Using Simulated Annealing to Investigate Sensitivity of SEM to External Model Misspecification.

Sensitivity analyses encompass a broad set of post-analytic techniques that are characterized as measuring the potential impact of any factor that has an effect on some output variables of a model. This research focuses on the utility of the simulated annealing algorithm to automatically identify path configurations and parameter values of omitted confounders in structural equation modeling (SEM). An empirical example based on a past published study is used to illustrate how strongly related an omitted variable must be to model variables for the conclusions of an analysis to change. The algorithm is outlined in detail and the results stemming from the sensitivity analysis are discussed.

Identifying auditory cortex encoding abnormalities in schizophrenia: The utility of low-frequency versus 40 Hz steady-state measures.

Magnetoencephalography (MEG) and EEG have identified poststimulus low frequency and 40 Hz steady-state auditory encoding abnormalities in schizophrenia (SZ). Negative findings have also appeared. To identify factors contributing to these inconsistencies, healthy control (HC) and SZ group differences were examined in MEG and EEG source space and EEG sensor space, with better group differentiation hypothesized for source than sensor measures given greater predictive utility for source measures. Fifty-five HC and 41 chronic SZ were presented 500 Hz sinusoidal stimuli modulated at 40 Hz during simultaneous whole-head MEG and EEG. MEG and EEG source models using left and right superior temporal gyrus (STG) dipoles estimated trial-to-trial phase similarity and percent change from prestimulus baseline. Group differences in poststimulus low-frequency activity and 40 Hz steady-state response were evaluated. Several EEG sensor analysis strategies were also examined. Poststimulus low-frequency group differences were observed across all methods. Given an age-related decrease in left STG 40 Hz steady-state activity in HC (HC > SZ), 40 Hz steady-state group differences were evident only in younger participants' source measures. Findings thus indicated that optimal data collection and analysis methods depend on the auditory encoding measure of interest. In addition, whereas results indicated that HC and SZ auditory encoding low-frequency group differences are generally comparable across modality and analysis strategy (and thus not dependent on obtaining construct-valid measures of left and right auditory cortex activity), 40 Hz steady-state group-difference findings are much more dependent on analysis strategy, with 40 Hz steady-state source-space findings providing the best group differentiation.

By our bootstraps: Comparing methods for measuring auditory 40 Hz steady-state neural activity.

Although the 40 Hz auditory steady-state response (ASSR) is of clinical interest, the construct validity of EEG and MEG measures of 40 Hz ASSR cortical microcircuits is unclear. This study evaluated several MEG and EEG metrics by leveraging findings of (a) an association between the 40 Hz ASSR and age in the left but not right hemisphere, and (b) right- > left-hemisphere differences in the strength of the 40 Hz ASSR. The contention is that, if an analysis method does not demonstrate a left 40 Hz ASSR and age relationship or hemisphere differences, then the obtained measures likely have low validity. Fifty-three adults were presented 500 Hz stimuli modulated at 40 Hz while MEG and EEG were collected. ASSR activity was examined as a function of phase similarity (intertrial coherence) and percent change from baseline (total power). A variety of head models (spherical and realistic) and a variety of dipole source modeling strategies (dipole source localization and dipoles fixed to Heschl's gyri) were compared. Several sensor analysis strategies were also tested. EEG sensor measures failed to detect left 40 Hz ASSR and age associations or hemisphere differences. A comparison of MEG and EEG head-source models showed similarity in the 40 Hz ASSR measures and in estimating age and left 40 Hz ASSR associations, indicating good construct validity across models. Given a goal of measuring the 40 Hz ASSR cortical microcircuits, a source-modeling approach was shown to be superior in measuring this construct versus methods that rely on EEG sensor measures.

Translating Adult Electrophysiology Findings to Younger Patient Populations: Difficulty Measuring 40-Hz Auditory Steady-State Responses in Typically Developing Children and Children with Autism Spectrum Disorder.

BACKGROUND: x03B3; (∼30-80 Hz) brain rhythms are thought to be abnormal in neurodevelopmental disorders such as schizophrenia and autism spectrum disorder (ASD). In adult populations, auditory 40-Hz click trains or 40-Hz amplitude-modulated tones are used to assess the integrity of superior temporal gyrus (STG) 40-Hz x03B3;-band circuits. As STG 40-Hz auditory steady-state responses (ASSRs) are not fully developed in children, tasks using these stimuli may not be optimal in younger patient populations. The present study examined this issue in typically developing (TD) children as well as in children with ASD, using source localization to directly assess activity in the principal generators of the 40-Hz ASSR in the left and right primary/secondary auditory cortices. METHODS: 40-Hz amplitude-modulated tones of 1 s duration were binaurally presented while magnetoencephalography data were obtained from 48 TD children (45 males; 7-14 years old) and 42 ASD children (38 males; 8-14 years old). T1-weighted structural MRI was obtained. Using single dipoles anatomically constrained to each participant's left and right Heschl's Gyrus, left and right 40-Hz ASSR total power (TP) and intertrial coherence (ITC) measures were obtained. Associations between 40-Hz ASSR TP, ITC and age as well as STG gray matter cortical thickness (CT) were assessed. Group STG function and structure differences were also examined. RESULTS: TD and ASD did not differ in 40-Hz ASSR TP or ITC. In TD and ASD, age was associated with left and right 40-Hz ASSR ITC (p < 0.01). The interaction term was not significant, indicating in both groups a ∼0.01/year increase in ITC. 40-Hz ASSR TP and ITC were greater in the right than left STG. Groups did not differ in STG CT, and no associations were observed between 40-Hz ASSR activity and STG CT. Finally, right STG transient x03B3; (50-100 ms and 30-50 Hz) was greater in TD versus ASD (significant for TP, trend for ITC). CONCLUSIONS: The 40-Hz ASSR develops, in part, via an age-related increase in neural synchrony. Greater right than left 40-Hz ASSRs (ITC and TP) suggested earlier maturation of right versus left STG neural network(s). Given a ∼0.01/year increase in ITC, 40-Hz ASSRs were weak or absent in many of the younger participants, suggesting that 40-Hz driving stimuli are not optimal for examining STG 40-Hz auditory neural circuits in younger populations. Given the caveat that 40-Hz auditory steady-state neural networks are poorly assessed in children, the present analyses did not point to atypical development of STG 40-Hz ASSRs in higher-functioning children with ASD. Although groups did not differ in 40-Hz auditory steady-state activity, replicating previous studies, there was evidence for greater right STG transient x03B3; activity in TD versus ASD.