Brian J. Higginbotham and Dr. Erin Bigler, Psychology
Transcranial magnetic stimulation (TMS) is a relatively new technology that extends the ability to noninvasively stimulate cortical brain structures (Walsh and Rushworth, 1999). TMS involves placing an electromagnet on the scalp and turning it rapidly on and off through the discharge of capacitors, thereby producing a time-varying magnetic field that passes unimpeded through the skull and soft tissue. This altering magnetic field induces a changing electric field, which causes current flow in cortical tissue, resulting in neuronal depolarization.
Though stimulators can indefinitely produce fields, the majority of TMS work has been done with single treatments of three to five seconds each. Since little research has looked at the effects of treatment quantity it would be beneficial to identify a relationship between number of treatments and effect. For example, do three treatments increase anti-depressant effects more than a single treatment? The goal of my project was to optimize the anti-depressant effects of TMS by determining the most effective number of transcranial magnetic stimulation treatments in a rat-model of human depression.
The Porsolt swim test is a rat-model of depression used to evaluate antidepressant properties of drugs. The test involves placing the rat into a beaker of water and determining the amount of time that the animal remains immobile. The typical procedure that has been used is to place the animal in the tank of fifteen minutes on day one; as a result of this exposure, active coping attempts are extinguished so that the animal ceases movement by the end of the session. The following day, the animal is returned to the water tank for five minutes where immobility is timed. Between the first and second exposure to the swim tank, the drug is given. Effective antidepressants cause animals to show less immobility on the second (test) exposure than is shown by untreated animals (Schatzberg and Nemeroff, 1995).
The Porsolt detects a wide range of antidepressant treatments, including standard antidepressant (such as tricyclic antidepressants and monoamine oxidase inhibitors), atypical antidepressants, as well as electroconvulsive (ECT) treatment (Borsini and Meli, 1988). Based on these factors it was hypothesized that TMS will show an antidepressant like effect on the Porsolt swim test.
Analysis of variance statistics were used to compare treatments in terms of immobility. Statistical analysis revealed no significant differences among treatments. Furthermore, T tests comparing baseline immobility with experimental immobility found no significant differences in groups receiving either three treatments, one treatment or no treatment of TMS. There was, however, a trend towards greater immobility in the rats that received treatment, with the rats receiving three treatments demonstrating more immobility than the ones receiving only one treatment.
The findings suggest that fewer treatments of TMS at lower intensities may not possess antidepressant activity. If TMS given at these parameters does indeed have antidepressant effects, its mechanism of action may differ from that of both antidepressants and ECT.
The trend towards increased immobility also suggests that TMS may possess anxiolytic properties as buspirone, a known anxiolytic, has been shown to increase immobility in the Porsolt swim test in rats (Skrebuhhova et al, 1999) . Weiss et al reported that rats selectively bred for high immobility showed decreased immobility when chronically treated with desipramine and phenelzine but no decrease when given buspirone (Weiss et al, 1998). Chlordiazepoxide and diazepam do not diminish immobility in rats either (Borsine and Meli, 1988). Finally, it is possible that TMS is enhancing memory and increasing immobility as the Porslt swim test also has been used to assess learning (Montkowski et al, 1997).
Our results differ from those of Fleischmann et al. (1995) who reported decreased immobility time in mice treated with TMS. These differences could be due to the use of different species, as it has been reported that the Porsolt swim test appears suitable for detecting antidepressant response in rats but not in mice (Borsini and Meli, 1988). Another source of difference could be different dosing parameters. Fleischmann et al used 25 Hz at 100% power in the smaller mouse brain, whereas we used 15 Hz at 80% power in the larger rat brain. Differences in experimental conditions such as strain of rat used, diameter of cylinder, and depth of water may also explain this discrepancy (Borsini and Meli, 1988). It is also possible that lower frequency TMS or TMS given over a shorter period increases immobility whereas TMS administered at higher frequencies or for a longer period reduces immobility, although further research is required to evaluate this hypothesis.
References
test, Methods-Find-Exp-Clin-Pharmacol, 21(3) (1999) 173-178.