Neuromodulation is a process that changes the physiological states of neuronal networks. This represents one of the fundamental ways in which we define how the nervous system responds to a specific combination of sensory inputs. Although this concept is a normal and routine process in shaping how we respond to internal and external environmental clues, its popularity has risen substantially over the last decades. For example, one’s physiological state routinely defines one’s mood and therefore how we respond to food. We can see, or smell or taste food differently depending on whether we have only recently finished eating a large meal or have not eaten for a prolonged period of time. But the more recent interest in the concept of neuromodulation has become evident as a result of the scientific development of experimental and technological approaches to impose changes in the physiological states using chemical, electrical, visual and/or mechanical techniques to different tissues. For rehabilitative purposes some of the more popular approaches are to implant electrical devices to stimulate specific areas of the nervous system using either surgical or noninvasive techniques. Some of the strategies can result in almost immediate changes in physiological states which in effect changes how different neuronal networks are interconnected. Other strategies use the application of selected techniques repetitively to facilitate a more long term change in connectivity among neural networks. For example, this has become recognized as a significant facilitator of some type of learning. One of the most common strategies used in animal experiments has been to combine electrical and biochemical strategies to obtain more desirable results. More specifically, it has been demonstrated repeatedly that an animal that has been completely paralyzed from the thoracic area to the more caudal part of the body can be transformed to a state in which the experimental animal can generate full weight-bearing stepping of the hindlimbs within a matter of minutes. The mechanisms by which these physiological states occur, in most cases, remain relatively unclear. But it is clear that these changes can be imposed using a wide variety of physiological processes that can modulate neural conductivity at biological levels of organization ranging from ionic to systems and to the organismic level of neuromodulatory events. 

At this early stage in the recognition and development of these multidisciplinary biological events, it is evident that these transformations can be highly undesirable or desirable, thus making it essential that we understand in as much detail as possible the mechanisms that we are activating to modulate the physiological states that are most likely to result in highly positive results which can enable basic physiological dysfunctions to recover to a higher level of desirable functionality. At this early stage of our understanding of neuromodulation strategies, there appears to be two conceptual levels in play when observing significant levels of functional recovery. It seems rather certain that at least one phase of this neuromodulatory process is to impose a higher state of plasticity, perhaps, more like that which is present at the early stages in development. A second concept is that given the higher state of plasticity, it provides a physiological state that enables the transformation of higher functional levels the a use -dependent mechanisms which involve some aspect of training and learning as one might surmise based on the age old concept of those connections that are used more often tend to be reinforced, while those that are used more sparingly, be become less likely to be engaged in response to a given ensemble of stimuli.

Finally, we hypothesize that a critical concept to keep in mind when achieving the more optimal functional transformation is to take advantage of the neural control mechanisms that are intrinsic to the normal and impaired neural control mechanisms. Thus a basic principle that is most likely to achieve the most desirable results is to adhere to the basic design of the neural networks that enables it to function in such a highly state of automaticity. In effect, when there is some dysfunctional state and loss of some components of the neural networks, our rehabilitative processes should engage the intact control mechanisms that remain in the injured or somewhat dysfunctional state; that is, engage strategies that take advantage of the control mechanisms that are intrinsic to the remaining nervous system. An alternative is to impose changes in neural networks that can push the control mechanisms to become dependent on externally imposed stimuli. In these inducement mechanisms the body’s intrinsic control mechanisms are most likely to be much “smarter” after millions of years of evolution than the “identified” remarkable basic biological processes that are still only slowly being recognized by scientists. Is it likely that our engineering confidence can match these millions of years of evolution that has resulted in an amazingly clever system that can anticipate and execute actions that are most likely to result in a successful outcome that will result in survival of a specific overcome. Thus, our strategies are most likely to succeed when we are attempting to engage these strategies of automaticity that are most likely to translate an extremely complicated sensory environment, both externally and internally, continuously throughout one’s life.