Effects of age and left hemisphere lesions on audiovisual integration of speech.

Neuroimaging studies have implicated left temporal lobe regions in audiovisual integration of speech and inferior parietal regions in temporal binding of incoming signals. However, it remains unclear which regions are necessary for audiovisual integration, especially when the auditory and visual signals are offset in time. Aging also influences integration, but the nature of this influence is unresolved. We used a McGurk task to test audiovisual integration and sensitivity to the timing of audiovisual signals in two older adult groups: left hemisphere stroke survivors and controls. We observed a positive relationship between age and audiovisual speech integration in both groups, and an interaction indicating that lesions reduce sensitivity to timing offsets between signals. Lesion-symptom mapping demonstrated that damage to the left supramarginal gyrus and planum temporale reduces temporal acuity in audiovisual speech perception. This suggests that a process mediated by these structures identifies asynchronous audiovisual signals that should not be integrated.

Meta-analytic connectivity modeling of the human superior temporal sulcus.

The superior temporal sulcus (STS) is a critical region for multiple neural processes in the human brain Hein and Knight (J Cogn Neurosci 20(12): 2125-2136, 2008). To better understand the multiple functions of the STS it would be useful to know more about its consistent functional coactivations with other brain regions. We used the meta-analytic connectivity modeling technique to determine consistent functional coactivation patterns across experiments and behaviors associated with bilateral anterior, middle, and posterior anatomical STS subregions. Based on prevailing models for the cortical organization of audition and language, we broadly hypothesized that across various behaviors the posterior STS (pSTS) would coactivate with dorsal-stream regions, whereas the anterior STS (aSTS) would coactivate with ventral-stream regions. The results revealed distinct coactivation patterns for each STS subregion, with some overlap in the frontal and temporal areas, and generally similar coactivation patterns for the left and right STS. Quantitative comparison of STS subregion coactivation maps demonstrated that the pSTS coactivated more strongly than other STS subregions in the same hemisphere with dorsal-stream regions, such as the inferior parietal lobule (only left pSTS), homotopic pSTS, precentral gyrus and supplementary motor area. In contrast, the aSTS showed more coactivation with some ventral-stream regions, such as the homotopic anterior temporal cortex and left inferior frontal gyrus, pars orbitalis (only right aSTS). These findings demonstrate consistent coactivation maps across experiments and behaviors for different anatomical STS subregions, which may help future studies consider various STS functions in the broader context of generalized coactivations for individuals with and without neurological disorders.

An ALE meta-analysis on the audiovisual integration of speech signals.

The brain improves speech processing through the integration of audiovisual (AV) signals. Situations involving AV speech integration may be crudely dichotomized into those where auditory and visual inputs contain (1) equivalent, complementary signals (validating AV speech) or (2) inconsistent, different signals (conflicting AV speech). This simple framework may allow the systematic examination of broad commonalities and differences between AV neural processes engaged by various experimental paradigms frequently used to study AV speech integration. We conducted an activation likelihood estimation metaanalysis of 22 functional imaging studies comprising 33 experiments, 311 subjects, and 347 foci examining "conflicting" versus "validating" AV speech. Experimental paradigms included content congruency, timing synchrony, and perceptual measures, such as the McGurk effect or synchrony judgments, across AV speech stimulus types (sublexical to sentence). Colocalization of conflicting AV speech experiments revealed consistency across at least two contrast types (e.g., synchrony and congruency) in a network of dorsal stream regions in the frontal, parietal, and temporal lobes. There was consistency across all contrast types (synchrony, congruency, and percept) in the bilateral posterior superior/middle temporal cortex. Although fewer studies were available, validating AV speech experiments were localized to other regions, such as ventral stream visual areas in the occipital and inferior temporal cortex. These results suggest that while equivalent, complementary AV speech signals may evoke activity in regions related to the corroboration of sensory input, conflicting AV speech signals recruit widespread dorsal stream areas likely involved in the resolution of conflicting sensory signals.

Distinct cortical locations for integration of audiovisual speech and the McGurk effect.

Audiovisual (AV) speech integration is often studied using the McGurk effect, where the combination of specific incongruent auditory and visual speech cues produces the perception of a third illusory speech percept. Recently, several studies have implicated the posterior superior temporal sulcus (pSTS) in the McGurk effect; however, the exact roles of the pSTS and other brain areas in "correcting" differing AV sensory inputs remain unclear. Using functional magnetic resonance imaging (fMRI) in ten participants, we aimed to isolate brain areas specifically involved in processing congruent AV speech and the McGurk effect. Speech stimuli were composed of sounds and/or videos of consonant-vowel tokens resulting in four stimulus classes: congruent AV speech (AVCong), incongruent AV speech resulting in the McGurk effect (AVMcGurk), acoustic-only speech (AO), and visual-only speech (VO). In group- and single-subject analyses, left pSTS exhibited significantly greater fMRI signal for congruent AV speech (i.e., AVCong trials) than for both AO and VO trials. Right superior temporal gyrus, medial prefrontal cortex, and cerebellum were also identified. For McGurk speech (i.e., AVMcGurk trials), two clusters in the left posterior superior temporal gyrus (pSTG), just posterior to Heschl's gyrus or on its border, exhibited greater fMRI signal than both AO and VO trials. We propose that while some brain areas, such as left pSTS, may be more critical for the integration of AV speech, other areas, such as left pSTG, may generate the "corrected" or merged percept arising from conflicting auditory and visual cues (i.e., as in the McGurk effect). These findings are consistent with the concept that posterior superior temporal areas represent part of a "dorsal auditory stream," which is involved in multisensory integration, sensorimotor control, and optimal state estimation (Rauschecker and Scott, 2009).

Assessing bioenergetic compromise in autism spectrum disorder with 31P magnetic resonance spectroscopy: preliminary report.

We sought to examine, via Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) in a case-control design, whether bioenergetic deficits in autism spectrum disorders extend to the brain and muscle. Six cases with autism spectrum disorder with suspected mitochondrial dysfunction (age 6-18 years) and 6 age/sex-matched controls underwent (31)P magnetic resonance spectroscopy. The outcomes of focus were muscle resting phosphocreatine and intracellular pH as well as postexercise phosphocreatine recovery time constant and frontal brain phosphocreatine. Intracellular muscle pH was lower in each autism spectrum disorder case than their matched control (6/6, P = .03; P = .0048, paired t test). Muscle phosphocreatine (5/6), brain phosphocreatine (3/4), and muscle phosphocreatine recovery time constant (3/3) trends were in the predicted direction (not all participants completed each). This study introduces (31)P magnetic resonance spectroscopy as a noninvasive tool for assessment of mitochondrial function in autism spectrum disorder enabling bioenergetic assessment in brain and provides preliminary evidence suggesting that bioenergetic defects in cases with autism spectrum disorder are present in muscle and may extend to brain.

Recruiting a special sample with sparse resources: lessons from a study of Gulf War veterans.

BACKGROUND: Recruitment is the most common failure point for clinical studies, with recruitment failure adversely affecting science, dollar costs, human capital, and the ethical risk-benefit trade-off to study participants. Added problems attend recruitment of special and/or challenging candidate populations, particularly in settings of sparse recruitment resources. Obstacles to study recruitment and participation of ill Gulf War veterans (GWVs) include health barriers, work and family obligations, mistrust of the medical/scientific community, and challenges to identifying/reaching potential participants. PURPOSE: We sought to identify and implement a minimal-cost multipronged recruitment approach for a small single-site (<50 participants) study of a special group, ill GWVs, with approaches substantially applicable to other recruitment settings and larger multisite studies. METHODS: Categories of recruitment approach included directed as well as general media, collaborations with support groups/interest groups, local free advertising resources (Craigslist and Backpage), physician outreach, Internet-based approaches, and referrals from study participants and screenees. We describe the subcategories and yield of each approach within each approach. RESULTS: Each approach contributed candidates to the final recruitment tally, with the largest fractional contribution by directed media (52%). Among the remainder, no other individual approach was clearly dominant (largest contribution: 13%). LIMITATIONS: Special population subsamples present special challenges; all approaches cited may not be useful in all settings and subpopulations. CONCLUSIONS: A multipronged suite of minimal-cost approaches led to successful recruitment to target for this single-site clinical trial for a special population with significant recruitment challenges. It additionally yielded a nation-wide corpus of several hundred individuals interested in participation in future studies of GWVs. While certain approaches produced disproportionate yield, it was not possible to predict these a priori. We suggest that this model, which incorporates a suite of approaches, and delineates backup approaches in the event of recruitment shortfall, may provide a template applicable to recruitment of other special samples in settings of limited resources and also is germane to cost-effective recruitment in studies more generally.

Brief report: approaches to 31P-MRS in awake, non-sedated children with and without autism spectrum disorder.

We piloted a suite of approaches aimed to facilitate a successful series of up to four brain and muscle (31)Phosphorus-Magnetic Resonance Spectroscopy ((31)P-MRS) scans performed in one session in 12 awake, non-sedated subjects (ages 6-18), 6 with autism spectrum disorders (ASD) and 6 controls. We targeted advanced preparation, parental input, physical comfort, short scan protocols, allocation of extra time, and subject emotional support. 100% of subjects completed at least one brain scan and one leg muscle scan: 42 of 46 attempted scans were completed (91%), with failures dominated by exercise muscle scans (completed in 6/6 controls but 3/6 cases). One completed scan lacked usable data unrelated to subject/scan procedure (orthodonture affected a frontal brain scan). As a group, these methods provide a foundation for conduct and enhancement of future MR studies in pediatric subjects with ASD.

What's in placebos: who knows? Analysis of randomized, controlled trials.

BACKGROUND: No regulations govern placebo composition. The composition of placebos can influence trial outcomes and merits reporting. PURPOSE: To assess how often investigators specify the composition of placebos in randomized, placebo-controlled trials. DATA SOURCES: 4 English-language general and internal medicine journals with high impact factors. STUDY SELECTION: 3 reviewers screened titles and abstracts of the journals to identify randomized, placebo-controlled trials published from January 2008 to December 2009. DATA EXTRACTION: Reviewers independently abstracted data from the introduction and methods sections of identified articles, recording treatment type (pill, injection, or other) and whether placebo composition was stated. Discrepancies were resolved by consensus. DATA SYNTHESIS: Most studies did not disclose the composition of the study placebo. Disclosure was less common for pills than for injections and other treatments (8.2% vs. 26.7%; P = 0.002). LIMITATION: Journals with high impact factors may not be representative. CONCLUSION: Placebos were seldom described in randomized, controlled trials of pills or capsules. Because the nature of the placebo can influence trial outcomes, placebo formulation should be disclosed in reports of placebo-controlled trials.