**6. Reconsidering lesions: AD and KS in top-down strategic analysis**

The promise of top-down analysis predicts that global organization is selectively impaired at intermediate and even higher levels of brain function, such as those now being investigated through the motor plan. Indeed, disturbances in the sense of self that mark schizophrenia, for example, in prodromal and acute stages, have led to the recognition of the loss of self as a core symptom [35] where both body ownershipa nd sense of agency are impacted [36]. Current evidence on how representational content of the self may be affected and how this may be linked to the body suggest, in fact, that it is mediated through the motor plan, which thereby offers a strategic investigative tool. Insight into the neural features that these results may implicate, for example, can be inferred from misattribution errors that are experimentally evoked in normal individuals and that appear to be pathologically exacerbated in schizophrenic individuals [37].

By extension, memory losses in AD and KS are in their broad features consistent with functional losses that have organismal bearing and that can be revealed through such top-down analysis. Accordingly, this volume represents an effort to forward an argument for global strategies that can be pursued in cognitive etiopathologies. It is a proposal that emerges from the intractability of reductive study faced with the incredible complexity of operation that is intrinsic to cognition. While lacking in the tangible manifestations that have come to mark genetic and molecular study, the reality of global operation is nonetheless manifestly evident. Moreover, it is a reality for which new investigative tools are emerging from research studies, such as the motor plan. Revelation of distinct functional differences in memory loss in diseases like AD and KS, therefore, can be expected to further options for global, top-down study.

*Redirecting Alzheimer Strategy - Tracing Memory Loss to Self Pathology*

sent only causal outcomes of organizational form.

need, seen, for instance, in goal directed activity.

is determined from the top down.

design, principle to be functional, which is to say that the explanation for the motor's function must include a dimension beyond that of the succession of internal events leading to functional output. This latter explanation, termed the "why" question, is significant for revealing that efficient causal interactions require the design principle as an a priori condition for their realization, hence, answers to the 'how' question repre-

This invocaton of design principle is significant for identifying the primary causal origin of a function. Rather than determined from below, the mechanistic steps emerge from a predetermined order that is critical for defining material composition and operation. Moreover, the elicited function—the motor's operation, for example—is framed within the context of global organismal need. Accordingly, the emergence of the function is fundamentally related to non-reductive, top-down effects that reflect two aspects of organismal operation; first, an organizational order that governs associations of larger-order complexes (e.g., evident in motifs and network analysis) and, second, a global requirement to satisfy organismal

Conceiving of neural function from this higher-order perspective—i.e, dynamically oriented and not static as in the conception of metabolites—has implications for considering the primacy of causes eliciting neural organization—not chiefly through the structuring of its anatomical features, where it is built from the bottom up, but as a dynamic and functional order that has a purposeful orientation, which

**5. Pursuing top-down strategy in autonomy and goal-directed behavior**

Viewed from the dynamic aspect of function, the order of causal priority is reversed where the chief influences underlying organization and performance are systemic and teleological. Lesions of higher-order neural functions, like memory, appear thereby as dysfunctional properties of global representations. Risk alleles, in this reading, and similar reductive approaches can be expected to offer little insight into cognitive operation at the level of neural constructs likely to be impaired in cognitive diseases. Investigations into cognition, instead, seem better directed when exploring the operation of extended networks that function as components of larger systemic or even global operations. By extension, lesions that may fruitfully reveal aspects of large-scale operation are more likely to involve systemic effects that are more closely apposed to global processes mediating organismal tasking. Models that define the source of this tasking, accordingly, are likely to be helpful for identifying the sorts of lesions that can be usefully exploited for cognitive study. Key features underwriting global cognition notably include those preserving existential independence and the integration of the organism as a whole, that is, those providing for autonomous existence [28]. Understood as a capacity, autonomy implicates dispositional qualities of self-recognition and self-directedness; that is, it invokes self-constructs that elicit higher order operations, which, accordingly, can be disrupted by cognitive disease. As one such higher order operation, for instance, memory is directly elicited by such self constructs in order to facilitate autonomy. Lesions of higher-order capacities like memory, which are evoked by global constructs, may thus

be usefully exploited for their properties and manner of elicitation [29, 30].

Emerging from the global operation of the brain, constructs like the self are clearly extraordinarily complex and in many respects seem less tangible than material constituents of reductive and low-level functions. Nonetheless, their organismal reality is clearly evident in manifestations of behavioral activity. For example, the association between a representation of the whole individual by his body and its

**8**

*Redirecting Alzheimer Strategy - Tracing Memory Loss to Self Pathology*
