Reentry: a key mechanism for integration of brain function.

Reentry in nervous systems is the ongoing bidirectional exchange of signals along reciprocal axonal fibers linking two or more brain areas. The hypothesis that reentrant signaling serves as a general mechanism to couple the functioning of multiple areas of the cerebral cortex and thalamus was first proposed in 1977 and 1978 (Edelman, 1978). A review of the amount and diversity of supporting experimental evidence accumulated since then suggests that reentry is among the most important integrative mechanisms in vertebrate brains (Edelman, 1993). Moreover, these data prompt testable hypotheses regarding mechanisms that favor the development and evolution of reentrant neural architectures.

Biology of consciousness.

The Dynamic Core and Global Workspace hypotheses were independently put forward to provide mechanistic and biologically plausible accounts of how brains generate conscious mental content. The Dynamic Core proposes that reentrant neural activity in the thalamocortical system gives rise to conscious experience. Global Workspace reconciles the limited capacity of momentary conscious content with the vast repertoire of long-term memory. In this paper we show the close relationship between the two hypotheses. This relationship allows for a strictly biological account of phenomenal experience and subjectivity that is consistent with mounting experimental evidence. We examine the constraints on causal analyses of consciousness and suggest that there is now sufficient evidence to consider the design and construction of a conscious artifact.

Retrospective and prospective responses arising in a modeled hippocampus during maze navigation by a brain-based device.

Recent recordings of place field activity in rodent hippocampus have revealed correlates of current, recent past, and imminent future events in spatial memory tasks. To analyze these properties, we used a brain-based device, Darwin XI, that incorporated a detailed model of medial temporal structures shaped by experience-dependent synaptic activity. Darwin XI was tested on a plus maze in which it approached a goal arm from different start arms. In the task, a journey corresponded to the route from a particular starting point to a particular goal. During maze navigation, the device developed place-dependent responses in its simulated hippocampus. Journey-dependent place fields, whose activity differed in different journeys through the same maze arm, were found in the recordings of simulated CA1 neuronal units. We also found an approximately equal number of journey-independent place fields. The journey-dependent responses were either retrospective, where activity was present in the goal arm, or prospective, where activity was present in the start arm. Detailed analysis of network dynamics of the neural simulation during behavior revealed that many different neural pathways could stimulate any single CA1 unit. That analysis also revealed that place activity was driven more by hippocampal and entorhinal cortical influences than by sensory cortical input. Moreover, journey-dependent activity was driven more strongly by hippocampal influence than journey-independent activity.

Characterizing functional hippocampal pathways in a brain-based device as it solves a spatial memory task.

Analyzing neural dynamics underlying complex behavior is a major challenge in systems neurobiology. To meet this challenge through computational neuroscience, we have constructed a brain-based device (Darwin X) that interacts with a real environment, and whose behavior is guided by a simulated nervous system incorporating detailed aspects of the anatomy and physiology of the hippocampus and its surrounding regions. Darwin X integrates cues from its environment to solve a spatial memory task. Place-specific units, similar to place cells in the rodent, emerged by integrating visual and self-movement cues during exploration without prior assumptions in the model about environmental inputs. Because synthetic neural modeling using brain-based devices allows recording from all elements of the simulated nervous system during behavior, we were able to identify different functional hippocampal pathways. We did this by tracing back from reference neuronal units in the CA1 region of the simulated hippocampus to all of the synaptically connected units that were coactive during a particular exploratory behavior. Our analysis identified a number of different functional pathways within the simulated hippocampus that incorporate either the perforant path or the trisynaptic loop. Place fields, which were activated by the trisynaptic circuit, tended to be more selective and informative. However, place units that were activated by the perforant path were prevalent in the model and were crucial for generating appropriate exploratory behavior. Thus, in the model, different functional pathways influence place field activity and, hence, behavior during navigation.

Neural reapportionment: an hypothesis to account for the function of sleep.

Sleep is a ubiquitous component of animal life, and prolonged sleep deprivation is fatal in both vertebrates and invertebrates. The physiologic function of sleep, however, is not known. We propose here that sleep provides a period of time necessary to reapportion resources within neurons and neural systems that become sub-optimally distributed during active waking. Three specific examples of such reapportionment during sleep are suggested: (1) the return of the neurotransmitter, glutamate, to synaptic vesicles at presynaptic sites most active during waking, (2) the intracellular movement of mitochondria from neuronal processes to the cells soma where mitochondrial replication can occur, and (3) the readjustment of the level and distribution of neurotransmitters within the brainstem modulatory systems and elsewhere that must function in an integrated fashion during waking. Experimental approaches that might be utilized to test these hypotheses are suggested.

Spike-timing dynamics of neuronal groups.

A neuronal network inspired by the anatomy of the cerebral cortex was simulated to study the self-organization of spiking neurons into neuronal groups. The network consisted of 100 000 reentrantly interconnected neurons exhibiting known types of cortical firing patterns, receptor kinetics, short-term plasticity and long-term spike-timing-dependent plasticity (STDP), as well as a distribution of axonal conduction delays. The dynamics of the network allowed us to study the fine temporal structure of emerging firing patterns with millisecond resolution. We found that the interplay between STDP and conduction delays gave rise to the spontaneous formation of neuronal groups--sets of strongly connected neurons capable of firing time-locked, although not necessarily synchronous, spikes. Despite the noise present in the model, such groups repeatedly generated patterns of activity with millisecond spike-timing precision. Exploration of the model allowed us to characterize various group properties, including spatial distribution, size, growth, rate of birth, lifespan, and persistence in the presence of synaptic turnover. Localized coherent input resulted in shifts of receptive and projective fields in the model similar to those observed in vivo.

The power of human brain magnetoencephalographic signals can be modulated up or down by changes in an attentive visual task.

This paper presents evidence indicating that the signals generated by neural responses to visual input can be either enhanced by increasing or suppressed by decreasing the area of the stimuli to which attention is directed. We used magnetoencephalography (MEG) to measure the frequency-tagged steady-state visual evoked responses of 11 subjects presented with two superimposed images flickering at different frequencies. Each image consisted of seven parallel bars of equal length; in any image, all bars were either red or green and either horizontal or vertical. At randomly chosen times during the experiments, any one of the three middle bars in either image transiently increased or decreased in width. Subjects were asked to attend to one image and ignore the other and to respond to changes in bar width in the attended image with a key press. In one condition, subject responses were required for changes in any of the three central bars of the attended image. We found that visual steady-state evoked responses to the attended image were enhanced relative to those evoked by the unattended image in this condition. In a second condition, subject responses were required for changes only in the middle bar. In this condition, the responses to the attended image were suppressed relative to those of the unattended image. These results may reflect relative differences in the synchronization and desynchronization of responding neuronal populations.