Neurorehabilitation of hand functions using brain computer interface

Introduction: Brain computer interface (BCI) is a promising new technology with possible application in neurorehabilitation after spinal cord injury. Movement imagination or attempted movement-based BCI coupled with functional electrical stimulation (FES) enables the simultaneous activation of the motor cortices and the muscles they control. When using the BCI- coupled with FES (known as BCI-FES), the subject activates the motor cortex using attempted movement or movement imagination of a limb. The BCI system detects the motor cortex activation and activates the FES attached to the muscles of the limb the subject is attempting or imaging to move. In this way the afferent and the efferent pathways of the nervous system are simultaneously activated. This simultaneous activation encourages Hebbian type learning which could be beneficial in functional rehabilitation after spinal cord injury (SCI). The FES is already in use in several SCI rehabilitation units but there is currently not enough clinical evidence to support the use of BCI-FES for rehabilitation. Aims: The main aim of this thesis is to assess outcomes in sub-acute tetraplegic patients using BCI-FES for functional hand rehabilitation. In addition, the thesis explores different methods for assessing neurological rehabilitation especially after BCI-FES therapy. The thesis also investigated mental rotation as a possible rehabilitation method in SCI. Methods: Following investigation into applicable methods that can be used to implement rehabilitative BCI, a BCI based on attempted movement was built. Further, the BCI was used to build a BCI-FES system. The BCI-FES system was used to deliver therapy to seven sub-acute tetraplegic patients who were scheduled to receive the therapy over a total period of 20 working days. These seven patients are in a 'BCI-FES' group. Five more patients were also recruited and offered equivalent FES quantity without the BCI. These further five patients are in a 'FES-only' group. Neurological and functional measures were investigated and used to assess both patient groups before and after therapy. Results: The results of the two groups of patients were compared. The patients in the BCI-FES group had better improvements. These improvements were found with outcome measures assessing neurological changes. The neurological changes following the use of the BCI-FES showed that during movement attempt, the activation of the motor cortex areas of the SCI patients became closer to the activation found in healthy individuals. The intensity of the activation and its spatial localisation both improved suggesting desirable cortical reorganisation. Furthermore, the responses of the somatosensory cortex during sensory stimulation were of clear evidence of better improvement in patients who used the BCI-FES. Missing somatosensory evoked potential peaks returned more for the BCI-FES group while there was no overall change in the FES-only group. Although the BCI-FES group had better neurological improvement, they did not show better functional improvement than the FES-only group. This was attributed mainly to the short duration of the study where therapies were only delivered for 20 working days. Conclusions: The results obtained from this study have shown that BCI-FES may induce cortical changes in the desired direction at least faster than FES alone. The observation of better improvement in the patients who used the BCI-FES is a good result in neurorehabilitation and it shows the potential of thought-controlled FES as a neurorehabilitation tool. These results back other studies that have shown the potential of BCI-FES in rehabilitation following neurological injuries that lead to movement impairment. Although the results are promising, further studies are necessary given the small number of subjects in the current study.

A study of the electrical basis for the inhibition and excitation in autonomically innervated smooth muscle

The aim of this thesis was to investigate the electrical and mechanical responses to inhibitory non-adrenergic noncholinergic (NANC) nerve stimulation in the bovine retractor penis muscle (BRP) and compare them with those to an inhibitory extract made from this muscle. The extract may contain the NANC inhibitory transmitter of the BRP and possibly of other smooth muscles. Because of species differences in the electrical response to NANC nerves in the rat and rabbit anococcygeus the effects of the extract on these tissues was also investigated. Prior to the investigation of the extract, both the excitatory and inhibitory responses to field stimulation in the BRP, and the effects of passive membrane potential displacement were studied using conventional intra- or extracellular (sucrose gap) recording techniques. The majority of cells in the BRP were electrically quiescent independent of the resting tone. The most frequent (in approximately 25% of preparations) form of spontaneous activity, oscillations in membrane potential and tone, may represent a pacemaker activity. The BRP had cable properties; the time constant and space constant indicated a high membrane resistance. In the absence of tone, field stimulation of the BRP evoked excitatory junction potentials (ejps) in every cell impaled and contractions, graded with the strength, frequency and number of pulses; spikes were not observed. Guanethidine (1-3 x 10-5M) abolished the ejps and contractions, confirming their adrenergic origin. Noradrenaline added exogenously depolarised and contracted the muscle. These effects were blocked by the a-adrenoceptor antagonists, phentolamine and prazosin. However, phentolamine (2.5x 10-6M) inhibited the contraction without reducing the ejp significantly. These effects may be independent of adrenoceptor blockade or the ejp may be mediated by a substance other than noradrenaline (e.g. ATP) released from adrenergic nerves. Prazosin (1.4 x lO-6M) failed to block either the ejp or contraction, indicating the possible existence of two types of adrenoceptor in the BRP; one activated by neuronally-released and the other by exogenously-added noradrenaline. ATP, a contaminant in the extract, also depolarised and contracted the BRP. Physostigmine reduced whilst atropine enhanced the ejps and contractions without similarly affecting the response to exogenous noradrenaline. This confirmed the presence of a cholinergic inhibitory innervation acting on the excitatory adrenergic fibres (Klinge and Sjostrand, 1977). TEA (1 x lO-4M) enhanced the ejp and contraction. Higher concentrations (0.5 to 10 x 10-3M) depolarised, increased the tone and evoked electrical and mechanical oscillations but no spikes. The depolarisation and contraction to exogenous noradrenaline were not enhanced, indicating that TEA acts on the adrenergic nerves. Some post-synaptic effect to block K+ channels also seems likely. The relationship between ejp amplitude and membrane potential in the double sucrose gap was linear and indicated a reversal potential more positive than -30mV. Electrotonic pulse amplitude decreased during the ejp, indicating an increased membrane conductance. Ejps and contractions were reduced following the replacement of the NaCl of the Krebs solution with sodium glutamate. This may be due to the effects of glutamate itself (e.g. Ca2+ chelation) rather than reduction in the membrane Cl- gradient. Tone usually developed spontaneously and was accompanied by membrane depolarisation (from -53 to -45mV) which may open voltage-dependent channels, causing Ca2+ entry and/or its release from intracellular binding sites. Field stimulation produced inhibitory potentials (ijps) and relaxations graded with the strength and number of pulses but showing little frequency dependence. Rebound depolarisation and contraction often followed the ijp and relaxation. Tetrodotoxin (3 x IO-6M), but not adrenergic or cholinergic antagonists, abolished the ijp and relaxation, confirming their non-adrenergic non-cholinergic neurogenic nature. The extract, prepared and acid-activated as described by Gillespie, Hunter and Martin (1981), hyperpolarised and relaxed the BRP, as did sodium nitroprusside and adenosine triphosphate (ATP). Unlike the activated extract or sodium nitroprusside, desensitisation to ATP occurred rapidly and without any change in the inhibitory electrical or mechanical responses to field stimulation. The ijp and relaxation in the BRP were insensitive to apamin but abolished by oxyhaemoglobin (4-8 x 10-6M), as were the responses to extract and sodium nitroprusside. In TEA (10-2M), field stimulation evoked relaxations with no accompanying electrical change. The ijp may be unconnected with or additional to another mechanism producing relaxation. The relationship between membrane potential and ijp in the BRP was non-linear. Ijp amplitude was initially increased during membrane potential displacement from -45mV to approximately -60mV. Thereafter (-60 to -l03mV) the ijp was reduced. Ijps were abolished at -27 and -103mV; reversal was not observed. The hyperpolarisation to extract was also enhanced during passive displacement of the membrane potential to more negative values (-57mV). Membrane resistance increased during the ijp. The extract produced inconsistent changes in membrane resistance, possibly because of the presence of more than one active component. K+ withdrawal failed to enhance the ijp or hyperpolarisation to extract and 20mM K+ did not abolish the the ijp at membrane potentials exceeding EK (-49mV). Thus, the ijp or hyperpolarisation to extract are unlikely to be mediated by an increased K+ conductance. Reducing the Cl- abolished the hyperpolarisation to field stimulation and extract. This occurred more quickly than the anticipated reduction in the Cl- gradient and may be due to Ca2+ chelation by the anion substitute (glutamate or benzenesulphonate) or blockade of the resting conductance which is normally inactivated by the transmitter. Ouabain (1-5x 10-5M), which reduces both the Na+ and Cl- gradients, abolished the ijp, implicating either of these ions as the ionic species involved. In the rat and rabbit anococcygeus, field stimulation and extract each reduced guanethidine-induced tone. This was unaccompanied in the majority of cells in the rat by any significant electrical response. In the remaining cells, inhibition of the membrane potential oscillations occurred. The rabbit anococcygeus differed in that inhibition of the electrical oscillations was observed in every cell exhibiting this behaviour. However, the majority of cells in the rabbit were electrically quiescent and showed only small hyperpolarisations to field stimulation and no electrical response to extract. Apamin (1 x 10-7M) failed to block the electrical and mechanical response to field stimulation in the rabbit but did inhibit transiently that to extract. The latter effect may be due to the initial excitatory effects of apamin. The similarities between the electrical effects of the extract and those of inhibitory nerve stimulation in the BRP, rat and rabbit anococcygeus muscles are generally consistent with their being mediated by the same active component. Moreover, the ijp in the BRP shows properties which have not been reported in other non-adrenergic noncholinergically innervated smooth muscles.