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.

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)

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.

Mealey's evolutionary reasoning is logically flawed. Furthermore, the evidence presented in favor of a genetic contribution to the causation of sociopathy is overinterpreted. Given the potentially large societal impact of sociobiological speculation on the roots of criminality, more-than-usual caution in interpreting data is called for.

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.

Approach–avoidance theories describe the major systems that motivate behaviours in reaction to classes of appetitive (rewarding) and aversive (punishing) stimuli. The literature points to two major “avoidance” systems, one related to pure avoidance and escape of aversive stimuli, and a second, to behavioural inhibition induced by the detection of goal conflict (in addition, there is evidence for nonaffective behavioural constraint). A third major system, responsible for approach behaviour, is reactive to appetitive stimuli, and has several subcomponents. A number of combined (...) effects of these systems are outlined. Finally, the hierarchical nature of behavioural control is delineated, including the role played by conscious awareness in behavioural inhibition. (shrink)

Mealey's interesting interpretation of sociopathy is based on an inappropriate two-person game model. A multiperson, compound game version of Chicken would be more suitable, because a population engaging in random pairwise interactions with that structure would evolve to an equilibrium in which a fixed proportion of strategic choices was exploitative, antisocial, and risky, as required by Mealey's interpretation.

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.

In the Frank (1988) model, a small increase in the number of cheaters will soon be reversed. It is not clear that this prediction holds for sociopathy. There are also many attractive evolutionary models that do not admit a small, stable proportion of cheaters. Hence, without definitive evidence about the character of early human society, we cannot conclude that sociopathy has an evolutionary origin.

Definitional slippage threatens to equate secondary sociopathy with mere criminality and leaves the status of noncriminal sociopaths ambiguous. Primary sociopathy appears to show more environmental contingency than would be implied by a strong genetic trait approach. A reinterpretation in terms of hypermasculinity and hypofemininity is compatible with the data.