Faculty Bibliography

Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals' resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included.

Extraction of relevant information from highly complex environments is a prerequisite to survival. Within odour mixtures, such information is contained in the odours of specific elements or in the mixture configuration perceived as a whole unique odour. For instance, an AB mixture of the element A (ethyl isobutyrate) and the element B (ethyl maltol) generates a configural AB percept in humans and apparently in another species, the rabbit. Here, we examined whether the memory of such a configuration is distinct from the memory of the individual odorants. Taking advantage of the newborn rabbit's ability to learn odour mixtures, we combined behavioural and pharmacological tools to specifically eliminate elemental memory of A and B after conditioning to the AB mixture and evaluate consequences on configural memory of AB. The amnesic treatment suppressed responsiveness to A and B but not to AB. Two other experiments confirmed the specific perception and particular memory of the AB mixture. These data demonstrate the existence of configurations in certain odour mixtures and their representation as unique objects: after learning, animals form a configural memory of these mixtures, which coexists with, but is relatively dissociated from, memory of their elements. This capability emerges very early in life.

Theories of brain function have evolved through multiple stages. The first proposition was that brain networks support a set of reflex responses, with current sensory inputs producing immediate motor outputs. The behaviorist paradigm suggested that actions can always be explained as a response to immediate external cues. In response to these views, the cognitive paradigm argued that behavior cannot be understood simply as input-output functions because the hidden layers of brain generate unpredictability. The central processing was termed "cognition." Here we propose a neuroscience-based model of cognition. Our core hypothesis is that cognition depends on internal models of the animal and its world, where internally generated sequences can serve to perform "what if" scenarios and anticipate the possible consequences of alternative actions without actually testing them, and aid in the decisions of overt actions. We support our hypotheses by several examples of recent experimental findings and show how externally guided cell assembly sequences become internalized to support cognitive functions.

Recent results have shown the possibility of both reconstructing connectomes of small but biologically interesting circuits and extracting from these connectomes insights into their function. However, these reconstructions were heroic proof-of-concept experiments, requiring person-months of effort per neuron reconstructed, and will not scale to larger circuits, much less the brains of entire animals. In this paper we examine what will be required to generate and use substantially larger connectomes, finding five areas that need increased attention: firstly, imaging better suited to automatic reconstruction, with excellent z-resolution; secondly, automatic detection, validation, and measurement of synapses; thirdly, reconstruction methods that keep and use uncertainty metrics for every object, from initial images, through segmentation, reconstruction, and connectome queries; fourthly, processes that are fully incremental, so that the connectome may be used before it is fully complete; and finally, better tools for analysis of connectomes, once they are obtained.

The placement of neuronal cell bodies relative to the neuropile differs among species and brain areas. Cell bodies can be either embedded as in mammalian cortex or segregated as in invertebrates and some other vertebrate brain areas. Why are there such different arrangements? Here we suggest that the observed arrangements may simply be a reflection of wiring economy, a general principle that tends to reduce the total volume of the neuropile and hence the volume of the inclusions in it. Specifically, we suggest that the choice of embedded versus segregated arrangement is determined by which neuronal component - the cell body or the neurite connecting the cell body to the arbor - has a smaller volume. Our quantitative predictions are in agreement with existing and new measurements.

BACKGROUND: Understanding normal volume asymmetry is essential for accurate assessment of limb volume changes following breast cancer (BC) treatment in which lymphatic function is disrupted. The purposes of this study were to evaluate for differences in dominant and nondominant limb volumes and to evaluate for interactions between the effects of dominance and side of cancer on limb volume. METHODS AND RESULTS: This study evaluated preoperative limb volumes of 397 women enrolled in a prospective, longitudinal study of neuropathic pain and lymphedema. Volume was calculated from circumference. Limb resistance was measured with bioimpedance. Women were dichotomized into two groups: those whose cancer was on their dominant side and those whose cancer was on their nondominant side. Analyses of variance were used to evaluate for differences. In 47%, BC occurred on the side of the dominant limb. Except for the 30 to 40 centimeter (cm) limb volume segment, a main effect of dominance was found for all measures. The volume of the dominant limb was significantly greater than that of the nondominant limb. No main effects were found for side of cancer. A statistically significant interaction was found only at the 0 to 10 cm limb volume segment. CONCLUSIONS: Prior to BC treatment, the dominant limb demonstrated lower bioimpedance resistance (-2.09%) and greater total limb volume (1.12%) than the nondominant limb. Segmental volume differences were greatest at the proximal forearm segment (2.31%) and least at the proximal arm segment (0.21%). This study provides evidence that preoperative volume assessment is important due to normal variability associated with limb dominance.