Faculty Bibliography

Selective attention to phonology, i.e., the ability to attend to sub-syllabic units within spoken words, is a critical precursor to literacy acquisition. Recent functional magnetic resonance imaging evidence has demonstrated that a left-lateralized network of frontal, temporal, and posterior language regions, including the visual word form area, supports this skill. The current event-related potential (ERP) study investigated the temporal dynamics of selective attention to phonology during spoken word perception. We tested the hypothesis that selective attention to phonology dynamically modulates stimulus encoding by recruiting left-lateralized processes specifically while the information critical for performance is unfolding. Selective attention to phonology was captured by manipulating listening goals: skilled adult readers attended to either rhyme or melody within auditory stimulus pairs. Each pair superimposed rhyming and melodic information ensuring identical sensory stimulation. Selective attention to phonology produced distinct early and late topographic ERP effects during stimulus encoding. Data-driven source localization analyses revealed that selective attention to phonology led to significantly greater recruitment of left-lateralized posterior and extensive temporal regions, which was notably concurrent with the rhyme-relevant information within the word. Furthermore, selective attention effects were specific to auditory stimulus encoding and not observed in response to cues, arguing against the notion that they reflect sustained task setting. Collectively, these results demonstrate that selective attention to phonology dynamically engages a left-lateralized network during the critical time-period of perception for achieving phonological analysis goals. These findings suggest a key role for selective attention in on-line phonological computations. Furthermore, these findings motivate future research on the role that neural mechanisms of attention may play in phonological awareness impairments thought to underlie developmental reading disabilities.

In the accompanying Annual Research Review, Horga and colleagues provide a comprehensive overview of the current limitations of magnetic resonance imaging (MRI) of developmental psychopathologies focusing particularly on experimental design. Horga et al. are unsparing in their assessment of the problems that plague current clinical neuroimaging studies. We will not reiterate the long list of deficiencies in the imaging literature, which persist despite its impressive volume (PubMed lists more than 135,000 papers with the terms 'magnetic resonance imaging' and 'brain'). Rather, in this Commentary, while we agree with Horga et al. that neuroimaging approaches merely represent one more types of tool, we look at where this leave us and the prospects (by attending to the lessons thoughtfully laid out by Horga and colleagues on how to place research design at the forefront in clinical neuroimaging) of better times ahead for our understanding of the pathophysiology of child- and adult-onset developmental psychiatric conditions.

ERP responses to spoken words are sensitive to both rhyming effects and effects of associated spelling patterns. Are such effects automatically elicited by spoken words or dependent on selectively attending to phonology? To address this question, ERP responses to spoken word pairs were investigated under two equally demanding listening tasks that directed selective attention either to sub-syllabic phonology (i.e., rhyme judgments) or to melodies embedded within the words. ERPs elicited when participants selectively attended to phonology demonstrated a rhyming effect that was concurrent with online stimulus encoding and an orthographic effect that emerged later. ERP responses to the same stimuli presented under melodic focus, however, showed no evidence of sensitivity to rhyme or spelling patterns. Results reveal limitations to the automaticity of such ERP effects, suggesting that rhyme effects may depend, at least to some degree, on allocation of attention to phonology, which may in turn activate task-incidental orthographic information.

Selective attention to speech versus nonspeech signals in complex auditory input could produce top-down modulation of cortical regions previously linked to perception of spoken, and even visual, words. To isolate such top-down attentional effects, we contrasted 2 equally challenging active listening tasks, performed on the same complex auditory stimuli (words overlaid with a series of 3 tones). Instructions required selectively attending to either the speech signals (in service of rhyme judgment) or the melodic signals (tone-triplet matching). Selective attention to speech, relative to attention to melody, was associated with blood oxygenation level-dependent (BOLD) increases during functional magnetic resonance imaging (fMRI) in left inferior frontal gyrus, temporal regions, and the visual word form area (VWFA). Further investigation of the activity in visual regions revealed overall deactivation relative to baseline rest for both attention conditions. Topographic analysis demonstrated that while attending to melody drove deactivation equivalently across all fusiform regions of interest examined, attending to speech produced a regionally specific modulation: deactivation of all fusiform regions, except the VWFA. Results indicate that selective attention to speech can topographically tune extrastriate cortex, leading to increased activity in VWFA relative to surrounding regions, in line with the well-established connectivity between areas related to spoken and visual word perception in skilled readers.

Adults produce left-lateralized N170 responses to visual words relative to control stimuli, even within tasks that do not require active reading. This specialization begins in preschoolers as a right-lateralized N170 effect. We investigated whether this developmental shift reflects an early learning phenomenon, such as attaining visual familiarity with a script, by training adults in an artificial script and measuring N170 responses before and afterward. Training enhanced the N170 response, especially over the right hemisphere. This suggests N170 sensitivity to visual familiarity with a script emerges before reading becomes sufficiently automatic to drive left-lateralized effects in a shallow encoding task.

Reading instruction can direct attention to different unit sizes in print-to-speech mapping, ranging from grapheme-phoneme to whole-word relationships. Thus, attentional focus during learning might influence brain mechanisms recruited during reading, as indexed by the N170 response to visual words. To test this, two groups of adults were trained to read an artificial script under instructions directing attention to grapheme-phoneme versus whole-word associations. N170 responses were subsequently contrasted within an active reading task. Grapheme-phoneme focus drove a left-lateralized N170 response relative to the right-lateralized N170 under whole-word focus. These findings suggest a key role for attentional focus in early reading acquisition.

Escherichia coli grows over a wide range of pHs (pH 4.4 to 9.2), and its own metabolism shifts the external pH toward either extreme, depending on available nutrients and electron acceptors. Responses to pH values across the growth range were examined through two-dimensional electrophoresis (2-D gels) of the proteome and through lac gene fusions. Strain W3110 was grown to early log phase in complex broth buffered at pH 4.9, 6.0, 8.0, or 9.1. 2-D gel analysis revealed the pH dependence of 19 proteins not previously known to be pH dependent. At low pH, several acetate-induced proteins were elevated (LuxS, Tpx, and YfiD), whereas acetate-repressed proteins were lowered (Pta, TnaA, DksA, AroK, and MalE). These responses could be mediated by the reuptake of acetate driven by changes in pH. The amplified proton gradient could also be responsible for the acid induction of the tricarboxylic acid (TCA) enzymes SucB and SucC. In addition to the autoinducer LuxS, low pH induced another potential autoinducer component, the LuxH homolog RibB. pH modulated the expression of several periplasmic and outer membrane proteins: acid induced YcdO and YdiY; base induced OmpA, MalE, and YceI; and either acid or base induced OmpX relative to pH 7. Two pH-dependent periplasmic proteins were redox modulators: Tpx (acid-induced) and DsbA (base-induced). The locus alx, induced in extreme base, was identified as ygjT, whose product is a putative membrane-bound redox modulator. The cytoplasmic superoxide stress protein SodB was induced by acid, possibly in response to increased iron solubility. High pH induced amino acid metabolic enzymes (TnaA and CysK) as well as lac fusions to the genes encoding AstD and GabT. These enzymes participate in arginine and glutamate catabolic pathways that channel carbon into acids instead of producing alkaline amines. Overall, these data are consistent with a model in which E. coli modulates multiple transporters and pathways of amino acid consumption so as to minimize the shift of its external pH toward either acidic or alkaline extreme.