“For years the goal of SCI regenerative science has been to repair the chronically injured spinal cord through cell replacement, remyelination, or axon growth,” says neuroscientist Jean Peduzzi, Ph.D. of Wayne State’s (Detroit) School of Medicine. “But researchers and clinicians are increasingly realizing that another hurdle may exist – the brain and spinal cord must be able to activate these new spinal-cord connections.”

Part 1 reviewed biofeedback’s theory and benefits, as well as Dr. Bernard Brucker’s seminal contributions in developing this methodology.

Basically, biofeedback helps users find neural pathways whose signals are too weak to sense. Because the subjects are unaware of the connections, the signals remain unused and undeveloped. However, by using an EMG device (electromyography) to sense them, and by displaying signal strength in real time on a computer screen, therapists can assist users to strengthen and control the signals, improving motor functions.   

Although to date biofeedback is primarily a rehabilitation tool, its full potential may only now be realized, when it is used in combination with therapeutic interventions that improve connections across the injury site. Part 2 explores this possibility.

Objective Measure of Success

“Evaluating the efficacy of new treatments presents problems,” says Peduzzi, who tests potential regenerative treatments in animal models. “Obviously patients’ spinal cords can’t be sectioned to discover a treatment’s biological effect. Nor is it ethical to expect patients to undergo placebo treatments when it involves invasive surgery. If the treatment isn’t part of a funded trial, few patients would agree to pay when they might receive a placebo instead of treatment.”

Peduzzi points out that SCI reparative treatments are currently offered by several foreign clinics, which have reported some functional improvements that occur soon after treatment. Some researchers have questioned whether these improvements stem from regeneration, or if the treatments triggered metabolic or inflammatory changes that allowed signals to pass through existing, but previously masked, neural connections.

“Biofeedback will not reveal the mechanism of a treatment’s effects,” Peduzzi says. “But it offers a sensitive method for measuring changes in conduction induced by a treatment, provided the patient’s improvements through biofeedback have reached a plateau prior to the treatment.”

This data would offer researchers valuable insights that functional evaluation alone (e.g., changes in movements, sensations, or bodily functions) can’t offer.

Regarding pre-treatment testing, Peduzzi says that biofeedback “might identify patients that have the greatest potential for recovery after a specific therapeutic intervention. For example, those that have even the smallest signal across the injury site might show the greatest recovery after a treatment that encourages myelination. If a treatment stimulates axonal processes to grow, the presence of a few axons that still cross the injury site may guide the new axonal growth.” 

Similarly, biofeedback evaluations after a treatment might clarify the treatment’s success.

Part 1 explained that patients with too much atrophy or with contractures might not be able to effectively use newly available neural signals without first undergoing therapies that correct these concerns. In other words, a treatment might succeed in allowing neural signals to pass through the injured cord while appearing to have functionally failed. However, by measuring neural conduction, biofeedback offers a proven means for avoiding this pitfall.

Biofeedback-produced data could also suggest the general biological effects of emerging treatments. For example, functional improvements that occur soon after treatment are unlikely to result from neuron replacement or nerve regrowth, but more likely from the release of growth factors. Peduzzi explains, “Spinal-cord axons grow approximately one millimeter per day. So regardless whether growing neurites (axons and dendrites) sprout from new or existing neurons, their functional effects would be delayed.”

Several factors, however, can cause immediate or short-term functional changes. According to Peduzzi, these can include:

1.      Changes in molecules released by a chronic inflammatory condition that might chronically suppress a nerve’s conduction.

2.      Improved metabolic conditions, allowing previously dormant neurons to conduct.

3.      Remyelination – recoating an existing axon’s myelin sheath (would likely produce functional changes sooner than neuron replacement or growth, since the neural connection would already exist.)

4.      Transplanted cells (may form a connection between axons and dendrites that are located around the lesion.)

Therefore, by offering insights into the timing of a treatment’s effects on neural conduction - i.e., whether neural signals were reaching target muscles before a treatment was given, if they began passing through the spinal cord soon after treatment, or whether they first appeared after a longer duration - biofeedback might allow clinicians to deduce whether functional changes are most likely due to improvements in the above conditions, to repairs of existing connections, or to regeneration.

Finding Connections & Assisting Repairs

“I thought I was doing all that I could do, but I could do more!” 19-year-old Kadi De Haan (photo, above) said in amazement to her mother after her initial biofeedback session. “But I wouldn’t have known it without first seeing it on the computer screen.”

De Haan suffered an incomplete C-5/6 SCI in 2004. Beginning last June, she traveled to Russia four times to receive stem-cell treatments. Since her initial one, she’s noticed improvements in overall strength, hand and torso control, temperature sensations in the feet, and bladder sensations and control. But recent biofeedback at Mary Free Bed Hospital (Grand Rapids, Mich.) revealed that her forearms may have experienced additional, but unsuspected motor improvements.

Peduzzi collaborates with Portugal’s Carlos Lima, who surgically transplants regenerative-rich olfactory tissue from the patient back into the injury site.

“Lima finds improvement in patients soon after treatment.” Says Peduzzi, “However, many patients continue to improve more than a year later, suggesting that a much slower mechanism of action might also be occurring. Biofeedback has great potential for speeding up or maximizing this improvement.”

Treatments that stimulate existing but dormant nerves to conduct, or that repair existing neural connections, have a huge advantage over those that primarily aim to reconnect broken neural connections; the brain already knows in the former where to find its connection to a specific muscle. In the latter, it’s unlikely that new neural connections (resulting from axon regrowth) will reconnect a specific locus in the brain’s motor cortex to the muscle it controlled before SCI.

“The brain tries to initiate muscle contractions by firing specific neurons that it learned to use during development, but these neurons are no longer connected to the original target muscle.” Peduzzi explains. “However, a regenerative treatment might connect another neuron to this muscle. If the patient can find and fire this neuron, its signal would reach the muscle, which in turn might assist further repairs, such as myelination or guiding additional axonal growth.”

Therefore, biofeedback may offer four benefits:

·         Providing insights into which patients are good candidates for specific treatments,

·         Assisting patients to find and activate their new connections,

·         Helping to strengthen and control the signals that cross these connections, 

·         Stimulating and directing further repairs. 

After being surprised to discover that she possessed unsuspected abilities, De Haan said of biofeedback, “I think this is going to be really good for me!”

Conclusion

The body is a physical symphony requiring the precise orchestration of many functions. As such, the eventual success of regenerative science may depend on communication, cooperation, and collaboration…not only between scientists whose research offers solutions to individual sections of our musical score… but also between the brain, the spinal cord, and the body. Therefore, biofeedback – in tandem with regenerative treatments and rehabilitative medicine – may be the conductor that’s needed to allow our physical symphony to again play its music to its full potential. 

Adapted from article appearing in July 2007 Paraplegia News (For subscriptions, call 602-224-0500) or go to http://www.pvamagazines.com/pnnews/) .