rTMS on cognitive functions and mood in healthy volunteers

A. Clinical

[A-311 The prolonged rTMS: EEG activity and plasma hormone levels in healthy humans T. Zyss’, E. M&02, Medical Krakow,

College, Poland

A. Brodkiewicg.

Jagellonian

University;

‘Department of Psychiatry, ‘Rydygier ‘s Regional Hospital,

Transcranial magnetic stimulation (TMS) method is considered to be a safe neurophysiologic method. The main known side effect is seizure induction. Possibility of its emergence increases with higher stimulation frequency (rapid rate TMS = rTMS). Therefore the majority of studies dealing with safety issues consider rTMS with frequency (stimulus rate) of more than 1 Hz. Technique of rTMS seems to be effective in treating depression. According to Zyss, its antidepressive efficacy increases when the time of stimulation session is longer than 1 min. For now the effect can be achieved by application of several l& 15 sec. stimulation sessions divided with several minutes long breaks needed to cool the stimulator (coil). With a prototype stimulator MS3 we tried to assessthe safety of prolonged rTMS. Method: 17 healthy volunteers (9 men, 8 women, average age 23 y.) took part in the examination. All of them were thoroughly acquainted with the procedures of the examination and had the opportunity to ask questions connected with all aspects of magnetic stimulation. All participants agreed to take part in the examination and the protocol was approved by the local bioethic committee. A prototype magnetic stimulator MS3 was used (B = 1.4 T; f = 20 Hz; tese = 100 psek.; t = 5 min). The magnetic field was generated by a special core coil cooled with water in closed system. In the case of 8 persons the coil was placed over the right dorsofrontal area, in 9 other over the left forebrain. The examination consisted of a single 5 minutes long session.The stimulation was carried out in horizontal position of the body. Because of technical reasons MEP and so called motor threshold (MT) were not estimated. Therefore the same magnetic field induction value was administered to all participants and not the value dependant on MT. Effects of stimulation were assessedon the basis of standard EEG examination (preliminary record before the stimulation) and of serial (6 x) blood samples for hormones estimation (prolactin, TSH, and cortisol). Results: Strong artefacts made EEG during the stimulation impossible to record. EEG recording was started immediately after stimulation. Neither clinical symptoms of seizure induction nor changes in EEG traces were observed in any of the subjects. Also the sense of weakening and dizziness reported by two persons did not change the EEG records. Sequential estimation of prolactin and TSH showed that the magnetic field applied was not capable to excite the hypothalamic-pituitary axis resulting in increasing of hormone concentration. Lack of changes in concentration of cortisol proved that the whole stimulation procedure was not stressful for the examined. Conclusions: Even the prolonged stimulation with rTMS method is safe. It would be advisable to carry out not only prolonged but also chronic (repeated) rTMS stimulation in the same individuals. Objective:

s19

Studies

and/or adverse effects were made. Adverse effects - apart from seizure induction - are considered to be less important. Some works describe prevalence of cognitive and behavioral effects, underlining safety of TMS. Eventual effects connected with memory, attention, speech function, are essentially temporal. There are no observations available regarding the effects of prolonged (more than l&20 set duration of stimulation train) rapid rate TMS (rTMS). Method:

The study included

17 healthy

volunteers,

20-30

years old.

The examined were exposed to single TMS session of the dorsofrontal area (I3 = 1.4 T; f = 20 Hz; t = 5 min). The effects of stimulation were assessed with panel of neuropsychological tests examining cognitive functions (Auditory Verbal Learning Test, Controlled Oral Word Association, Stroop Color Word Test, Serial Subtraction Test, Trail Making Test), and examining affective sphere (Pascual-Leone Visual Analogue Scales, Spielberger Self-Esteem Questionnaire - “fear as state” sheet, Thayer List of Adjectives). Preliminary examination took place at least a month before the main examination, which was carried out immediately after the transcranial magnetic stimulation. Results: There was no need to stop the stimulation of any volunteer. First phase (l-2 min) of stimulation was particularly the exposed had unpleasant sensorial phenomena.

burdensome; all of In 2 persons vertigo

and weakness appeared. Statistically significant neurophysiological effects were found in two tests: Controlled Oral Word Association (COWA) and Serial Subtraction Test (SST). Test COWA showed significant improvement of word fluency. The effect appeared after stimulation of both sides of forehead, however the effect was stronger in the case stimulation of the right dorsofrontal area (41% improvement versus 29% after stimulation of the left side). Reverse effects were observed in test SST. The worsening in serial subtraction (count down) was particularly seen after stimulation of the right dorsofrontal lengthened 50%.

region

- the average

time

of test accomplishing

All test examining the mood showed reduction of anxiety and increase though the statistically significant effect was found only in Pascual-Leone Visual Analogue Scales ‘anxiety’ and

of sense of discomfort, ‘pain/discomfort’.

In the case of both subscales,

statistically

significant

differences showed up only in persons in which rTMS was applied to right forebrain. Conclusions: Technique disturbances in cognitive

of rTMS

seems to be safe and not evoking

functions, it does not significantly influence the mood in healthy volunteers. The right dorsofrontal area seems to be much more sensitive to magnetic stimulation than the left forebrain. References

[l]

Bridgers S.L.: The safety of transcranial magnetic stimulation reconsidered: evidence regarding cognitive and other cerebral effects. EEG clin. Neurophysiol. 1991, Sippl. i3, iwi79. [2] Pascual-Leone A., Catala M.D., Pascual-Leone Pascual A: Lateralized effect of rapid-rate transcranial magnetic stimulation of the prefrontal cortex on mood. Neurology 1996, 46, 499-502.

References

[l] Pascual-Leone A., Houser CM., Reese K., et al.: Safety of rapid-rate transcranial magnetic stimulation in normal volunteers. EEG clin. Neurophysiol. 1993, 89, 120-130. [2] Thomas S., Merton W.L., Boyd S.G.: Pituitary hormones in relation to magnetic stimulation of the brain. J. Neural. Neurosurg. Psychiatr. 1991, 54, 89-90.

[A-321 Influence of prolonged rTMS on cognitive and mood In healthy volunteers

functions

T. Zyss’, M. Orlowiejska-Gillert2, D. Szwabowska*, J. Kaises. ‘Department of Psychiaw, Medical College, Jagellonian University; ‘Department of Neurology MCJU: 3Department of Neurophysiology Jl,( Krakdw, Poland Objective: During 13 years of transcranial magnetic stimulation (TMS) application numerous observations concerning possible side effects

IA-33] Association between VNTR polymorphism of the MAO-A gene and antisocial personality tendencies male alcoholics

in

J. Samochowiec’, J. Horodnicki’ , T. Sanded, H. Rommelspacheg, K-I? Lesch3, L.G. Schmidt2. ‘Department of Psychiatry, Broniewskiego 26, Szczecin, Poland 2Departments of Psychiatry, Eschenallee 3, Free University of Berlin and ‘Fuechleinstl: 15, Uniuersity of Wtirzburg, Germany

There is an evidence that abnormal activity in monoamine oxidases in metabolism of biogenic amines implicated abnormal (ag-

Object:

gressive,

impulsive)

behavior

and also plays

a role in a wide

range

of

psychiatric disorders, including alcoholism. Therefore, we analyzed a 30 base-pair variable number of tandem repeats (VNTR) in the promoter region of X-linked MAO-A gene to test the hypothesis, whether they might

confer

susceptibility

to alcohol

dependence.