What’s in the web for family physicians - neuroplasticity

Sio-pan Chan 陳少斌，Wilbert WB Wong 王維斌，Alfred KY Tang 鄧權恩

Neuroplasticity is defined as the ability of the nervous system to change its activity in response to intrinsic or extrinsic stimuli by reorganising its structure, functions, or connections to compensate for brain injuries or new environmental challenges. The synaptic connections among the neurons in our brains and the grey matter can reorganise and remodel themselves in response to our changing needs. Studies have shown that there is a redistribution of grey matter in hippocampus of London taxi drivers acquiring the knowledge of the London's traffic layout compared to control. More studies have demonstrated that our brain is constantly changing and rewiring in response to repetitive externa stimuli, trainings and emotional stresses. Neurogenesis (the birth of new brain cells) has been proven to exist in the adult brain and will last far into old age. This new concept challenges the established dogma that the brain is structurally fixed once it has fully developed into an adult brain.

Neuroplasticity can help us in a positive way, e.g. learning new skills can improve our cognitive functioning and slow down aging. On the other hand, neuroplasticity can adversely affect our brain function by exhibiting dysuse atrophy in some areas. Furthermore, stress induced neuroplasticity plays a critical role in almost all mental disorders.

In the last two decades, the concept of neuroplasticity has revolutionalised the field of rehabilitation medicine. Neuroplasticity has greatly transformed our approaches, methodologies and treatment goals in rehabilitation treatment in patients with strokes, dementia, traumatic brain and spinal cord injuries. The concept of neuroplasticity is also widely applied in the fields of clinical psychology, psychiatry, neuroscience and many other specialties.

Broadly speaking, neuroplasticity can be divided into

Structural neuroplasticity

Structural plasticity is the brain's ability to change its neuronal connections. New neurons are constantly produced and integrated into the central nervous system throughout the life span in response to external stimuli such as learning. Structural neuroplasticity encompasses the brain's anatomical reorganisation, the changes of grey matter proportion or the synaptic strength in the brain. The hippocampal change of London taxi drivers is one of such example

Functional neuroplasticity

Functional plasticity is the brain's ability to move functions from a damaged area of the brain after trauma, to other undamaged areas. Existing neural pathways that are inactive or used for other purposes can take over and carry out functions that were lost because of the injury.

Application & examples of neuroplasticity:

Stroke and traumatic brain injury

The concept of neuroplasticity has completely revolutionalised the treatment goal and methodologies in treatment of stroke and traumatic brain injuries. Behavioural experience is the most potent modulator of brain plasticity. While there is substantial evidence for this principle in normal, healthy brains, the injured brain is particularly malleable. Based on the quantity and quality of motor experience, the brain can be reshaped after injury in either adaptive or maladaptive ways. This paper reviews selected studies that have demonstrated the neurophysiological and neuroanatomical changes that are triggered by motor experience, by injury, and the interaction of these processes. In addition, recent studies using new and elegant techniques are providing novel perspectives on the events that take place in the injured brain, providing a real-time window into post-injury plasticity. These new approaches are likely to accelerate the pace of basic research, and provide a wealth of opportunities to translate basic principles into therapeutic methodologies.

Phantom limb syndrome

Phantom limb syndrome is a notoriously difficult condition to treat. Traditional theories suggest that phantom limb pain arises from "maladaptive plasticity" whereby a change in the brain results in a negative (maladaptive) outcome. According to this theory, neighbouring body parts in the brain "invade " the missing hand area creating a signal mismatch that is interpreted as painful. Treatments attempting to reverse the invasion – such as mirror therapy, where the visual reflection of the intact hand aims to reinstate the missing hand’s brain representation – have had limited success. A new technique called transcranial direct current stimulation (tDCS) targeted towards brain activity in the missing hand area could lead to more profound phantom limb pain relief.

Chronic pain

Individuals who have chronic pain experience prolonged pain at sites that may have been previously injured, despite that the original injury has long recovered. 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 perception sensitisation. Chronic pain typically responses poorly to traditional analgesic therapy.

In this study, the researchers developed a pain reprocessing therapy (PRT) based on this understanding of primary chronic pain. Leading psychological interventions for pain typically present the causes of pain as multifaceted and aim primarily to improve functioning and secondarily to reduce pain. PRT emphasises that the brain actively constructs primary chronic pain in the absence of tissue damage and that reappraising the causes and threat value of pain can reduce or eliminate it. At the conclusion of the trial, a total of 33 of 50 patients randomised to PRT (66%), corresponding to 73% of the 45 patients who initiated PRT, were pain-free or nearly pain-free at posttreatment, compared with 10 of 51 patients (20%) in the placebo group and 5 of 50 patients (10%) in the usual care group.

Physical exercise delay Alzheimer's disease

Accumulating evidence indicates that exercise can improve learning and memory as well as attenuate neurodegeneration, including Alzheimer ’s disease (AD). In addition to improving neuroplasticity by altering the synaptic structure and function in various brain regions, exercise also modulates systems like angiogenesis and glial activation that are known to support neuroplasticity. Moreover, exercise helps to maintain a cerebral microenvironment that facilitates synaptic plasticity by enhancing the clearance of Amyloid-beta, one of the main culprits of AD pathogenesis.

Novel treatment of depression (ketamine)

In 2019, US Food and Drug Administration approved a novel antidepressant, Ketamine nasal spray, for treatment of resistant depression. Earlier studies had shown that ketamine is very effective in treatment resistant major depression as an non invasive alternative to ECT. Ketamine, (and most psychedelic drugs for that matter) are very potent agents to increase neuroplasticity. It is believed that the rapid action of ketamine in changing the plasticity of the brain, thereby making it more susceptible to re-wiring/anti-depressant therapy. Whether such use is appropriate or ethically acceptable is a different issue.

Transcranial magnetic stimulation treatment (TMS) and repetitive transcranial magnetic stimulation (rTMS) and a timeline of FDA approved applicable conditions

TMS or rTMS work by stimulating the brain directly with strong magnetic impulses to influence brain plasticity, Such impulses can be given continuously or intermittently and frequency can vary from high or low according to different protocol. The FDA first approved TMS for treatment of resistant major depressive disorder in 2008. Subsequently, Migraine with aura was approved in 2013 followed by obsessive compulsive disorder in 2017 and smoking cessation in 2021. More conditions will be added to the list as the technique continues to develop.

Translingual neurostimulation (TLNS) plus physical therapy for treatment of balance deficit

A prospective multicentre study to assess the safety and efficacy of TLNS plus physical therapy for the treatment of chronic balance deficit in mild to moderate brain injury patients,

it was concluded that there were significant improvements in balance in gait, in addition to headache, sleep quality and fall frequency were observed with TLNS plus targeted physical therapy compared with pariticipants who had a chronic balance deficit and had plateaued on prior convention physiotherapy. Similar results were reported for patients with balance deficit due to other neurological condition such as multiple sclerosis.