Kristen Merkle

Early Behavioral Intervention Is Associated With Normalized Brain Activity in Young Children With Autism

OBJECTIVE A previously published randomized clinical trial indicated that a developmental behavioral intervention, the Early Start Denver Model (ESDM), resulted in gains in IQ, language, and adaptive behavior of children with autism spectrum disorder. This report describes a secondary outcome measurement from this trial, EEG activity. METHOD Forty-eight 18- to 30-month-old children with autism spectrum disorder were randomized to receive the ESDM or referral to community intervention for 2 years. After the intervention (age 48 to 77 months), EEG activity (event-related potentials and spectral power) was measured during the presentation of faces versus objects. Age-matched typical children were also assessed. RESULTS The ESDM group exhibited greater improvements in autism symptoms, IQ, language, and adaptive and social behaviors than the community intervention group. The ESDM group and typical children showed a shorter Nc latency and increased cortical activation (decreased α power and increased θ power) when viewing faces, whereas the community intervention group showed the opposite pattern (shorter latency event-related potential [ERP] and greater cortical activation when viewing objects). Greater cortical activation while viewing faces was associated with improved social behavior. CONCLUSIONS This was the first trial to demonstrate that early behavioral intervention is associated with normalized patterns of brain activity, which is associated with improvements in social behavior, in young children with autism spectrum disorder.

The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: the VISIONS prospective cohort magnetic resonance imaging study*.

Objective:Evidence is emerging that delirium duration is a predictor of long-term cognitive impairment in intensive care unit survivors. Relationships between 1) delirium duration and brain white matter integrity, and 2) white matter integrity and long-term cognitive impairment are poorly understood and could be explored using magnetic resonance imaging. Design, Setting, Patients:A two-center, prospective cohort study incorporating delirium monitoring, neuroimaging, and cognitive testing in intensive care unit survivors. Measurements:Delirium was evaluated with the Confusion Assessment Method for the Intensive Care Unit and cognitive outcomes were tested at 3 and 12-month follow-up. Following the intensive care unit stay, fractional anisotropy, a measure of white matter integrity, was calculated quantitatively using diffusion tensor imaging with a 3-T magnetic resonance imaging scanner at hospital discharge and 3-month follow-up. We examined associations between 1) delirium duration and fractional anisotropy and 2) fractional anisotropy and cognitive outcomes using linear regression adjusted for age and sepsis. Results:A total of 47 patients with a median age of 50 yrs completed the diffusion tensor imaging-magnetic resonance imaging protocol. Greater duration of delirium (3 vs. 0 days) was associated with lower fractional anisotropy (i.e., reduced fractional anisotropy = white matter disruption) in the genu (−0.02; p = .04) and splenium (−0.01; p = .02) of the corpus callosum and anterior limb of the internal capsule (−0.02; p =.01) at hospital discharge. These associations persisted at 3 months for the genu (−0.02; p =.02) and splenium (−0.01; p = .004). Lower fractional anisotropy in the anterior limb of internal capsule at discharge and in genu of corpus callosum at three months was associated with worse cognitive scores at 3 and 12 months. Conclusions:In this pilot investigation, delirium duration in the intensive care unit was associated with white matter disruption at both discharge and 3 months. Similarly, white matter disruption was associated with worse cognitive scores up to 12 months later. This hypothesis-generating investigation may help design future studies to explore these complex relationships in greater depth.

The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: the VISIONS cohort magnetic resonance imaging study*.

Objective:Delirium duration is predictive of long-term cognitive impairment in intensive care unit survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and long-term cognitive impairment, we conducted this exploratory investigation of the associations between delirium duration, brain volumes, and long-term cognitive impairment. Design, Setting, and Patients:A prospective cohort of medical and surgical intensive care unit survivors with respiratory failure or shock. Measurements:Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and 3-month follow-up. Delirium was evaluated using the confusion assessment method for the intensive care unit; cognitive outcomes were tested at 3- and 12-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes. Results:A total of 47 patients completed the magnetic resonance imaging protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio at hospital discharge (0.76, 95% confidence intervals [0.10, 1.41]; p = .03) and at 3-month follow-up (0.62 [0.02, 1.21], p = .05). Longer duration of delirium was associated with smaller superior frontal lobe (−2.11 cm3 [−3.89, −0.32]; p = .03) and hippocampal volumes at discharge (−0.58 cm3 [−0.85, −0.31], p < .001)—regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher ventricle-to-brain ratio) at 3 months was associated with worse cognitive performances at 12 months (lower Repeatable Battery for the Assessment of Neuropsychological Status score −11.17 [−21.12, −1.22], p = .04). Smaller superior frontal lobes, thalamus, and cerebellar volumes at 3 months were associated with worse executive functioning and visual attention at 12 months. Conclusions:These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to 3 months after discharge, and that smaller brain volumes are associated with long-term cognitive impairment up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.

ERP responses differentiate inverted but not upright face processing in adults with ASD

Individuals with autism spectrum disorders (ASD) have documented deficits in face processing, face memory and abnormal activation of the neural circuitry that supports these functions. To examine speed of processing of faces in ASD, high density event-related brain potentials were recorded to images of faces, inverted faces and non-face objects from 32 high-functioning adults with ASD and controls. Participants were instructed to focus on a cross hair prior to stimulus onset; the cross-hair location directed the participants eye gaze to the eye region at stimulus onset. Although the ASD group preformed more poorly on behavioral tests of face and object memory, both groups demonstrated similar ERP responses, characterized by greater (positive) P1 and (negative) N170 amplitude to faces vs houses. N170 speed of processing to faces did not differ between groups. However, only the control group demonstrated differential responses to upright vs inverted faces. For the ASD group, the differential response to inverted vs upright faces was associated with better performance on face memory and self-reported social skills. It is possible that the use of attention cues may facilitate face processing in high-functioning adults with ASD, suggesting that the underlying neural circuitry can be activated in adults with ASD under specific demands.

The effects of face expertise training on the behavioral performance and brain activity of adults with high functioning autism spectrum disorders.

The effect of expertise training with faces was studied in adults with ASD who showed initial impairment in face recognition. Participants were randomly assigned to a computerized training program involving either faces or houses. Pre- and post-testing included standardized and experimental measures of behavior and event-related brain potentials (ERPs), as well as interviews after training. After training, all participants met behavioral criteria for expertise with the specific stimuli on which they received training. Scores on standardized measures improved after training for both groups, but only the face training group showed an increased face inversion effect behaviorally and electrophysiological changes to faces in the P100 component. These findings suggest that individuals with ASD can gain expertise in face processing through training.

Response to familiar faces, newly familiar faces, and novel faces as assessed by ERPs is intact in adults with autism spectrum disorders.

Individuals with autism spectrum disorders (ASD) have pervasive impairments in social functioning, which may include problems with processing and remembering faces. In this study, we examined whether posterior ERP components associated with identity processing (P2, N250 and face-N400) and components associated with early-stage face processing (P1 and N170) are atypical in ASD. We collected ERP responses to a familiar repeated face (Familiar), an unfamiliar repeated face (Other) and novel faces (Novels) in 29 high-functioning adults with ASD and matched controls. For both groups, the P2 and N250 were sensitive to repetition (Other vs. Novels) and personal familiarity (Familiar vs. Other), and the face-N400 was sensitive to repetition. Adults with ASD did not show significantly atypical processing of facial familiarity and repetition in an ERP paradigm, despite showing significantly poorer performance than controls on a behavioral test of face memory. This study found no evidence that early-stage facial identity processing is a primary contributor to the face recognition deficit in high-functioning ASD.

TODDLERS WITH ELEVATED AUTISM SYMPTOMS SHOW SLOWED HABITUATION TO FACES

We explored social information processing and its relation to social and communicative symptoms in toddlers with Autism Spectrum Disorder (ASD) and their siblings. Toddlers with more severe symptoms of autism showed slower habituation to faces than comparison groups; slower face learning correlated with poorer social skills and lower verbal ability. Unaffected toddlers who were siblings of children with ASD also showed slower habituation to faces compared with toddlers without siblings with ASD. We conclude that slower rates of face learning may be an endophenotype of ASD and is associated with more severe symptoms among affected individuals.

Brief Report: Face Configuration Accuracy and Processing Speed Among Adults with High-Functioning Autism Spectrum Disorders

The present study investigates the accuracy and speed of face processing employed by high-functioning adults with autism spectrum disorders (ASDs). Two behavioral experiments measured sensitivity to distances between features and face recognition when performance depended on holistic versus featural information. Results suggest adults with ASD were less accurate, but responded as quickly as controls for both tasks. In contrast to previous findings with children, adults with ASD demonstrated a holistic advantage only when the eye region was tested. Both groups recognized large manipulations to second-order relations more accurately than no change or small changes, but controls responded more quickly than participants with ASD when recognizing these large manipulations to configural information.

Neural and Cortisol Responses during Play with Human and Computer Partners in Children with Autism

Children with autism spectrum disorder (ASD) exhibit impairment in reciprocal social interactions, including play, which can manifest as failure to show social preference or discrimination between social and nonsocial stimuli. To explore mechanisms underlying these deficits, we collected salivary cortisol from 42 children 8-12 years with ASD or typical development during a playground interaction with a confederate child. Participants underwent functional MRI during a prisoners dilemma game requiring cooperation or defection with a human (confederate) or computer partner. Search region of interest analyses were based on previous research (e.g. insula, amygdala, temporal parietal junction-TPJ). There were significant group differences in neural activation based on partner and response pattern. When playing with a human partner, children with ASD showed limited engagement of a social salience brain circuit during defection. Reduced insula activation during defection in the ASD children relative to TD children, regardless of partner type, was also a prominent finding. Insula and TPJ BOLD during defection was also associated with stress responsivity and behavior in the ASD group under playground conditions. Children with ASD engage social salience networks less than TD children during conditions of social salience, supporting a fundamental disturbance of social engagement.

Variables influencing the neural correlates of perceived risk of physical harm

Many human activities involve a risk of physical harm. However, not much is known about the specific brain regions involved in decision making regarding these risks. To explore the neural correlates of risk perception for physical harms, 19 participants took part in an event-related fMRI study while rating risky activities. The scenarios varied in level of potential harm (e.g., paralysis vs. stubbed toe), likelihood of injury (e.g., 1 chance in 100 vs. 1 chance in 1,000), and format (frequency vs. probability). Networks of brain regions were responsive to different aspects of risk information. Cortical language- processing areas, the middle temporal gyrus, and a region around the bed nucleus of stria terminalis responded more strongly to high- harm conditions. Prefrontal areas, along with subcortical ventral striatum, responded preferentially to high- likelihood conditions. Participants rated identical risks to be greater when information was presented in frequency format rather than probability format. These findings indicate that risk assessments for physical harm engage a broad network of brain regions that are sensitive to the severity of harm, the likelihood of risk, and the framing of risk information.