Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) to the contralesional hemisphere and intensive occupational therapy (iOT) have been shown to contribute to a significant improvement in upper limb hemiparesis in patients with chronic stroke. However, the effect of the combined intervention program of LF-rTMS and iOT on cognitive function is unknown. We retrospectively investigated whether the combined treatment influence patient’s Trail-Making Test part B (TMT-B) performance, which is a group of easy and inexpensive neuropsychological tests that evaluate several cognitive functions. Twenty-five patients received 11 sessions of LF-rTMS to the contralesional hemisphere and 2 sessions of iOT per day over 15 successive days. Patients with right- and left-sided hemiparesis demonstrated significant improvements in upper limb motor function following the combined intervention program. Only patients with right-sided hemiparesis exhibited improved TMT-B performance following the combined intervention program, and there was a significant negative correlation between Fugl-Meyer Assessment scale total score change and TMT-B performance. The results indicate the possibility that LF-rTMS to the contralesional hemisphere combined with iOT improves the upper limb motor function and cognitive function of patients with right-sided hemiparesis. However, further studies are necessary to elucidate the mechanism of improved cognitive function.
Upper limb hemiparesis is reported to be observed in 55–75% of post-stroke patients, and affects the patient’s activities of daily living and quality of life (Nichols-Larsen et al., 2005; Wolf et al., 2006). Duncan et al. (1992) reported that dramatic recovery of motor function was completed by 1month post-stroke, and that recovery often plateaued by 6 months. In recent years, repetitive transcranial magnetic stimulation (rTMS) has attracted attention as a treatment technique for the sequelae of stroke. It is a non-invasive, painless method to stimulate regions of the cerebral cortex, in which a figure-8 or a round coil converts electrical current into a rapidly variable magnetic field that is orthogonal to the current. Eddy currents generated by the changes of the magnetic field directly affect neurons (Barker, 1999). In addition, it has been known that different stimulation frequencies have different effects on the activities of the cerebral cortex, with high-frequency (> 5 Hz) stimulation facilitating local neuronal excitability and low-frequency (< 1 Hz) stimulation showing inhibitory effects (Lefaucheur, 2006; Butler and Wolf, 2007). Low-frequency rTMS (LF-rTMS) aims at increasing the excitability of the ipsilesional hemisphere by exerting its effects on the disrupted interhemispheric inhibition following stroke and thereby providing inhibitory stimulation to the contralesional hemisphere. Meta-analyses of rTMS in patients with stroke indicate that LF-rTMS is recommended for stroke patients in the chronic phase (> 6 months post-stroke), showing a strong possibility of a significant improvement of their upper limb function (Hsu et al., 2012; Le et al., 2014). In the past, our research group implemented a 15-day treatment protocol consisting of LF-rTMS and an intensive individualized rehabilitation program for patients with upper limb hemiparesis following stroke, and demonstrated a significant improvement of upper limb hemiparesis (Kakuda et al., 2011, 2012, 2016). Furthermore, we investigated the effects of our treatment protocol on brain activity and demonstrated a significant increase in the fMRI laterality index, indicating increased neuronal activity in the ipsilesional hemisphere (Yamada et al., 2013). Our single photon emission computed tomography (SPECT) study also demonstrated a significant decrease in perfusion in the middle frontal gyrus (Brodmann area; BA6), precentralgyrus (BA4), and post central gyrus (BA3) of the contralesional hemisphere, as well as an increased perfusion in the insula (BA13) and precentral gyrus (BA44) of the ipsilesional hemisphere (Hara et al., 2013). Thus, we demonstrated changes in brain activity between pre- and post-treatment that combined LF-rTMS and an intensive occupational therapy (iOT) program.
In recent studies, rTMS was used not only in treating upper limb hemiparesis after stroke, but also for other conditions, including neurological and psychiatric disorders, pain, and Parkinson’s disease (Lefaucheur et al., 2014). Furthermore, some studies conducted neuropsychological examinations at the time of rTMS to evaluate its effect on cognitive function (Nardone et al., 2014; Drumond Marra et al., 2015). One study reported an improvement in cognitive function following rTMS in patients with mild cognitive impairment (Nardone et al., 2014). Drumond Marra et al. (2015) reported an improved performance on the Rivermead Behavioral Memory Test following high-frequency rTMS (HF-rTMS) to the left dorsolateral prefrontal cortex (DLPFC).
Furthermore, the effects of rTMS on cognitive function in addition to motor disorders, aphasia, and affective disorders have been attracting attention (Lefaucheur et al., 2014; Nardone et al., 2014; Drumond Marra et al., 2015). One study reported an improvement in Trail-Making Test part B (TMT-B) performance by HF-rTMS, while another study reported a lack of significant improvement relative to a control group (Moser et al., 2002; Mittrach et al., 2010). However, few studies have investigated the effects of LF-rTMS on cognitive function. As described earlier, LF-rTMS exerts an inhibitory stimulation to the side of administration and is considered to affect the contralateral cerebral cortices via a modulation of interhemispheric inhibition. Therefore, LF-rTMS possibly affects a broader region than that affected by HF-rTMS. Meta-analyses of rTMS in patients with stroke indicate that LF-rTMS is recommended for stroke patients in the chronic phase (> 6 months post-stroke).
Although previous studies indicate a possibility of positive effects of rTMS on cognitive function; however, to the best of our knowledge, there has been no report describing the effect of a combined intervention program of LF-rTMS and intensive occupational therapy (iOT) on cognitive function in post-stroke patients. Therefore, the present study aimed to explore the therapeutic effect of the combined intervention program on patients with post-stroke upper limb hemiparesis.
Continue —> Does a combined intervention program of repetitive transcranial magnetic stimulation and intensive occupational therapy affect cognitive function in patients with post-stroke upper limb hemiparesis? Hara T, Abo M, Kakita K, Masuda T, Yamazaki R – Neural Regen Res