Part 2: Applications: Traumatic Brain Injury Research, Treating Brain Injury, Chronic Pain, Phantom Limbs, Vision and Sensory Prostheses

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The adult brain is not entirely “hardwired” with fixed neuronal circuits, and there are many instances of cortical and subcortical rewiring of neuronal circuits in response to training as well as in response to injury.

There is solid evidence that neurogenesis (birth of brain cells) occurs in the adult, mammalian brain, and such changes can persist well into old age (Rakik, 2002).

Although the evidence for neurogenesis is mainly restricted to the hippocampus and olfactory bulb, current research has revealed that other parts of the brain, including the cerebellum, may be involved as well (Ponti, Peretto and Bonfanti, 2008).

However, the degree of rewiring induced by the integration of new neurons in the established circuits is not known, and such rewiring may well be functionally redundant (Franca, 2018).

There is now ample evidence for the active, experience-dependent reorganisation of the synaptic networks of the brain involving multiple interrelated structures including the cerebral cortex (e.g. Wolff et al., 1995; Holmaat and Svoboda, 2009; Lendvai et al., 2000).

The specific details of how this process occurs at the molecular and ultrastructural levels are topics of active neuroscience research. The way experience can influence the synaptic organisation of the brain is also the basis for a number of theories of brain function including the general theory of mind and Neural Darwinism.

The concept of neuroplasticity is also central to theories of memory and learning that are associated with experience driven alteration of synaptic structure and function in studies of classical conditioning in invertebrate animal models such as Aplysia.

Neuroplasticity makes our brain extremely resilient. It is the process by which all permanent learning takes place in our brain, such as playing a musical instrument or mastering a different language (Hampton, 2015).

It also enables people to recover from stroke, injury, and birth abnormalities, overcome autism, ADD and ADHD, learning disabilities and other brain deficits, overcome addictions and depression and reverse obsessive compulsive patterns (Hampton, 2015).

Neuroplasticity has significantly far reaching implications and possibilities for almost every aspect of human life and culture from education to medicine and it’s limits are not yet known. However, the nature of neuroplasticity, which makes your brain amasingly resilient, also makes it vulnerable to outside and internal, usually unconscious, influences (Hampton, 2015).

In his book ‘The Brain That Changes Itself: Stories of Personal Triumph from the Frontiers of Brain Science’, Norman Doidge calls this the “plastic paradox.”

Traumatic Brain Injury Research

Randy Nudo’s group found that if a small stroke (an infarction) is induced by obstruction of blood flow to a portion of a monkey’s motor cortex, the part of the body that responds by movement moves when areas adjacent to the damaged brain area are stimulated.

In one study, intracortical microstimulation (ICMS) mapping techniques were used in nine normal monkeys.

Some underwent ischemic-infarction procedures and the others, ICMS procedures.

The monkeys with ischemic infarctions retained more finger flexion during food retrieval, and after several months this deficit returned to preoperative levels.

With respect to the distal forelimb representation, “postinfarction mapping procedures revealed that movement representations underwent reorganisation throughout the adjacent, undamaged cortex” (Barbay et al., 2003).

Understanding of interaction between the damaged and undamaged areas provides a basis for better treatment plans in stroke patients.

Current research includes the tracking of changes that occur in the motor areas of the cerebral cortex as a result of a stroke, and thus, events that occur in the reorganisation process of the brain can be ascertained.

Nudo is also involved in studying the treatment plans that may enhance recovery from strokes, such as physiotherapy, pharmacotherapy and electrical-stimulation therapy.

Adult brains have the ability to change as a result of injury but the extent of the reorganisation depends on the extent of the injury.

His recent research focuses on the somatosensory system, which involves a sense of the body and its movements using many senses.

Usually, damage of the somatosensory cortex results in impairment of the body perception. Kaas’ research project is focused on how these systems – somatosensory, cognitive and motor systems, respond with plastic changes resulting from injury.

One recent study of neuroplasticity involves work done by Dr. Donald Stein (Stein, 2008).

This was the first treatment in 40 years that had significant results in treating traumatic brain injuries while also incurring no known side effects and being cheap to administer.

Dr. Stein noticed that female mice seemed to recover from brain injuries better than male mice, and that at certain points in the estrus cycle, females recovered even better.

This difference may be attributed to different levels of progesterone, with higher levels of progesterone leading to the faster recovery from brain injury in mice. However, clinical trials showed progesterone offers no significant benefit for traumatic brain injury in human patients (Skolnick et al., 2014; Stein and Wright, 2010).

Treatment of Brain Injury

A surprising consequence of neuroplasticity is that the brain activity associated with a given function can be transferred to a different location, and this can result from normal experience and also occurs in the process of recovery from brain injury.

Neuroplasticity is the fundamental issue that supports the scientific basis for treatment of acquired brain injury with goal-directed experiential therapeutic programs in the context of rehabilitation approaches to the functional consequences of the injury.

Neuroplasticity is gaining popularity as a theory that, at least in part, explains improvements in functional outcomes with physical therapy post-stroke.

Rehabilitation techniques that are supported by evidence which suggest cortical reorganisation as the mechanism of change include:

  • Constraint induced movement therapy
  • Functional electrical stimulation
  • Treadmill training with bodyweight support
  • Virtual reality therapy

Robot assisted therapy is an emerging technique, which is also hypothesized to work by way of neuroplasticity, though there is currently insufficient evidence to determine the exact mechanisms of change when using this method (Tolentino and Young, 2011).

One group has developed a treatment that includes increased levels of progesterone injections in brain-injured patients.

“Administration of progesterone after traumatic brain injury (TBI) and stroke reduces edema, inflammation, and neuronal cell death, and enhances spatial reference memory and sensory motor recovery” (Cutler et al., 2005).

In a clinical trial, a group of severely injured patients had a 60% reduction in mortality after three days of progesterone injections (Stein, 2008).

As can be gathered, from both the above and the previous section, there having been inconsistent conclusions regarding the efficacy of progesterone in traumatic brain injury treatment for human patients.

Further, a study published in the New England Journal of Medicine in 2014 detailing the results of a multi-center NIH-funded phase III clinical trial of 882 patients found that treatment of acute traumatic brain injury with the hormone progesterone provides no significant benefit to patients when compared with placebo (Emory health sciences, 2014).

Chronic Pain

Individuals who suffer from chronic pain experience prolonged pain at sites that may have been previously injured, yet are otherwise currently healthy.

This phenomenon is related to neuroplasticity due to a maladaptive reorganisation of the nervous system, both peripherally and centrally.

During the period of tissue damage, noxious stimuli and inflammation cause an elevation of nociceptive input from the periphery to the central nervous system.

Prolonged nociception from the periphery then elicits a neuroplastic response at the cortical level to change its somatotopic organisation for the painful site, inducing central sensitisation (Maihofner and Seifert, 2011).

For instance, individuals experiencing complex regional pain syndrome demonstrate a diminished cortical somatotopic representation of the hand contralaterally as well as a decreased spacing between the hand and the mouth (Birklein et al., 2003).

Additionally, chronic pain has been reported to significantly reduce the volume of grey matter in the brain globally, and more specifically at the prefrontal cortex and right thalamus (Apkarian et al., 2004).

However, following treatment, these abnormalities in cortical reorganisation and grey matter volume are resolved, as well as their symptoms.

Similar results have been reported for:

  • Phantom limb pain (Birbaumer et al., 2001)
  • Chronic low back pain (Braun et al., 1997)
  • Carpal tunnel syndrome (Napadow et al., 2006)

Application in Phantom Limbs

An interesting phenomenon involving plasticity of cortical maps is the phenomenon of phantom limb sensation.

Phantom limb sensation is experienced by people who have undergone amputations in hands, arms and legs, but it is not limited to extremities. Although the neurological basis of phantom limb sensation is still not entirely understood, it is believed (e.g. Flor, 2003) that cortical reorganisation plays an important role (Doidge, 2007).

A diagrammatic explanation of the mirror box: a patient places the intact limb into one side of the box (in this case the right hand) and the amputated limb into the other side, and due to the mirror, the patient sees a reflection of the intact hand where the missing limb would be and thus receives artificial visual feedback that the “resurrected” limb is now moving when they move the good hand.

In the phenomenon of phantom limb sensation, a person continues to feel pain or sensation within a part of their body that has been amputated.

This is strangely common, occurring in 60–80% of amputees (Beaumont, Malouin and Mercier, 2011).

An explanation for this is based on the concept of neuroplasticity, as the cortical maps of the removed limbs are believed to have become engaged with the area around them in the postcentral gyrus.

This results in activity within the surrounding area of the cortex being misinterpreted by the area of the cortex formerly responsible for the amputated limb.

The relationship between phantom limb sensation and neuroplasticity is a complex one.

In the early 1990s V.S. Ramachandran theorised that phantom limbs were the result of cortical remapping.

However, in 1995 Herta Flor and her colleagues demonstrated that cortical remapping occurs only in patients who have phantom pain (Flor e al., 1995).

Her research showed that phantom limb pain (rather than referred sensations) was the perceptual correlate of cortical reorganisation (Flor, 2003).

This phenomenon is sometimes referred to as maladaptive plasticity.

In 2009 Lorimer Moseley and Peter Brugger carried out a remarkable experiment in which they encouraged arm amputee subjects to use visual imagery to contort their phantom limbs into impossible configurations.

Four of the seven subjects succeeded in performing impossible movements of the phantom limb.

This experiment suggests that the subjects had modified the neural representation of their phantom limbs and generated the motor commands needed to execute impossible movements in the absence of feedback from the body (Moseley and Brugger, 2009).

The authors stated that: “In fact, this finding extends our understanding of the brain’s plasticity because it is evidence that profound changes in the mental representation of the body can be induced purely by internal brain mechanisms—the brain truly does change itself.”


For decades, researchers assumed that humans had to acquire binocular vision, in particular stereopsis, in early childhood or they would never gain it.

However in recent years, successful improvements in people with amblyopia, convergence insufficiency or other stereo vision anomalies have become prime examples of neuroplasticity, and binocular vision improvements and stereopsis recovery are now active areas of scientific and clinical research (Maino, 2009; Vedamurthy et al., 2012; Hess and Thompson, 2013).

Sensory Prostheses

Neuroplasticity is also involved in the development of sensory function.

The brain is born immature and it adapts to sensory inputs after birth.

In the auditory system, congenital hearing impairment, a rather frequent inborn condition affecting 1 of 1000 newborns, has been shown to affect auditory development, and implantation of a sensory prostheses activating the auditory system has prevented the deficits and induced functional maturation of the auditory system (Kral and Sharma, 2012).

Due to a sensitive period for plasticity, there is also a sensitive period for such intervention within the first 2-4 years of life. Consequently, in prelingually deaf children, early cochlear implantation, as a rule, allows the children to learn the mother language and acquire acoustic communication (Kral and O’Donoghue).

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