Broca's Area, Sentence Comprehension, and Working Memory: An fMRI Study

The role of Broca's area in sentence processing remains controversial. According to one view, Broca's area is involved in processing a subcomponent of syntactic processing. Another view holds that it contributes to sentence processing via verbal working memory. Sub-regions of Broca's area have been identified that are more active during the processing of complex (object-relative clause) sentences compared to simple (subject-relative clause) sentences. The present study aimed to determine if this complexity effect can be accounted for in terms of the articulatory rehearsal component of verbal working memory. In a behavioral experiment, subjects were asked to comprehend sentences during concurrent speech articulation which minimizes articulatory rehearsal as a resource for sentence comprehension. A finger-tapping task was used as a control concurrent task. Only the object-relative clause sentences were more difficult to comprehend during speech articulation than during the manual task, showing that articulatory rehearsal does contribute to sentence processing. A second experiment used fMRI to document the brain regions underlying this effect. Subjects judged the plausibility of sentences during speech articulation, a finger-tapping task, or without a concurrent task. In the absence of a secondary task, Broca's area (pars triangularis and pars opercularis) demonstrated an increase in activity as a function of syntactic complexity. However, during concurrent speech articulation (but not finger-tapping) this complexity effect was eliminated in the pars opercularis suggesting that this region supports sentence comprehension via its role in articulatory rehearsal. Activity in the pars triangularis was modulated by the finger-tapping task, but not the speech articulation task

Response Bias Modulates the Speech Motor System during Syllable Discrimination

Recent evidence suggests that the speech motor system may play a significant role in speech perception. Repetitive transcranial magnetic stimulation (TMS) applied to a speech region of premotor cortex impaired syllable identification, while stimulation of motor areas for different articulators selectively facilitated identification of phonemes relying on those articulators. However, in these experiments performance was not corrected for response bias. It is not currently known how response bias modulates activity in these networks. The present functional magnetic resonance imaging experiment was designed to produce specific, measureable changes in response bias in a speech perception task. Minimal consonant-vowel stimulus pairs were presented between volume acquisitions for same-different discrimination. Speech stimuli were embedded in Gaussian noise at the psychophysically determined threshold level. We manipulated bias by changing the ratio of same-to-different trials: 1:3, 1:2, 1:1, 2:1, 3:1. Ratios were blocked by run and subjects were cued to the upcoming ratio at the beginning of each run. The stimuli were physically identical across runs. Response bias (criterion, C) was measured in individual subjects for each ratio condition. Group mean bias varied in the expected direction. We predicted that activation in frontal but not temporal brain regions would co-vary with bias. Group-level regression of bias scores on percent signal change revealed a fronto-parietal network of motor and sensory-motor brain regions that were sensitive to changes in response bias. We identified several pre- and post-central clusters in the left hemisphere that overlap well with TMS targets from the aforementioned studies. Importantly, activity in these regions covaried with response bias even while the perceptual targets remained constant. Thus, previous results suggesting that speech motor cortex participates directly in the perceptual analysis of speech should be called into question

Predictive Coding and Internal Error Correction in Speech Production

AbstractSpeech production involves the careful orchestration of sophisticated systems, yet overt speech errors rarely occur under naturalistic conditions. The present functional magnetic resonance imaging study sought neural evidence for internal error detection and correction by leveraging a tongue twister paradigm that induces the potential for speech errors while excluding any overt errors from analysis. Previous work using the same paradigm in the context of silently articulated and imagined speech production tasks has demonstrated forward predictive signals in auditory cortex during speech and presented suggestive evidence of internal error correction in left posterior middle temporal gyrus (pMTG) on the basis that this area tended toward showing a stronger response when potential speech errors are biased toward nonwords compared to words (Okada et al., 2018). The present study built on this prior work by attempting to replicate the forward prediction and lexicality effects in nearly twice as many participants but introduced novel stimuli designed to further tax internal error correction and detection mechanisms by biasing speech errors toward taboo words. The forward prediction effect was replicated. While no evidence was found for a significant difference in brain response as a function of lexical status of the potential speech error, biasing potential errors toward taboo words elicited significantly greater response in left pMTG than biasing errors toward (neutral) words. Other brain areas showed preferential response for taboo words as well but responded below baseline and were less likely to reflect language processing as indicated by a decoding analysis, implicating left pMTG in internal error correction

A Neural Dissociation Within Language: Evidence that the Mental Dictionary is Part of Declarative Memory, and that Grammatical Rules are Processed by the Procedural System

Language comprises a lexicon for storing words and a grammar for generating rule-governed forms. Evidence is presented that the lexicon is part of a temporal-parietalhnedial-temporal “declarative memory” system and that granlmatical rules are processed by a frontamasal-ganglia “procedural” system. Patients produced past tenses of regular and novel verbs (looked and plagged), which require an -ed-suffixation rule, and irregular verbs (dug), which are retrieved from memory. Word-finding difficulties in posterior aphasia, and the general declarative memory impairment in Alzheimer's disease, led to more errors with irregular than regular and novel verbs. Grammatical difficulties in anterior aphasia, and the general impairment of procedures in Parkinson's disease, led to the opposite pattern. In contrast to the Parkinson's patients, who showed suppressed motor activity and rule use, Huntington's disease patients showed excess motor activity and rule use, underscoring a role for the basal ganglia in grammatical processing.Psycholog

Effects of age on American Sign Language sentence repetition.

The study of deaf users of signed languages, who often experience delays in primary language (L1) acquisition, permits a unique opportunity to examine the effects of aging on the processing of an L1 acquired under delayed or protracted development. A cohort of 107 congenitally deaf adult signers ages 45–85 years who were exposed to American Sign Language (ASL) either in infancy, early childhood, or late childhood were tested using an ASL sentence repetition test. Participants repeated 20 sentences that gradually increased in length and complexity. Logistic mixed-effects regression with the variables of chronological age (CA) and age of acquisition (AoA) was used to assess sentence repetition accuracy. Results showed that CA was a significant predictor, with increased age being associated with decreased likelihood to reproduce a sentence correctly (odds ratio [OR] = 0.56, p = .010). In addition, effects of AoA were observed. Relative to native deaf signers, those who acquired ASL in early childhood were less likely to successfully reproduce a sentence (OR = 0.42, p = .003), as were subjects who learned ASL in late childhood (OR = 0.27, p < .001). These data show that aging affects verbatim recall in deaf users of ASL and that the age of sign language acquisition has a significant and lasting effect on repetition ability, even after decades of sign language use. These data show evidence for life-span continuity of early life effects

Individualized Response to Semantic Versus Phonological Aphasia Therapies in Stroke

Attempts to personalize aphasia treatment to the extent where it is possible to reliably predict individual response to a particular treatment have yielded inconclusive results. The current study aimed to (i) compare the effects of phonologically versus semantically focussed naming treatment and (ii) examine biographical and neuropsychological baseline factors predictive of response to each treatment. One hundred and four individuals with chronic post-stroke aphasia underwent 3 weeks of phonologically focussed treatment and 3 weeks of semantically focussed treatment in an unblinded cross-over design. A linear mixed-effects model was used to compare the effects of treatment type on proportional change in correct naming across groups. Correlational analysis and stepwise regression models were used to examine biographical and neuropsychological predictors of response to phonological and semantic treatment across all participants. Last, chi-square tests were used to explore the association between treatment response and phonological and semantic deficit profiles. Semantically focussed treatment was found to be more effective at the group-level, independently of treatment order (P = 0.041). Overall, milder speech and language impairment predicted good response to semantic treatment (r range: 0.256–0.373) across neuropsychological tasks. The Western Aphasia Battery-Revised Spontaneous Speech score emerged as the strongest predictor of semantic treatment response (R2 = 0.188). Severity of stroke symptoms emerged as the strongest predictor of phonological treatment response (R2 = 0.103). Participants who showed a good response to semantic treatment were more likely to present with fluent speech compared to poor responders (P = 0.005), whereas participants who showed a good response to phonological treatment were more likely to present with apraxia of speech (P = 0.020). These results suggest that semantic treatment may be more beneficial to the improvement of naming performance in aphasia than phonological treatment, at the group-level. In terms of personalized predictors, participants with relatively mild impairments and fluent speech responded better to semantic treatment, while phonological treatment benefitted participants with more severe impairments and apraxia of speech

Observer weighting of interaural cues in positive and negative envelope slopes of amplitude-modulated waveforms

The auditory system can encode interaural delays in highpass-filtered complex sounds by phase locking to their slowly modulating envelopes. Spectrotemporal analysis of interaurally time-delayed highpass waveforms reveals the presence of a concomitant interaural level cue. The current study systematically investigated the contribution of time and concomitant level cues carried by positive and negative envelope slopes of a modified sinusoidally amplitude-modulated (SAM) high-frequency carrier. The waveforms were generated from concatenation of individual modulation cycles whose envelope peaks were extended by the desired interaural delay, allowing independent control of delays in the positive and negative modulation slopes. In experiment 1, thresholds were measured using a 2-interval forced-choice adaptive task for interaural delays in either the positive or negative modulation slopes. In a control condition, thresholds were measured for a standard SAM tone. In experiment 2, decision weights were estimated using a multiple-observation correlational method in a single-interval forced-choice task for interaural delays carried simultaneously by the positive, and independently, negative slopes of the modulation envelope. In experiment 3, decision weights were measured for groups of 3 modulation cycles at the start, middle, and end of the waveform to determine the influence of onset dominance or recency effects. Results were consistent across experiments: thresholds were equal for the positive and negative modulation slopes. Decision weights were positive and equal for the time cue in the positive and negative envelope slopes. Weights were also larger for modulations cycles near the waveform onset. Weights estimated for the concomitant interaural level cue were positive for the positive envelope slope and negative for the negative slope, consistent with exclusive use of time cues.We thank Virginia M. Richards and Bruce G. Berg for helpful discussions. We also thank Brian C. J. Moore and an anonymous reviewer for their insightful comments on an earlier draft of the manuscript. Work supported by grants from the National Science Council, Taiwan NSC 98-2410-H-008-081-MY3 and NIH R01DC009659

The what and why of perceptual asymmetries in the visual domain

Perceptual asymmetry is one of the most important characteristics of our visual functioning. We carefully reviewed the scientific literature in order to examine such asymmetries, separating them into two major categories: within-visual field asymmetries and between-visual field asymmetries. We explain these asymmetries in terms of perceptual aspects or tasks, the what of the asymmetries; and in terms of underlying mechanisms, the why of the asymmetries. Tthe within-visual field asymmetries are fundamental to orientation, motion direction, and spatial frequency processing. between-visual field asymmetries have been reported for a wide range of perceptual phenomena. foveal dominance over the periphery, in particular, has been prominent for visual acuity, contrast sensitivity, and colour discrimination. Tthis also holds true for object or face recognition and reading performance. upper-lower visual field asymmetries in favour of the lower have been demonstrated for temporal and contrast sensitivities, visual acuity, spatial resolution, orientation, hue and motion processing. Iin contrast, the upper field advantages have been seen in visual search, apparent size, and object recognition tasks. left-right visual field asymmetries include the left field dominance in spatial (e.g., orientation) processing and the right field dominance in non-spatial (e.g., temporal) processing. left field is also better at low spatial frequency or global and coordinate spatial processing, whereas the right field is better at high spatial frequency or local and categorical spatial processing. All these asymmetries have inborn neural/physiological origins, the primary why, but can be also susceptible to visual experience, the critical why (promotes or blocks the asymmetries by altering neural functions)

Molecular control of nitric oxide synthesis through eNOS and caveolin-1 interaction regulates osteogenic differentiation of adipose-derived stem cells by modulation of Wnt/β-catenin signaling

BACKGROUND: Nitric oxide (NO) plays a role in a number of physiological processes including stem cell differentiation and osteogenesis. Endothelial nitric oxide synthase (eNOS), one of three NO-producing enzymes, is located in a close conformation with the caveolin-1 (CAV-1(WT)) membrane protein which is inhibitory to NO production. Modification of this interaction through mutation of the caveolin scaffold domain can increase NO release. In this study, we genetically modified equine adipose-derived stem cells (eASCs) with eNOS, CAV-1(WT), and a CAV-1(F92A) (CAV-1(WT) mutant) and assessed NO-mediated osteogenic differentiation and the relationship with the Wnt signaling pathway. METHODS: NO production was enhanced by lentiviral vector co-delivery of eNOS and CAV-1(F92A) to eASCs, and osteogenesis and Wnt signaling was assessed by gene expression analysis and activity of a novel Runx2-GFP reporter. Cells were also exposed to a NO donor (NONOate) and the eNOS inhibitor, l-NAME. RESULTS: NO production as measured by nitrite was significantly increased in eNOS and CAV-1(F92A) transduced eASCs +(5.59 ± 0.22 μM) compared to eNOS alone (4.81 ± 0.59 μM) and un-transduced control cells (0.91 ± 0.23 μM) (p < 0.05). During osteogenic differentiation, higher NO correlated with increased calcium deposition, Runx2, and alkaline phosphatase (ALP) gene expression and the activity of a Runx2-eGFP reporter. Co-expression of eNOS and CAV-1(WT) transgenes resulted in lower NO production. Canonical Wnt signaling pathway-associated Wnt3a and Wnt8a gene expressions were increased in eNOS-CAV-1(F92A) cells undergoing osteogenesis whilst non-canonical Wnt5a was decreased and similar results were seen with NONOate treatment. Treatment of osteogenic cultures with 2 mM l-NAME resulted in reduced Runx2, ALP, and Wnt3a expressions, whilst Wnt5a expression was increased in eNOS-delivered cells. Co-transduction of eASCs with a Wnt pathway responsive lenti-TCF/LEF-dGFP reporter only showed activity in osteogenic cultures co-transduced with a doxycycline inducible eNOS. Lentiviral vector expression of canonical Wnt3a and non-canonical Wnt5a in eASCs was associated with induced and suppressed osteogenic differentiation, respectively, whilst treatment of eNOS-osteogenic cells with the Wnt inhibitor Dkk-1 significantly reduced expressions of Runx2 and ALP. CONCLUSIONS: This study identifies NO as a regulator of canonical Wnt/β-catenin signaling to promote osteogenesis in eASCs which may contribute to novel bone regeneration strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-016-0442-9) contains supplementary material, which is available to authorized users