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1.  Threat-related processing supports prospective memory retrieval for people with obsessive tendencies 
Memory (Hove, England)  2009;17(6):679-686.
Obsessive-compulsive disorder can result in a variety of deficits to cognitive performance, including negative consequences for attention and memory performance. The question addressed in the current study concerned whether this disorder influenced performance in an event-based prospective memory task. The results from a subclinical population indicated that, relative to non-anxious controls and mildly depressed controls, people with obsessive-compulsive tendencies (washing compulsions) incur decrements in remembering to respond to cues related to a neutral intention (respond to animals). This deficit was ameliorated by giving the subclinical group an intention about a threat-related category (respond tobodily fluids) and cueing them with concepts that they had previously rated as particularly disturbing to them. Thus, their normal attentional bias for extended processing of threat-related information overcame their natural deficit in event-based prospective memory.
PMCID: PMC4003884  PMID: 19585346
2.  Data mining neocortical high-frequency oscillations in epilepsy and controls 
Brain  2011;134(10):2948-2959.
Transient high-frequency (100–500 Hz) oscillations of the local field potential have been studied extensively in human mesial temporal lobe. Previous studies report that both ripple (100–250 Hz) and fast ripple (250–500 Hz) oscillations are increased in the seizure-onset zone of patients with mesial temporal lobe epilepsy. Comparatively little is known, however, about their spatial distribution with respect to seizure-onset zone in neocortical epilepsy, or their prevalence in normal brain. We present a quantitative analysis of high-frequency oscillations and their rates of occurrence in a group of nine patients with neocortical epilepsy and two control patients with no history of seizures. Oscillations were automatically detected and classified using an unsupervised approach in a data set of unprecedented volume in epilepsy research, over 12 terabytes of continuous long-term micro- and macro-electrode intracranial recordings, without human preprocessing, enabling selection-bias-free estimates of oscillation rates. There are three main results: (i) a cluster of ripple frequency oscillations with median spectral centroid = 137 Hz is increased in the seizure-onset zone more frequently than a cluster of fast ripple frequency oscillations (median spectral centroid = 305 Hz); (ii) we found no difference in the rates of high frequency oscillations in control neocortex and the non-seizure-onset zone neocortex of patients with epilepsy, despite the possibility of different underlying mechanisms of generation; and (iii) while previous studies have demonstrated that oscillations recorded by parenchyma-penetrating micro-electrodes have higher peak 100–500 Hz frequencies than penetrating macro-electrodes, this was not found for the epipial electrodes used here to record from the neocortical surface. We conclude that the relative rate of ripple frequency oscillations is a potential biomarker for epileptic neocortex, but that larger prospective studies correlating high-frequency oscillations rates with seizure-onset zone, resected tissue and surgical outcome are required to determine the true predictive value.
PMCID: PMC3187540  PMID: 21903727
high-frequency oscillations; epilepsy; intracranial EEG
3.  Gait-specific energetics contributes to economical walking and running in emus and ostriches 
A widely held assumption is that metabolic rate (Ėmet) during legged locomotion is linked to the mechanics of different gaits and this linkage helps explain the preferred speeds of animals in nature. However, despite several prominent exceptions, Ėmet of walking and running vertebrates has been nearly uniformly characterized as increasing linearly with speed across all gaits. This description of locomotor energetics does not predict energetically optimal speeds for minimal cost of transport (Ecot). We tested whether large bipedal ratite birds (emus and ostriches) have gait-specific energetics during walking and running similar to those found in humans. We found that during locomotion, emus showed a curvilinear relationship between Ėmet and speed during walking, and both emus and ostriches demonstrated an abrupt change in the slope of Ėmet versus speed at the gait transition with a linear increase during running. Similar to human locomotion, the minimum net Ecot calculated after subtracting resting metabolism was lower in walking than in running in both species. However, the difference in net Ecot between walking and running was less than is found in humans because of a greater change in the slope of Ėmet versus speed at the gait transition, which lowers the cost of running for the avian bipeds. For emus, we also show that animals moving freely overground avoid a range of speeds surrounding the gait-transition speed within which the Ecot is large. These data suggest that deviations from a linear relation of metabolic rate and speed and variations in transport costs with speed are more widespread than is often assumed, and provide new evidence that locomotor energetics influences the choice of speed in bipedal animals. The low cost of transport for walking is probably ecologically important for emus and ostriches because they spend the majority of their active day walking, and thus the energy used for locomotion is a large part of their daily energy budget.
PMCID: PMC3107644  PMID: 21123267
gait; cost of transport; energetics; locomotion; preferred speeds
4.  Behavioral Measures of Impulsivity and the Law 
Behavioral sciences & the law  2008;26(6):691-707.
The General Theory of Crime proposes that crime is explained by the combination of situational opportunity and lack of self-control. Impulsivity is one of the important components of self-control. Because behavioral measures of impulsivity are becoming more commonly utilized to assess forensic populations, this manuscript provides an overview of three current behavioral measures. In doing so, an example of their application is provided using a group of individuals likely to come into contact with the legal system: adolescents with Conduct Disorder. Earlier age of onset of Conduct Disorder symptoms has been shown to be an important predictor of the persistence of poor outcomes into adulthood including participation in criminal activities. This study found differential behavioral profiles across distinct measures of impulsivity by those with childhood- versus adolescent-onset Conduct Disorder. Legal implications for defining behavioral deficits using behavioral measures of impulsivity and their current limitations are discussed.
PMCID: PMC3279729  PMID: 19039792
Impulsivity; Conduct Disorder; Adolescence; Continuous Performance Task; Stop Task; Delay Discounting
5.  Impulsivity and Clinical Symptoms among Adolescents with Non-Suicidal Self-Injury with or without Attempted Suicide 
Psychiatry research  2009;169(1):22-27.
This study examined clinical characteristics and laboratory-measured impulsive behavior of adolescents engaging in either non-suicidal self-injury with (NSSI+SA; n = 25) or without (NSSI-Only; n = 31) suicide attempts. We hypothesized that adolescent with NSSI+SI would exhibit more severe clinical symptoms and higher levels of behavioral impulsivity compared to adolescents with NSSI-Only. Adolescents were recruited from an inpatient psychiatric hospital unit and the two groups were compared on demographic characteristics, psychopathology, self-reported clinical ratings, methods of non-suicidal self-injury, and two laboratory impulsivity measures. Primary evaluations were conducted during psychiatric hospitalization, and a subset of those tested during hospitalization was retested 4-6 weeks after discharge. During hospitalization, NSSI+SA patients reported worse depression, hopelessness, and impulsivity on standard clinical measures, and demonstrated elevated impulsivity on a reward-directed laboratory measure compared to NSSI-Only patients. In the preliminary follow-up analyses, depression, hopelessness, suicidal ideation, and laboratory impulsivity were improved for both groups, but the NSSI+SA group still exhibited significantly more depressive symptoms, hopelessness, and impulsivity than the NSSI-Only group. Risk assessments for adolescents with NSSI+SA should include consideration not only of the severity of clinical symptoms but of the current level impulsivity as well.
PMCID: PMC3062197  PMID: 19631392
6.  Distinctions in Behavioral Impulsivity: Implications for Substance Abuse Research 
Researchers have clearly implicated impulsivity as having a key role in substance use disorders, and comparisons of self-report measures suggest there are measurably different components of impulsive behavior. However comparatively little research has been devoted to understanding the multidimensional nature of this construct using laboratory measures of impulsivity that may be more sensitive to tracking changes across time. Many studies have measured impulsivity, but this construct has been measured using methodologically different types of laboratory impulsivity paradigms that are often used in isolation. As a result, it is important to determine whether some of the most frequently used types of behavioral measures of impulsivity account for unique variance.
Here, we used factor analytical techniques in two studies to evaluate the independence of three of the most commonly used behavioral impulsivity paradigms. First, a factor analysis was conducted using previously collected data (n = 204), and second, data was gathered specifically to replicate and extend the results of our original analysis (n = 198).
Both studies revealed three distinct factors, confirming our hypothesis of at least three components of impulsive behavior that can be measured by these methodological approaches.
These findings suggest that researchers should carefully consider their selection of laboratory-behavioral impulsivity measures, and that the measure(s) selected should be related to the particular underlying processes relevant to substance use disorders and treatment success.
PMCID: PMC2882111  PMID: 20535237
impulsivity; behavior; factor analysis; human; substance abuse
7.  Activation of Liver Tryptophan Pyrrolase Mediates the Decrease in Tryptophan Availability to the Brain after Acute Alcohol Consumption by Normal Subjects 
Aims: We have previously suggested that acute ethanol consumption by normal subjects decreases the availability of circulating tryptophan (Trp) to the brain by activating liver Trp pyrrolase, the first and rate-limiting enzyme of the (major) kynurenine pathway of Trp degradation. The aim of the present study was to examine this hypothesis further by measuring plasma levels of kynurenine metabolites following alcohol consumption. Methods: After an overnight fast and a light breakfast, each of 10 healthy subjects received one of five drinks (placebo and doses of ethanol of 0.2, 0.4, 0.6 and 0.8 g/kg body weight in tonic water) on five different occasions. Blood samples were withdrawn 2 h later and plasma was analysed for concentrations Trp, competing amino acids (CAA) and kynurenine metabolites. Results: Along with the depletion of plasma Trp and the decrease in its availability to the brain, as expressed by the ratio of [Trp]/[CAA], plasma kynurenine was elevated by doses of ethanol of 0.2–0.8 g/kg body weight. The ratio% of [kynurenine]/[Trp], an index of the expression of Trp pyrrolase activity, was also increased by all doses of ethanol. Conclusions: We conclude that activation of liver Trp pyrrolase mediates the depletion of plasma Trp and the decrease in its availability to the brain induced by acute ethanol consumption.
PMCID: PMC2720730  PMID: 19201692
8.  Differentiating Impulsive and Premeditated Aggression: Self and Informant Perspectives Among Adolescents with Personality Pathology 
Previous research has articulated the conceptual differentiation of impulsive and premeditated aggression. Little, if any, of this research has examined personological differences among adolescents with aggression-oriented pathology, and little, if any, has examined both self and informant perspectives. The current study examined such differentiation within a Conduct Disorder population in which normal and pathological personality characteristics were examined via self- and informant-report. Results indicated the two forms of aggression were independent: high impulsive aggression was associated with high Neuroticism, but high premeditated aggression was associated with low Agreeableness and high Extraversion. Overall, adolescents high in impulsive aggression had a pattern of personality characteristics that are seen as socially-detached and emotionally volatile. In contrast, adolescents high in premeditated aggression had a pattern of characteristics seen as egocentric and socially-engaged but without concern for others. The results have implications for the social and motivational mechanisms producing the two forms of aggression.
PMCID: PMC2854006  PMID: 19267663
9.  Epilepsy surgery outcomes in temporal lobe epilepsy with a normal MRI 
Epilepsia  2009;50(9):2053-2060.
To determine the long-term efficacy of anterior temporal lobectomy for medically refractory temporal lobe epilepsy in patients with nonlesional magnetic resonance imaging (MRI).
We identified a retrospective cohort of 44 patients with a nonlesional modern “seizure protocol” MRI who underwent anterior temporal lobectomy for treatment of medically refractory partial epilepsy. Postoperative seizure freedom was determined by Kaplan-Meyer survival analysis. Noninvasive preoperative diagnostic factors potentially associated with excellent surgical outcome were examined by univariate analysis in the 40 patients with follow-up of >1 year.
Engel class I outcomes (free of disabling seizures) were observed in 60% (24 of 40) patients. Preoperative factors associated with Engel class I outcome were: (1) absence of contralateral or extratemporal interictal epileptiform discharges, (2) subtraction ictal single photon emission computed tomography (SPECT) Coregistered to MRI (SISCOM) abnormality localized to the resection site, and (3) subtle nonspecific MRI findings in the mesial temporal lobe concordant to the resection.
In carefully selected patients with temporal lobe epilepsy and a nonlesional MRI, anterior temporal lobectomy can often render patients free of disabling seizures. This favorable rate of surgical success is likely due to the detection of concordant abnormalities that indicate unilateral temporal lobe epilepsy in patients with nonlesional MRI.
PMCID: PMC2841514  PMID: 19389144
Partial seizures; Epilepsy surgery; Temporal lobe; Nonlesional–MRI
10.  Comparison of 50g and 100g L-tryptophan Depletion and Loading Formulations for Altering 5-HT Synthesis: Pharmacokinetics, Side Effects, and Mood States 
Psychopharmacology  2008;198(3):431.
Differences in 5-HT function have been the subject of extensive research in psychiatric studies. Many studies have manipulated L-tryptophan (Trp) levels to temporarily decrease (depletion) or increase (loading) 5-HT synthesis. While most researchers have used a 100g formulation, there has been ongoing interest in using smaller-sized formulations.
This study examined the time-course of multiple plasma indicators of brain 5-HT synthesis following 50g depletion and loading as a comparison to the typical 100g formulation.
Plasma was collected from 112 healthy adults at 7 hourly intervals following consumption of either a 50g or 100g depletion or loading. Self-ratings of mood and somatic symptoms were completed before and after Trp manipulations.
The primary findings were that: (1) the 50g and 100g formulations produced the expected changes in plasma indicators following both depletion (−89% and −96%, respectively) and loading (+570% and +372%, respectively); (2) the 100g depletion showed more robust effects at the 4, 5, and 6 h measurements than the 50g depletion; (3) there was significant attrition following both the 100g depletion and loading, but not after either 50g formulation; and (4) both 50g and 100g depletions produced increases in negative self-ratings of mood and somatic symptoms, while loading significantly increased negative ratings following the 100g only.
There are important considerations when choosing among formulation sizes for use in Trp manipulation studies, and the complete 7-hr time-course data set of the typical plasma Trp measures presented here may help researchers decide which methodology best suits their needs.
PMCID: PMC2818099  PMID: 18452034
L-tryptophan; depletion; serotonin; time course; human; competing amino acids; side effects; mood
11.  Neural Correlates of Attentional and Mnemonic Processing in Event-Based Prospective Memory 
Prospective memory (PM), or memory for realizing delayed intentions, was examined with an event-based paradigm while simultaneously measuring neural activity with high-density EEG recordings. Specifically, the neural substrates of monitoring for an event-based cue were examined, as well as those perhaps associated with the cognitive processes supporting detection of cues and fulfillment of intentions. Participants engaged in a baseline lexical decision task (LDT), followed by a LDT with an embedded PM component. Event-based cues were constituted by color and lexicality (red words). Behavioral data provided evidence that monitoring, or preparatory attentional processes, were used to detect cues. Analysis of the event-related potentials (ERP) revealed visual attentional modulations at 140 and 220 ms post-stimulus associated with preparatory attentional processes. In addition, ERP components at 220, 350, and 400 ms post-stimulus were enhanced for intention-related items. Our results suggest preparatory attention may operate by selectively modulating processing of features related to a previously formed event-based intention, as well as provide further evidence for the proposal that dissociable component processes support the fulfillment of delayed intentions.
PMCID: PMC2821175  PMID: 20161996
prospective memory; preparatory attention; EEG; ERP; cue detection; lexical decision task
12.  High-frequency oscillations in human temporal lobe: simultaneous microwire and clinical macroelectrode recordings 
Brain : a journal of neurology  2008;131(Pt 4):928-937.
Neuronal oscillations span a wide range of spatial and temporal scales that extend beyond traditional clinical EEG. Recent research suggests that high-frequency oscillations (HFO), in the ripple (80–250Hz) and fast ripple (250–1000Hz) frequency range, may be signatures of epileptogenic brain and involved in the generation of seizures. However, most research investigating HFO in humans comes from microwire recordings, whose relationship to standard clinical intracranial EEG (iEEG) has not been explored. In this study iEEG recordings (DC − 9000Hz) were obtained from human medial temporal lobe using custom depth electrodes containing both microwires and clinical macroelectrodes. Ripple and fast-ripple HFO recorded from both microwires and clinical macroelectrodes were increased in seizure generating brain regions compared to control regions. The distribution of HFO frequencies recorded from the macroelectrodes was concentrated in the ripple frequency range, compared to a broad distribution of HFO frequencies recorded from microwires. The average frequency of ripple HFO recorded from macroelectrodes was lower than that recorded from microwires (143.3 ± 49.3 Hz versus 116.3 ± 38.4, Wilcoxon rank sum P<0.0001). Fast-ripple HFO were most often recorded on a single microwire, supporting the hypothesis that fast-ripple HFO are primarily generated by highly localized, sub-millimeter scale neuronal assemblies that are most effectively sampled by microwire electrodes. Future research will address the clinical utility of these recordings for localizing epileptogenic networks and understanding seizure generation.
PMCID: PMC2760070  PMID: 18263625
high-frequency oscillations; ripple; fast ripple; intracranial EEG; epilepsy
13.  A Test of Alcohol Dose Effects on Multiple Behavioral Measures of Impulsivity 
Drug and alcohol dependence  2008;96(1-2):111-120.
Acute alcohol administration affects impulsive behavior, although these effects vary as a function of alcohol dose, assessment instrument, and time of measurement following administration.
We concurrently examined the dose-dependent effects of alcohol on three distinct types of impulsivity tasks (continuous performance [IMT], stop-signal [GoStop], and delay-discounting [SKIP] tasks). Ninety healthy alcohol drinkers were assigned to one of the three task groups (n = 30 each), each group experienced placebo, 0.2, 0.4, 0.6, and 0.8 g/kg alcohol doses across 5 experimental days, and task performance was assessed at 0.5 h before and 0.25, 1.0, and 2.0 h after alcohol administration. We hypothesized that impulsive responding on all tasks would be increased by acute alcohol administration both across time and during the peak BrAC, but the magnitude would depend on the task being tested. Analyses included the time-course and the peak BrAC effects. Task comparisons of peak behavioral changes following each dose are illustrated using standardized scores.
While alcohol consumption increased impulsive responding during all three tasks to some extent, our hypothesis was only partially supported. During the IMT, the 0.6 and 0.8 g/kg doses produced increased impulsive responding across time and at the peak BrAC. However, during the GoStop and SKIP, impulsivity increased across time regardless of the alcohol dose size, with no differences in impulsive responding among dose conditions at peak BrAC.
This study demonstrated alcohol-induced changes in impulsivity are not uniformly affected by alcohol. These data, in conjunction with previous studies, further support that impulsivity is not a unitary construct.
PMCID: PMC2566966  PMID: 18378098
Alcohol; Doses; Impulsivity; Behavior; Task Comparison; Human; Adults
14.  Adaptive Visual Analog Scales (AVAS): A Modifiable Software Program for the Creation, Administration, and Scoring of Visual Analog Scales 
Behavior research methods  2009;41(1):99-106.
The Adaptive Visual Analog Scales is a freely available computer software package designed to be a flexible tool for the creation, administration, and automated scoring of both continuous and discrete visual analog scale formats. The continuous format is a series of individual items that are rated along a solid line and scored as a percentage of distance from one of the two anchors of the rating line. The discrete format is a series of individual items that use a specific number of ordinal choices for rating each item. This software offers separate options for the creation and use of standardized instructions, practice sessions, and rating administration, all of which can be customized by the investigator. A unique participant/patient ID is used to store scores for each item and individual data from each administration is automatically appended to that scale’s data storage file. This software provides flexible, time-saving access for data management and/or importing data into statistical packages. This tool can be adapted to gather ratings for a wide range of clinical and research uses and is freely available at
PMCID: PMC2635491  PMID: 19182128
16.  Interspecies Transmission of Chronic Wasting Disease Prions to Squirrel Monkeys (Saimiri sciureus) 
Journal of Virology  2005;79(21):13794-13796.
Chronic wasting disease (CWD) is an emerging prion disease of deer and elk. The risk of CWD transmission to humans following exposure to CWD-infected tissues is unknown. To assess the susceptibility of nonhuman primates to CWD, two squirrel monkeys were inoculated with brain tissue from a CWD-infected mule deer. The CWD-inoculated squirrel monkeys developed a progressive neurodegenerative disease and were euthanized at 31 and 34 months postinfection. Brain tissue from the CWD-infected squirrel monkeys contained the abnormal isoform of the prion protein, PrP-res, and displayed spongiform degeneration. This is the first reported transmission of CWD to primates.
PMCID: PMC1262585  PMID: 16227298
17.  Adaptation and Selection of Prion Protein Strain Conformations following Interspecies Transmission of Transmissible Mink Encephalopathy 
Journal of Virology  2000;74(12):5542-5547.
Interspecies transmission of the transmissible spongiform encephalopathies (TSEs), or prion diseases, can result in the adaptation and selection of TSE strains with an expanded host range and increased virulence such as in the case of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease. To investigate TSE strain adaptation, we serially passaged a biological clone of transmissible mink encephalopathy (TME) into Syrian golden hamsters and examined the selection of distinct strain phenotypes and conformations of the disease-specific isoform of the prion protein (PrPSc). The long-incubation-period drowsy (DY) TME strain was the predominate strain, based on the presence of its strain-specific PrPSc following interspecies passage. Additional serial passages in hamsters resulted in the selection of the hyper (HY) TME PrPSc strain-dependent conformation and its short incubation period phenotype unless the passages were performed with a low-dose inoculum (e.g., 10−5 dilution), in which case the DY TME clinical phenotype continued to predominate. For both TME strains, the PrPSc strain pattern preceded stabilization of the TME strain phenotype. These findings demonstrate that interspecies transmission of a single cloned TSE strain resulted in adaptation of at least two strain-associated PrPSc conformations that underwent selection until one type of PrPSc conformation and strain phenotype became predominant. To examine TME strain selection in the absence of host adaptation, hamsters were coinfected with hamster-adapted HY and DY TME. DY TME was able to interfere with the selection of the short-incubation HY TME phenotype. Coinfection could result in the DY TME phenotype and PrPSc conformation on first passage, but on subsequent passages, the disease pattern converted to HY TME. These findings indicate that during TSE strain adaptation, there is selection of a strain-specific PrPSc conformation that can determine the TSE strain phenotype.
PMCID: PMC112040  PMID: 10823860

Results 1-18 (18)