The neural response to changing semantic and perceptual complexity during language processing

Speech comprehension involves processing at different levels of analysis, such as acoustic, phonetic, and lexical. We investigated neural responses to manipulating the difficulty of processing at two of these levels. Twelve subjects underwent positron emission tomographic scanning while making decisions based upon the semantic relatedness between heard nouns. We manipulated perceptual difficulty by presenting either clear or acoustically degraded speech, and semantic difficulty by varying the degree of semantic relatedness between words. Increasing perceptual difficulty was associated with greater activation of the left superior temporal gyrus, an auditory‐perceptual region involved in speech processing. Increasing semantic difficulty was associated with reduced activity in both superior temporal gyri and increased activity within the left angular gyrus, a heteromodal region involved in accessing word meaning. Comparing across all the conditions, we also observed increased activation within the left inferior prefrontal cortex as the complexity of language processing increased. These results demonstrate a flexible system for language processing, where activity within distinct parts of the network is modulated as processing demands change. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Biological changes in auditory function following training in children with autism spectrum disorders

Background  

Children with pervasive developmental disorders (PDD), such as children with autism spectrum disorders (ASD), often show auditory processing deficits related to their overarching language impairment. Auditory training programs such as Fast ForWord Language may potentially alleviate these deficits through training-induced improvements in auditory processing.     

Challenging behavior and co-morbid psychopathology in adults with intellectual disability and autism spectrum disorders

We investigated the relationship between challenging behavior and co-morbid psychopathology in adults with intellectual disability (ID) and autism spectrum disorders (ASDs) (N = 124) as compared to adults with ID only (N = 562). All participants were first time referrals to specialist mental health services and were living in community settings. Clinical diagnoses were based on ICD-10 criteria and presence of challenging behavior was assessed with the Disability Assessment Schedule (DAS-B). The analyses showed that ASD diagnosis was significantly associated with male gender, younger age and lower level of ID. Challenging behavior was about four times more likely in adults with ASD as compared to non-ASD adults. In those with challenging behavior, there were significant differences in co-morbid psychopathology between ASD and non-ASD adults. However, after controlling for level of ID, gender and age, there was no association between co-morbid psychopathology and presence of challenging behavior. Overall, the results suggest that presence of challenging behavior is independent from co-morbid psychopathology in adults with ID and ASD.     

Paracingulate Sulcus Length Is Shorter in Voice-Hearers Regardless of Need for Care

Hallucinations—while often considered an indication of mental illness—are commonly experienced by those without a need for clinical care. These nonclinical voice-hearers offer an opportunity to investigate hallucinations in the absence of confounds inherent to the clinical state. Recent work demonstrates an association between auditory verbal hallucinations (AVH) and structural variability in paracingulate sulcus (PCS) of medial prefrontal cortex in a clinical population. However, before PCS length may be considered a biomarker for clinical hallucination risk, it is necessary to investigate PCS structure in a nonclinical population of voice-hearers with AVH phenomenology similar to those of their clinical counterparts. In the current study, PCS length was measured from T1-weighted structural MRI scans of four groups of participants: (1) voice-hearers with a psychotic disorder (n = 15); (2) voice-hearers without a psychotic disorder (n = 15); (3) nonvoice-hearers with a psychotic disorder (n = 14); and (4) nonvoice-hearers without a psychotic disorder (n = 15). There was a main effect of AVH status—but not psychosis—on right PCS length, with no interaction of AVH and psychosis. Participants with AVH exhibited reduced right PCS length compared to participants without AVH (mean reduction = 8.8 mm, P < 0.05). While past studies have demonstrated decreased PCS length in clinical voice-hearers, ours is the first demonstration that shorter right PCS extends to nonclinical voice-hearers. Our findings support the hypothesis that differences in PCS length are related to the propensity to hear voices and not to illness, consistent with a continuum model of voice-hearing.     

The effects of old age and distraction on the assessment of prospective memory in a simulated naturalistic environment

BACKGROUND: The ability to remember to complete future intentions, prospective memory, often begins to fail in old age. The aim of the present study was to examine the sensitivity of a computer-based procedure using naturalistic stimuli to age-related increases in forgetting under conditions of high (increased visual and auditory noise) or low distraction. METHODS: Participants were tested in a virtual shopping precinct constructed from linked photographs, sounds, and video segments. Groups of 32 older and younger persons completed two concurrent memory tasks while moving along the street. In one task, participants were given errands to complete with an accessible checklist, in the other, they were required to remember to respond to three different targets that appeared repeatedly. RESULTS: The results confirmed previous findings that older adults have difficulty remembering future intentions, even on a self-paced task using naturalistic stimuli, and showed that this was accentuated in noisy environments. CONCLUSIONS: Older persons have particular difficulty remembering in noisy environments, and results from testing in the clinic may underestimate the practical memory problems experienced by older adults with mild cognitive impairments. The findings provide encouragement for the construction of computer-generated environments to measure functional deficits in cognition.     

Juvenile Alpers disease

BACKGROUND: Alpers disease is commonly associated with polymerase gamma deficiency and usually affects infants or young children. OBJECTIVE: To report a juvenile case of Alpers disease due to mutations in the polymerase gamma gene (POLG1). DESIGN: Clinical, pathologic, biochemical, and molecular analysis. SETTING: Tertiary care university hospital and academic institutions. PATIENT: A 17-year-old adolescent girl with intractable epilepsy and liver disease. MAIN OUTCOME MEASURES: Clinical course and pathologic, biochemical, and molecular features. RESULTS: Biochemical and pathologic evidence suggested a respiratory chain defect, which was confirmed by enzyme analysis of the liver. Mutational analysis of POLG1 showed 2 novel mutations: T851A and R1047W. CONCLUSION: The POLG1 mutations can cause juvenile and childhood Alpers disease.     

Neutrophil CD40 enhances platelet-mediated inflammation

INTRODUCTION: CD40 is a transmembrane protein expressed on monocytes, macrophages, endothelial cells, and platelets. Platelets are the richest source of soluble CD40 ligand (sCD40L) and interact with monocytes and endothelial cells via CD40. While CD40 was recently reported to be present on neutrophils, the detailed mechanism of its interaction with platelets via CD40-CD40L has not been examined. MATERIALS AND METHODS: The existence of neutrophil CD40 was verified by real-time PCR and western blot. Platelet sCD40L release was measured by ELISA. Neutrophil superoxide generation was measured by chemiluminescence and confocal microscopy. The neutrophil-platelet conjugates were measured by flow cytometry. RESULTS AND CONCLUSION: The presence of neutrophils enhances stimulation-induced platelet release of sCD40L. The addition of platelets leads to an enhancement of neutrophil superoxide and reactive oxygen species (ROS) generation. The specificity of the CD40-CD40L pathway in the neutrophil-platelet interaction was confirmed by using recombinant soluble CD40L (rsCD40L) and an anti-CD40L antibody. The involvement of the PI3 kinase/Akt pathway in neutrophil superoxide production was revealed by using LY294002 in isolated neutrophils/platelets experiments, as well as during whole blood aggregation-mediated neutrophil-platelet conjugation. N-acetylcysteine, a scavenger of ROS, eliminates both neutrophil superoxide generation and sCD40L release from activated platelets. These data suggest that activated neutrophils release ROS in a PI3 kinase-dependent manner, contributing to platelet activation and further sCD40L release in a redox-controlled positive feed-back loop. In conclusion, our results define a new pathway by which platelets and neutrophils interact and modulate each other's function, and may be relevant in understanding acute thrombo-inflammatory processes.     

Should children with cerebral palsy and normal imaging undergo testing for inherited metabolic disorders?

Aim  For the 9% to 16% of children with cerebral palsy (CP) who have normal brain imaging, further testing for metabolic and/or genetic conditions has been recommended. This study aimed to identify a cohort of children with CP with normal magnetic resonance imaging (MRI), clinically review and describe the cases, and assess the value of testing for inherited metabolic disorders in these children. Method  Children with congenital CP born from 1999 to 2005 were selected from a population register. Normal MRI reports were identified and the scans reassessed. Children whose scans were performed before 18 months were excluded, as were children with spastic CP (Gross Motor Function Classification System [GMFCS] level I). The remainder were reviewed clinically and offered investigations. Results  Of 730 children identified, 515 had available imaging and 54 were confirmed as normal. Cases with non‐spastic CP and those with milder clinical severity were more likely to have normal imaging. Twenty‐three children (17 males, six females; mean age 6y 11mo, SD 1y 10mo, range 3y 0mo to 10y 0mo) were reviewed clinically and offered investigations. Twelve children had spasticity (11 with diplegia, one quadriplegia), three had dyskinesia, five ataxia, and three hypotonia. Two children functioned in GMFCS level I, 11 in level II, seven in level III and three in level IV. Four children with spasticity had unusual features. No alternative diagnoses were made. Interpretation  Although important to consider in individual cases, comprehensive metabolic testing failed to clarify the aetiology of CP further in this large cohort of children with normal MRIs, even those with atypical features.     

Prefrontal Responses during Proactive and Reactive Inhibition Are Differentially Impacted by Stress in Anorexia and Bulimia Nervosa

Binge eating is a distressing, transdiagnostic eating disorder symptom associated with impulsivity, particularly in negative mood states. Neuroimaging studies of bulimia nervosa (BN) report reduced activity in frontostriatal regions implicated in self-regulatory control, and an influential theory posits that binge eating results from self-regulation failures under stress. However, there is no direct evidence that psychological stress impairs self-regulation in binge-eating disorders, or that any such self-regulatory deficits generalize to binge eating in underweight individuals (i.e., anorexia nervosa bingeing/purging subtype; AN-BP). We therefore determined the effect of acute stress on inhibitory control in 85 women (BN, 33 women; AN-BP, 22 women; 30 control participants). Participants underwent repeated functional MRI scanning during performance of the Stop-signal anticipation task, a validated measure of proactive (i.e., anticipation of stopping) and reactive (outright stopping) inhibition. Neural and behavioral responses to induced stress and a control task were evaluated on 2 consecutive days. Women with BN had reduced proactive inhibition, while prefrontal responses were increased in both AN-BP and BN. Reactive inhibition was neurally and behaviorally intact in both diagnostic groups. Both AN-BP and BN groups showed distinct stress-induced changes in inferior and superior frontal activity during both proactive and reactive inhibition. However, task performance was unaffected by stress. These results offer novel evidence of reduced proactive inhibition in BN, yet inhibitory control deficits did not generalize to AN-BP. Our findings identify intriguing alterations of stress responses and inhibitory function associated with binge eating, but they counsel against stress-induced failures of inhibitory control as a comprehensive explanation for loss-of-control eating.SIGNIFICANCE STATEMENT Binge eating is a common psychiatric syndrome that feels uncontrollable to the sufferer. Theoretically, it has been related to reduced self-regulation under stress, but there remains no direct evidence for this link in binge-eating disorders. Here, we examined how experimentally induced stress affected response inhibition in control participants and women with anorexia nervosa and bulimia nervosa. Participants underwent repeated brain scanning under stressful and neutral conditions. Although patient groups had intact action cancellation, the slowing of motor responses was impaired in bulimia nervosa, even when the likelihood of having to stop increased. Stress altered brain responses for both forms of inhibition in both groups, yet performance remained unimpaired. These findings counsel against a simple model of stress-induced disinhibition as an adequate explanation for binge eating.