Cerebro-vascular accident or brain stroke is one of the significant health problems across countries including India. The average annual incidence rate of stroke was found to be 123.57 per 100,000 persons in a community based longitudinal study conducted in the rural Eastern India. Surprisingly the case fatality rate was reported highest (42%) in Kolkata among stroke studies conducted across the nation. (Pandian and Sudhan 2013).The impact of stroke is not only restricted to its immediate fatality but also to its long term sequelae, which impairs the daily living of the survivors.46% of survivors were reported to develop residual spasticity during a year of follow-up (Bhattacharya, Saha et al. 2005).Stroke survivors are affected by various neuro-psychological sequelae including autonomic and psychiatric manifestations and movement abnormalities. A monoparesis or hemiparesis is not uncommon after a cortical or sub-cortical brain stroke which further leads to spastic limbs. Several efforts has been made to restore hand function among stroke survivors. Rehabilitation is often centered on physical therapy, however the use of robotic device and functional electrical stimulation of muscles has shown considerable potential in restoring hand functions.

Stroke survivors frequently experience an initial paralysis, after which flexor muscles become increasingly active, sometimes developing into an unhelpful spasticity. In contrast, the extensors remain weak; the imbalance can result in a permanently closed hand, which is functionally useless because the fingers cannot extend to allow grasping (Twitchell 1951). Restoration of the ability to activate extensors voluntarily is often an important aim of physical therapy (Cauraugh, Light et al. 2000), and extensor strength can predict functional outcomes (Fritz, Light et al. 2005). Possibly due to this reason, botulinum toxin failed to improve a functional outcome measure in spite of reduction in muscle tone (Childers, Brashear et al. 2004). 

The mechanism of restoration of hand function after stroke is a complex biological process and not yet fully elucidated. Work in the Baker group in Newcastle University, UK, has recently revealed an important role for the reticulospinal tract, which is generally considered to be subservient to the much more prominent corticospinal tract in primates including man. In healthy monkeys, this group showed that stimulation within the reticular formation could activated hand muscles (Soteropoulos, Williams et al. 2012) – an unexpected finding, as the reticulospinal tract is typically considered to control gross movements such as postural adjustments rather than fine control as of the hand. In animals which had recovered from damage to the corticospinal tract, they showed that the reticulospinal tract strengthened its output to motoneurons controlling the hand, partially underlying the recovery of function (Zaaimi, Edgley et al. 2012). However, this strengthening of reticulospinal connectivity was selective: it occurred to forearm flexor and intrinsic hand muscles, but not to forearm extensors. This mirrors the extensor weakness and flexor spasm which in neurological experience is a common limitation to recovery in stroke survivors.

In macaque monkeys the rubrospinal tract is an important contributor to recovery alongside the reticulospinal tract. However, in humans the rubrospinal projection is thought to be very weak (Nathan and SMITH 1955, Onodera and Hicks 2010). It is likely that recovery of function in human patients after corticospinal damage is even more reliant on reticulospinal pathways than in monkeys following experimental lesions.

One of the fascinating property of mammalian central nervous system is ’synaptic plasticity’. It is the ability of experiences to modify neural circuitry and thereby transform future thoughts, behavior and activities. When two stimuli are delivered sequentially within a short interval, the synaptic response can be enhanced or depressed dependent on the stimulustiming. This phenomenon is known as ’Spike Time Dependent Plasticity’(Dan and Poo 2006).

The Baker group have recently shown that reticulospinal neurons can be activated by a loud auditory click stimulus (Fisher, Zaaimi et al. 2012); this is likely to act not only via the cochlea, but also via the saccule of the vestibular system (Didier and Cazals 1989, McCue and Guinan 1994, Murofushi, Curthoys et al. 1996). In addition, it is well known that afferent inputs from muscle receptors provide input to the reticular formation, via a pathway which includes the cuneate nucleus (Leiras, Velo et al. 2010). We have therefore developed a plasticity protocol which pairs click stimuli with electrical stimuli delivered to a muscle, using a ‘wearable electronic device’ capable of delivering stimuli in a portable format which can be worn whilst carrying out everyday tasks. In healthy volunteers, we have shown that this can modify the strength of reticulospinal connections to a muscle (Foysal & Baker, manuscript in preparation). By contrast, delivering only clicks, or only electrical stimuli, did not change reticulospinal outputs.

We now intend to extend these findings to stroke survivors, attempting to enhance wrist and finger extensor muscle activation using auditory and electrical stimuli with the wearable device. One group will receive stimuli in which the precise timing between stimuli is fixed, in a configuration expected to produce synaptic plasticity. A second group will receive the same rate of stimuli, but the timing of auditory and electrical stimuli will be randomized relative to each other – we would not expect this to generate synaptic plasticity.  The third group will receive standard treatment.