Sunday 18 February 2018

Ideological Entrainment vs Interventional Possibility in Brain Disease

by Denis Larrivee


Growing up in an era of rapid scientific advance it is possible to see the currents and ebbs that mark preferred ways of thinking in a way that cannot be captured post-hoc about older eras. Yet it is also a characteristic of this kind of personal intimacy that the dominance of its principal tenets makes the masking of idea rivulets barely perceptible. Cases in point are themes now emerging from the neuroscientific groundswell that has reached decibels not heard since the Concorde’s sonic booms. Cellular levels of nerve understanding that were its first love now comprise but a small fraction of the knowledge since accumulated, which has grown to include global state interactions, tasking networks, dynamical activity patterns, and large-scale circuits, just to name several. For one of these themes, the working out of underlying mechanisms of brain diseases, the newly accumulated knowledge has assisted not only in sketching a panorama of the brain’s geographical terrain, but it has also acted as a springboard for investigative strategies intended to unravel the complexities of its operation gone awry. A leading premise that underpins much of this latter work, and frequently expressed by former director of NIMH Tom Insel, is that of disease modified circuit architectures. In this manner of thinking normal brain operation is structured by information flow along defined paths of transmission analogous to electrical circuits; hence, brain diseases, as seen by this model, are as the result of inexact, incorrect, or deficient manners of forming these routes. For example, OCD behaviors are thought to be the result of circuit rewiring in striatal - as you may guess - nerve circuits
     Influenced by this conception, and developing in parallel with strategies for approaching circuit based, disease models, is an extensive and expanding research domain that is devoted to characterizing neural network operation. Networks, by way of explanation, are the background frameworks on which the individual circuits are situated.   The evolution of the network and circuit based research enterprise that is directed to disease study is illustrative for the way in which a battery of widely differing experimental technologies can be entrained to focus on a single, powerful, conceptual image to elucidate the details that structure the concept. However, it is also illustrative of how the power of a single image of brain operation can so entrain the process of hypothesis construction that avenues to other explanatory visions may be shielded from discovery. Thus, it is also a testimony to the ever-receding geographical horizon of brain complexity, or in the cosmic metaphors of the director of Paris’s Brain and Spine Institute, Yves Agid, more like that of galactic intervals, that needs to become amenable to characterization in order to yield fruitful forms of neurological intervention for brain disease therapy. Something of this discrepancy between the knowledge gleaned in early stages of neuroscience with its limited relevance to medical intervention, and the receding horizon of therapeutic goal setting, is now seen in treatments intended to minister to the patient who exhibits some form of conscious impairment. Conscious impairment is increasing in prevalence, and it is, therefore, highly desirable to have treatment options. Among other factors affecting this situation, improved emergency room care and life-saving technologies have increased the survival rate of patients who experienced an incident of brain damage. Such patients may and often do become comatose, a condition predisposed by stroke. Coupled with population demographics that are trending grayward, the improved medical scenario thus portends a distinct upward swing in the incidence of this type of brain disease.
It is at this level of assessment, however, where the current methodological and technological approaches not only show the great amount of knowledge that has been accumulated, with its improved understanding that may be used to better patient oversight, but where also the sort of information provided offers still just a little glimmer of the physical features that contribute to patient status; hence, where the challenge to the prevailing, politically correct science, arises. It thus reveals a horizon yet to be reached at a conceptual level with regard to patient physiology, and at a clinical level with regard to determining the salient features needed in order to therapeutically intervene. These current methods now largely used for consciousness assessments, for example, no longer rely predominantly on behavioral monitoring, instead turning to imaging technologies that make it possible to make objective inferences that may complement behavioral assessments. Their objective reliability thus offers to the physician the opportunity for a presumed closer correspondence to patient status than might be availed from a patient either incapable of knowing, communicating, or of reliably assessing – and perhaps even being liminally influenced by – physician monitoring. Yet their improved insight into status also metaphorically replicates the consciousness paradigm that is awaiting the next upward stage in its trajectory.
Despite significant advances in the ability to assess consciously impaired patients, however, the parameters actually monitored by these technologies do not directly reveal information that is salient with regard to consciousness, particularly the patient’s sense of awareness. This latter remains a distant horizon for objective inferences diagnostically and prognostically. It is with the intention of managing the semantic content to be inferred from brain activity, as opposed to simple inferences about brain state activation, that even more qualitatively new ground has been explored to elucidate what brain states actually mean. These additional approaches have yet to see entry into the medical setting as viable medical devices or device/approaches. Nonetheless they afford the prospectus for revealing distinguishing features of brain activity patterns that can be correlated with objective features of the world. For the consciously impaired patient these new technologies begin to offer the promise of communication at a level more closely approximating the sorts of symbolical representations that humans use to convey conceptual content to others. The answers to the questions of what the patient may be thinking, how well or poorly he is doing so, and what may be affecting this are, therefore, made more tractable than in the solely qualitative answers obtained from the current medical imaging analysis alone. These latter reveal a capacity for consciousness, while not quantitatively indicating the level at which that capacity may be used.
On the other hand, while these new technologies may offer significant qualitative advances to the physician in the type of knowledge acquired, they do relatively little to explain either the mechanism that generates the particular form of brain activity that is being classified or what information, if any, is internally activated by the patient. This gap in understanding is revealing for again opening the spectrum of explanatory possibilities to a wider and, to date, largely unidentified property scope than is encompassed by strictly neuronal features. It is likely that representations are not, for example, the exclusive province of connectivity architectures; thus, they reveal the insufficiency of the circuit model as a conceptual device for brain operation. While it is clear that connectivity organization plays a very significant role in structuring representational activity it is much less clear that such activity is structured either solely by circuits, or confined only to circuits. Existing emphases on circuit based operation, that have the effect of entraining hypothesis building around it, therefore, like limit cycle attractors, leave research impoverished with regard to insights that may be better used to charting the terrain ahead. Importantly, they reveal that there are as yet many unknown features about how the brain functions to engage our subjective sense. It is this revelation, perhaps, that is most promissory – more so even than the possibility of ever new therapies helpful for treatment of tragic personal scourges – that the human person is a special mystery always awaiting new discovery.

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