Various apparently incompatible theories of hippocampal function have been proposed but integration is now needed. It is argued that the involvement of the hippocampus is most clearly seen when the animal needs to extrapolate beyond current sensory information. Such control can involve both the initiation of behaviour in the absence of appropriate sensory input and the inhibition of behaviour that might otherwise be triggered by current sensory input.

Our response to the commentators covers four general issues: (1) How useful is our proposed conceptualization of the real-life/laboratory controversy in terms of the contrast between the correspondence and storehouse metaphors? (2) What is the relationship between these two metaphors? (3) What are the unique implications of the correspondence metaphor for memory assessment and theory? (4) What are the nature and role of memory metaphors in memory research? We stress that the correspondence metaphor can be usefully exploited independent of the (...) real-life/laboratory controversy, but that a variety of other metaphors, including the storehouse, should also be utilized in order to more fully capture the myriad facets and functions of memory in everyday life. (shrink)

The research guided by the correspondence metaphor is lauded for its emphasis on functional analysis, but the term “correspondence” itself needs clarification. Of the two terms in the relationship, only one is well defined. It is suggested that behavior at acquisition needs to be analyzed and that molecular principles from the learning laboratory might be useful in doing so.

The distinction that Koriat & Goldsmith have drawn between laboratory and naturalistic research is largely valid, but the metaphor they have chosen to characterize the latter may not be optimal. The “correspondence” approach is vulnerable on conceptual grounds and is not applicable to significant portions of empirical research.

In spite of Stein and Glasier's justifiable conclusion that initial optimism concerning the immediate clinical applicability of neural transplantation was premature, there exists much experimental evidence to support the potential for incorporating this procedure into a therapeutic arsenal in the future. To realize this potential will require continued evolution of our knowledge at multiple levels of the clinical and basic neurosciences.

The concept of structure, operation, and functionality, as they may be understood by clinicians or researchers using neural transplantation techniques, are briefly defined. Following Stein & Glasier, we emphasize that the question of whether an intracerebral graft is really functional should be addressed not only in terms of what such a graft does in a given brain structure, but also in terms of what it does at the level of the organism.

Over the past two decades, research on neural transplantation in animal models of neurodegeneration has provided provocative in sights into the therapeutic use of grafted tissue for various neurological diseases. Although great strides have been made and functional benefits gained in these animal models, much information is still needed with regard to transplantation in human patients. Several factors are unique to human disease, for example, age of the recipient, duration of disease, and drug interaction with grafted cells; these need to (...) be explored before grafting can be considered a safe and effective therapeutic tool. (shrink)

Gray's neuropsychological model of consciousness uses a hierarchical feedback loop framework that has been extensively discussed by many others in psychology. This commentary therefore urges Gray to integrate with, or at least acknowledge previous models. It also points out flaws in his feedback model and suggests directions for further theoretical work.

Quantitative losses of memory content imply replicative processing; correspondence losses imply reconstructive processing. Research should focus on the relationship between these processes by obtaining accuracy- and quantity-based indicators of memory within the same framework. This approach will also yield information about the effects of task and individual-difference variables on loss and distortion, as well as the time course of each process.

Gene therapy approaches have great promise in the treatment of neurodegenerative disorders and malignant brain tumors. Neuwelt et al. review available viral-mediated gene therapy methods and their blood-brain-barrier (BBB) disruption delivery technique, briefly mentioning nonviral mediated gene therapy methods. This commentary discussed the BBB disruption delivery technique, viral and nonviral mediated gene therapy approaches to Parkinson's disease, and the potential use of antisense oligo to suppress malignant brain tumors.

By utilizing new information from both clinical and experimental (lesion, electrophysiological, and gene-activation) studies with animals, the anatomy underlying anterograde amnesia has been reformulated. The distinction between temporal lobe and diencephalic amnesia is of limited value in that a common feature of anterograde amnesia is damage to part of an comprising the hippocampus, the fornix, the mamillary bodies, and the anterior thalamic nuclei. This view, which can be traced back to Delay and Brion (1969), differs from other recent models in (...) placing critical importance on the efferents from the hippocampus via the fornix to the diencephalon. These are necessary for the encoding and, hence, the effective subsequent recall of episodic memory. An additional feature of this hippocampalanterior thalamic and the perirhinal–medial dorsal thalamic systems are compromised, leading to severe deficits in both recall and recognition. (shrink)

This commentary elaborates on Gray's conclusion that his neurophysiological model of consciousness might explain how consciousness arises from the brain, but does not address how consciousness evolved, affects behaviour or confers survival value. The commentary argues that such limitations apply to all neurophysiological or other third-person perspective models. To approach such questions the first-person nature of consciousness needs to be taken seriously in combination with third-person models of the brain.

Compositionality has been a central concept in linguistics and philosophy for decades, and it is increasingly prominent in many other areas of cognitive science. Its status, however, remains contentious. Here, I reassess the nature and scope of the principle of compositionality (Partee, 1995) from the perspective of psycholinguistics and cognitive neuroscience. First, I review classic arguments for compositionality and conclude that they fail to establish compositionality as a property of human language. Next, I state a new competence argument, acknowledging the (...) fact that any competent user of a language L can assign to most expressions in L at least one meaning which is a functiononlyof the meanings of the expression's parts and of its syntactic structure. I then discuss selected results from cognitive neuroscience, indicating that the human brain possesses the processing capacities presupposed by the competence argument. Finally, I outline a language processing architecture consistent with the neuroscience results, where semantic representations may be generated by a syntax‐driven streamandby an “asyntactic” processing stream, jointly or independently. Compositionality is viewed as a constraint on computation in the former stream only. (shrink)

This commentary reviews data supporting circuitry reconstruction, replacement neurotransmitters, and trophic action as mechanisms whereby transplants promote recovery of function. Issue is taken with the thesis of Sinden et al. that adequate data exist to indicate that reconstruction of hippocampal circuitry damaged by hypoxia with CA1 transplants is a confirmed mechanism whereby these transplants produce recovery. Sinden et al.'s and Stein & Glasier's proposal that there is definitive evidence showing that all transplants produce trophic effects is also questioned.

The transplantation of cholinergic neurons into the hippocampal formation has been well characterized. We describe our studies on the effects of cholinergic transplants in the retrosplenial cortex. These transplants were capable of ameliorating spatial navigation deficits in rats with septohippocampal lesions. In addition, we provide evidence for the modulation of transplanted neurons by the host brain.

Complementation and correction of a genetic defect with CNS manifestations lags behind gene therapy for inherited disorders affecting other organ systems because of shortcomings in delivery vehicles and access to the CNS. The effects of improvements in viral and nonviral vectors, coupled with the development of delivery strategies designed to transfer genetic material thoughout the CNS are being investigated by a number of laboratories in efforts to overcome these problems.

An active role for conscious processes in the production of behaviour is proposed, involving top level controls in a hierarchy of behavioural control. It is suggested that by inhibiting or sensitizing lower levels in the hierarchy conscious processes can play a role in the organization of ongoing behaviour. Conscious control can be more or less evident, according to prevailing circumstances.

As Gray insists, his comparator model proposes a brute correlation only – of consciousness with septohippocampal output. I suggest that the comparator straddles a feedback loop that boosts the activation ofnovelrepresentations, thus helping them feature in present or recollected experience. Such a role in organizing conscious contents would transcend correlation and help explain how consciousness emerges from brain function.

Neural cell transplants have been introduced in clinical practice during the last decade with mixed results, encouraged by success with simple animal models. This commentary is a reminder that although the ideas and techniques of transplantation appear simple, the variables involved in host-transplant integration still require further study. The field may benefit from a concerted, multidisciplinary approach.

The lesion and transplantation data cited by Sinden et al., when considered in tandem, seem to harbor an internal inconsistency, raising questions of false localization of function. The extrapolation of such data to cognitive impairment and potential treatment strategies in Alzheimer's disease is problematic. Patients with focal basal forebrain lesions (e.g., anterior communicating artery aneurysm rupture) might be a more appropriate target population.

Grafts of embryonic neural tissue into the brains of adult patients are currently being used to treat Parkinson's disease and are under serious consideration as therapy for a variety of other degenerative and traumatic disorders. This target article evaluates the use of transplants to promote recovery from brain injury and highlights the kinds of questions and problems that must be addressed before this form of therapy is routinely applied. It has been argued that neural transplantation can promote functional recovery through (...) the replacement of damaged nerve cells, the reestablishment of specific nerve pathways lost as a result of injury, the release of specific neurotransmitters, or the production of factors that promote neuronal growth. The latter two mechanisms, which need not rely on anatomical connections to the host brain, are open to examination for nonsurgical, less intrusive therapeutic use. Certain subjective judgments used to select patients who will receive grafts and in assessment of the outcome of graft therapy make it difficult to evaluate the procedure. In addition, little long-term assessment of transplant efficacy and effect has been done in nonhuman primates. Carefully controlled human studies, with multiple testing paradigms, are also needed to establish the efficacy of transplant therapy. (shrink)

Koriat & Goldsmith provide an excellent analysis of the flexibility of retrieval processes and how they are situationally dependent. I agree with their emphasis on functional considerations and argue that the traditional laboratory experiment motivates the subject to be accurate. However, I disagree with their strong claim that the quantity–accuracy distinction implies an essential discontinuity between traditional and naturalistic approaches to the study of memory.

The target article interprets current psychological research on everyday memory in terms of a correspondence metaphor. This metaphor is based on a reduction of everyday memory to autobiographical and eyewitness memory. This commentary focuses on everyday memory as it functions in activity. Viewed from this perspective, the joining of everyday memory to a correspondence metaphor is problematic. A more natural way to frame the processes of everyday memory is in terms of context, practice, and pragmatics.

Stein & Glasier suggest embryonic neural tissue grafts as a potential treatment strategy for Alzheimer's and Parkinson's disease. As an alternative, we suggest that the family of nerve growth factor-related neurotrophins and their trk (tyrosine kinase) receptors underlie cholinergic basal forebrain (CBF) and dopaminergic substantia nigra neuron degeneration in these diseases, respectively. Therefore, treatment approaches for these disorders could utilize neurotrophins.

We concur that basic research on the use of CNS grafts is needed. Two important model systems for functional studies of grafts are ignored by Stein & Glasier. In the first, reproductive function is restored in hypogonadal mice by transplantation of GnRH-synthesizing neurons. In the second, circadian rhythmicity is restored by transplantation of the suprachiasmatic nucleus.

Gene replacement therapy holds great promise in the treatment of many genetic CNS disorders. This commentary discusses the feasibility of gene replacement therapy in the unique context of the retina, with regard to: (1) the genetics of retinal neoplasia and degeneration, (2) available gene transfer technology, and (3) potential gene delivery vehicles.

The correspondence view of memory is not a metaphor. However, correspondence is the essential feature of the archaeology metaphor, which harks back to Freud and Neisser. A modern version of this metaphor and some of its implications are briefly described. The archaeology metaphor integrates the idea of stored traces in a nonmechanistic framework.

Koriat & Goldsmith propose that the correspondence metaphor captures the essence of everyday memory research. We suggest that correspondence is often not at issue because objective assessments of everyday events are frequently lacking. In these cases, other questions arise, such as how individuals evaluate the validity of memories and the significance they attach to those evaluations.

Gray's comparator model fails to provide an adequate explanation of consciousness for two reasons. First, it is based on a narrow definition of consciousness that excludes basic phenomenology and active functions of consciousness. Second, match/mismatch decisions can be made without producing an experience of consciousness. The model thus violates the sufficiency criterion.

Gray extrapolates from circuit models of psychopathology to propose neural substrates for the contents of consciousness. I raise three concerns: knowledge of synaptic arrangements may be inadequate to fully support his model; latent inhibition deficits in schizophrenia, a focus of this and related models, are complex and deserve replication; and this conjecture omits discussion of the neuropsychological basis for the contents of the unconscious.

In contrast to its aims, Koriat & Goldsmith's article vividly demonstrates(1) the complementarity of ecological and traditional approaches and (2) the difficulty of characterising the growing diversity of memory research with a single set of distinctions. Moreover, the contrast between correspondence and storehouse metaphors is important enough to stand alone without reference to an everyday/laboratory controversy, which is neither acute nor necessary.

The function of memory is to allow past experience to subserve present goal-oriented thought and action. The defining characteristic of goal-oriented approach/avoidance is value. Value lies beyond the reproductive conception of memory that is basic to both metaphors discussed in Koriat & Goldsmith's target article. Functional memory requires a quite different metaphor, for which a grounded theory is available.

The process-dissociation procedure was developed to separate the controlled and automatic contributions of memory. It has spawned the development of a host of new measurement approaches and has been applied across a broad range of fields in the behavioral sciences, ranging from studies of memory and perception to neuroscience and social psychology. Although it has not been without its shortcomings or critics, its growing influence attests to its utility. In the present article, we briefly review the factors motivating its development, (...) describe some of the early applications of the general method, and review the literature examining its underlying assumptions and boundary conditions. We then highlight some of the specific issues that the methods have been applied to and discuss some of the more recent applications of the procedure, along with future directions. (shrink)

Within Piaget there is an implicit theory of the development of explicit memory. It rests in the dynamical trajectory underlying the development of causality, object, space and time – a complex (COST) supporting a symbolic relationship integral to the explicit. Cassirer noted the same dependency in the phenomena of aphasias, insisting that a symbolic function is being undermined in these deficits. This is particularly critical given the reassessment of Piaget’s stages as the natural bifurcations of a self-organizing dynamic system. The (...) elements of a theoretical framework required to support explicit memory are developed, to include, (1) the complex developmental trajectory supporting the emergence of the explicit in Piaget, (2) the concrete dynamical system and the concept of a non-differentiable time contained in Bergson’s theory required to support a conscious, as opposed to an implicit remembrance, (3) the relation to current theories of amnesia, difficulties posed by certain retrograde amnesic phenomena, the role of the hippocampus and limitations of connectionist models, (4) the fact that nowhere in this overall framework does the loss of explicit memory imply or require the destruction of experience “stored in the brain.”. (shrink)

Starting from Marr's ideas about levels of explanation, a theory of the data structures and access processes in human memory is demonstrated on 10 tasks. Functional characteristics of human memory are captured implementation-independently. Our theory generates a multidimensional task classification subsuming existing classifications such as the distinction between tasks that are implicit versus explicit, data driven versus conceptually driven, and simple associative (two-way bindings) versus higher order (threeway bindings), providing a broad basis for new experiments. The formal language clarifies the (...) binding problem in episodic memory, the role of input pathways in both episodic and semantic (lexical) memory, the importance of the input set in episodic memory, and the ubiquitous calculation of an intersection in theories of episodic and lexical access. (shrink)

Gray has expanded his account of schizophrenia to explain consciousness as well. His theory explains neither phenomenon adequately because he treats individual minds in isolation. The primary function of consciousness is to permit high level interactions with other conscious beings. The key symptoms of schizophrenia reflect a failure of this mechanism.

It is accepted that “primary awareness” may emerge from the integration of two classes of information. It is unclear, however, why this cannot take place within the comparator rather than in conjunction with feedback to the perceptual systems. The model has plausibility in relation to the continuity of conscious experience in the normal waking state and may be extended to encompass certain aspects of the “sense of self” which are frequently disrupted in psychotic patients.

Perspective and reflection have each been considered in some way basic to phenomenal consciousness. Each has possible evolutionary value, though neither seems sufficient for consciousness. Consider an account of consciousness in terms of the combination of perspective and reflection, its relationship to the problem of other minds, and its capacity to inherit evolutionary explanation from its components.

Gray's account is remarkable in its depth and scope but too little attention is paid to poor correspondences with the literature on hippocampal/subicular damage, the theta rhythm, and novelty detection. An alternative account, focusing on hippocampal involvement in organizing memories in a way that makes them accessible to conscious recollection but not in access to consciousness per se, avoids each of these limitations.

Gray hypothesizes that the contents of consciousness correspond to the outputs of a subicular (hippocampal/temporal lobe) comparator that compares the current state of the organism's perceptual world with a predicted state. I argue that Gray has identified a key contributing system to conscious awareness, but that his model is inadequate for explaining how conscious contents are generated in the brain. An alternative model is offered.

Drawing on previous models of anxiety, intermediate memory, the positive symptoms of schizophrenia, and goal-directed behaviour, a neuropsychological hypothesis is proposed for the generation of the contents of consciousness. It is suggested that these correspond to the outputs of a comparator that, on a moment-by-moment basis, compares the current state of the organism's perceptual world with a predicted state. An outline is given of the information-processing functions of the comparator system and of the neural systems which mediate them. The hypothesis (...) appears to be able to account for a number of key features of the contents of consciousness. However, it is argued that neitherthis nor any existing comparable hypothesis is yet able to explain why the brain should generate conscious experience of any kind at all. (shrink)