Cognitive functioning after repetitive transcranial magnetic stimulation in patients with cerebrovascular disease without dementia: a pilot study of seven patients
Introduction
Transcranial magnetic stimulation (TMS) has been used as a tool to investigate the mechanisms and consequences of cortical plasticity at a regional level. Repetitive TMS (rTMS) can also be used to promote changes in the excitability of cortical circuits within a distributed functional network; these changes outlast the period of stimulation, and thus rTMS may have therapeutic potential in some neuropsychiatric disorders (for review, see Ref. [1]). The after-effects of rTMS depend on stimulation variables such as intensity, frequency, and the total number of stimuli, and on the site and the functional state of the cortex targeted by rTMS. High frequencies of rTMS, especially at high stimulation intensity, produce facilitatory after-effects on corticospinal excitability [2], [3], [4]. It is more difficult to demonstrate the behavioral effects of rTMS than it is to show changes in cortical excitability or functional cortico-cortical connectivity [5], [6]. It may be possible that healthy subjects are more easily able to recruit additional brain areas to compensate for the effects of rTMS. Thus, it may be easier to show the behavioural effects of rTMS in patients with a distinct neurological or psychiatric disorder, in whom the susceptibility to the conditioning effects of rTMS may differ from the susceptibility of healthy subjects, as a consequence of the underlying pathophysiology of their disease [1]. rTMS has already been used to temporarily improve symptoms of several movement and psychiatric disorders, as well as of epilepsy, with the results of greatest clinical interest found in major depression (for review, see Refs. [7], [8]). It has also been shown that selective cognitive functions, including executive functions [9], [10], [11], [12], memory [12], [13], [14], and fine motor speed domains [12] can be improved after rTMS in people with refractory depression.
Vascular risk factors and general vascular conditions are associated with poorer cognitive performance [15], [16], [17], and more severe white matter lesions have been associated with a more rapid cognitive decline over a mean follow-up period of 7.3 years [18]. Selective deficits in prefrontal functioning have been demonstrated in people with mild cognitive vascular impairment (i.e., with impairments associated with cerebrovascular disease, evidenced by both brain imaging and the presence or a history of neurological signs) [19].
The objective of our study was to examine whether one session of high frequency rTMS applied over the left dorsolateral prefrontal cortex (DLPFC) would induce any measurable cognitive changes in patients with cerebrovascular disease without dementia, who also had mild executive deficits.
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Patients and methods
Seven patients (5 men and 2 women; mean age 72.9±3.4 years) with cerebrovascular disease without dementia, determined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for dementia [20], who also had mild executive deficits [evidenced by a neuropsychological examination (e.g. initiation, planning, organizing, executing, abstracting, impaired recalling)] entered the study. Only patients who had a relevant cerebrovascular disease confirmed by both
Results
Apart from extensive subcortical changes revealed by brain imaging (CT and/or MRI) described above (see Patients and methods), one patient also had a cortical–subcortical territorial infarct (right parietal area), indicating large vessel disease. All patients had pyramidal signs and/or reflex asymmetry, as revealed by neurological examination; some patients also had mild hemiparesis and/or lower facial weakness (n=2), extrapyramidal signs (hypokinesia, rigidity and/or Parkinsonian gait
Discussion
The only mild but significant stimulation site-specific effect of rTMS was observed in the Stroop interference after the stimulation of DLPFC. It was not present after the MC stimulation. The dorsolateral pre-frontal cortex, together with associated subcortical structures, is important in mediating executive functions [29], [30]. The interference section of the Stroop test consists of words (names of colours) printed in ink colours differing from the written word (incongruent ink colour). The
Acknowledgement
We would like to thank assistant professor Mojmir Tyrlik, PhD, Dept. of Psychology, Phil. Faculty, Masaryk Univ., Brno, Czech Republic, for his assistance with data analysis. Supported by research program VZ MZCR No. 112801.
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