Adequately Targeted Brain Stimulation in Post-Stroke Motor Rehabilitation

Author: Livia Popa

Keywords: intermittent theta burst stimulation (iTBS), motor recovery, hand grip strength, primary motor cortex (M1), motor network connectivity,  brain-stimulation

Neurorehabilitation benefits of adequately targeted brain stimulation in post-stroke motor rehabilitation

In 2016, the scientific medical journal Cerebral Cortex published the results of an experimental study by a team of scientists from Cologne and Dusseldorf, in Germany, who hypothesized that superior motor rehabilitation outcomes could be achieved by “priming” the patient’s brain before physiotherapy sessions in the first weeks after a stroke [1].       

When the nervous system of an adult person is injured, some degree of adaptive neuroplasticity occurs even without rehabilitation treatment, mainly as synapse excitation and inhibition strength patterns [2]. For instance, neural “re-wiring” processes have been observed in lesioned brains immediately after a stroke [3]. Also, motor recovery in the weeks following a stroke has been associated with improved connectivity between the primary motor cortex and other brain areas involved in controlling movement [4, 5]. 

Figure 1. The location of the primary motor cortex [7]

One way in which the M1 area can be aroused safely is with short, repetitive, high-frequency bursts of transcranial magnetic stimuli (abbreviated rTMS). At the time of the study mentioned above and ever since, this non-invasive method has been considered for various clinical applications, such as treating chronic depression by engaging other brain areas relevant to emotional status [8]. Many TMS protocols are possible; one is called intermittent theta-burst stimulation or iTBS. What sets iTBS apart from conventional rTMS is that shorter stimulation periods at lower intensity produce similar or stronger cortical excitation while being logistically easier and cheaper to administer [9 –11].

Experimental stimulation protocol and patient enrolment 

Volz and his collaborators designed an experimental protocol of iTBS to be delivered to acute stroke patients on five consecutive days immediately before their first daily physiotherapy sessions. One iTBS procedure took approximately three and a half minutes, during which 600 pulses at a frequency of 50 Hz were applied (ten bursts of three pulses every two seconds, repeated every ten seconds). The method had already been described in the literature, but the German researchers modified it slightly by setting the stimulation intensity at 70% of each patient’s individual resting motor threshold triggering the minimum motor response. This served to consider the impaired motor function and muscle contraction ability in the studied hand of the patients [1, 12].

The twenty-six consenting patients enrolled in the study were all in the first one or two weeks after their first-ever stroke event; in this way, iTBS could be studied in an existing clinical context of “early” rehabilitation, in this case at the University Hospital of Cologne, in Germany. Only patients with impaired hand movement after the stroke were included and whose primary motor cortex (M1) did not appear to have been damaged by the stroke according to functional magnetic resonance imaging (fMRI) investigations. Other post-stroke symptoms, visual deficits, or pre-existing neurological conditions were criteria for exclusion [1]. 

The patients were assessed the day before the stimulation treatment began (baseline), then again, the day after the last stimulation session (post-intervention), and a third-time several months later (follow-up). The tests included functional magnetic resonance imaging (fMRI), electromyograms (EMG), and grip strength measurements using a device called “vigorimeter” (see Figure 2). This measures the user’s force while gripping and pressing their hand on a flexible rubber ball. In this study, at each mentioned stage, the patients had to perform 3 presses taking 5-second breaks in between. The affected and unaffected hands were evaluated this way [1].

Figure 2. Vigorimeter [13]

Specific terms in scientific research  

The German team described their study as “sham-controlled, pseudo-randomized, single-blinded, between-subject” [1]. To be able to appreciate carefully designed and thorough research, it is useful to understand what words like “sham”, “pseudo”, and “single” mean in a scientific context. 

As with placebo medication that does not contain the active ingredient, a sham procedure is one where the intervention appears to be the same, but the specific therapeutic action or step that makes the object of the study is omitted or replaced with one that has no significant effect. This helps to isolate the impact of the experimental therapy by comparing the results to those of a control group of patients who experience the same overall process [14]. In the study of Lukas Volz and his colleagues, the patients forming the control group received stimulation at an angle and intensity which ensured that the cortex would be out of range even if the sensation on the skin felt the same, making the patients unable to tell the difference [1]. 

Also, in single-blind experiments, the individual patients do not know if they are receiving the studied treatment or not [15]. In double-blind ones, the doctors implementing the experiment and the researchers analyzing the data do not know this either [16]. Volz and his colleagues opted for a single-blind design for the reasons explained next [1]. 

A randomized study is one where the participating patients are assigned to either the experimental or the control groups in an arbitrary, indiscriminate way, such as by a computer randomization program, to prevent selection biases from influencing the results [14, 17]. This is not always possible or effective. For instance, Volz’s team could test their hypothesis on a relatively small number of patients whose individual differences were relevant factors. Thus, they had first to ensure that the control and treatment groups were as balanced as possible concerning the patients’ age, initial hand grip strength, and duration of symptoms.

After the first ten enrolled patients were indeed randomly assigned, the next ones were distributed according to matching initial characteristics (“between-subject”) by a team member who was not involved in patient assessment [1, 18].

Stronger hand grip and better neural connectivity after iTBS application

At baseline, there were no significant differences between the two patient groups in terms of number, age, and time passed since the stroke. Also, the hand grip strength levels assessed initially were similar, and so were the characteristics of the stroke-related brain lesions: their volume, location, and damage to corticospinal tract fibers responsible for carrying movement information [1].

The day after the last session, all the patients demonstrated superior grip strength in the affected hand while their unaffected one performed the same as at baseline. However, their progress was two times greater in the group of patients who had received M1 stimulation compared to the control group. Various statistical analyses confirmed the significance of this noteworthy difference. Several months later, the experimental group of patients demonstrated significantly higher grip strength in the affected hand than the control patients (see Figure 3) [1].

Figure 3. The measured hand grip strength of patients in control versus the experimental groups at baseline, after the intervention, and at follow-up, respectively [1].

Figure 4. Functional magnetic imaging data show motor network connectivity in the two study groups at baseline, after the intervention and at follow-up, respectively [1].

Conclusions

Stimulating the primary motor cortex at the start of physiotherapy sessions can lead to improved hand motor recovery after a stroke [1, 10, 11]. 

The research of Volz et al. shows that motor rehabilitation after a stroke can be better and longer lasting when relevant areas of the patient’s brain are primed by adequate stimulation before proceeding with physiotherapy. Specifically, stimulation of the primary motor cortex, or M1 area, appears to promote increased motor network connectivity which, in turn, provides the neural framework for better recovery of grip strength in an affected hand [1].

It might be tempting to expect clinicians to incorporate new ideas with therapeutic value in their practices immediately, but readers should be aware that there is much to learn about neuroplasticity after a stroke or an accident that causes brain damage and related motor deficits. As Lukas Volz and his colleagues acknowledged in their article, further research is necessary to confirm new insights’ purported mechanisms, benefits, and safety by replicating pilot trials with a more significant number of patients. Complementary studies are also needed to facilitate meaningful motor recovery for daily activities that involve more than gripping, which are substantially more complex in required coordination and speed [1, 11].

To better understand post-stroke neurorehabilitation, visit:

• Constraint-Induced Movement Therapy improves short-term motor function of early stroke patients
• SENSe: Assessing neurorehabilitation’s impact on the somatosensory function in stroke patients

Moreover, check out the interview with Prof. Surjo Soekadar from World Congress on Neurorehabilitation (WCNR) 2022:

• Adapted Interview with Prof. Surjo R. Soekadar – World Congress for Neurorehabilitation (WCNR) Vienna 2022

References

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