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.

Eichenbaum et al. (1994a) hypothesized that perceptually distinct items and the relations among them are processed sequentially by the parahippocampal region and the hippocampal formation, respectively. Predictions based solely on their model's sequential-processing feature might prove easier to disconfirm than those based on its representational features. Two such predictions are discussed: (1) double dissociations should be impossible following hippocampal vs. parahippocampal lesions, and (2) hippocampal lesions should not exacerbate impairments that follow complete parahippocampal lesions.

It is often presumed that effects of neural tissue transplants are due to release of neurotransmitter. In many cases, however, effects attributed to transplants may be related to phenomena such as trophic effects mediated by glial cells or even tissue reactions to injury. Any conclusion regarding causation of graft effects must be based on the control groups or other comparisons used. In human clinical studies, for example, comparing the same subject before and after transplantation allows for many interpretations of the (...) causes of clinical changes. (shrink)

Despite reports of recovery of function after neural transplantation, the biological interactions between transplanted neurons and the host brain that are necessary to mediate recovery are unclear at present. One source of confusion is in the variety of models and protocols used in these studies. It is suggested that multisite experimentation using standard protocols, models, and recovery criteria would be helpful in moving neural transplantation from the laboratory to the clinic.

The spinal cord provides an alternative model for nerve tissue grafting experiments. Anatomo-functional correlations are easier to make here than in any other region of the CNS because of a direct implication of spinal cord neurons in sensorimotor activities. Lesions can be easily performed to isolate spinal cord neurons from descending inputs. The anatomy of descending monoaminergic systems is well defined and these systems offer a favourable paradigm for lesion-graft experiments.

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)

Studies on the snailMelampusreveal that connectivity is crucial to the survival of transplanted ganglia. Transplanted CNS ganglia can innervate targets or induce supernumerary structures. Neuron survival is optimized by the neural incorporation that occurs when a transplanted ganglion is substituted for an excised ganglion. Better provision for the trophic requirements of neurons will improve the success of mammalian fetal transplants.

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

Gray's integration of the different levels of description and explanation in his theory is problematic: The introduction of consciousness into his theorising consists of the mind-brain identity assumption, which tells us nothing new. There need not be correlations between levels of description. Gray's account does not extend beyond “brute” correlation. Integration must be achieved in a principled, mutually constraining way.

The communicative aspects of the contents of consciousness are analyzed in the framework of a neural network model of animal communication. We discuss some issues raised by Gray, such as the control of the contents of consciousness, the adaptive value of consciousness, conscious and unconscious behaviors, and the nature of a model's consciousness.

Parallel to Koriat & Goldsmith's accounting of human memory, there are two distinct approaches in animal learning. Behaviorist approaches focus on quantitative aspects of conditioned response probability, whereas cognitive and ethological approaches focus on qualitative aspects of how memory is used in real life. Moreover, in animal research these distinguishable measures of memory are dissociated in experimental amnesia.

Everyday memory tasks often require that researchers focus on output-bound measures of memory. As a result, nonmemorial processes (e.g., report option and grain size) may influence recall accuracy. These nonmemorial processes, usually eliminated by laboratory researchers, have the potential to explain some anomalous results and may even be useful to enhance everyday recollection.

The novel correspondence metaphor outlined by Koriat & Goldsmith offers important advantages for studying critical issues of memory-accuracy. It also fits well with the current emphasis on the reconstructive nature of memory and on the role of cognitive, metacognitive, and motivational factors in memory performance. These positive features notwithstanding, the storehouse/correspondence framework faces potential perils having to do with its implied linkage to the laboratory/real-life controversy and its proposal of studying correspondence issues in isolation from memory phenomena captured by the (...) storehouse paradigm. (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)

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)

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)

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.

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.

It is well established that neural grafts can exert functional effects on the host animal by a multiplicity of different mechanisms – by diffuse release of trophic molecules, neurohormones, and deficient neurotransmitters, as well as by growth and reformation of neural circuits. Our challenge is to understand how these different mechanisms complement each other.

To avoid teleological interpretations, it is important to make a distinction between functions and uses of consciousness, and to address questions concerning the consequences of consciousness. Assumptions about the phylogenetic distribution of consciousness are examined. It is concluded that there is some value in identifying consciousness an exclusively human attribute.

This commentary deals with criteria for assigning truth values to memory contents. A parallel with perception shows how truth values can be assigned by considering subjects' beliefs about the truth state of the memory content. This topic is also relevant to the study of processes of control over retrieval.

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.

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.

To explore the mechanism of sensation correlations between EP component amplitude and signal detection indices were studied. The time of sensation coincided with the peak latency of those EP components that showed a correlation with both indices. The components presumably reflected information synthesis in projection cortical neurons. A mechanism providing the synthesis process is proposed.

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 work of Sinden et al. suggests that it may be possible to produce improvement in the areas of brain function by transplanting brain tissue. What appears to be the limiting factor is not the complexity of the mental process under consideration but the discreteness of the lesion which causes the impairment and the appropriateness and accuracy of placement of the grafted tissue.

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)

It is a consensus that familiarity and recollection contribute to episodic recognition memory. However, it remains controversial whether familiarity and recollection are qualitatively distinct processes supported by different brain regions, or whether they reflect different strengths of the same process and share the same support. In this review, I discuss how adapting standard human recognition memory paradigms to rats, performing circumscribed brain lesions and using receiver operating characteristic methods contributed to solve this controversy. First, I describe the validation of the (...) animal ROC paradigms and report evidence that familiarity and recollection are distinct processes in intact rats. Second, I report results from rats with hippocampal dysfunction which confirm this finding and lead to the conclusion that the hippocampus supports recollection but not familiarity. Finally, I describe a recent study focusing on the medial entorhinal cortex that investigates the contribution of areas upstream of the hippocampus to recollection and familiarity. (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'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.

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.

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.

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.

The study of memory is witnessing a spirited clash between proponents of traditional laboratory research and those advocating a more naturalistic approach to the study of “real-life” or “everyday” memory. The debate has generally centered on the “what” (content), “where” (context), and “how” (methods) of memory research. In this target article, we argue that the controversy discloses a further, more fundamental breach between two underlying memory metaphors, each having distinct implications for memory theory and assessment: Whereas traditional memory research has (...) been dominated by thestorehousemetaphor, leading to a focus on thenumberof items remaining in store and accessible to memory, the recent wave of everyday memory research has shifted toward acorrespondencemetaphor, focusing on theaccuracyof memory in representing past events. The correspondence metaphor calls for a research approach that differs from the traditional one in important respects: in emphasizing the intentional –representational function of memory, in addressing the wholistic and graded aspects of memory correspondence, in taking an output-bound assessment perspective, and in allowing more room for the operation of subject-controlled metamemory processes and motivational factors. This analysis can help tie together soine of the what, where, and how aspects of the “real-life/laboratory” controversy. More important, however, by explicating the unique metatheoretical foundation of the accuracy-oriented approach to memory we aim to promote a more effective exploitation of the correspondence metaphor inbothnaturalistic and laboratory research contexts. (shrink)