Memory beyond the synapse

Based on studies of the molecular and cellular cascades that occur during memory consolidation for a one-trial passive-avoidance learning task in the young chick, I review the evidence that memory is encoded in permanent changes in synaptic connectivity ina specific brain region, the Hebb hypothesis. I conclude that despite the fact that such a cascade occurs, culminating in the synthesis of cell-adhesion molecules that are involved in synaptic remodelling, synaptic events are not in themselves sufficient to account for the phenomena of memory. Both whole brain (neuromodulator) and whole body (hormonal) processes are engaged.Memories are labile, disarticulated and stored in a distributed manner; how the mind/brain recreates coherent memories from this pattern is a mystery.     

Agents of the mind

The higher order circuitry of the brain is comprised of a large-scale network of cerebral cortical areas that are individually regulated by loops through subcortical structures, particularly through the basal ganglia and cerebellum. These subcortical loops have powerful computational architectures. Using, as an example, the relatively well-understood processing that occurs in the cortical/basal ganglionic/cerebellar distributed processing module that generates voluntary motor commands, I postulate that a network of analogous agents is an appropriate framework for exploring the dynamics of the mind.     

The Environments of Our Hominin Ancestors, Tool-usage, and Scenario Visualization

In this paper, I give an account of how our hominin ancestors evolved a conscious ability I call scenario visualization that enabled them to manufacture novel tools so as to survive and flourish in the ever-changing and complex environments in which they lived. I first present the ideas and arguments put forward by evolutionary psychologists that the mind evolved certain mental capacities as adaptive responses to environmental pressures. Specifically, Steven Mithen thinks that the mind has evolved cognitive fluidity, viz., an ability to exchange information flexibly between and among mental modules. Showing the deficiency in Mithen’s view, I then argue that the flexible exchange of information between and among modules together with scenario visualization is what explains the ability to construct the novel tools needed to survive and flourish in the environments in which our hominin ancestors resided. Finally, I trace the development of the multi-purposed javelin, from its meager beginnings as a stick, in order to illustrate scenario visualization in novel tool manufacturing.     

Adaptiveness and adaptation

This essay is structured as follows. First, I describe the adaptationist program, or teleonomy, in biology. Second, I review the methodologies of this program. Third, I discuss the role that the environment of evolutionary adaptedness plays in the adaptationist program. Fourth, I argue that studies of the “adaptiveness” of human behavior have not been conceptually anchored in the adaptationist program. Fifth, I analyze two studies of adaptiveness and show why they neither test nor inspire novel hypotheses about the design of the human brain/mind. Finally, I conclude that the “adaptivist” approach to human behavior does not begin with well formed hypotheses about the design of human brain/mind mechanisms and that it consists of procedures that could not test such hypotheses if they were proposed.     

Disentangling the dynamic core: a research program for a neurodynamics at the large-scale

My purpose in this paper is to sketch a research direction based on Francisco Varela's pioneering work in neurodynamics (see also Rudrauf et al. 2003, in this issue). Very early on he argued that the internal coherence of every mental-cognitive state lies in the global self-organization of the brain activities at the large-scale, constituting a fundamental pole of integration called here a "dynamic core". Recent neuroimaging evidence appears to broadly support this hypothesis and suggests that a global brain dynamics emerges at the large scale level from the cooperative interactions among widely distributed neuronal populations. Despite a growing body of evidence supporting this view, our understanding of these large-scale brain processes remains hampered by the lack of a theoretical language for expressing these complex behaviors in dynamical terms. In this paper, I propose a rough cartography of a comprehensive approach that offers a conceptual and mathematical framework to analyze spatio-temporal large-scale brain phenomena. I emphasize how these nonlinear methods can be applied, what property might be inferred from neuronal signals, and where one might productively proceed for the future. This paper is dedicated, with respect and affection, to the memory of Francisco Varela.     

Social brains,simple minds: does social complexity really require cognitive complexity?

The social brain hypothesis is a well-accepted and well-supported evolutionary theory of enlarged brain size in the non-human primates. Nevertheless, it tends to emphasize an anthropocentric view of social life and cognition. This often leads to confusion between ultimate and proximate mechanisms, and an over-reliance on a Cartesian, narratively structured view of the mind and social life, which in turn lead to views of social complexity that are congenial to our views of ourselves, rather than necessarily representative of primate social worlds. In this paper, we argue for greater attention to embodied and distributed theories of cognition, which get us away from current fixations on 'theory of mind' and other high-level anthropocentric constructions, and allow for the generation of testable hypotheses that combine neurobiology, psychology and behaviour in a mutually reinforcing manner.     

Constructivist Models of Mind, Contemporary Psychoanalysis, and the Development of Culture Theory

Researchers in a number of fields, including contemporary psychoanalysis, are contributing to the development of a dynamic model of mind that acknowledges the contributions of biology and social experience to the construction of human consciousness and subjectivity. In this paper, I examine this emerging model of mind and I discuss its implications for the development of Culture theory. I argue that theories of culture must reflect the fluidity and complexity of the psychological states that underlie the culture process, and I suggest that even highly conventional models of action, thought, and feeling are rarely, if ever, internalized, appropriated, or reproduced without some degree of modification, refashioning, and personalization. I propose person-centered ethnography as one of the methods by which we can explore the complex relations among culture, mind, and behavior, [constructivist models of mind, contemporary psychoanalysis, culture theory, self and subjectivity, person-centered ethnography]     

Quantum-like brain: "Interference of minds"

We present a contextualist statistical realistic model for quantum-like representations in physics, cognitive science, and psychology. We apply this model to describe cognitive experiments to check quantum-like structures of mental processes. The crucial role is played by interference of probabilities for mental observables. Recently one such experiment based on recognition of images was performed. This experiment confirmed our prediction on the quantum-like behavior of mind. In our approach "quantumness of mind" has no direct relation to the fact that the brain (as any physical body) is composed of quantum particles. We invented a new terminology "quantum-like (QL) mind." Cognitive QL-behavior is characterized by a nonzero coefficient of interference lambda. This coefficient can be found on the basis of statistical data. There are predicted not only cos theta-interference of probabilities, but also hyperbolic cosh theta-interference. This interference was never observed for physical systems, but we could not exclude this possibility for cognitive systems. We propose a model of brain functioning as a QL-computer (there is a discussion on the difference between quantum and QL computers).     

Vulnerable minds,bodily thoughts,and sensory spirits: local theory of mind and spiritual experience in Ghana

This essay looks at the resonances between common cultural models of the mind in the central region of Ghana and patterns of spiritual experience among charismatic evangelical Christians and practitioners of southern Ghana's indigenous religion, known as traditionalists. In particular, I examine the resonance between the model of the mind that construes it as porous, as vulnerable to forcible take-over by hostile entities, and experiences of divine beings insistently pushing people to do their will. It is also relatively common for people in Ghana to report seeing the divine with their eyes and hearing it with their ears. I argue that this experience resonates with, and is perhaps facilitated by, a tendency of local models of mind in Ghana to blend sense and percept.     

Alzheimer's beta-secretase cleaves a glycosyltransferase as a physiological substrate

Alzheimer's beta-secretase (BACE1) is a membrane-bound protease that cleaves the amyloid precursor protein (APP) in the trans-Golgi network, an initial step in the pathogenesis of Alzheimer's disease. Although BACE1 is distributed among various tissues including brain, its physiological substrate other than APP have not been identified. We have recently found that when BACE1 was overexpressed in COS cells together with alpha2,6-sialyltransferase (ST6Gal I), the secretion of ST6Gal I markedly increased, suggesting that BACE1 cleaves ST6Gal I as a physiological substrate. Thus BACE1 is the first identified protease that is responsible for the cleavage and secretion of glycosyltransferases.     

Differential expression of two sodium channel subtypes in human brain.

Two partial human brain sodium channel cDNA sequences (designated HBSC I and II) have been cloned and mapped to chromosome 2q23-2q24 by chromosome microdissection-PCR (CMPCR). The distribution of HBSC I and II mRNA in human brain was studied by means of a novel approach based on the ligase detection reaction. These studies demonstrate that HBSC I and II mRNA is heterogeneously distributed in brain, and that the relative ratio of the two forms can vary as much as 7-fold between different regions.     

Automated scanning for phylogenetically informative transposed elements in rodents

Transposed elements constitute an attractive, useful source of phylogenetic markers to elucidate the evolutionary history of their hosts. Frequent and successive amplifications over evolutionary time are important requirements for utilizing their presence or absence as landmarks of evolution. Although transposed elements are well distributed in rodent taxa, the generally high degree of genomic sequence divergence among species complicates our access to presence/absence data. With this in mind we developed a novel, high-throughput computational strategy, called CPAL (Conserved Presence/Absence Locus-finder), to identify genome-wide distributed, phylogenetically informative transposed elements flanked by highly conserved regions. From a total of 232 extracted chromosomal mouse loci we randomly selected 14 of these plus 2 others from previous test screens and attempted to amplify them via PCR in representative rodent species. All loci were amplifiable and ultimately contributed 31 phylogenetically informative markers distributed throughout the major groups of Rodentia.     

Distribution and characterisation of somatostatin receptor mRNA and binding sites in the brain and periphery.

The distribution and nature of (somatostatin) SRIF receptors and receptor mRNAs was studied in the brain and periphery of various laboratory animals using in situ hybridisation, autoradiography and radioligand binding. The messenger RNA (mRNA) expression of SRIF receptors msst1, msst2, msst3, msst4 and msst5 was studied in the adult mouse brain by in situ hybridisation histochemistry using specific oligonucleotide probes and compared to that of adult rats. As observed in rat brain, sst3 receptor mRNA is prominently expressed across the mouse brain, although equivalent binding has not yet been identified in situ. Sst1 and sst2 receptor mRNA expression, was prominent and again comparable to that observed in rat brain, whereas sst4 and especially sst5 receptor mRNA show comparatively low levels, although the former appears to be widely distributed while the latter could only be identified in a few nuclei. Altogether, the data are compatible with current knowledge, i.e. sst1 and sst2 receptor mRNA is prominent (both receptors have been functionally identified in the brain and for sst2 in the periphery), sst3 mRNA is highly expressed but in the absence of any functional correlate remains elusive. The expression of sst4 mRNA is comparatively low (especially when compared to what is seen in the lung, where high densities of sst4 receptors are present) and it remains to be seen whether sst5 receptor mRNA, which is confined to a few nuclei, will play a role in the brain, keeping in mind that high levels are found in the pituitary. Radioligand binding studies were performed in CCL39 cells expressing the five human recombinant receptors and compared to binding in membranes of rat cerebral cortex with [125I]Tyr11-SRIF14 which in the presence of 120 mM labels primarily sst1 receptor as suggested by the better correlation hsst1 and similar rank order of potency. The profile of [125I]Tyr3-octreotide labelled sites in rat cortex correlates better with recombinant sst2 than sst3 or sst5 binding profiles. Finally, [125I]LTT-SRIF28-labelled sites in rat lung express a sst4 receptor profile in agreement with previous findings. SRIF receptor autoradiography was performed in the brain and peripheral tissue of rat and/or guinea-pig using a number of ligands known to label recombinant SRIF receptors: [125I]LTT-SRIF28, [125I]CGP 23996, [125I]Tyr10-CST, or [125I]Tyr3-octreotide. Although, [125I]Tyr10-CST has been shown to label all five recombinant SRIF receptors, it is apparent that this radioligand is not useful for autoradiographic studies. By contrast, the other three ligands show good signal to noise ratios in rat or guinea-pig brain, rat lung, rat pancreas, or guinea-pig ileum. In most tissues, [125I]Tyr3-octreotide represents a prominent part of the binding (when compared to [125I]LTT-SRIF28 and [125I]CGP 23996), suggesting that sst2 receptors are strongly expressed in most tissues; it is only in rat lung that [125I]LTT-SRIF28 and [125I]CGP 23996 show marked binding, whereas [125I]Tyr3-octreotide does apparently label no sites, in agreement with the sole presence of sst4 receptors in this tissue.     

Light enough to travel or wise enough to stay? Brain size evolution and migratory behavior in birds

Brain size relative to body size is smaller in migratory than in nonmigratory birds. Two mutually nonexclusive hypotheses had been proposed to explain this association. On the one hand, the “energetic trade‐off hypothesis” claims that migratory species were selected to have smaller brains because of the interplay between neural tissue volume and migratory flight. On the other hand, the “behavioral flexibility hypothesis” argues that resident species are selected to have higher cognitive capacities, and therefore larger brains, to enable survival in harsh winters, or to deal with environmental seasonality. Here, I test the validity and setting of these two hypotheses using 1466 globally distributed bird species. First, I show that the negative association between migration distance and relative brain size is very robust across species and phylogeny. Second, I provide strong support for the energetic trade‐off hypothesis, by showing the validity of the trade‐off among long‐distance migratory species alone. Third, using resident and short‐distance migratory species, I demonstrate that environmental harshness is associated with enlarged relative brain size, therefore arguably better cognition. My study provides the strongest comparative support to date for both the energetic trade‐off and the behavioral flexibility hypotheses, and highlights that both mechanisms contribute to brain size evolution, but on different ends of the migratory spectrum.     

Single-neuron theory of consciousness

By most accounts, the mind arises from the integrated activity of large populations of neurons distributed across multiple brain regions. A contrasting model is presented in the present paper that places the mind/brain interface not at the whole brain level but at the level of single neurons. Specifically, it is proposed that each neuron in the nervous system is independently conscious, with conscious content corresponding to the spatial pattern of a portion of that neuron's dendritic electrical activity. For most neurons, such as those in the hypothalamus or posterior sensory cortices, the conscious activity would be assumed to be simple and unable to directly affect the organism's macroscopic conscious behavior. For a subpopulation of layer 5 pyramidal neurons in the lateral prefrontal cortices, however, an arrangement is proposed to be present such that, at any given moment: (i) the spatial pattern of electrical activity in a portion of the dendritic tree of each neuron in the subpopulation individually manifests a complexity and diversity sufficient to account for the complexity and diversity of conscious experience; (ii) the dendritic trees of the neurons in the subpopulation all contain similar spatial electrical patterns; (iii) the spatial electrical pattern in the dendritic tree of each neuron interacts non-linearly with the remaining ambient dendritic electrical activity to determine the neuron's overall axonal response; (iv) the dendritic spatial pattern is reexpressed at the population level by the spatial pattern exhibited by a synchronously firing subgroup of the conscious neurons, thereby providing a mechanism by which conscious activity at the neuronal level can influence overall behavior. The resulting scheme is one in which conscious behavior appears to be the product of a single macroscopic mind, but is actually the integrated output of a chorus of minds, each associated with a different neuron.     

Dreaming and offline memory processing

The activities of the mind and brain never cease. Although many of our waking hours are spent processing sensory input and executing behavioral responses, moments of unoccupied rest free us to wander through thoughts of the past and future, create daydreams, and imagine fictitious scenarios. During sleep, when attention to sensory input is at a minimum, the mind continues to process information, using memory fragments to create the images, thoughts, and narratives that we commonly call 'dreaming'. Far from being a random or meaningless distraction, spontaneous cognition during states of sleep and resting wakefulness appears to serve important functions related to processing past memories and planning for the future. From single-cell recordings in rodents to behavioral studies in humans, recent studies in the neurosciences suggest a new conception of dreaming as part of a continuum of adaptive cognitive processing occurring across the full range of mind/brain states.     

Alzheimer's β-secretase cleaves a glycosyltransferase as a physiological substrate

Alzheimer's beta-secretase (BACE1) is a membrane-bound protease that cleaves the amyloid precursor protein (APP) in the trans-Golgi network, an initial step in the pathogenesis of Alzheimer's disease. Although BACE1 is distributed among various tissues including brain, its physiological substrate other than APP have not been identified. We have recently found that when BACE1 was overexpressed in COS cells together with α2,6-sialyltransferase (ST6Gal I), the secretion of ST6Gal I markedly increased, suggesting that BACE1 cleaves ST6Gal I as a physiological substrate. Thus BACE1 is the first identified protease that is responsible for the cleavage and secretion of glycosyltransferases. Published in 2004. This revised version was published online in August 2006 with corrections to the Cover Date.     

A CHOLESTEROL-ESTERIFYING ENZYME IN RAT CENTRAL NERVOUS SYSTEM MYELIN1

Aontrary to our earlier finding (Eto & Suzuki , 1971), the myelin fraction purified from young adult rat brain consistently showed cholesterol-esterifying activity. The specific activity in myelin was the highest among subcellular fractions. Extensive washing wiih various aqueous salt solutions failed to remove the activity from myelin. The enzyme was evenly distributed among the arbitrarily defined light, medium and heavy myelin subfractions. The myelin-localized activity showed the pH optimum and heat stability identical to the microsome-bound activity. Although there were minor differences in the effect of detergents or exogenous lipids added to the reaction mixture, no firm evidence was obtained to indicate that the myelin-bound cholesterol-esterifying enzyme is different from that in other subcellular fractions. On the other hand, the distribution among the myelin subfractions and heat stability of the myelin-bound cholesterol-esterifying activity were different from those of the myelin-specific cholesterol ester hydrolase. Therefore, the esterification does not appear to be a mere reverse reaction catalyzed by the previously known myelin-specific hydrolase. The rat brain myelin, therefore, is capable of both synthesizing and hydrolyzing cholesterol esters.     

Agency and intervention

Novel ways to intervene on brain function raise questions about agency and responsibility. Here, I discuss whether direct brain interventions, and in particular, deep brain stimulation, pose a threat to agency in individual cases, or to our general conceptualization of what it is to be a responsible agent. While I do not currently see evidence that these interventions constitute a global challenge to our concept of agency, they do have the potential to diminish agency in individuals. I consider whether the lack of evidence for a global challenge ratifies our folk conceptions, or is a necessary consequence of them. In closing, I propose that our theoretical understanding of agency and our therapeutic approaches could be improved with a more nuanced, multidimensional view of agency.     

Working together may be better: activation of reward centers during a cooperative maze task

Humans use theory of mind when predicting the thoughts and feelings and actions of others. There is accumulating evidence that cooperation with a computerized game correlates with a unique pattern of brain activation. To investigate the neural correlates of cooperation in real-time we conducted an fMRI hyperscanning study. We hypothesized that real-time cooperation to complete a maze task, using a blind-driving paradigm, would activate substrates implicated in theory of mind. We also hypothesized that cooperation would activate neural reward centers more than when participants completed the maze themselves. Of interest and in support of our hypothesis we found left caudate and putamen activation when participants worked together to complete the maze. This suggests that cooperation during task completion is inherently rewarding. This finding represents one of the first discoveries of a proximate neural mechanism for group based interactions in real-time, which indirectly supports the social brain hypothesis.