Gray mistakenly thinks I have rejected the sort of theoretical enterprise he is undertaking, because, according to him, I think that "more data" is all that is needed to resolve all the issues. Not at all. My stalking horse was the bizarre (often pathetic) claim that no amount of empirical, "third-person point-of-view" science (data plus theory) could ever reduce the residue of mystery about consciousness to zero. This "New Mysterianism" (Flanagan, 1991) is one that he should want to combat as (...) vigorously as I have done. (shrink)

Robust theories concerning the connection between consciousness and brain function should derive not only from empirical evidence but also from a well grounded inind-body ontology. In the case of the comparator hypothesis, Gray develops his ideas relying extensively on empirical evidence, but he bounces irresolutely among logically incompatible metaphysical theses which, in turn, leads him to excessively skeptical conclusions concerning the naturalization of consciousness.

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.

The neural transplantation research described by Sinden and colleagues provides part of the rationale for the clinical application of neural transplantation. The authors are asked to clarify their view of the role of the cholinergic system in cognition, to address extrahippocampal damage caused by transient forebrain ischemia, and to consider the effects of delayed neural degeneration in their structure-function analysis.

Eichenbaum et al.'s (1994a) theory suffers from a lack of ecological validation. It is not at all clear why the hypothesized faculties would have evolved and what their adaptive value would be. I argue that hippocampal function can only be understood if the animal is seen in its natural context.

In addition to the scientific and medical issues surrounding the use of fetal tissue transplants, the ethical implications should be considered. Two major ethical issues are relevant. The first of these is whether this experimental procedure can be justified on the basis of potential benefit to the patient. The second is whether the use of tissue obtained from intentionally aborted fetuses can be justified in the context of historical and existing guidelines for the protection of human subjects. The separation of (...) ethical decisions from medical practice and scientific research is necessary to prevent the exploitation of innocent human life. (shrink)

Segmentalized consciousness in schizophrenia reflects a loss of the normal Gestalt organization and contextualization of perception. Grays model explains such segmentalization in terms of septohippocampal dysfunction, which is consistent with known neuropsychological impairment in schizophrenia. However, other considerations suggest that everyday perception and its failure in schizophrenia also involve prefrontal executive mechanisms, which are only minimally elaborated by Gray.

Neither the storehouse nor the correspondence metaphor is an appropriate conceptual framework for memory research. Instead a meaning-based account of human memory is required. The correspondence metaphor is an advance over previous suggestions but entails an oversimple view of “accuracy.” Freud's account of memory may provide a more fruitful approach to memory and meaning.

We raise three issues concerning the Eichenbaum, Otto & Cohen (1994) model. (1) We argue against the strict division of labor that Eichenbaum et al. attribute to neocortical and limbic regions. (2) We raise the possibility that the anterior and posterior portions of the hippocampus may be important for different types of information processing. (3) We argue that, rather than reflecting relational processing, different neural responses to “match” and “nonmatch” trials may relate to different required spatial responses.

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.

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.

Koriat & Goldsmith's abstract correspondence metaphor is unlikely to prove useful to memory science. It aims to motivate and inform the investigation of everyday memory, but that movement has prospered without it. The irrelevance of its competitor – the more concrete storehouse metaphor – as a guiding force in memory research presages a similar fate for the correspondence perspective.

Three experiments on neural grafting with adult rat hosts are described. Working memory impairments were produced by lesioning the hippocampus or severing its connections with the septum by ablating the fimbria-fornix. The results suggest that the survival and growth of a neural graft, whether an autograft or a xenograft, is not a necessary condition for functional recovery on a task tapping working memory.

In contrast to the views put forth by Stein & Glasier, we support the use of inbred strains of rodents in studies of the immunobiology of neural transplants. Inbred strains demonstrate homology of the major histocompatibility complex (MHC). Virtually all experimental work in transplantation immunology is performed using inbred strains, yet very few published studies of immune rejection in intracerebral grafts have used inbred animals.

Koriat & Goldsmith's distinction between encoding processes and metamnemonic decision processes is theoretically and practically important, as is their methodology for separating the two. However, their accuracy measure is a conditional statistic, subject to the unfathomable selection effects that have hindered analogous measures in the past. We also find their arguments concerning basic and applied research mostly beside the point.

Topics in Cognitive Science, Volume 13, Issue 1, Page 128-141, January 2021.

Koriat and Goldsmith clearly show the need for an alternative to the storehouse metaphor; however, the alternative metaphor they choose – the correspondence metaphor – is problematic. A more suitable one is the capacity metaphor.

Koriat & Goldsmith raise important questions about memory, but there is need for caution: first, if we define accuracy by output measures, there is a danger that a perfectly accurate memory can be nearly useless. Second, when we focus on correspondence, there is a danger that syntactic correspondence will be mistaken for historical truth.

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.

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.

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)

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.

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 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.

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.

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)

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)

Koriat & Goldsmith's distinction between the correspondence and storehouse metaphors is valuable for both memory theory and methodology. It is questionable, however, whether this distinction underlies the heated debate about so called “everyday memory” research. The distinction between experimental and naturalistic methodologies better characterizes this debate. I compare these distinctions and discuss how the methodological distinction, between experimental and naturalistic designs, could give rise to different theoretical approaches.

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.

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 correspondence view is consistent with a theory of direct remembering that assumes continuity between perception and memory. Two implications of direct remembering for correspondence are suggested. It is assumed that forgetting is exponential, and that remembering at one time is independent of factors influencing remembering at another. Elaboration of the correspondence view in the same terms as perception offers a novel approach to the study of memory.

Grafting embryonic brain tissue into the brain of patients with visual field loss due to cerebral lesions may become a method to restore visual function. This method is not without risk, however, and will only be considered in cases of complete blindness after bilateral occipital lesions, when other, risk-free neuropsychological methods fail.

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.

On the basis of neuropsychological evidence, it is clear that attention should be given a role in any model of consciousness. What is known about the many instances of dissociation between explicit and implicit knowledge after brain damage suggests that conscious experience might not be linked to a restricted area of the brain. Even if it were true that there is a single brain area devoted to consciousness, the subicular area would seem to be an unlikely possibility.

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.

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.

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.

A major problem in developing an effective gene therapy for the nervous system lies in understanding the principles that maintain or turn off the expression of genes following their transfer into the CNS.

A lesion to the brain is not necessary for a successful neural transplantation. Embryonic Purkinje cells placed on the surface of an uninjured adult cerebellum can develop and migrate into the host molecular layer. Both the Purkinje cells that migrated into the host cerebellum and those that remained in the graft were innervated by collateral sprouting of adult intact climbing fibers.

Gray unwisely melds together two distinguishable contributions of consciousness: one to epistemology, the other to evolution. He also renders consciousness needlessly invisible behaviorally.

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)

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)

Despite some clinical promise, using fetal transplants for degenerative and traumatic brain injury remains controversial and a number of issues need further attention. This response reexamines a number of questions. Issues addressed include: temporal factors relating to neural grafting, the role of behavioral experience in graft outcome, and the relationship of rebuilding of neural circuitry to functional recovery. Also discussed are organization and type of transplanted tissue, the of transplant viability, and whether transplants are really needed to obtain functional recovery (...) after brain damage. (shrink)

The responses displayed by an injured or diseased nervous system are complex. Some of the responses may effect a functional reorganization of the affected neural circuitry. Strategies aimed at the restoration of function, whether or not these involve transplantation, need to recognize the innate reactive capacity of the nervous system to damage. More successful strategies will probably incorporate, rather than ignore, the adaptive responses of the compromised neural systems.

In Gray's conjecture, mismatches in the subicular comparator and matches have equal prominence in consciousness. In rival cognitive views novelty and difficulty especially elicit more conscious modes of cognition and higher levels of self-regulation. The mismatch between Gray's conjecture and these views is discussed.