I argue that academic psychology’s quest to achieve scientific respectability by reliance on quantification and objectification is deeply flawed. Specifically, psychological theory typically cannot support prognostication beyond the binary opposition of “effect present/effect absent”. Accordingly, the “numbers” assigned to experimental results amount to little more than affixing names (e.g., more than, less than) to the members of an ordered sequence of outcomes. This, in conjunction with the conceptual under-specification characterizing the targets of experimental inquiry, is, I contend, a primary reason (...) why psychologists find it difficult to discriminate between competing, explanations of the effects of mind on behavior. Absent well-specified theory capable of enabling precise and detailed quantitative prediction, inferring underlying mental mechanisms from experimental outcomes becomes a difficult, if not impossible, task. (shrink)

This article builds on ideas presented in Klein (2015a) concerning the importance of a more nuanced, conceptually rigorous approach to the scientific understanding and use of the construct “memory”. I first summarize my model, taking care to situate discussion within the terminological practices of contemporary philosophy of mind. I then elucidate the implications of the model for a particular operation of mind – the manner in which content presented to consciousness realizes its particular phenomenological character (i.e., mode of presentation). Finally, (...) I discuss how the model offers a reconceptualization of the technical language used by psychologists and neuroscientists to formulate and test ideas about memory. (shrink)

Challenges the revised standard historiography on Wundt as a psychologist. Considers the concept of psychology as a natural science. Examines the relations between psychology and philosophy before and after 1900. Reflects on the notion of disciplinehood as it affects historical narratives.

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.

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.

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)

For focal neurodegenerative diseases or brain tumors, localized delivery of protein or genetic vectors may be sufficient to alleviate symptoms, halt disease progression, or even cure the disease. One may circumvent the limitation imposed by the blood-brain barrier by transplantation of genetically altered cell grafts or focal inoculation of virus or protein. However, permanent gene replacement therapy for diseases affecting the entire brain will require global delivery of genetic vectors. The neurotoxicity of currently available viral vectors and the transient nature (...) of transgene expression invivomust be overcome before their use in human gene therapy becomes clinically applicable. (shrink)

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.

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.

Resumo: A finalidade deste artigo é bastante pontual e específica: evidenciar os problemas do tratamento acrítico dado à psicologia por Brian Leiter em seu recente Moral Psychology with Nietzsche. O autor inclui, sem se empenhar em qualquer discussão metodológica, a psicologia no rol do que chama de “ciências bem-sucedidas”, tomadas como i) certificadoras do m-naturalismo nietzschiano; ii) dotadas de primazia sobre a própria filosofia na determinação do que é um “raciocínio filosófico” significativo; iii) fornecedoras de um amplo e inconteste corpo (...) de evidências de que a psicologia moral de Nietzsche “está certa” em relação a teses profundamente complexas. Minha exposição consiste em mapear a construção conceitual desse m-naturalismo, e, posteriormente, evidenciar que não há, na psicologia empírica contemporânea, nada próximo da caracterização pretendida por Leiter.: This article has a very specific purpose: to highlight the problems of Brian Leiter's uncritical treatment of psychology in his recent Moral Psychology with Nietzsche. The author includes, without engaging in any methodological discussion, psychology in the list of what he calls "successful sciences" as certifiers of Nietzschean m-naturalism; ii) as endowed with primacy over philosophy itself in determining what is meaningful "philosophical reasoning"; iii) as providing a broad and uncontested body of evidence that Nietzsche's moral psychology “is right” in profoundly complex theses. My expository strategy is to map, initially, the path taken by Leiter in the conceptual construction of his m-naturalism, and, later, to show that there is nothing in contemporary empirical psychology that legitimizes Leiter’s characterization. (shrink)

Neuwelt et al. have proposed gene-transfer experiments utilizing an animal model that offers many important advantages for investigating the feasibility of gene therapy in the human brain. A variety of tissues concerning the viral vector and mode of delivery of the corrective genes need to be resolved, however, before such therapy is scientifically supportable.

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.

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.

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.

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.

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.

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)

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)

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.

Neural transplantation as a recovery strategy for neuro-degenerative diseases in humans has used mainly grafting following acute denervation strategies in young adult hosts. Our work in aged mice and rats demonstrates an age-related increase in susceptibility to oxidative damage from neurotoxins, a remarkably poor recovery of C57BL/6 mice from MPTP insult with transplantation and growth factors, even at 12 months of age, and diminished plasticity of host neurons. We believe that extrapolation of data from young adult animal models to aged (...) humans without thorough investigation of transplantation and host response in aged recipients is scientifically and ethically inappropriate. (shrink)

The use of neural transplantation to alleviate cognitive deficits is still in its infancy. We have an inadequate understanding of the deficits induced by different types of brain damage and their homologies in animal models against which to assess graft-induced recovery, and of the ways in which graft growth and function are influenced by factors within the host brain and the environment in which the host is operating. Further, use of fetal tissue may only be a transitory phase in the (...) search for appropriate donor sources. Nevertheless, findings from our laboratory and elsewhere have made a prima facie case for successful cognitive reconstruction by graft methods. (shrink)

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.

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)

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.