Transcranial Magnetic Stimulation and Mental Representation Techniques for the Treatment of Stroke Patients

An immersive multimodal BCI-VR training and bilateral rTMS protocols are likely to complement their effects achieving a stronger neuroplasticity enhancement in stroke patients. Both have been used separately for the treatment of motor sequelae in the upper limbs after stroke. The main objective of this study is to carry out a double-blind, randomized, controlled trial aiming to study the clinical effect of Neurow system (NeuroRehabLab, Lisbon, Portugal) over bilateral rTMS plus conventional rehabilitation in upper limb motor sequelae after subacute stroke (3 to 12 months). We will look for changes in 1. Isometric strength in upper limb, 2. Functional motor scales of upper limb, 3. Hand dexterity 4. Cortical excitability changes. The investigators in the present project hypothesize that both neuromodulation techniques combined will be superior to the use of rTMS alone as adjuvant therapy to conventional rehabilitation.

Stroke is a leading cause of long-term disability, it reduces mobility in more than half of stroke survivors age 65 and over.

Despite the lack of objective prognostic factors regarding the patient´s functionality after a stroke, we know that age, the level of initial disability, and the location and size of the lesion are elements that affect the evolution of post-stroke rehabilitation.

After stroke, the recovery of lost functions in the brain is achieved thanks to reorganizing networks in a process known as plasticity. Some damaged brain tissue may recover, or undamaged areas take over some functions.

One of the most relevant aspects of the rehabilitation prognosis is the time of evolution. After stroke, improvement is noticeably reduced over the second month, finding stabilization around the sixth month. One of the reasons for this is the reduction of neuroplasticity. There are indicative studies that reflect that, six months after a stroke, more than 60% of subjects will have a non-functional hand for Basic Activities of Daily Living (BADL), and 20-25% will not be able to walk without assistance. This determines the important global burden that stroke represents. It is relevant to emphasize the degree of disability after the rehabilitation process will be determined by the combination of existing motor, sensory and neuropsychological deficiencies.

In the last years, several non-invasive neuromodulation techniques have been shown efficient to enhance plasticity and stroke recovery. Among these interventions we can find exogenous neuromodulation, meaning that the neuromodulator stimulus comes from an external source, as is the case with rTMS (repetitive transcranial magnetic stimulation) which has the capacity to change the cortical excitability depending on the frequency of the magnetic pulses. Low frequencies (≤ 1 Hz) reduce local neural activity and high frequencies (≥ 5 Hz) increase cortical excitability. This technique has been successfully used bilaterally, stimulating the injured hemisphere and inhibiting the healthy one, to treat the interhemispheric inhibition phenomenon in stroke patients as it influences stroke recovery.

On the other hand, there are endogenous neuromodulation techniques that depend on the capacity of the subject to modulate its own brain activity. This can be achieved using neurofeedback (NFB), this consists of recording information of brain activity using electroencephalography (EEG) or functional magnetic resonance (fMRI) and displaying it to the subject in such way that he can receive a real time information of his own brain function. Virtual reality allows a new dimension on the neurofeedback immersion, and is likely to increase its efficacy. Stroke patients have been trained to reinforce certain EEG rhythms related with motor performance using NFB technique showing favourable effects on rehabilitation outcomes.

Some other techniques aiming to increase brain plasticity use the practice of imagination of movement of the affected hemibody. This is known as motor imagery and can be also enhanced through the use of brain computer interfaces. All the neuromodulation techniques are used to complement but not as a replacement of conventional rehabilitation.

On one hand exogenous neuromodulation effects are produced mainly by changes directly induced in cortical excitability and on the other hand endogenous neuromodulation is believed to have more widespread subcortical effects. One of the probable causes of the short-term effects of these techniques is the ceiling effect of changes in cortical excitability that can be achieved non-invasively, but despite of the good results achieved with the use of non-invasive neuromodulation techniques individually, there is a shortage of validated neurorehabilitation protocols that integrate different approaches that have been proven to be effective individually.

Neurow system (NeuroRehabLab, Lisbon, Portugal) is an immersive multimodal BCI-VR training system that combines motor imagery and neurofeedback through BCIs, using virtual reality has been designed to be used in chronic stroke patients, its efficacy has been shown in a pilot study.

Both approaches, the Neurow system (NeuroRehabLab, Lisbon, Portugal) and bilateral rTMS protocols are likely to complement their effects achieving a stronger neuroplasticity enhancement in stroke patients. Both have been used separately for the treatment of motor sequelae in the upper limbs after stroke. The effects of these combined techniques are not likely to be based only in the increase of cortical excitability but also on subcortical mechanisms.

The main objective of this study is to carry out a double-blind, randomized, controlled trial aiming to study the clinical effect of Neurow system (NeuroRehabLab, Lisbon, Portugal) over bilateral rTMS plus conventional rehabilitation in upper limb motor sequelae after subacute stroke (3 to 12 months). We will look for changes in 1. Isometric strength in upper limb, 2. Functional motor scales of upper limb, 3. Hand dexterity 4. Cortical excitability changes. Our main hypothesis is that both neuromodulation techniques combined will be superior to the use of rTMS alone as adjuvant therapy to conventional rehabilitation.

This protocol combines techniques that have proven to be cost-effective. If it is shown that the clinical improvement with this combination is significant, it will be open a new line of combined neuromodulation approaches to reach and effective method for the upper limb motor neurorehabilitation of after a stroke.

Eligibility Criteria:
Inclusion Criteria:

Older than 18 years old.

Ischemic or hemorrhagic cerebrovascular injury diagnosed by a neurologist and who have at least one brain-imaging test.

The onset of hemispheric ischemic or hemorrhagic stroke\> 3 months.

Presence of upper limb motor sequelae due to stroke.

Sufficient cognitive ability to understand and perform tasks: Token Test\> 11.

Stability in antispastic medication for more than 5 days.

Able to read and write.

Exclusion Criteria:

History of seizure or brain

Pacemakers, medication pumps, metal implants in the head (except dental implants)

Clinical unstability

Other pre-existing neurological diseases or previous cerebrovascular accidents with sequelae.

Sensory aphasia

Previous TMS after stroke

Hemispatial neglect,

Flaccid paralysis Brunnstrom's stage \< 1

Visual problems