Per B. Sederberg - US grants

[unreadable] DESCRIPTION (provided by applicant): The proposed research seeks to illuminate the mechanisms of human learning and memory and, in particular, the role of brain oscillations in this vital human capacity. While it has recently been shown that certain brain oscillations increase during learning and memory tasks (an oscillatory subsequent memory effect, or SME), the exact nature of their involvement in memory function remains unknown. In the proposed studies brain waves will be recorded from patients undergoing surgical/invasive monitoring as part of the clinical treatment of medically refractory epilepsy. By performing cognitive tasks that pose no health risks whatsoever, these patients can provide exquisite data on the involvement of brain waves in memory formation. The proposed research aims to determine: (1) the relative roles of oscillations in hippocampus and neocortex in supporting memory formation, (2) the relation of the phase of oscillatory activity and the cognitive processes underlying memory formation, (3) the relation between the oscillatory SME and the traditionally studied event related potential SMEs, and (4), the roles of temporal and semantic information in producing SMEs in free recall. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): The proposed research seeks to illuminate the mechanisms of human memory and, in particular, how we search memory to recall specific details from an event. Behavioral studies demonstrate that subjects use two types of associations to cue memory during recall: those based on temporal contiguity of items and those based on pre-existing semantic relations. The first aim seeks to dissociate the neural correlates of these two types of memory cues by means of a cued- and free- recall study with both functional magnetic-resonance imaging (fMRI) and scalp electroencephalographic (EEG) recordings. Univariate statistical methods will indicate the brain areas and type of neural activity associated with the trade-off between semantic and episodic memory cues. In addition, multivariate pattern classification of the fMRI and scalp EEG data will provide a neural readout of a subject's cue state at any given time. The second aim makes use of this neural readout to constrain a computational model of the interaction between semantic and temporal cues during memory retrieval. Relevance: In many cases, memory problems arise not just due to the inability to encode new information, but the inability to access information that we have stored in our brains. An improved understanding of memory retrieval can be expected to have important health consequences for both the enhancement of memory performance in general and the treatment of memory impairments due to head traumas or disease. [unreadable] [unreadable] [unreadable]

? DESCRIPTION (provided by applicant): This is an application to continue research originally started in 2001, and expanded into a longitudinal study, known as the Virginia Cognitive Aging Project (VCAP), in 2005. Over 2,300 adults 18 - 95 years old have now completed at least two longitudinal occasions, with an average of 2.7 occasions and an average time in study of 5.1 years. The research proposed in the next funding period will extend the investigation of short-term longitudinal change in a broad variety of cognitive measures, with particular emphasis on adults under the age of 80. Although previous studies have found little or no cognitive change in longitudinal comparisons involving young and middle-aged adults, this research employs three methodological innovations, variable retest intervals, measurement bursts at each occasion, and continuous recruitment of new participants, that help distinguish age effects from experience (retest) effects, and that increase sensitivity to detect change by taking into account normal short-term variability in performance. Among the primary questions to be investigated are when does normal age-related cognitive change begin, the degree to which changes in different cognitive variables are independent of one another at different periods in adulthood, the role of prior test experience on the direction and magnitude of cognitive change at different ages, the degree to which factors such as one's cognitive or physical lifestyle moderate the amount of age-related change in different cognitive abilities at various periods in adulthood, and how early can normal and pathological trajectories of cognitive aging be distinguished. Specific aims during the next grant period are to: (1) Expand the characterization of normal cognitive aging across the range from about 18 to 80 years old; (2) Extend the investigation of the role of experience effects on cognitive change; (3) Investigate the structure and nature of cognitive change across different levels of analysis and across a wide range of ages; and (4) Increase sensitivity of VCAP tests to detect early stages of cognitive pathology among VCAP participants.

ABSTRACT Perceptual decision-making is a fundamental cognitive ability that is vital to healthy, daily functioning and is impaired in many diseases. Although many brain regions are known to be involved, there is no clear brain-wide model of how perceptual decisions are formed and executed and the underlying circuit mechanisms are still largely unknown. Here, a team of investigators propose a series of experiments that will use behavioral measures, imaging, physiology, circuit dissection, and computational modeling to study how the midbrain superior colliculus (SC) participates in visual decision-making. Specifically, this new team of investigators will probe the contribution of two SC neuronal cell types, wide field vertical (WFV) cells in the visuosensory layers and predorsal bundle (PDB) cells in the motor layers. These experiments will be done in mice and tree shrews, to reveal the underlying circuits and computational principles across species and to lay the foundation for future experiments designed to dissect decision-making circuits in primates. In Aim 1, the investigators will establish and perform psychophysical experiments to assess perceptual decision-making in both species. The behavioral data will be fitted with computational models to arbitrate between different theories of decision-making. In Aim 2, two photon calcium imaging and/or physiological recording will be performed in mice and tree shrews to determine the activity of WFV and PDB neurons during the psychophysical measures established in Aim 1. In addition, WFV and PDB neurons will be silenced optogenetically during the behavioral tasks to reveal their specific roles in decision-making. In Aim 3, the investigators will use intersectional monosynaptic viral tracing techniques, multiplexed peroxidase labeling for confocal and ultrastructural analysis of synaptic connections and and optogenetics-assisted brain slice recording to investigate the intrinsic and extrinsic circuits that link WFV and PDB cells. Together, these experiments will generate novel knowledge of the synapse to circuit mechanisms underlying perceptual decision-making, and provide technical and theoretical foundations for future mechanistic studies of cognitive function in higher mammalian species directly relevant to humans.