Daniel Carey

Whole-Brain In-vivo Measurements of the Axonal G-Ratio in a Group of 37 Healthy Volunteers.

The g-ratio, quantifying the ratio between the inner and outer diameters of a fiber, is an important microstructural characteristic of fiber pathways and is functionally related to conduction velocity. We introduce a novel method for estimating the MR g-ratio non-invasively across the whole brain using high-fidelity magnetization transfer (MT) imaging and single-shell diffusion MRI. These methods enabled us to map the MR g-ratio in vivo across the brains prominent fiber pathways in a group of 37 healthy volunteers and to estimate the inter-subject variability. Effective correction of susceptibility-related distortion artifacts was essential before combining the MT and diffusion data, in order to reduce partial volume and edge artifacts. The MR g-ratio is in good qualitative agreement with histological findings despite the different resolution and spatial coverage of MRI and histology. The MR g-ratio holds promise as an important non-invasive biomarker due to its microstructural and functional relevance in neurodegeneration.

Functional and Quantitative MRI Mapping of Somatomotor Representations of Human Supralaryngeal Vocal Tract.

Abstract Speech articulation requires precise control of and coordination between the effectors of the vocal tract (e.g., lips, tongue, soft palate, and larynx). However, it is unclear how the cortex represents movements of and contact between these effectors during speech, or how these cortical responses relate to inter‐regional anatomical borders. Here, we used phase‐encoded fMRI to map somatomotor representations of speech articulations. Phonetically trained participants produced speech phones, progressing from front (bilabial) to back (glottal) place of articulation. Maps of cortical myelin proxies (R1 = 1/T1) further allowed us to situate functional maps with respect to anatomical borders of motor and somatosensory regions. Across participants, we found a consistent topological map of place of articulation, spanning the central sulcus and primary motor and somatosensory areas, that moved from lateral to inferior as place of articulation progressed from front to back. Phones produced at velar and glottal places of articulation activated the inferior aspect of the central sulcus, but with considerable across‐subject variability. R1 maps for a subset of participants revealed that articulator maps extended posteriorly into secondary somatosensory regions. These results show consistent topological organization of cortical representations of the vocal apparatus in the context of speech behavior.

Quantitative MRI provides markers of intra-, inter-regional, and age-related differences in young adult cortical microstructure

Abstract Measuring the structural composition of the cortex is critical to understanding typical development, yet few investigations in humans have charted markers in vivo that are sensitive to tissue microstructural attributes. Here, we used a well‐validated quantitative MR protocol to measure four parameters (R1, MT, R2*, PD*) that differ in their sensitivity to facets of the tissue microstructural environment (R1, MT: myelin, macromolecular content; R2*: myelin, paramagnetic ions, i.e., iron; PD*: free water content). Mapping these parameters across cortical regions in a young adult cohort (18–39 years, N = 93) revealed expected patterns of increased macromolecular content as well as reduced tissue water content in primary and primary adjacent cortical regions. Mapping across cortical depth within regions showed decreased expression of myelin and related processes – but increased tissue water content – when progressing from the grey/white to the grey/pial boundary, in all regions. Charting developmental change in cortical microstructure cross‐sectionally, we found that parameters with sensitivity to tissue myelin (R1 & MT) showed linear increases with age across frontal and parietal cortex (change 0.5–1.0% per year). Overlap of robust age effects for both parameters emerged in left inferior frontal, right parietal and bilateral pre‐central regions. Our findings afford an improved understanding of ontogeny in early adulthood and offer normative quantitative MR data for inter‐ and intra‐cortical composition, which may be used as benchmarks in further studies. HighlightsWe mapped multi‐parameter maps (MPMs) across and within cortical regions.We charted age effects (ages 18–39) on myelin and related processes.MPMs sensitive to myelin (R1, MT) showed elevated values in primary areas over most cortical depths.R2* map foci tended to overlap MPMs sensitive to myelin (R1, MT).R1 and MT increased with age (0.5–1.0% per year) at mid‐depth in frontal and parietal cortex.

Vocal Tract Images Reveal Neural Representations of Sensorimotor Transformation During Speech Imitation

&NA; Imitating speech necessitates the transformation from sensory targets to vocal tract motor output, yet little is known about the representational basis of this process in the human brain. Here, we address this question by using real‐time MR imaging (rtMRI) of the vocal tract and functional MRI (fMRI) of the brain in a speech imitation paradigm. Participants trained on imitating a native vowel and a similar nonnative vowel that required lip rounding. Later, participants imitated these vowels and an untrained vowel pair during separate fMRI and rtMRI runs. Univariate fMRI analyses revealed that regions including left inferior frontal gyrus were more active during sensorimotor transformation (ST) and production of nonnative vowels, compared with native vowels; further, ST for nonnative vowels activated somatomotor cortex bilaterally, compared with ST of native vowels. Using test representational similarity analysis (RSA) models constructed from participants’ vocal tract images and from stimulus formant distances, we found that RSA searchlight analyses of fMRI data showed either type of model could be represented in somatomotor, temporal, cerebellar, and hippocampal neural activation patterns during ST. We thus provide the first evidence of widespread and robust cortical and subcortical neural representation of vocal tract and/or formant parameters, during prearticulatory ST.

Auditory semantic processing in dichotic listening: Effects of competing speech, ear of presentation, and sentential bias on N400s to spoken words in context

The effects of ear of presentation and competing speech on N400s to spoken words in context were examined in a dichotic sentence priming paradigm. Auditory sentence contexts with a strong or weak semantic bias were presented in isolation to the right or left ear, or with a competing signal presented in the other ear at a SNR of -12 dB. Target words were congruent or incongruent with the sentence meaning. Competing speech attenuated N400s to both congruent and incongruent targets, suggesting that the demand imposed by a competing signal disrupts the engagement of semantic comprehension processes. Bias strength affected N400 amplitudes differentially depending upon ear of presentation: weak contexts presented to the le/RH produced a more negative N400 response to targets than strong contexts, whereas no significant effect of bias strength was observed for sentences presented to the re/LH. The results are consistent with a model of semantic processing in which the RH relies on integrative processing strategies in the interpretation of sentence-level meaning.

Longitudinal Association Between Orthostatic Hypotension at 30 Seconds Post-Standing and Late-Life DepressionNovelty and Significance

There is an established cross-sectional association between orthostatic hypotension (OH) and late-life depression. The aim of this observational study was to clarify the longitudinal association between baseline symptomatic OH (sOH-30) and incident depression in a sample of >3000 older people without baseline depression (mean age: 62 years at baseline). This study was embedded within the Irish Longitudinal Study on Ageing using data from waves 1 to 3, collected between 2009 and 2014. At 2- and 4-year follow-up, a score ≥9 on the 8-item Center for Epidemiological Studies Depression Scale was used to define incident depression. sOH-30 was defined as a drop in systolic blood pressure ≥20 mm Hg or diastolic blood pressure ≥10 mm Hg at 30 seconds post-standing in conjunction with orthostatic symptoms, such as dizziness, using beat-to-beat measurements. Almost one fifth (proportion, 18%; 95% confidence interval [CI], 16–20) of the study sample had sOH-30. One tenth (proportion, 10%; 95% CI, 9–12) had incident depression. Participants with incident depression were twice as likely to have sOH-30 at baseline compared with those without incident depression (linear regression, 13% [95% CI, 8–19] versus 7% [95% CI, 6–8]). Weighted logistic regression models demonstrated that sOH-30 predicted incident depression with an odds ratio of 1.90 (95% CI, 1.15–3.15) after controlling for covariates, including subthreshold depression, hypotension, cognitive impairment, and antidepressant use. Asymptomatic OH at 30 seconds and initial OH did not predict depression. This study demonstrates that sOH-30 predicts incident depression in a population-representative sample of older people and may, therefore, represent a potentially modifiable risk factor for late-life depression.

What is the Longitudinal Relationship between Gait Abnormalities and Depression in a Cohort of Community-Dwelling Older People? Data From the Irish Longitudinal Study on Ageing (TILDA)

OBJECTIVE Does baseline gait disturbance predict incident depression in a cohort of community-dwelling older people? METHODS This is a longitudinal study, embedded within the Irish Longitudinal Study on Ageing (TILDA), examining the association between baseline depression and incident gait abnormalities, as well as between baseline gait abnormalities and incident depression at 2 year follow-up. Depression was defined as a score of ≥16 on the Centre for Epidemiological Studies Depression Scale (CES-D). Gait abnormality was defined as a Timed Up and Go Test (TUG) ≥12 seconds. Assessments were carried out at baseline and at 2 year follow-up. RESULTS 7% (179/2,638) had baseline depression and 11% (296/2,638) had a gait abnormality at baseline. The incidence of new-onset depression and gait abnormality at Wave 2 was 4% (95/2,364) and 13% (308/2,342) respectively. Logistic regression models demonstrated that baseline gait abnormality was a significant predictor of incident depression with an Incidence Rate Ratio (IRR) of 2.00 (95% CI: 1.18 - 3.40, p =0.010, t =2.57, df =625), which was not attenuated after controlling for covariates. Baseline depression was a predictor of incident gait abnormality at Wave 2 with an IRR of 1.68 (95% CI: 1.16 - 2.43, p =0.006, t =2.75, df =625) but this association was no longer statistically significant when analysis was adjusted for clinical variables. CONCLUSIONS This study demonstrates that baseline gait disturbance, measured by TUG, predicts incident depression, defined by CES-D, in a population-representative cohort of community-dwelling older people. Possible biological mechanisms for this relationship include white matter disease and executive dysfunction.

Fractionating nonword repetition: The contributions of short-term memory and oromotor praxis are different.

The ability to reproduce novel words is a sensitive marker of language impairment across a variety of developmental disorders. Nonword repetition tasks are thought to reflect phonological short-term memory skills. Yet, when children hear and then utter a word for the first time, they must transform a novel speech signal into a series of coordinated, precisely timed oral movements. Little is known about how children’s oromotor speed, planning and co-ordination abilities might influence their ability to repeat novel nonwords, beyond the influence of higher-level cognitive and linguistic skills. In the present study, we tested 35 typically developing children between the ages of 5−8 years on measures of nonword repetition, digit span, memory for non-verbal sequences, reading fluency, oromotor praxis, and oral diadochokinesis. We found that oromotor praxis uniquely predicted nonword repetition ability in school-age children, and that the variance it accounted for was additional to that of digit span, memory for non-verbal sequences, articulatory rate (measured by oral diadochokinesis) as well as reading fluency. We conclude that the ability to compute and execute novel sensorimotor transformations affects the production of novel words. These results have important implications for understanding motor/language relations in neurodevelopmental disorders.

Validation of the 8-item Centre for Epidemiological Studies Depression Scale in a cohort of community-dwelling older people: data from The Irish Longitudinal Study on Ageing (TILDA)

BackgroundThe aim of this study was to validate the 8-item Centre for Epidemiological Studies Depression Scale (CES-D-8) against the 20-item version (CES-D-20) in a large sample of community-dwelling older people.MethodsScales were compared for correlation and internal consistency. The ideal cut-off score for the CES-D-8 was determined by comparing scores ranging from 7 to 12 on the CES-D-8 to CES-D-20.Results8033 participants were included. The Spearman co-efficient between the scales was 0.8980 indicating high degree of correlation. At a score of 9/24, the sensitivity and specificity of the CES-D-8 were 98 and 83%, respectively. The Cohen’s κ for a score of 9 was 0.7855, indicating strong agreement and the ROC area was 0.88.ConclusionWhen compared to the CES-D-20, the CES-D-8 is a valid and reliable measure of depressive symptoms in community-dwelling older people, and a score of 9 can be used to identify those with clinically significant symptoms.

Voluntary fortification is ineffective to maintain the vitamin B 12 and folate status of older Irish adults: evidence from the Irish Longitudinal Study on Ageing (TILDA)

Mandatory fortification of staple grains with folic acid and/or vitamin B12 (B12) is under debate in many countries including Ireland, which has a liberal, but voluntary, fortification policy. Older adults can be at risk of both deficiency and high folate status, although little is known on the actual prevalence and the major predictors. Population prevalence estimates from older adults (n 5290 ≥50 years) from the Irish Longitudinal Study on Ageing (TILDA) (Wave 1) are presented here. Measures included plasma total vitamin B12 and folate, whereas predictors included detailed demographic, socio-economic, geographic, seasonal and health/lifestyle data. The prevalence of deficient or low B12 status (45 nmol/l) was observed in 8·9 %, whereas high B12 status was observed in 3·1 % (>601 pmol/l). The largest positive predictor of B12 concentration was self-reported B12 injection and/or supplement use (coefficient 51·5 pmol/; 95 % CI 9·4, 93·6; P=0·016) followed by sex and geographic location. The largest negative predictor was metformin use (-33·6; 95 % CI -51·9, -15·4; P<0·0001). The largest positive predictor of folate concentration was folic acid supplement use (6·0; 95 % CI 3·0, 9·0 nmol/l; P<0·001) followed by being female and statin medications. The largest negative predictor was geographic location (-5·7; 95 % CI -6·7, -4·6; P<0·0001) followed by seasonality and smoking. B-vitamin status in older adults is affected by health and lifestyle, medication, sampling period and geographic location. We observed a high prevalence of low B12 and folate status, indicating that the current policy of voluntary fortification is ineffective for older adults.