Faculty Bibliography

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.

OBJECTIVE: A substantial proportion of children with attention-deficit/hyperactivity disorder (ADHD) also display emotion regulation deficits manifesting as chronic irritability, severe temper outbursts, and aggression. The amygdala is implicated in emotion regulation, but its connectivity and relation to emotion regulation in ADHD has yet to be explored. The purpose of this study was to examine the relationship between intrinsic functional connectivity (iFC) of amygdala circuits and emotion regulation deficits in youth with ADHD. METHOD: Bilateral amygdala iFC was examined using functional magnetic resonance imaging in 63 children with ADHD, aged 6 to 13 years. First, we examined the relationship between amygdala IFC and parent ratings of emotional lability (EL) in children with ADHD. Second, we compared amygdala iFC across subgroups of children with ADHD and high EL (n = 18), ADHD and low EL (n = 20), and typically developing children (TDC), all with low EL (n = 19). RESULTS: Higher EL ratings were associated with greater positive iFC between the amygdala and rostral anterior cingulate cortex in youth with ADHD. EL scores were also negatively associated with iFC between bilateral amygdala and posterior insula/superior temporal gyrus. Patterns of amygdala-cortical iFC in ADHD participants with low EL were not different from the comparison group, and the effect sizes for these comparisons were smaller than those for the trend-level differences observed between the high-EL and TDC groups. CONCLUSIONS: In children with ADHD and a range of EL, deficits in emotion regulation were associated with altered amygdala-cortical iFC. When comparing groups that differed on ADHD status but not EL, differences in amygdala iFC were small and nonsignificant, highlighting the specificity of this finding to emotional deficits, independent of other ADHD symptoms.

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.

d-Cycloserine (DCS) has been shown to enhance memory and, in a previous trial, once-weekly DCS improved negative symptoms in schizophrenia subjects. We hypothesized that DCS combined with a cognitive remediation (CR) program would improve memory of a practiced auditory discrimination task and that gains would generalize to performance on unpracticed cognitive tasks. Stable, medicated adult schizophrenia outpatients participated in the Brain Fitness CR program 3-5 times per week for 8weeks. Subjects were randomly assigned to once-weekly adjunctive treatment with DCS (50mg) or placebo administered before the first session each week. Primary outcomes were performance on an auditory discrimination task, the MATRICS cognitive battery composite score and the Scale for the Assessment of Negative Symptoms (SANS) total score. 36 subjects received study drug and 32 completed the trial (average number of CR sessions=26.1). Performance on the practiced auditory discrimination task significantly improved in the DCS group compared to the placebo group. DCS was also associated with significantly greater negative symptom improvement for subjects symptomatic at baseline (SANS score >/=20). However, improvement on the MATRICS battery was observed only in the placebo group. Considered with previous results, these findings suggest that DCS augments CR and alleviates negative symptoms in schizophrenia patients. However, further work is needed to evaluate whether CR gains achieved with DCS can generalize to other unpracticed cognitive tasks.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) has been associated with deficits in self-regulatory cognitive processes, some of which are thought to lie at the heart of the disorder. Slowing of reaction times (RTs) for correct responses following errors made during decision tasks has been interpreted as an indication of intact self-regulatory functioning and has been shown to be attenuated in school-aged children with ADHD. This study attempted to examine whether ADHD symptoms are associated with an early-emerging deficit in posterror slowing. METHOD: A computerized two-choice RT task was administered to an ethnically diverse sample of preschool-aged children classified as either "control" (n = 120) or "hyperactive/inattentive" (HI; n = 148) using parent- and teacher-rated ADHD symptoms. Analyses were conducted to determine whether HI preschoolers exhibit a deficit in this self-regulatory ability. RESULTS: HI children exhibited reduced posterror slowing relative to controls on the trials selected for analysis. Supplementary analyses indicated that this may have been due to a reduced proportion of trials following errors on which HI children slowed rather than due to a reduction in the absolute magnitude of slowing on all trials following errors. CONCLUSIONS: High levels of ADHD symptoms in preschoolers may be associated with a deficit in error processing as indicated by posterror slowing. The results of supplementary analyses suggest that this deficit is perhaps more a result of failures to perceive errors than of difficulties with executive control.

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.

There are no established screening criteria to help identify mothers of premature infants who are at risk for symptoms of emotional distress. The current study, using data obtained from recruitment and screening in preparation for a randomized controlled trial, aimed to identify potential risk factors associated with symptoms of depression, anxiety and posttraumatic stress in a sample of mothers with premature infants hospitalized in a neonatal intensive care unit. One hundred, thirty-five mothers of preterm infants born at 26-34 weeks of gestation completed three self-report measures: the Stanford Acute Stress Reaction Questionnaire, the Beck Depression Inventory (2nd ed.), and the Beck Anxiety Inventory to determine their eligibility for inclusion in a treatment intervention study based on clinical cut-off scores for each measure. Maternal sociodemographic measures, including race, ethnicity, age, maternal pregnancy history, and measures of infant medical severity were not helpful in differentiating mothers who screened positive on one or more of the measures from those who screened negative. Programs to screen parents of premature infants for the presence of symptoms of posttraumatic stress, anxiety, and depression will need to adopt universal screening rather than profiling of potential high risk parents based on their sociodemographic characteristics or measures of their infant's medical severity.

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.

Enophthalmos, the posterior displacement of a normal-size ocular globe relative to the orbital cavity, is usually repaired using autogenous grafts or alloplastic materials. We present the case of a 40-year-old man with bilateral idiopathic enophthalmos whose symptoms recurred 8 years after initial successful surgical repair. We describe the successful and safe use of a bilateral temporoparietal adipofascial flap in the treatment of recurrent idiopathic enophthalmos.

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.