Testing the relationship between lateralization on sequence-based motor tasks and language laterality using an online battery.

ABSTRACTStudies have highlighted an association between motor laterality and speech production laterality. It is thought that common demands for sequential processing may underlie this association. However, most studies in this area have relied on relatively small samples and have infrequently explored the reliability of the tools used to assess lateralization. We, therefore, established the validity and reliability of an online battery measuring sequence-based motor laterality and language laterality before exploring the associations between laterality indices on language and motor tasks. The online battery was completed by 621 participants, 52 of whom returned to complete the battery a second time. The three motor tasks included in the battery showed good between-session reliability (r ≥ .78) and were lateralized in concordance with hand preference. The novel measure of speech production laterality was left lateralized at population level as predicted, but reliability was less satisfactory (r = .62). We found no evidence of an association between sequence-based motor laterality and language laterality. Those with a left-hand preference were more strongly lateralized on motor tasks requiring midline crossing; this effect was not observed in right-handers. We conclude that there is little evidence of the co-lateralization of language and sequence-based motor skill on this battery.

Reproducibility of 2 Liver 2-Dimensional Shear Wave Elastographic Techniques in the Fasting and Postprandial States.

OBJECTIVES: The purpose of this study was to compare the reliability and agreement of 2 methods of 2-dimensional (2D) shear wave elastography (SWE) on liver stiffness in healthy volunteers. We also assessed effects of the prandial state and operator experience on measurements. METHODS: Two operators, 1 experienced and 1 novice, independently examined 20 healthy volunteers with 2D SWE on 2 ultrasound machines (Aixplorer [SuperSonic Imagine, Aix-en-Provence, France] and Aplio 500 [Canon Medical Systems Corporation, Otawara, Japan]). Volunteers were scanned 8 times by the operators using both machines in fasting and postprandial states. Agreement was evaluated by a Bland-Altman analysis, and the correlation was assessed by the Pearson correlation and intraclass correlation coefficients (ICCs). An analysis of variance was conducted to determine the contribution of the machine, prandial state, and operator experience to the variability. RESULTS: Agreement assessed by Bland-Altman plots showed no statistically significant difference in measured liver stiffness between the machines (mean difference, -0.8%; 95% confidence interval, -3.7%, 2.1%), with a critical difference of 1.36 kPa. The correlation was good to excellent for both the crude overall Pearson coefficient and the ICC, both measuring 0.88 (95% confidence interval, 0.82, 0.92). Subclass ICCs for the fasting state, postprandial state, novice operator, and experienced operator were 0.89, 0.88, 0.90, and 0.86, respectively. The 2-way mixed effect analysis of variance showed that the volunteers accounted for 86.3% of variation in median liver stiffness, with no statistically significant contribution from operator experience, the prandial state, or the machine (P = .108, .067, and .296, respectively). CONCLUSIONS: Our study showed that the 2D SWE techniques had a high degree of reliability and agreement in measurement of liver stiffness in a healthy population. Operator experience and the prandial state did not impart significant variability to stiffness measurements.

The prognostic and predictive value of vascular response parameters measured by dynamic contrast-enhanced-CT, -MRI and -US in patients with metastatic renal cell carcinoma receiving sunitinib.

OBJECTIVES: To identify dynamic contrast-enhanced (DCE) imaging parameters from MRI, CT and US that are prognostic and predictive in patients with metastatic renal cell cancer (mRCC) receiving sunitinib. METHODS: Thirty-four patients were monitored by DCE imaging on day 0 and 14 of the first course of sunitinib treatment. Additional scans were performed with DCE-US only (day 7 or 28 and 2 weeks after the treatment break). Perfusion parameters that demonstrated a significant correlation (Spearman p < 0.05) with progression-free survival (PFS) and overall survival (OS) were investigated using Cox proportional hazard models/ratios (HR) and Kaplan-Meier survival analysis. RESULTS: A higher baseline and day 14 value for Ktrans (DCE-MRI) and a lower pre-treatment vascular heterogeneity (DCE-US) were significantly associated with a longer PFS (HR, 0.62, 0.37 and 5.5, respectively). A larger per cent decrease in blood volume on day 14 (DCE-US) predicted a longer OS (HR, 1.45). We did not find significant correlations between any of the DCE-CT parameters and PFS/OS, unless a cut-off analysis was used. CONCLUSIONS: DCE-MRI, -CT and ultrasound produce complementary parameters that reflect the prognosis of patients receiving sunitinib for mRCC. Blood volume measured by DCE-US was the only parameter whose change during early anti-angiogenic therapy predicted for OS and PFS. KEY POINTS: • DCE-CT, -MRI and ultrasound are complementary modalities for monitoring anti-angiogenic therapy. • The change in blood volume measured by DCE-US was predictive of OS/PFS. • Baseline vascular heterogeneity by DCE-US has the strongest prognostic value for PFS.

Radical Spin Polarization and Magnetosensitivity from Reversible Energy Transfer.

Molecular spins provide potential building units for future quantum information science and spintronic technologies. In particular, doublet (S = 1/2) and triplet (S = 1) molecular spin states have the potential for excellent optical and spin properties for these applications if useful photon-spin mechanisms at room temperature can be devised. Here we explore the potential of exploiting reversible energy transfer between triplet and doublet states to establish magnetosensitive luminescence and spin polarization. We investigate the dependence of the photon-spin mechanism on the magnitude and sign of the exchange interaction between the doublet and triplet spin components in amorphous and crystalline model systems. The design of a magnetic field inclination sensor is proposed from understanding the required "structure" (spin interactions) to "function" (magnetosensitivity).

Prostate high dose-rate brachytherapy as monotherapy for low and intermediate-risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy: A 9-year update.

BACKGROUND AND PURPOSE: High dose-rate (HDR) brachytherapy as a monotherapy is an accepted treatment for localized prostate cancer, but the optimal dose and fractionation schedule remain unknown. We report on the efficacy of a randomized Phase II trial comparing HDR monotherapy delivered as 27 Gy in 2 fractions vs. 19 Gy in 1 fraction with a median follow-up of 9 years. MATERIALS AND METHODS: Enrolled patients had low or intermediate-risk disease, <60 cc prostate volume and no androgen deprivation use. Patients were randomized to 27 Gy in 2 fractions delivered one week apart vs a single fraction of 19 Gy. RESULTS: 170 patients were randomized: median age 65 years, median follow-up 107 months and median baseline PSA 6.35 ng/ml. NCCN risk categories comprised low (19 %), favourable (51 %), and unfavourable intermediate risk (30 %). The median PSA at 8 years was 0.08 ng/ml in the 2-fraction arm vs. 0.89 ng/ml in the single-fraction arm. The cumulative incidence of local failure at 8 years was 11.2 % in the 2-fraction arm vs. 35.9 % in the single-fraction arm (p < 0.001). The incidence of distant failure at 8 years was 3.8 % in the 2-fraction arm and 2.5 % in the single-fraction arm (p = 0.6). CONCLUSIONS: HDR monotherapy delivered in two fractions of 13.5 Gy demonstrated a persistent cancer control rate at 8 years and was well-tolerated. Single-fraction monotherapy yielded poor oncologic control and is not recommended. These findings contribute to the ongoing discourse on optimal HDR monotherapy strategies for low and intermediate-risk prostate cancer.

The Cognitive Daisy (COG-D) for improving care for residents with dementia in care homes: protocol of a feasibility RCT.

BACKGROUND: Cognitive problems associated with dementia affect a large proportion of older adults living in residential care. Knowledge of cognitive impairments is important for providing person-centred care (PCC). The impact of specific cognitive impairments on residents' needs is often overlooked in dementia training and information about residents' individual cognitive profiles are frequently underspecified in care-plans, potentially undermining the delivery of PCC. This can lead to reduced resident quality of life and increased distressed behaviours-a major cause of staff stress and burnout. The COG-D package was developed to fill this gap. Daisies provide a visual representation of a resident's individual cognitive strengths and weaknesses in a colourful flower (Daisy) representing five cognitive domains. By viewing a resident's Daisy, care-staff can flexibly adjust in-the-moment care-decisions and can consult Daisies in care-plans for longer-term planning. The primary aim of this study is to assess the feasibility of implementing the COG-D package in residential care homes for older adults. METHODS/DESIGN: This 24-month feasibility cluster randomized controlled trial involves a 6-month intervention of the use of Cognitive Daisies in 8-10 residential care homes for older adults after training of care staff on the use of Cognitive Daisies in daily care (basic training) and on conducting the COG-D assessments with residents (advanced training). The key feasibility outcomes include % residents recruited, % COG-D assessments completed, and % staff completing the training. Candidate outcome measures for residents and staff will be obtained at baseline, and at 6 and 9 months post-randomization. COG-D assessments of residents will be repeated 6 months after the first assessment. A process evaluation will assess intervention implementation and barriers and facilitators to this through care-plan audits, interviews and focus groups with staff, residents, and relatives. Feasibility outcomes will be analysed against progression criteria to a full trial. DISCUSSION: The results of this study will provide important information about the feasibility of using COG-D in care homes and will inform the design of a future large-scale cluster RCT to assess the effectiveness and cost-effectiveness of the COG-D intervention in care homes. TRIAL REGISTRATION: This trial was registered on 28/09/2022 (ISRCTN15208844) and is currently open to recruitment.

Beliefs about Alzheimer's disease in Britain.

OBJECTIVES: Alzheimer's disease (AD) represents one of the most debilitating conditions affecting the elderly. Despite the prevalence and consequences of AD, surveys have revealed that the general public in North America and Australia hold numerous misconceptions of the disease. The aim of this study was to examine whether misconceptions of AD are also endorsed by adults in Britain. METHOD: The Alzheimer's disease knowledge scale (ADKS) was completed by 312 adults residing in Lincolnshire, UK. The ADKS contains 30 true or false statements pertaining to risk factors, assessment and diagnosis, symptoms, course, life impact, caregiving, and treatment and management of AD. RESULTS: Regardless of age, education, and familiarity with AD, respondents in this survey demonstrated a good understanding (≥80% mean correct) of some items from all categories. However, knowledge gaps exist about the course of the disease, and of conditions that can exacerbate (inadequate nutrition) or simulate (depression) the symptoms of AD. Moreover, a large proportion of respondents (~75%) are unaware that hypertension or hypercholesterolemia may increase ones predisposition to developing AD. CONCLUSION: Respondents revealed knowledge gaps pertaining to conditions that masquerade as AD, increase ones vulnerability to AD, and exacerbate AD symtomatology. Educational campaigns that specifically target these issues may help reduce the impact of AD.

Dynamic microbubble contrast-enhanced US to measure tumor response to targeted therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy.

PURPOSE: To develop and implement an evidence-based protocol for characterizing vascular response of renal cell carcinoma (RCC) to targeted therapy by using dynamic contrast material-enhanced (DCE) ultrasonography (US). MATERIALS AND METHODS: The study was approved by the institutional research ethics board; written informed consent was obtained from all patients. Seventeen patients (four women; median age, 58 years; range, 42-72 years; 13 men, median age, 62 years; range, 45-81 years) with metastatic RCC were examined by using DCE US before and after 2 weeks of treatment with sunitinib (May 2007 to October 2009). Two contrast agent techniques--bolus injection and disruption-replenishment infusion of microbubbles--were compared. Changes in tumor blood velocity and fractional blood volume were measured with both methods, together with reproducibility and effect of compensation for respiratory motion. Tumor changes were assessed with computed tomography, by using the best response with the Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free survival (PFS). Follow-up RECIST measurements were performed at 6-week intervals until progressive disease was detected. RESULTS: In response to treatment, median tumor fractional blood volume measured with the disruption-replenishment infusion method decreased by 73.2% (interquartile range, 46%-87%) (P < .002), with repeated-measure reproducibility of 9%-15%. Significant decreases were also seen with the bolus method, but with poor correlation of changes in bolus peak (r = 0.46, P = .066) and area under the curve (r = 0.47, P = .058), compared with infusion measurements. Changes in DCE US parameters over 2 weeks did not correlate with PFS and could not be used to predict long-term assessment of best response by using RECIST. Follow-up times ranged 28-501 days; the median was 164 days. CONCLUSION: DCE US provides reproducible and sensitive assessment of vascular changes in response to antiangiogenic therapy. The disruption-replenishment infusion protocol is a flexible method suitable for many tumor types, but further studies are needed to assess whether this protocol may be predictive of patient outcome.

The relationship between lateralization patterns from sequence based motor tasks and hemispheric speech dominance.

Objective: Skilled motor praxis and speech production display marked asymmetries at the individual and the population level, favoring the right hand and the left hemisphere, respectively. Theories suggesting a common processing mechanism between praxis and speech are supported by evidence that shared neural architecture underlies both functions. Despite advances in understanding the neurobiology of this left-hemisphere specialization the cortical networks linking these 2 functions are rarely investigated on a behavioral level. Method: This study deploys functional transcranial doppler (fTCD) ultrasound to directly measure hemispheric activation during skilled manual praxis tasks shown to be correlated to hemispheric speech lateralization indices. In a new paradigm we test the hypothesis that praxis tasks are highly dependent on the left hemisphere's capacity for processing sequential information will be better correlated with direction and strength of hemispheric speech lateralization. Results: Across 2 experiments we first show that only certain praxis tasks (pegboard and coin-rotation) correlated with direct measurements of speech lateralization despite shared properties across all tasks tested. Second, through novel imaging of hemispheric activation during praxis, results showed that the pegboard differed in the lateralization pattern created and furthermore that it was significantly related to speech laterality indices, which was not the case for either of the other two tasks. Conclusion: These results are discussed in terms of a lateralized speech-praxis control mechanism and demonstrates that measurements of motor paradigms through the use of fTCD are reliable enough to provide a new insight to the behavioral relationship been speech and handedness. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Beliefs about brain injury in Britain.

PRIMARY OBJECTIVE: Surveys have revealed that a high proportion of the public in the US and Canada hold misconceptions pertaining to the sequelae of brain injury. This study examined whether similar misconceptions are endorsed by adults in Britain. RESEARCH DESIGN: Survey. METHODS AND PROCEDURES: Three hundred and twenty-two participants completed a 17-item questionnaire containing true or false statements about general knowledge of brain injury, coma and consciousness, memory impairments and recovery. MAIN OUTCOMES AND RESULTS: Regardless of age, sex, level of education and familiarity with brain injury, participants held mistaken beliefs about consciousness, were inclined to under-estimate the extent of memory deficits and were unaware that patients are more vulnerable and less resistant to further injury. A large proportion of respondents indicated that their knowledge of brain injury had been derived from the popular media. CONCLUSIONS: Similar misconceptions to those reported in previous studies exist in Britain. Notably in this study these misconceptions were endorsed by a greater percentage of respondents. Greater public awareness is needed for decisions concerning funding and patient care. It is therefore important for healthcare professionals and public health campaigns to dispel myths about brain injury.

The Cognitive Daisy - A novel method for recognising the cognitive status of older adults in residential care: Innovative Practice.

The Cognitive Daisy is an innovative assessment system created to provide healthcare staff with an instant snapshot of the cognitive status of older adults in residential care. The Cognitive Daisy comprises a flower head consisting of 15 colour coded petals depicting information about: visual-spatial perception, comprehension, communication, memory and attention. This study confirmed the practicality of the Cognitive Daisy protocol for assessing cognition in a sample of 33 older adults living in residential care and endorsed the use of the Cognitive Daisy as a tool for recognising the cognitive status of care home residents.

Disrupting the speech motor network: Exploring hemispheric specialization for verbal and manual sequencing using a dual-task approach.

OBJECTIVE: The concept of overlapping neural networks supporting both speech production and fine motor praxis is well accepted; however, few studies have explored the lateralized behavioral characteristics of both functions when performed simultaneously. METHOD: This study probes the characteristics of the dominant hemisphere by overloading cognitive processing via a novel dual-task paradigm. In 2 experiments, participants performed sets of motor and speech tasks under single-task and dual-task conditions. The sets of tasks differed as to the extent to which they relied on sequential processing, and we hypothesized that tasks more reliant on this type of processing would suffer a greater performance decrement under dual-task conditions. A reliable measure of hemispheric language dominance was obtained via functional transcranial Doppler (fTCD) ultrasound. RESULTS: Speech production scores in the experimental set (i.e., sequential processing) were consistently impaired under dual-task conditions, a distinction that was not seen in the control set. Results of Experiment 2 confirm those of Experiment 1, whereby speech scores were most strongly impaired under dual-task conditions, especially in the experimental set. Motor performance suffered less than speech performance in dual-task conditions in both the experimental and control sets across both experiments. CONCLUSION: Data suggest that the common processing capacity for speech and fine motor praxis can be disrupted through a dual-task paradigm. This novel behavioral data supports theories of a motor-based gestural origin for language and indicates that speech production is more sensitive to the effects of increased processing requirements than are motor skills. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Automatic memory processes in normal ageing and Alzheimer's disease.

This study examined the contribution of automatic and controlled uses of memory to stem completion in young, middle-aged and older adults, and compared these data with a study involving patients with Alzheimer's disease (AD) who performed the same task (Hudson and Robertson, 2007). In an inclusion task participants aimed to complete three-letter word stems with a previously studied word, in an exclusion task the aim was to avoid using studied words to complete stems. Performances under inclusion and exclusion conditions were contrasted to obtain estimates of controlled and automatic memory processes using process-dissociation calculations (Jacoby, 1991). An age-related decline, evident from middle age was observed for the estimate of controlled processing, whereas the estimate of automatic processing remained invariant across the age groups. This pattern stands in contrast to what is observed in AD, where both controlled and automatic processes have been shown to be impaired. Therefore, the impairment in memory processing on stem completion that is found in AD is qualitatively different from that observed in normal ageing.

Speech lateralization and motor control.

A relationship between motor control and speech lateralization has long been postulated by researchers and clinicians with an interest in the functional organization of the human brain. Exactly how motor control might be related to speech representation, however, is rarely examined. This chapter examines current issues relating to the organization, development, and measurement of motor control and speech representation. We further consider from neuropsychological, developmental, neurological, and genetic perspectives that speech and fine motor control involve planning and sequencing processes, which are mediated by an integrated neural network localized to the left hemisphere. Specifically, we discuss studies from our laboratory using functional transcranial Doppler ultrasonography to determine speech laterality, correlating this with hand preference and pegboard measures of motor laterality. Our findings show that handedness, as measured by a motor skill task, can be predictive of speech laterality, both in typically developing adults and children. We have also shown that individuals with developmental motor coordination impairments also show atypical speech lateralization, providing further evidence that neurological motor and speech systems are intrinsically connected. We consider these results in the context of a left-lateralized speech-praxis center model, which could account for the relationship shown between sequence-based motor and speech tasks.

Automatic and controlled uses of memory in Alzheimer's disease.

This study used the process-dissociation procedure (Jacoby, 1991) to examine the contribution of automatic and controlled uses of memory to a stem completion task in 16 patients with Alzheimer's disease (AD) and a matched group of healthy elderly subjects (EC). In an inclusion task subjects attempted to use a studied word to complete three-letter word stems, in an exclusion task they were instructed to complete stems with unstudied words. Relative to patients with AD, EC subjects produced more target word completions under inclusion conditions, and less target word completions under exclusion conditions. The probability of the AD group using studied words to complete stems was invariant across inclusion and exclusion conditions. Estimates derived from the process-dissociation calculations, showed that the performance of the AD patients was mediated entirely by automatic uses of memory, whereas for EC subjects controlled and automatic processes codetermined task performance. Both estimates of controlled and to a lesser extent automatic uses of memory were greater for the EC than the AD subjects, indicating that the stem completion impairment in AD may not be entirely attributable to a deficiency in controlled memory processes but also due to reduced automatic processing.

Atypical speech lateralization in adults with developmental coordination disorder demonstrated using functional transcranial Doppler ultrasound.

Research using clinical populations to explore the relationship between hemispheric speech lateralization and handedness has focused on individuals with speech and language disorders, such as dyslexia or specific language impairment (SLI). Such work reveals atypical patterns of cerebral lateralization and handedness in these groups compared to controls. There are few studies that examine this relationship in people with motor coordination impairments but without speech or reading deficits, which is a surprising omission given the prevalence of theories suggesting a common neural network underlying both functions. We use an emerging imaging technique in cognitive neuroscience; functional transcranial Doppler (fTCD) ultrasound, to assess whether individuals with developmental coordination disorder (DCD) display reduced left-hemisphere lateralization for speech production compared to control participants. Twelve adult control participants and 12 adults with DCD, but no other developmental/cognitive impairments, performed a word-generation task whilst undergoing fTCD imaging to establish a hemispheric lateralization index for speech production. All participants also completed an electronic peg-moving task to determine hand skill. As predicted, the DCD group showed a significantly reduced left lateralization pattern for the speech production task compared to controls. Performance on the motor skill task showed a clear preference for the dominant hand across both groups; however, the DCD group mean movement times were significantly higher for the non-dominant hand. This is the first study of its kind to assess hand skill and speech lateralization in DCD. The results reveal a reduced leftwards asymmetry for speech and a slower motor performance. This fits alongside previous work showing atypical cerebral lateralization in DCD for other cognitive processes (e.g., executive function and short-term memory) and thus speaks to debates on theories of the links between motor control and language production.

Measurement reliability of atypical language lateralisation assessed using functional transcranial Doppler ultrasound.

It is well established that some individuals present with atypical, non-left hemisphere, cerebral lateralisation for language processing. However previous studies exploring the reliability of functional blood flow responses to detect lateralised activation during speech have focused only on individuals with typical left sided dominance. Here we report test-retest and between-task reliability measures obtained with functional transcranial Doppler ultrasound in 47 participants, including 9 with atypical language presentation. Results showed good test-retest reliability in atypically lateralised individuals, even after an interval of 120 days. Between-task reliability was weaker, but still within acceptable ranges.

In Vivo Validation of Volume Flow Measurements of Pulsatile Flow Using a Clinical Ultrasound System and Matrix Array Transducer.

The goal of this study was to evaluate the accuracy of a non-invasive C-plane Doppler estimation of pulsatile blood flow in the lower abdominal vessels of a porcine model. Doppler ultrasound measurements from a matrix array transducer system were compared with invasive volume flow measurements made on the same vessels with a surgically implanted ultrasonic transit-time flow probe. For volume flow rates ranging from 60 to 750 mL/min, agreement was very good, with a Pearson correlation coefficient of 0.97 (p < 0.0001) and a mean bias of -4.2%. The combination of 2-D matrix array technology and fast processing gives this Doppler method clinical potential, as many of the user- and system-dependent parameters of previous methods, including explicit vessel angle and diameter measurements, are eliminated.

Is digit ratio (2D:4D) a reliable pointer to speech laterality?

The relative length of the second and fourth digits (2D:4D ratio) is sexually dimorphic and a retrospective biomarker of prenatal hormonal exposure. Low ratios indicate higher prenatal testosterone (pT) and lower estrogen exposure, whereas the reverse pattern is associated with high ratios. Elevated levels of pT exposure have long been thought to modulate hemispheric specialisation; subsequently many studies use the 2D:4D ratio as a proxy index for pT to examine the effects of prenatal hormonal exposure on lateralised cognitive abilities. Here we used Transcranial Doppler ultrasonography and digit ratio to investigate whether pT has an influence on speech laterality. We tested 34 right and 14 left handed adults. Our results indicate that speech representation is unrelated to digit characteristics and therefore purportedly pT. We discuss these findings in relation to androgen theories of lateralisation.

Hemispheric speech lateralisation in the developing brain is related to motor praxis ability.

Commonly displayed functional asymmetries such as hand dominance and hemispheric speech lateralisation are well researched in adults. However there is debate about when such functions become lateralised in the typically developing brain. This study examined whether patterns of speech laterality and hand dominance were related and whether they varied with age in typically developing children. 148 children aged 3-10 years performed an electronic pegboard task to determine hand dominance; a subset of 38 of these children also underwent functional Transcranial Doppler (fTCD) imaging to derive a lateralisation index (LI) for hemispheric activation during speech production using an animation description paradigm. There was no main effect of age in the speech laterality scores, however, younger children showed a greater difference in performance between their hands on the motor task. Furthermore, this between-hand performance difference significantly interacted with direction of speech laterality, with a smaller between-hand difference relating to increased left hemisphere activation. This data shows that both handedness and speech lateralisation appear relatively determined by age 3, but that atypical cerebral lateralisation is linked to greater performance differences in hand skill, irrespective of age. Results are discussed in terms of the common neural systems underpinning handedness and speech lateralisation.