Showing papers by "Rob Knight published in 2004"

Rapid Prefrontal-Hippocampal Habituation to Novel Events

Abstract: Unexpected novel events generate an orienting response that plays an important role in some forms of learning and memory. The orienting response involuntarily captures attention and rapidly habituates as events become familiarized. Although evidence from patients with focal lesions and scalp and intracranial event-related brain potential recordings supports the involvement of a distributed neural network involving association cortex and the limbic system in novelty detection, the key neural substrates and temporal dynamics have not been defined. While subjects performed a bi-field visual-selective attention task with random novel stimuli embedded in either attended or unattended visual fields, we measured rapid changes of regional blood oxygenation level-dependent (BOLD) signal to target and novel stimuli using single-trial analysis of event-related functional magnetic resonance imaging with a 4T scanner. Habituation was quantified by serial BOLD signal changes during the first 10 novel stimuli for each subject. Novel stimuli activated the bilateral superior/middle frontal gyrus, temporal-parietal junction, superior parietal lobe, cingulate gyrus, hippocampus, and fusiform gyrus. The superior/middle frontal gyrus and hippocampus showed significant reduction of BOLD signal during the first few novel stimuli, whereas the signals in the fusiform and cingulate gyrus were constant. Prefrontal and hippocampal responses to attended and unattended novel stimuli were comparably habituated. These results, and previous data from lesion studies, support the view that prefrontal and hippocampal regions are involved in rapid automatic detection and habituation to unexpected environmental events and are key elements of the orienting response in humans.

Hemispheric asymmetries for kinematic and positional aspects of reaching

Abstract: Kinematic analyses of reaching have suggested that the left hemisphere is dominant for controlling the open loop component of the movement, which is more dependent on motor programmes; and the right hemisphere is dominant for controlling the closed loop component, which is more dependent on sensory feedback. This open and closed loop hypothesis of hemispheric asymmetry would also predict that advance planning should be dependent on the left hemisphere, and on-line response modification, which defines closed loop processes, should be dependent on the right hemisphere. Using kinematic analyses of reaching in patients with left or right hemisphere damage (LHD or RHD), we examined the ability: (i) to plan reaching movements in advance by examining changes in reaction time (RT) when response amplitude and visual feedback were cued prior to the response; and (ii) to modify the response during implementation when target location changed at the RT. Performance was compared between the stroke groups, using the ipsilesional arm, and age-matched control groups using their right (RNC) or left (LNC) arm. Aiming movements to a target that moved once or twice, with the second step occurring at the RT, were performed with or without visual feedback of hand position. There were no deficits in advance planning in either stroke group, as evidenced by comparable group changes in RT with changes in amplitude and visual feedback. Response modification deficits were seen for the LHD group in secondary velocity only. In addition, LHD produced slower initial peak velocity with prolongation of the deceleration phase and faster secondary peak velocities, and the RHD group produced deficits in final error only. These differences are more consistent with the dynamic dominance hypothesis, which links left hemisphere specialization to movement trajectory control and right hemisphere specialization to position control, rather than to global deficits in open and closed loop processing.

Research report Dissociable neural correlates for familiarity and recollection during the encoding and retrieval of pictures

Abstract: Results from behavioral studies have supported the idea that recognition memory can be supported by at least two different processes, recollection and familiarity. However, it remains unclear whether these two forms of memory reflect neurally distinct processes. Furthermore, it is unclear whether recollection and familiarity can be best conceived as differing primarily in terms of retrieval processing, or whether they additionally differ at encoding. To address these issues, we used event-related brain potentials (ERPs) to monitor neural correlates of familiarity and recollection at both encoding and retrieval. Participants studied pictures of objects in two types of study blocks and subsequently made remember–know and source memory judgments during retrieval. Results showed that, during encoding, neural correlates of subsequent familiarity and recollection onsetted in parallel, but exhibited differences in scalp topography and time course. Subsequent familiarity-based recognition was associated with a left-lateralized enhanced positivity and observed at anterior scalp sites from 300 to 450 ms, whereas subsequent recollection was associated with a topographically distinct right-lateralized positivity at anterior scalp sites from 300 to 450 ms and bilateral activity from 450 to 600 ms. During retrieval, neural correlates of familiarity emerged earlier than correlates of recollection. Familiarity was associated with an enhanced positivity at frontopolar scalp sites from 150 to 450 ms, whereas recollection was associated with positive ERP modulations over bilateral frontal (300–600 ms) and parietal (450–800 ms) sites. These results demonstrate that familiarity and recollection reflect the outcome of neurally distinct memory processes at both encoding and retrieval. D 2003 Elsevier B.V. All rights reserved. Theme: Neural basis of behavior Topic: Cognition

Skeletal and pigment cell defects in the lockjaw mutant reveal multiple roles for zebrafish tfap2a in neural crest development

Abstract: Members of the AP-2 transcription factor family have critical roles in many aspects of embryonic development. The zebrafish tfap2a mutant lockjaw (low) displays defects in skeletal and pigment cell derivatives of the neural crest. Here we show essential roles for tfap2a in subsets of embryonic cartilages and pigment cells. Defects in cartilage of the hyoid arch in low correlate with a loss of Hox group 2 gene expression and are suggestive of a transformation to a mandibular fate. In contrast, loss of joints in the mandibular arch and defects in certain types of pigment cells suggest a requirement for tfap2a independent of Hox regulation. Early melanophores do not develop in low mutants, and we propose that this results in part from a loss of kit function, leading to defects in migration, as well as kit-independent defects in melanophore specification. Iridophores are also reduced in low, in contrast to xanthophores, revealing a role for tfap2a in the development of pigment subpopulations. We propose a model of tfap2a function in the neural crest in which there are independent functions for tfap2a in specification of subpopulations of pigment cells and segmental patterning of the pharyngeal skeleton through the regulation of Hox genes. Developmental Dynamics 229:87–98, 2004. © 2003 Wiley-Liss, Inc.

The impact of orbital prefrontal cortex damage on emotional activation to unanticipated and anticipated acoustic startle stimuli

Abstract: Damage to the orbital prefrontal cortex has been implicated in selectively diminishing electrodermal autonomic nervous system responses to anticipated punishing stimuli (e.g., losing money; Bechara, Damasio, & Damasio, 2000), but not to unanticipated punishing stimuli (e.g., loud noises; Damasio, Tranel, & Damasio, 1990). We extended this research by examining the effects of orbitofrontal damage on emotional responses to unanticipated and anticipated acoustic startles and collecting a more extensive set of physiological measures, emotional facial behavior, and self-reported emotional experience. Consistent with previous research, patients showed intact physiology to an unanticipated startle but failed to show appropriate anticipatory cardiovascular responses (patients' heart rates decreased, controls' increased). In addition, patients displayed more surprise facial behavior and reported marginally more fear than did controls in response to the unanticipated startle. Thus, orbitofrontal damage may compromise the ability to anticipate physiologically the onset of aversive stimuli, despite intact or enhanced emotional responses when such stimuli occur unexpectedly.

BayesFold: Rational 2° folds that combine thermodynamic, covariation, and chemical data for aligned RNA sequences

Abstract: BayesFold is a Web application that folds an alignment of closely related sequences and evaluates hypotheses about their shared structure. It uses Bayes’s Theorem to combine information from several sources, including chemical mapping (if available), thermodynamic folding, and observed sequence variations. Its method provides a rational basis for integrating results, even when these methods conflict. On a gapped alignment of 86 tRNA Phe sequences each 77 bases long, BayesFold takes 31 sec to perform the calculations; the best structure contained 95% of the base pairs in the true structure, and the true structure was ranked second. Notably, similar results come from random samples of only 10 sequences from the alignment (running time 3 sec), suggesting that remarkably few sequences are required for good results. In contrast, folding single sequences with BayesFold produced structures 9.6 bp different, or with the Vienna package, 13.4 bp different, from the true structure . Similar results were obtained for other families of tRNAs. We especially recommend BayesFold for alignments of 3–50 closely related sequences, such as the sequence families frequently found in SELEX. In addition to providing a convenient way to explore the effects of each of the criteria on the plausibility of different structures, BayesFold also makes it easy to produce publicationquality secondary-structure graphics. The Web interface, available at http://bayes.colorado.edu/fold/, includes the flexibility to thread any of the sequences (or the consensus sequence) through any of the structures, including the one judged most probable.

Synchronization measures of bursting data: application to the electrocorticogram of an auditory event-related experiment.

Abstract: Synchronization measures have become an important tool for exploring the relationships between time series. We review three recently proposed nonlinear synchronization measures and expand their definitions in a straightforward way to apply to an ensemble of measurements. We also develop a synchronization measure in which nearest neighbors are determined across the ensemble. We compare these four nonlinear synchronization measures and show that our measure succeeds in physically motivated examples where the other methods fail. We apply the synchronization measure to human electrocorticogram data collected during an auditory event-related potential experiment. The results suggest a crude model of cortical connectivity.

Neurobiology: sleep on it.

Abstract: Is the function of sleep to replenish energy resources or to modify neural connections in the brain? Recordings of the brain's 'reverberating circuits' evident during sleep shed light on the question.

The Scope of Selection

Abstract: We have estimated the maximal size for an RNA motif recoverable from selection-amplification for new RNA activities, under conditions that span those in present laboratory use. The number of sequence pieces from which an active site is folded (the modularity) is a crucial variable. Routine laboratory experiments might isolate RNAs of modularity 4 containing ≤33 specified nudeotides. The probability of recovering shorter motifs increases rapidly, but the likely maximal motif size declines 1.66 nudeotides per 10-fold decrease in experimental scale. In such experiments, randomized tracts of 80–120 nucleotides extract most of the benefit of longer initially randomized pools. The same methods also permit extrapolation to conditions more plausible during the initiation of an RNA world. Under these conditions, active RNAs were likely highly modular, even more so than in modern experiments. Strikingly, several lines of evidence converge on the conclusion that 15 to 35-mer active sites would be the working material for an early RNA world. If initiation of an RNA world is synonymous with emergence of active structures from randomized sequences (the Axiom of Origin), populations containing only zeptomoles of RNA (hundreds to hundreds of thousands of molecules) might yield RNAs at the lower end of this size range. This makes the RNA world much more accessible than previously suspected.

Reply to: Evaluating the role of the cerebellum in temporal processing: beware of the null hypothesis

Abstract: The neural systems that regulate temporal aspects of behaviours within the range of several hundred milliseconds, several seconds and even longer periods remain debated Parametric studies of timing across these interval ranges, which seem to have psychological significance, have not yet been carried out by any single study using neuroscience methods Most research has studied patients with neurological damage on a single timing task, typically testing only one interval This body of work led to the influential neuropsychological model of Ivry and colleagues, in which the cerebellum is viewed as a central timekeeping mechanism that computes time for intervals in the range of several hundred milliseconds (Ivry et al , 1988; Ivry and Keele, 1989; Ivry, 1996) The strongest support for this proposal comes from studies demonstrating that patients with cerebellar damage are impaired on tests in which they must explicitly estimate or reproduce the duration of an interval lasting several hundred milliseconds As we pointed out in our paper, evidence for the cerebellar timing model has been limited in primarily two ways First, most studies have included patients with cerebellar atrophy The use of these patients to draw direct inferences about the role of the cerebellum in any behaviour is limited because degenerative cerebellar atrophy is rarely restricted to the cerebellum and may damage other brain regions Indeed, cerebellar atrophy patients show marked deficits in temporal processing relative to patients with cerebellar damage due to stroke (Casini and Ivry, 1999) This problem cannot be overstated, given that damage to various areas of the cerebral cortex also produces deficits in timing intervals in the range of hundreds of milliseconds and seconds (Nichelli et al , 1995; Rubia et al , 1997; Harrington et al , 1998; Mangels et al , 1998; Casini and Ivry, …

Adaptive Evolution of the Genetic Code

Abstract: All known genetic codes use 4 bases and 20 amino acids, but many other bases and amino acids have been synthesized and/or found in organisms. The coding relation ships between particular trinucleotides and amino acids can and have evolved, as shown by variants in both mitochondrial and nuclear lineages. Here we review the evidence that vari-ous aspects of the genetic code, including its composition, its degeneracy and the assignments of particular codons to particular amino acids are in some sense optimal, chosen over alterna-tives by natural selection. We also examine several specific proposals about how the code evolved prior to its fixation in the last common ancestor of extant life. Although the pattern of codon assignments appears nearly optimal, other claims for adaptive features are more speculative and many interesting questions remain unresolved.

The Poohsticks phenomenon.

Abstract: Transient ischaemic attacks often have very similar, sometimes identical, characteristics. This implies that the same area of the brain is rendered ischaemic at each attack. The cause is usually an atherothrombo-embolism. To produce stereotypical episodes of ischaemia, such emboli must lodge in the same small artery each time. As the embolus starts from a point far from its eventual destination, how do many emboli reach the same artery? The probable explanation is that currents and eddies in a major blood vessel are similar at different times. So, emboli released into the internal carotid artery at the same point, but at different times, might be expected to arrive at the same destination, or at least many might. This suggestion is hard to test, but the picture is in some ways similar to what happens in a river or stream. This is how the concept of the …