Cognitive functioning after repetitive transcranial magnetic stimulation in patients with cerebrovascular disease without dementia: a pilot study of seven patients

https://doi.org/10.1016/j.jns.2004.11.021Get rights and content

Abstract

Aims

Examine whether one session of high frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left dorsolateral prefrontal cortex (DLPFC) would induce any measurable cognitive changes in patients with cerebrovascular disease and mild cognitive deficits.

Patients and method

Seven patients with cerebrovascular disease and mild executive dysfunction entered the randomised, controlled, blinded study with a crossover design. rTMS was applied either over the left DLPFC (an active stimulation site) or over the left motor cortex (MC; a control stimulation site) in one session. Each patient participated in both stimulation sessions (days 1 and 4) and the order of stimulation sites (DLPFC or MC) was randomised. A short battery of neuropsychological tests was performed by a blinded psychologist prior to and after each rTMS session. Psychomotor speed, executive function, and memory were evaluated.

Results

The only mild but significant stimulation site-specific effect of rTMS was observed in the Stroop interference results (i.e. improvement) after the stimulation of DLPFC but not MC in comparison with the baseline scores (Wilcoxon, Z=−2.03, p=0.04). Patients improved in the digit symbols subtest of the Wechsler adult intelligence scale-revised after both rTMS sessions regardless of the stimulation site (DLPFC or MC; Z=−2.06, p=0.04 and Z=−2.06, p=0.04, respectively). There was no measurable effect of rTMS in any other neuropsychological test.

Conclusion

Our pilot study results showed that one session of the high frequency rTMS applied over the left DLPFC was safe in patients with cerebrovascular disease and mild executive deficits, and may induce measurable positive effects on executive functioning.

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.

Section snippets

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.

References (32)

  • M.S. George et al.

    Transcranial magnetic stimulation: applications in neuropsychiatry

    Arch. Gen. Psychiatry

    (1999)
  • D.J. Moser et al.

    Improved executive functioning following repetitive transcranial magnetic stimulation

    Neurology

    (2002)
  • A.M. Speer et al.

    Lack of adverse cognitive effects of 1 and 20 Hz repetitive transcranial magnetic stimulation at 100% of motor threshold over left prefrontal cortex in depression

    J. ECT

    (2001)
  • J.T. Little et al.

    Cognitive effects of 1- and 20-Hertz repetitive transcranial magnetic stimulation in depression: preliminary report

    Neuropsychiatry Neuropsychol. Behav. Neurol.

    (2000)
  • M.C. Polidori et al.

    Heart disease and vascular risk factors in the cognitively impaired elderly: implications for Alzheimer's dementia

    Aging (Milano)

    (2001)
  • D.W. Desmond et al.

    Incidence of dementia after ischemic stroke. Results of a longitudinal study

    Stroke

    (2002)
  • Cited by (76)

    • Different combinations of high-frequency rTMS and cognitive training improve the cognitive function of cerebral ischemic rats

      2021, Brain Research Bulletin
      Citation Excerpt :

      rTMS is deemed promising tools to improve poststroke recovery due to its long-lasting effects (van Lieshout et al., 2019). rTMS is a non-invasive and safe treatment strategy that has already been shown by both clinical (Fisicaro et al., 2019; Lage et al., 2016; Rektorova et al., 2005; Tsai et al., 2020) and animal (Guo et al., 2017; Zhang et al., 2018) studies to have promising effects on PSCI. Consistent with the findings of previous studies, our study indicated that rTMS treatment significantly improved the cognitive function of tMCAO rats, as assessed by the MWM test.

    View all citing articles on Scopus
    View full text