Glial cells for information routing?

We investigate a possible functional role of glial cells as information routing devices of the cerebral cortex. On the one hand, functionally motivated models of neural information processing were lately suggested which rely on short-term changes of connections between neural modules to dynamically route neural activity. Although successful in practice, the routing mechanisms of these models require synaptic efficacy control of large sets of synapses that is difficult to implement neurally. On the other hand, recent experiments show an active role of glial cells (astrocytes) in the interaction with large numbers of synapses. Astrocytes are sensitive to neurotransmitters released by the presynaptic terminal and in turn can influence synaptic efficacy by release of so called gliotransmitters. An analysis of the most recent literature shows that glial cells are a well-suited and natural candidate for the implementation of information routing mechanisms.     

Separate modifiability, mental modules, and the use of pure and composite measures to reveal them

How can we divide a complex mental process into meaningful parts? In this paper, I explore an approach in which processes are divided into parts that are modular in the sense of being separately modifiable. Evidence for separate modifiability is provided by an instance of selective influence: two factors F and G (usually experimental manipulations) such that part A is influenced by F but invariant with respect to G, while part B is influenced by G but invariant with respect to F. Such evidence also indicates that the modules are functionally distinct. If we have pure measures MA and MB, each of which reflects only one of the parts, we need to show that MA is influenced by F but not G, while MB is influenced by G but not F. If we have only a composite measure MAB of the entire process, we usually also need to confirm a combination rule for how the parts contribute to MAB. I present a taxonomy of separate-modifiability methods, discuss their inferential logic, and describe several examples in each category. The three categories involve measures that are derived pure (based on different transformations of the same data; example: separation of sensory and decision processes by signal detection theory), direct pure (based on different data; example: selective effects of adaptation on spatial-frequency thresholds), and composite (examples: the multiplicative-factor method for the analysis of response rate; the additive-factor method for the analysis of reaction time). Six of the examples concern behavioral measures and functional processes, while four concern brain measures and neural processes. They have been chosen for their interest and importance; their diversity of measures, species, and combination rules; their illustration of different ways of thinking about data; the questions they suggest about possibilities and limitations of the separate-modifiability approach; and the case they make for the fruitfulness of searching for mental modules.     

Complexity and coherency: integrating information in the brain

The brains of higher mammals are extraordinary integrative devices. Signals from large numbers of functionally specialized groups of neurons distributed over many brain regions are integrated to generate a coherent, multimodal scene. Signals from the environment are integrated with ongoing, patterned neural activity that provides them with a meaningful context. We review recent advances in neurophysiology and neuroimaging that are beginning to reveal the neural mechanisms of integration. In addition, we discuss concepts and measures derived from information theory that lend a theoretical basis to the notion of complexity as integration of information and suggest new experimental tests of these concepts.     

The dynamics of perceptual learning: an incremental reweighting model

The mechanisms of perceptual learning are analyzed theoretically, probed in an orientation-discrimination experiment involving a novel nonstationary context manipulation, and instantiated in a detailed computational model. Two hypotheses are examined: modification of early cortical representations versus task-specific selective reweighting. Representation modification seems neither functionally necessary nor implied by the available psychophysical and physiological evidence. Computer simulations and mathematical analyses demonstrate the functional and empirical adequacy of selective reweighting as a perceptual learning mechanism. The stimulus images are processed by standard orientation- and frequency-tuned representational units, divisively normalized. Learning occurs only in the "read-out" connections to a decision unit; the stimulus representations never change. An incremental Hebbian rule tracks the task-dependent predictive value of each unit, thereby improving the signal-to-noise ratio of their weighted combination. Each abrupt change in the environmental statistics induces a switch cost in the learning curves as the system temporarily works with suboptimal weights.     

Effects of aging on the neural correlates of successful item and source memory encoding

To investigate the neural basis of age-related source memory (SM) deficits, young and older adults were scanned with fMRI while encoding faces, scenes, and face-scene pairs. Successful encoding activity was identified by comparing encoding activity for subsequently remembered versus forgotten items or pairs. Age deficits in successful encoding activity in hippocampal and prefrontal regions were more pronounced for SM (pairs) as compared with item memory (faces and scenes). Age-related reductions were also found in regions specialized in processing faces (fusiform face area) and scenes (parahippocampal place area), but these reductions were similar for item and SM. Functional connectivity between the hippocampus and the rest of the brain was also affected by aging; whereas connections with posterior cortices were weaker in older adults, connections with anterior cortices, including prefrontal regions, were stronger in older adults. Taken together, the results provide a link between SM deficits in older adults and reduced recruitment of hippocampal and prefrontal regions during encoding. The functional connectivity findings are consistent with a posterior-anterior shift with aging previously reported in several cognitive domains and linked to functional compensation.     

Toward a Methodology of Experimental Analysis and Treatment of Aberrant Classroom Behaviors

A behavior analytic methodlogy for linking assessment and intervention for aberrant classroom behavior is presented. This methodology assists the behavioral consultant and classroom teacher in looking at the environmental variables that support undesirable behavior in three ways: structurally, functionally, or through some combination of the two approaches. Treatment strategies arising from the analysis may then be implemented. The methodology consists of the following steps: (a) problem identification, (b) data collection to generate hypotheses, (c) formulation of hypotheses regarding structural and functional relations, (d) design of analogue conditions to test the hypotheses, (e) conducting the analysis, and (f) treatment development and evaluation. An example of a structural analysis and treatment of the stereotypic behavior of an 8-year-old girl functioning in the severe-profound range of mental retardation conducted by her teacher in a special education classroom is presented.     

The role of frontal lobe functioning in the development of infant self-regulatory behavior.

In the last two decades, there has been tremendous growth in two fields of study related to human infant development: (1) the development of neural processes during the early postnatal years and (2) the development of self-regulatory behavior. In an attempt to stimulate research on the relation between early brain development and self-regulatory processes, several hypotheses pertaining to the role of frontal lobe functioning in the development of emotion regulation during infancy are proposed. The results of a study of the relation between frontal electroencephalographic (EEG) activity and emotional behavior of 21-month-old infants are reported. It was found that increases in frontal lobe activation were associated with increases in emotional arousal, while EEG activity recorded from the parietal region showed either a reciprocal pattern of activation or did not change as a function of level of emotional arousal. These results provide evidence for the specialized role of the frontal lobe in mediating emotional behavior during infancy.     

Activity Versus Reactivity in Psychology and Neurophysiology

The traditional reflex approach in neurophysiology is incompatible with modern psychology's concern with goal-directed activity. We try to show that a ne~roph~siological approach based on the theory of functional systems may help to solve this problem. According to functional systems theory, all the elements of the organism are organized in systems that are neither sensory nor motor, but functional; the elements of these systems are defined in terms of how they enable the achievement of useful results of behavior. To make our case for this functional systems approach, experimental data are reviewed to illustrate the significance of the behavioral context in determining the activity of both central and peripheral neurons. One key indicator of the functionally specific organization of neural elements is the role of efferent influences in the coordination of the central and peripheral neural processes, and this is discussed at some length here. We offer the present approach as a basis for a new integration of neurophysiology and psy- chology (systemic psychophysiology), an integration which aims not at correla- tions of psychological with neural phenomena, but at their methodologically consistent unification through an understanding of the organization of different levels of the organism-environment system.     

Some theorems in haploscopic vision

Three formal hypotheses are specified concerning the combination of neural signals from the two eyes. The hypotheses are (1) that a large uniform light presented to the opposite eye has no effect (independence), (2) that all information from one eye relevant to a given percept (for example, brightness) is encoded by a single neural signal (isolation), and (3) the mutually exclusive and exhaustive alternative to isolation (interaction). Though independence or isolation often has been claimed or simply assumed to hold, these hypotheses imply specific empirical relationships. These relationships are derived for brightness and for equilibrium colors. In addition, one model consistent with the interaction hypothesis is developed. The isolation hypothesis is important for generalizing results from monocular experiments to normal binocular vision. If it is false, monocular results can reflect a combination of one eye's neural signals that never occurs with binocular stimuli.     

Modules in spatial vision: intrinsic reasons of their functional attributes

Visual modules can be viewed as expressions of a marked analytic attitude in the study of vision. In vision psychology, this attitude is accompanied by hypotheses that characterize how visual modules are thought to operate in perceptual processes. Our thesis here is that there are what we call “intrinsic reasons” for the presence of such hypotheses in a vision theory, that is, reasons of a deductive kind, which are imposed by the partiality of the basic terms (input and output) in the definition of a module, and by peculiar characteristics of those terms. Specifically, we discuss three hypotheses of functional attributes: successive stages in the action of modules, residual indeterminacy of their effects, and the role of prior constraints. For each of the three, we indicate its occurrence in perceptual psychology, explain corresponding intrinsic reasons, and illustrate such reasons with examples.     

A Possible Role for Cholinergic Neurons of the Basal Forebrain and Pontomesencephalon in Consciousness

Excitation at widely dispersed loci in the cerebral cortex may represent a neural correlate of consciousness. Accordingly, each unique combination of excited neurons would determine the content of a conscious moment. This conceptualization would be strengthened if we could identify what orchestrates the various combinations of excited neurons. In the present paper, cholinergic afferents to the cerebral cortex are hypothesized to enhance activity at specific cortical circuits and determine the content of a conscious moment by activating certain combinations of postsynaptic sites in select cortical modules. It is proposed that these selections are enabled by learning-related restructuring that simultaneously adjusts the cytoskeletal matrix at specific constellations of postsynaptic sites giving all a similar geometry. The underlying mechanism of conscious awareness hypothetically involves cholinergic mediation of linkages between microtubules and microtubule-associated protein-2 (MAP-2). The first reason for proposing this mechanism is that previous studies indicate cognitive-related changes in MAP-2 occur in cholinoceptive cells within discrete cortical modules. These cortical modules are found throughout the cerebral cortex, measure 1–2 mm², and contain approximately 10³–10⁴cholinoceptive cells that are enriched with MAP-2. The subsectors of the hippocampus may function similarly to cortical modules. The second reason for proposing the current mechanism is that the MAP-2 rich cells throughout the cerebral cortex correspond almost exactly with the cortical cells containing muscarinic receptors. Many of these cholinoceptive, MAP-2 rich cells are large pyramidal cell types, but some are also small pyramidal cells and nonpyramidal types. The third reason for proposing the current mechanism is that cholinergic afferents are module-specific; cholinergic axons terminate wholly within individual cortical modules. The cholinergic afferents may be unique in this regard. Finally, the tapering apical dendrites of pyramidal cells are proposed as primary sites for cholinergic mediation of linkages between MAP-2 and microtubules because especially high amounts of MAP-2 are found here. Also, the possibility is raised that muscarinic actions on MAP-2 could modulate microtubular coherence and self-collapse, phenomena that have been suggested to underlie consciousness.     

Holistic Human Development

One of the tenets of holism is that the whole is greater than the sum of its parts. Applying this theorem epistemologically, we could say that a holistic view is greater than the sum of the specialized views that contribute to it. Within the framework of three divergent worldviews (mechanistic, organismic and contextual) as originally proposed by Pepper (World hypotheses: A study in evidence, University of California Press, Los Angeles, 1961), holism as both a philosophical position and a practical approach to research is applied to the study of adult human development. Because spiritual development has received less scholarly attention than biological, cognitive, or emotional functioning, topics such as meditation research, non-religious spirituality, and the concept of soul are covered to promote a balanced developmental perspective. Historical and philosophical factors leading to holism are described, a sampling of interdisciplinary dialogue between psychology and theology is presented, and conclusions regarding the need for holistic thinking and the relationship between religion and spirituality are offered.     

A theory of sulcal-gap signalization

Two sulcal-gap signalization systems are hypothesized to have evolved as emergent functional "exaptations" having the capacity to transmit two-way cortex-to-cortex signals across tissues embedded in opposing sulcal banks. Hypothesis 1 posits that a primary sulcal-gap signalization system evolved the capacity to transmit nonlanguage signals within hierarchically lower-order sensory, motor, and perceptual functional areas of the neocortex having elemental functional units consisting of columns of about 110 neurons. Hypothesis 2 posits that a secondary sulcal-gap signalization system evolved the capacity to transmit language signals within hierarchically higher-order cognitive functional areas of the "neo-neocortex" having elemental functional units consisting of modules of about 4,000 neurons. Neuroanatomical, neurophysiological neuroevolutionary, and neurodevelopmental evidence is presented in support of these two sulcal-gap hypotheses. It is speculated that the combined cognitive capacities of these two sulcal-gap signalization systems may contribute to the transduction of physiological brain into psychological mind.     

Nature, nurture, and the development of functional specializations: A computational approach

The roles assigned to nature and nurture in the acquisition of functional specializations have been modified in recent years due to increasing evidence that experience-dependent processes are more influential in determining a brain region’s functional properties than was previously supposed. Consequently, one may study the developmental principles that play a role in the acquisition of functional specializations. This article studies the hypothesis that a combination of structure-function correspondences plus the use of competition between modules leads to functional specializations. This principle has been instantiated in a family of neural network architectures referred to as “mixtures-ofexperts” architectures. These architectures are sensitive to structure-function relationships in the sense that they often learn to allocate to each task a network whose structure is well matched to that task. The viewpoint advocated here represents a middle ground between nativist and constructivist views of modularity.     

Cognitive processing in literate and illiterate subjects: a review of some recent behavioral and functional neuroimaging data

The study of illiterate subjects, which for specific socio-cultural reasons did not have the opportunity to acquire basic reading and writing skills, represents one approach to study the interaction between neurobiological and cultural factors in cognitive development and the functional organization of the human brain. In addition the naturally occurring illiteracy may serve as a model for studying the influence of alphabetic orthography on auditory-verbal language. In this paper we have reviewed some recent behavioral and functional neuroimaging data indicating that learning an alphabetic written language modulates the auditory-verbal language system in a non-trivial way and provided support for the hypothesis that the functional architecture of the brain is modulated by literacy. We have also indicated that the effects of literacy and formal schooling is not limited to language related skills but appears to affect also other cognitive domains. In particular, we indicate that formal schooling influences 2D but not 3D visual naming skills. We have also pointed to the importance of using ecologically relevant tasks when comparing literate and illiterate subjects. We also demonstrate the applicability of a network approach in elucidating differences in the functional organization of the brain between groups. The strength of such an approach is the ability to study patterns of interactions between functionally specialized brain regions and the possibility to compare such patterns of brain interactions between groups or functional states. This complements the more commonly used activation approach to functional neuroimaging data, which characterize functionally specialized regions, and provides important data characterizing the functional interactions between these regions.     

A neuronal retuning hypothesis of sentence-specificity in Broca’s area

It is clear that the left inferior frontal gyrus (LIFG) contributes in some fashion to sentence processing. While neuroimaging and neuropsychological evidence support a domain-general working memory function, recent neuroimaging data show that particular subregions of the LIFG, particularly the pars triangularis (pTri), show selective activation for sentences relative to verbal working memory and cognitive control tasks. These data suggest a language-specific function rather than a domain-general one. To resolve this apparent conflict, I propose separating claims of domain-generality and specificity independently for computations and representations—a given brain region may respond to a specific representation while performing a general computation over that representation, one shared with other systems. I hypothesize that the pTri underlies a language-specific working memory system, comprised of general memory retrieval/attention operations specialized for syntactic representations. There is a parallelism of top-down retrieval function among the phonological and semantic levels, localized to the pars opercularis and pars orbitalis, respectively. I further explore the idea of how such a system emerges in the human brain through the framework of neuronal retuning: the “borrowing” of domain-general mechanisms for language, either in evolution or development. The empirical data appear to tentatively support a developmental account of language-specificity in the pTri, possibly through connections to the posterior superior temporal sulcus (pSTS), a region that is both anatomically distinct for humans and functionally essential for language. Evidence of representational response specificity obtained from neuroimaging studies is useful in understanding how cognition is implemented in the brain. However, understanding the shared computations across domains and neural systems is necessary for a fuller understanding of this problem, providing potential answers to questions of how specialized systems, such as language, are implemented in the brain.     

Neural synchrony in stochastic resonance, attention, and consciousness.

We describe briefly three of our lab's ongoing projects studying the role of neural synchrony in human perception and cognition. These projects arise from two main interests: the role of noise both in human perception and in neural synchrony, and neural synchrony as a basis for integration of functional modules in the brain. Our experimental work on these topics began with a study of the possibility that noise-influenced neural synchrony might be responsible for the fact that small amounts of noise added to weak signals can enhance their detectability (stochastic resonance). We are also studying the role of neural synchrony in attention and consciousness in several paradigms. On the basis of our own and related work by others, we conclude that (1) neural synchrony plays an important role in the integration of functional modules in the brain and (2) neural synchrony is profoundly affected and possibly regulated, in part, by the "noisiness" of the brain.     

Cortical cell assemblies: a possible mechanism for motor programs

The concept of a motor program has been used to interpret a diverse range of empirical findings related to preparation and initiation of voluntary movement. In the absence of an underlying mechanism, its exploratory power has been limited to that of an analogy with running a stored computer program. We argue that the theory of cortical cell assemblies suggests a possible neural mechanism for motor programming. According to this view, a motor program may be conceptualized as a cell assembly, which is stored in the form of strengthened synaptic connections between cortical pyramidal neurons. These connections determine which combinations of corticospinal neurons are activated when the cell assembly is ignited. The dynamics of cell assembly ignition are considered in relation to the problem of serial order. These considerations lead to a plausible neural mechanism for the programming of movements and movement sequences that is compatible with the effects of precue information and sequence length on reaction times. Anatomical and physiological guidelines for future quantitative models of cortical cell assemblies are suggested. By taking into account the parallel re-entrant loops between the cerebral cortex and basal ganglia, the theory of cortical cell assemblies suggests a mechanism for motor plans that involve longer sequences. The suggested model is compared with other existing neural network models for motor programming.     

Growth-related neural reorganization and the autism phenotype: a test of the hypothesis that altered brain growth leads to altered connectivity

Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and effectiveness of short- and long-distance connections, and should thus impact the growth and retention of connections. Reduced brain size should favor long-distance connectivity; brain overgrowth should favor short-distance connectivity; and inconsistent deviations from the normal growth trajectory - as occurs in autism - should result in potentially disruptive changes to established patterns of functional and physical connectivity during development. To explore this hypothesis, neural networks which modeled inter-hemispheric interaction were grown at the rate of either typically developing children or children with autism. The influence of the length of the inter-hemispheric connections was analyzed at multiple developmental time-points. The networks that modeled autistic growth were less affected by removal of the inter-hemispheric connections than those that modeled normal growth - indicating a reduced reliance on long-distance connections - for short response times, and this difference increased substantially at approximately 24 simulated months of age. The performance of the networks showed a corresponding decline during development. And direct analysis of the connection weights showed a parallel reduction in connectivity. These modeling results support the hypothesis that the deviant growth trajectory in autism spectrum disorders may lead to a disruption of established patterns of functional connectivity during development, with potentially negative behavioral consequences, and a subsequent reduction in physical connectivity. The results are discussed in relation to the growing body of evidence of reduced functional and structural connectivity in autism, and in relation to the behavioral phenotype, particularly the developmental aspects.