Brain stimulation at your fingertips
Stimulation glove for stroke patients improves sense of touch and motor skills
by Hubert R. Dinse and Martin Tegenthoff
February 3, 2014
The principle underlying our learning processes is based on changes in communication between nerve cells, so-called neurons. On the cellular level, the learning process is determined by the signal transmission at the synapses (the contact points between two neurons) which can become more or less efficient. Such modification of synaptic efficiency is referred to as neuroplasticity. The molecular principles of synaptic plasticity have been studied in depth in individual cells, mainly those of rodents. The long-term changes of synaptic transmissions that occur in the course of the learning process are studied in a number of models, for example through long-term potentiation (LTP) and long-term depression (LTD). High-frequency electrical nerve cell stimulation, for example, triggers LTP; that means the communication between the stimulated cells is improved. Low-frequency stimulation, on the other hand, results in LTD; the communication efficiency between the cells declines. Consequently, LTD and LTP are two exemplary mechanisms that control the information flow within the brain network by controlling learning processes. The question is in what way does synaptic plasticity influence learning processes that are relevant for humans? Do LTP and LTD play a role at all in everyday life? In the Collaborative Research Centre 874, we attempt to provide answers to these questions.
Generally speaking, we distinguish between two types of learning: procedural and declarative. Declarative learning enables us to learn facts and memorise events; procedural learning enables us to acquire motor skills and improve perception. The best way to acquire such skills is training over a long period of time; learning to play an instrument, for example, takes many years. Our perception, too, can be improved through continuous training. Doctors, for example, find it easier to recognise structures in X-ray images with increasing experience. Blind people and musicians have a particularly good sense of touch, because they use their fingers a lot. Non-invasive imaging procedures have shown that heightened perception goes hand in hand with specific macroscopic changes to the brain organisation: in musicians and in blind people, the brain regions responsible for fingers and hands exhibit an enhanced and spatially more extensive activity; that means that the sense of touch, among others, recruits nerve cells for its purposes, thereby making information processing more efficient. However, scientists have not as yet been able to determine which cellular and molecular processes are responsible for this.
Modifying the tactile sense through repetitive stimulation. a) Immediately after 20 minutes of LTP-like high-frequency stimulation, the discrimination threshold improves (dark blue). This threshold specifies how large the distance between two stimuli has to be for a person to feel them as two discrete sensations. The effect was apparent 24 hours after the stimulation treatment, but it disappeared after one week. b) After LTD-like low-frequency stimulation, the tactile sense deteriorated. 24 hours after the stimulation session, the discrimination threshold went back to baseline. These effects only occurred on the stimulated hand; the other served as the control hand. The stars indicate which changes of discrimination thresholds were statistically significant; two stars indicate a change that is statistically particularly relevant. The diagram was compiled from the data of 14 participants. © RUBIN
In order to study in what way synaptic plasticity influences learning processes in humans, our work group has for many years chosen a different approach, namely one based on the following hypothesis: LTP and LTD-related processes constitute the foundation of learning, and learning can be induced on a cellular level through specific electrical stimulation protocols (fig. 1). Consequently, it should be possible to induce plastic processes in humans directly through sensory stimulation. In other words: an individual should be able to improve their sense of touch without any active contribution on their part. It should be sufficient to stimulate the skin surface repeatedly, either tactually by touching it repeatedly, or electrically through weak electrical impulses that cause a tingling sensation. However, this approach will only be successful if the same timing is applied that induces synaptic plasticity on the cellular level.
What seems improbable at first glance does indeed work: if we tactually stimulate the index finger of a young participant for the duration of 30 minutes with a LTP-like stimulation protocol, the sense of touch in the stimulated finger improves by some 15 per cent, but not in the index finger of the other hand. If, conversely, a LTD-related protocol is applied for the same length of time, the sense of touch in the stimulated finger declines (fig. 1). That means it is possible to control through the choice of the stimulation protocol if a person’s tactile perception weakens or strengthens. After a single stimulation session, all changes revert to the baseline after some 24 hours. If, however, the stimulation is repeated, for example five days a week over the period of several weeks, the induced effect is just as strong, and it remains constant for weeks.
The quality of the sense of touch is measured using the discrimination threshold, also called “differential threshold”. We determine whether a participant is able to tell the spatial difference between two discrete tactile stimuli in close proximity to each other. In the experiment described above, we altered the discrimination threshold by 15 per cent – is this a high or a low value? To compare: we know that blind people have a much better sense of touch than sighted people; in this case, the difference in the discrimination threshold amounts to up to 20 per cent. Consequently, passive stimulation causes a considerable change to the tactile perception.
Representation of the finger area in the somatosensory cortex. Repetitive stimulation of the fingers leads to an enlargement of the respective cortical maps. The figure shows brain sections with activation recorded with functional MRI. On the left: from the side (sagittal), on the right: from the front (coronal). © reprinted (adapted) from Neuron, 40/3, Pleger, Foerster, Ragert, Dinse, Schwenkreis, Malin, Nicolas, Tegenthoff, Functional Imaging of Perceptual Learning in Human Primary and Secondary Somatosensory Cortex, 643-653, Copyright (2003), with permission from Elsevier
What happens in the brain during and after behavioural changes? Is it possible to measure the neuronal signatures of the induced perception alterations? We examined this question using magnetic resonance imaging and high-density EEG measurements which require the participants to wear caps with up to 256 electrodes in order to record brain activity. In both studies, the sense of touch improved through repeated stimulation of the fingers, and the brain regions that process tactile information in and around the fingers were enlarged (fig. 2). The following interpretation suggests itself: the maps that are created in the brain (cortical maps) were enlarged, because the brain recruits additional resources in order to process signals from the hand more efficiently. Therefore, we assume that the modification of brain maps is causally related to the altered discrimination ability. Indeed, the changes to brain maps remained minimal in those participants in whom the discrimination ability only minimally improved. Conversely, the most significant improvements to the sense of touch happened in participants whose brain maps underwent the most significant changes. These findings indicate, on the one hand, that repetitive stimulation results in selective reorganisation in somatosensory areas of the cortex that are responsible for the sense of touch (fig. 3). Moreover, it is evident that the brain maps of individuals who do not benefit much from the repetitive stimulation change minimally. The fact that the learning outcome differs from individual to individual is a typical observation – everybody learns differently. What is interesting is that the differences apparently derive from the actual differences in the individual reorganisation in the brain.
Repetitive stimulation of the fingers results in a reorganisation of the somatosensory cortex (blue), in which the tactile sense is represented (red: hand region). The black line represents the tactile pathway. © RUBIN
Passive stimulation leads to a targeted modification of synaptic transmission in neural networks. In light of these findings, we have postulated the hypothesis that all neuronal processes related to tactile, haptic and sensorimotor information processing may be modified. This list is based on the assumption of a hierarchy of increasing behavioural complexity: tactile processing, for example, comes into play if something touches my finger. Haptic processes happen when I move my fingers actively in order to explore something, for example to feel for a key in the pocket. The sensorimotor performance describes the complex interactions between sensory and motor functions, for example if you have to skillfully manipulate small items. If our hypothesis is true, passive stimulation should modify not only tactile discrimination ability, on which all previous studies have focused, but the entire sensorimotor processing and associated behaviour. Indeed, this is exactly what happened: following passive stimulation, the test participants were able to better differentiate between different frequencies with which tactile stimuli were delivered; to differentiate between different braille patterns more easily; to recognise objects better by touch; to react more quickly to tactile stimuli; and the dexterity of their hands and fingers in general had improved. The wide variety of improvements is in stark contrast with the highly specific character of learning effects that are typically observed after training. The reasons for such specialised or generalised learning effects currently constitute a hot topic in the research communities.
If we wish to apply passive stimulation in the field of brain injury rehabilitation, a wide range of positive effects is the main requirement. A first step into that direction has been taken in the treatment of elderly individuals. Generally, all perception-related processes deteriorate with age. Typical aids include glasses and hearing devices; however, something comparable for the sense of touch does not exist. Instead, this sense deteriorates dramatically in the course of an individual’s life span – subtly and just about unnoticed. As a result, the sense of touch and the role it plays in everyday life are massively underestimated. In light of the demographic changes in industrial nations, huge efforts are being made to ensure independence in old age. Everyone agrees that an active lifestyle and physical and mental fitness, combined with ample sensory stimuli, are vitally important to remain healthy until old age, because they support neuroplastic processes.
In order to test the efficiency of our approach with regard to old people, we applied passive stimulation as a novel form of intervention in a test group comprised of 65- to 89-year-old participants. We then compared this cohort with participants aged 47 to 59 years. Prior to the stimulation treatment, the tactile discrimination efficiency of participants aged 60 years and older was much poorer than that of participants under the age of 60. That difference disappeared after the stimulation treatment: the average efficiency in older participants matched that in younger individuals (fig. 4). This suggests that the age-related deterioration of tactile perception efficiency is by no means irreversible; rather, it can be improved through specific stimulation protocols.
Older people have a higher (worse) discrimination threshold than younger people; i.e. the distance between two stimuli (e.g. the two tips of a pair of compasses) has to be greater to perceive the two stimuli as separate. However, the representation of the hand area takes up more space in their brain than in the brain of a young person (on the right) because the activation is more diffuse. Through repetitive stimulation, the discrimination threshold of older people improves much more significantly than that of younger people (on the left). © RUBIN
Can we use this effect to help people suffering from brain injury, for example stroke patients? Strokes often go hand in hand with massive sensorimotor impairments, which frequently have substantial physical, psychological, financial and social consequences despite exhaustive rehabilitation measures. It is therefore necessary to develop additional therapy approaches which would make treatment practicable in terms of cost and effort even across a long period of time.
In collaboration with a number of neurological rehabilitation clinics, we have initiated several studies that look into the feasibility and efficiency of passive stimulation as an intervention method – both in patients shortly after a stroke (sub-acute phase) and in chronic patients under long-term conditions. We tested all study participants very thoroughly in order to document the effects of the stroke as well as the effects of the therapy as comprehensively as possible. In addition, we examined not only the sensibility of the tactile sense and motor functions, but also the proprioception, i.e. the perception of one’s own body, for example the position of the body and the joints. Using standardised test batteries, we also recorded situations relevant for everyday life: picking up small items, mimicking a feeding motion or stacking objects; all these are actions that may constitute hurdles for stroke patients in their everyday life.
The motor functions and the tactile sense of stroke patients are improved through passive stimulation. These data come from two patients who were tested before the stimulation therapy (red) and three times during therapy (blue/grey). The testing intervals were longer for patient 1 (a and b) than for patient 2 (c and d). In the diagrams, the data of the healthy hand are contrasted with those of the impaired hand. a) When “aiming”, the task was to touch as many small boxes as possible with a pen. Whilst the time required was reduced by half in the impaired hand after nine weeks of passive stimulation (difference red to blue/grey), the times needed with the healthy hand remained more or less constant. b) The “skills task” required the patients to put small cylindrical objects into a holed-out board. In the impaired hand, the time required was reduced in the course of passive stimulation. c) After five weeks of passive stimulation, the touch threshold in the impaired hand was significantly reduced. The threshold value indicates the minimal force necessary to just perceive it. d) In the course of the stimulation treatment, the discrimination performance in the impaired hand was slowly improved. The threshold value indicates the minimal distance between two stimuli to perceive them as discrete. © RUBIN
The particular advantage of repetitive stimulation lies in its passive nature: it does not require a person to participate actively or attend to the stimulation. It is therefore possible to apply the stimulation during other activities such as going for a walk, watching television or reading. This increases the likelihood of the procedure being accepted and the drop-out rate remaining low. We have started to treat individual patients over long periods of time (longer than one year), some of whom had suffered an infarct longer than ten years ago. All seven patients applied repetitive stimulation regularly at home, 45 to 60 minutes per day, five days a week. The stimulation was carried out by means of computer-aided commercial equipment which also controlled time and duration of the stimulation sessions. To date, we have treated patients over a period of more than two years. In almost all cases, we clearly observed a positive effect with regard to the tactile, haptic and sensorimotor performance (fig. 5). The patients, for example, reported that, following the passive stimulation, they were able to recognise the surface structure of objects and to better manipulate objects, for example removing the cap from a pen. Interestingly enough, in individual cases it may take several months until the stimulation shows positive results, which then continue to intensify and manifest in the course of the following months.
We also examined the field of sub-acute treatment. The treatment commences two to three weeks after a stroke and runs over a period of two to three weeks, depending on the rehabilitation centre. In a randomised placebo-controlled study with 50 patients, we analysed in how far repetitive stimulation treatment in combination with standard therapy compares to mere standard therapy. The latter includes, for example, occupational therapy, training of everyday activities and curative pedagogy. We discovered that the effects of passive stimulation on patients in the sub-acute phase as well as in chronic patients were very beneficial, especially in terms of sensory information and proprioception improvement. Repetitive stimulation cannot work wonders, however; the impairments do not regress fully, but they can be significantly alleviated.
In order to facilitate the stimulation application, the study has pioneered the use of a special glove that we developed together with partners from the industry. Electrical contacts that are located at the finger tips and worked into the glove in form of a conductible material transmit short electric impulses to stimulate the nerves leading from the fingers to the brain. The users themselves can control the intensity of the stimulation; they should be able to feel it distinctly. Some users describe the feeling as “finger massage”. The patented product has been available in the market since the end of September 2013.
These data suggest that repetitive stimulation is an instrument suitable for additional or perhaps even exclusive brain injury treatment, the application of which is still in an early stage. Additional studies will be necessary to gain a better understanding of this remarkable phenomenon: electrical stimulation of the skin of the fingers activates the somatosensory cortex in an unspecific manner. Nevertheless, it does not result in a disorganised state in the relevant brain networks; on the contrary, it facilitates a new, highly organised state the relevance of which is reflected in an improved perception and an improved behaviour. At present, it is not clear which of the properties enable the cortical networks to emerge into new, stable and structured states and lead to better efficiency. This is the field on which our research will be focusing in future.
SFB 874: SENSORY PROCESSES IN THE BRAIN
The interdisciplinary Collaborative Research Centre SFB 874 “Integration and Representation of Sensory Processes” was launched at the Ruhr-Universität Bochum on July 1, 2010. The SFB members investigate in what way perception leads to plasticity, how different sensations are integrated and subsequently represented in the brain and how the processing of sensory information leads to memory building.
PASSIVE STIMULATION AND SYNAPTIC PLASTICITY
When passive stimulation changes both perception and behaviour, this is caused by a modulation of the synaptic transmission, i.e. by neuroplastic processes. It is assumed that synaptic transmission is controlled by only a few basic mechanisms. It is generally believed that the N-methyl-D-aspartate (NMDA) receptor plays a vital role in the regulation of synaptic plasticity. The efficiency of repetitive stimulation, too, is determined by such plasticity-conveying mechanisms, namely the activation of NMDA receptors. In order to demonstrate this, we administered memantine, a substance that selectively blocks NMDA receptors, to a group of participants. With the following result: the stimulation-induced learning was blocked completely, both on the perception level and on the cortical level. These findings were an additional link in the chain of evidence that learning through repetitive stimulation and the cortical changes related thereto are conveyed through basic synaptic plasticity mechanisms.
STROKE AND ITS CONSEQUENCES
In Germany, almost 270,000 people suffer from stroke every year. Due to the changing age patterns in our society, the number of patients is going to increase in the next decades. Even though many patients may regain their motor abilities to some degree, the extent to which a patient recovers depends on the individual. The consequences often include invalidity and very high socio-economic costs. The most severe impairment in 80 per cent of the patients suffering from acute stroke is hemiplegic paralysis. Effects of stroke frequently include impairments of voluntary motor functions, for example gripping, and of the somatosensory system, for example numbness, with the arms and legs both being affected to the same degree.