Composite Brains: Toward a Systems Theory of Neural Reconstruction

Abstract

The results of uncontrolled, open-label clinical trials indicate that reconstructive cellular therapies have the capacity to produce meaningful functional improvements in patients with brain disorders. However, the transplantation of fetal cells has not progressed to viable best practice treatment for any brain disorder. A conceptual approach, referred to as the Repair Model, has served as a useful heuristic for initiating research in the field and guiding the development of new practices. Analysis of evidence for the treatment of Parkinson's disease indicates that recovery following neural grafting is a complex process influenced by factors beyond the replacement of neurons. An alternative approach, the Composite Brain Model, is outlined to address limitations of the Repair Model. A hierarchical, open-system model is proposed, which aims to track the interactions between the grafted cells, the host brain, and the environment. The Composite Brain Model emphasizes the importance of the interactions between the patient, their physical and social environment, and the provision of rehabilitation during recovery. It is proposed that the Composite Brain Model is useful in providing an alternative perspective for research, theory building, and practice.

Stem Cell Therapy for Parkinson’s disease: Are Double-Blind Randomized Control Trials the Best Design for Quantifying Therapy Outcomes?

“…There is now strong evidence in animal studies that synaptic plasticity occurs at a cellular level and the brain can learn new ways to perform functions that have been disrupted with surgery, disability and brain injury [53]. This appears to be enhanced by enabling animals and people to practice in enriched environments that afford therapy experts, equipment, environmental conditions, rewards and a supportive atmosphere that maximizes positive recovery [26,43]. Functional connectivity following brain damage, brain surgery or stem cell therapy could be promoted through goal directed practice, gait retraining, hand rehabilitation and progressive resistance strength training and other "exercises" and by structuring the environment and the tasks they perform.…”

“…The CBM proposes a hierarchically organised, open system which explicitly includes the patient as a person living in an actual physical and social environment. There are reciprocal interactions among the constituent elements of the hypothesised system [26] as indicated in the diagram below.…”

“…Graft ↔ Host Brain ↔ Person with Graft ↔ Environment It is hypothesised that each level of the neuraxis the circuitry of the host brain is shaped by interacting influences from both the graft and the environment through both direct and polysynaptic pathways [26]. Evidence from pre-clinical studies indicates that the host system as a whole and the cells constituting the graft respond to environmental stimuli, and have been shown to participate in learning processes [41][42][43].…”

“…The Composite Brain Model [CBM] [26] was formulated as an alternative conceptual approach to the currently dominant understanding of the recovery process following neural grafts. The CBM postulates that intracerebral transplantation does not restore impaired brains to their premorbid states, but rather creates a new kind of "composite" structure, with the grafted cells enhancing the overall neural plasticity of the impaired host brain [40].…”

“…By controlling for sources of bias and confounding extraneous variables RCTs ensure the internal validity of the evaluation process [21]. The ideal design for conducting an RCT is the double-blind, placebo controlled, prospective trial where neither the recipients of the therapy, primary carers nor the assessors of the outcomes were aware of the exposure of the participants to the active or the control treatment [24][25][26].…”