Faculty Bibliography

Spike-wave discharges (SWDs) are thalamocortical oscillations that are often considered to be the EEG correlate of absence seizures. Genetic absence epilepsy rats of Strasbourg (GAERS) and Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) exhibit SWDs and are considered to be genetic animal models of absence epilepsy. However, it has been reported that other rat strains have SWDs, suggesting that SWDs may vary in their prevalence, but all rats have a predisposition for them. This is important because many of these rat strains are used to study temporal lobe epilepsy (TLE), where it is assumed that there is no seizure-like activity in controls. In the course of other studies using the Sprague-Dawley rat, a common rat strain for animal models of TLE, we found that approximately 19% of 2- to 3-month-old naive female Sprague-Dawley rats exhibited SWDs spontaneously during periods of behavioral arrest, which continued for months. Males exhibited SWDs only after 3months of age, consistent with previous reports (Buzsaki et al., 1990). Housing in atypical lighting during early life appeared to facilitate the incidence of SWDs. Spike-wave discharges were often accompanied by behaviors similar to stage 1-2 limbic seizures. Therefore, additional analyses were made to address the similarity. We observed that the frequency of SWDs was similar to that of hippocampal theta rhythm during exploration for a given animal, typically 7-8Hz. Therefore, activity in the frequency of theta rhythm that occurs during frozen behavior may not reflect seizures necessarily. Hippocampal recordings exhibited high frequency oscillations (>250Hz) during SWDs, suggesting that neuronal activity in the hippocampus occurs during SWDs, i.e., it is not a passive structure. The data also suggest that high frequency oscillations, if rhythmic, may reflect SWDs. We also confirmed that SWDs were present in a common animal model of TLE, the pilocarpine model, using female Sprague-Dawley rats. Therefore, damage and associated changes to thalamic, hippocampal, and cortical neurons do not prevent SWDs, at least in this animal model. The results suggest that it is possible that SWDs occur in rodent models of TLE and that investigators mistakenly assume that they are stage 1-2 limbic seizures. We discuss the implications of the results and ways to avoid the potential problems associated with SWDs in animal models of TLE.

BACKGROUND:In toxicology studies, perfluorinated compounds affect fetal growth, development, viability, and postnatal growth. There are limited epidemiologic studies on child development. METHODS:We recruited and evaluated 321 children who participated in the C8 Health Project, a 2005-06 survey in a mid-Ohio Valley community highly exposed to perfluorooctanoate (PFOA) through contaminated drinking water. We examined associations between measured childhood PFOA serum concentration and mother and teacher reports of executive function (Behaviour Rating Inventory of Executive Function), attention deficit hyperactivity disorder (ADHD)-like behaviour (Conner's ADHD Diagnostic and Statistical Manual of Mental Disorders IV Scales), and behavioural problems (Behaviour Assessment System for Children) assessed 3 to 4 years later at ages 6-12 years. RESULTS:Overall, neither reports from mothers nor teachers provided clear associations between exposure and child behaviour. Mother reports, however, did suggest favourable associations between exposure and behaviour among boys and adverse associations among girls. On the composite scale from the Behaviour Rating Inventory of Executive Function (n = 318), PFOA exposure had a favourable association among boys (highest vs. lowest quartile β = -6.39; 95% confidence interval [CI] -11.43, -1.35) and an adverse association among girls (highest vs. lowest quartile β = 4.42; 95% CI -0.03, 8.87; interaction P = 0.01). Teacher reports (n = 189) replicated some, but not all of the sex interactions observed in mothers' reports. CONCLUSIONS:Aggregate results did not suggest adverse effects of PFOA on behaviour, but sex-specific results raise the possibility of differing patterns by sex. Results are not consistent between mothers' and teachers' reports. Effect modification by sex may warrant further investigation.

The ascendancy of functional neuroimaging has facilitated the addition of network-based approaches to the neuropsychologist's toolbox for evaluating the sequelae of brain insult. In particular, intrinsic functional connectivity (iFC) mapping of resting state fMRI (R-fMRI) data constitutes an ideal approach to measuring macro-scale networks in the human brain. Beyond the value of iFC mapping for charting how the functional topography of the brain is altered by insult and injury, iFC analyses can provide insights into experience-dependent plasticity at the macro level of large-scale functional networks. Such insights are foundational to the design of training and remediation interventions that will best facilitate recovery of function. In this review, we consider what is currently known about the origin and function of iFC in the brain, and how this knowledge is informative in neuropsychological settings. We then summarize studies that have examined experience-driven plasticity of iFC in healthy control participants, and frame these findings in terms of a schema that may aid in the interpretation of results and the generation of hypotheses for rehabilitative studies. Finally, we outline some caveats to the R-fMRI approach, as well as some current developments that are likely to bolster the utility of the iFC paradigm for neuropsychology.

BACKGROUND: Cogmed Working Memory Training (CWMT) has received considerable attention as a promising intervention for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children. At the same time, methodological weaknesses in previous clinical trials call into question reported efficacy of CWMT. In particular, lack of equivalence in key aspects of CWMT (i.e., contingent reinforcement, time-on-task with computer training, parent-child interactions, supportive coaching) between CWMT and placebo versions of CWMT used in previous trials may account for the beneficial outcomes favoring CWMT. METHODS: Eighty-five 7- to 11-year old school-age children with ADHD (66 male; 78%) were randomized to either standard CWMT (CWMT Active) or a well-controlled CWMT placebo condition (CWMT Placebo) and evaluated before and 3 weeks after treatment. Dependent measures included parent and teacher ratings of ADHD symptoms; objective measures of attention, activity level, and impulsivity; and psychometric indices of working memory and academic achievement (Clinical trial title: Combined cognitive remediation and behavioral intervention for the treatment of Attention-Deficit/Hyperactivity Disorder; http://clinicaltrials.gov/ct2/show/NCT01137318). RESULTS: CWMT Active participants demonstrated significantly greater improvements in verbal and nonverbal working memory storage, but evidenced no discernible gains in working memory storage plus processing/manipulation. In addition, no treatment group differences were observed for any other outcome measures. CONCLUSIONS: When a more rigorous comparison condition is utilized, CWMT demonstrates effects on certain aspects of working memory in children with ADHD; however, CWMT does not appear to foster treatment generalization to other domains of functioning. As such, CWMT should not be considered a viable treatment for children with ADHD.

Thalamus is a key crossroad structure involved in various functions relative to visual, auditory, gustatory, and somatosensory senses. Because of the specific organization of the olfactory pathway (i.e., no direct thalamic relay between sensory neurons and primary cortex), relatively little attention has been directed toward the thalamus in olfaction. However, an olfactory thalamus exists: the mediodorsal nucleus of the thalamus (MDT) receives input from various olfactory structures including the piriform cortex. How the MDT contributes to olfactory perception remains unanswered. The present study is a first step to gain insight into the function of the MDT in olfactory processing. Spontaneous and odor-evoked activities were recorded in both the MDT (single unit and local field potential) and the piriform cortex (local field potential) of urethane-anesthetized rats. We demonstrate that: 1) odorant presentation induces a conjoint, coherent emergence of beta-frequency-band oscillations in both the MDT and the piriform cortex; 2) 51% of MDT single units were odor-responsive with narrow-tuning characteristics across an odorant set, which included biological, monomolecular, and mixture stimuli. In fact, a majority of MDT units responded to only one odor within the set; 3) the MDT and the piriform cortex showed tightly related activities with, for example, nearly 20% of MDT firing in phase with piriform cortical beta-frequency oscillations; and 4) MDT-piriform cortex coherence was state-dependent with enhanced coupling during slow-wave activity. These data are discussed in the context of the hypothesized role of MDT in olfactory perception and attention.

Contemporary models of obsessive-compulsive disorder emphasize the importance of harm avoidance (HA) and related dysfunctional beliefs as motivators of obsessive-compulsive (OC) symptoms. Recently, there has been a resurgence of interest in Janet's (1908) concept of incompleteness (INC) as another potentially important motivator. Contemporary investigators define INC as the sense that one's actions, intentions, or experiences have not been properly achieved. Janet defined INC more broadly to include alexithymia, depersonalization, derealization, and impaired psychological mindedness. We conducted two studies to address four issues: (a) the clinical correlates of INC; (b) whether INC and HA are distinguishable constructs; (c) whether INC predicts OC symptoms after controlling for HA; and (d) the relative merits of broad versus narrow conceptualizations of INC. Study 1 was a meta-analysis of the clinical correlates of narrowly defined INC (16 studies, N=5,940). INC was correlated with all types of OC symptoms, and was more strongly correlated with OC symptoms than with general distress. Study 2 (N=534 nonclinical participants) showed that (a) INC and HA were strongly correlated but factor analytically distinguishable; (b) INC statistically predicted all types of OC symptoms even after controlling for HA; and (c) narrow INC was most strongly correlated with OC symptoms whereas broad INC was most strongly correlated with general distress. Although the findings are limited by being correlational in nature, they support the hypothesis that INC, especially in its narrow form, is a motivator of OC symptoms.

In addition to motor and/or vocal tics, many individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) report frequent, uncomfortable sensory phenomena that immediately precede the tics. To date, examination of these premonitory sensations or urges has been limited by inconsistent assessment tools. In this paper, we examine the psychometric properties of a nine-item self-report measure, the Premonitory Urge to Tic Scale (PUTS) and examine the characteristics and correlates of the premonitory urge to tic in a clinical sample of 122 older adolescents and adults with TS or CTD. The PUTS demonstrated adequate internal consistency, temporal stability, and concurrent validity. Premonitory urges were endorsed by the majority of individuals. Most individuals reported some relief from the urges after completing a tic and being able to stop their tics even if only temporarily. Degree of premonitory urges was not significantly correlated with age, and we did not observe any gender differences. Degree of premonitory urges was significantly correlated with estimated IQ and tic severity, but not severity of comorbid obsessive-compulsive disorder or attention-deficit hyperactivity disorder. Also, it was not related to concomitant medication status. These findings represent another step forward in our understanding of the premonitory sensations associated with TS and CTD.

BACKGROUND: Extensive research indicates that obesity, defined by a body mass index (BMI) greater or equal to 30, is common in patients treated with antipsychotic drugs and is frequently associated with carbohydrate and lipid abnormalities leading to metabolic syndrome and diabetes. In contrast, the metabolic health of overweight patients (BMI=25-29.9) without metabolic syndrome or diabetes has not been thoroughly investigated. OBJECTIVE: To assess the metabolic health of overweight patients receiving antipsychotic drugs. METHODS: We compared standard metabolic parameters (BMI; waist circumference; hemoglobin A1c; fasting lipids; and fasting and post-challenge glucose and insulin) of normal weight, overweight and obese individuals from a consecutive cohort of antipsychotic-treated patients without metabolic syndrome and/or diabetes. RESULTS: Compared with the normal weight subjects (n=286), overweight patients (n=212) had higher fasting insulin resistance as assessed with the homeostatic model (P=0.023), insulin secretion during the oral glucose tolerance test (P=0.0037), triglycerides (P=0.0004) and low-density lipoprotein cholesterol (P=0.0089), and lower levels of high-density lipoprotein cholesterol (P=0.0014). The obese (n=50) were different from the overweight subjects only with respect to higher post-challenge insulin levels (P=0.0002). The average fasting glucose, post-challenge glucose, and hemoglobin A1c, severity of psychiatric disorders and antipsychotics used were similar in the three groups. CONCLUSIONS: Overweight (BMI=25-29.9) patients receiving antipsychotics are metabolically closer to the obese than to normal weight counterparts. The findings suggest that interventions promoting weight loss and metabolic health are required for overweight patients even in the absence of metabolic syndrome or diabetes.

Evidence is emerging to support the promise of Attention Bias Modification Treatment (ABMT), a computer-based attention training program, in reducing anxiety in children. ABMT has not been tested as an adjuvant for children with anxiety disorders who do not respond to Cognitive-Behavioral Therapy (CBT). This case series presents findings from an open trial of ABMT among six children (four girls; M age = 11.2 years) who completed a CBT protocol and continued to meet diagnostic criteria for an anxiety disorder. All children completed the ABMT protocol with no canceled or missed sessions. Child self-ratings on anxiety symptoms and depressive symptoms significantly decreased from pretreatment to posttreatment, as did parent ratings on child anxiety-related impairment. Parent ratings on child anxiety and internalizing symptoms displayed non-significant decreases from pretreatment to posttreatment. These findings support the potential promise of ABMT as a feasible adjuvant treatment that reduces anxiety and impairment among child anxiety CBT nonresponders.