An International and Multidisciplinary Consensus on the Labeling of Spatial Neglect Using a Modified Delphi Method.

Survivors of neurologic injury (most commonly stroke or traumatic brain injury) frequently experience a disorder in which contralesionally positioned objects or the contralesional features of individual objects are often left unattended or underappreciated. The disorder is known by >200 unique labels in the literature, which potentially causes confusion for patients and their families, complicates literature searches for researchers and clinicians, and promotes a fractionated conceptualization of the disorder. The objective of this Delphi was to determine if consensus (≥75% agreement) could be reached by an international and multidisciplinary panel of researchers and clinicians with expertise on the topic. To accomplish this aim, we used a modified Delphi method in which 66 researchers and/or clinicians with expertise on the topic completed at least 1 of 4 iterative rounds of surveys. Per the Delphi method, panelists were provided with results from each round prior to responding to the survey in the subsequent round with the explicit intention of achieving consensus. The panel ultimately reached consensus that the disorder should be consistently labeled spatial neglect. Based on the consensus reached by our expert panel, we recommend that researchers and clinicians use the label spatial neglect when describing the disorder in general and more specific labels pertaining to subtypes of the disorder when appropriate.

A scoping review and critique of the Input-Output subtyping dimension of spatial neglect.

Spatial neglect is a common and debilitating disorder after stroke whereby individuals have difficulty reporting, orienting, and/or responding to the contralesional side of space. Given the heterogeneity of neglect symptom presentation, various neglect subtypes have been proposed to better characterize the disorder. This review focuses on the distinction between Input neglect (i.e., difficulty perceiving and/or attending to contralesional stimuli) and Output neglect (i.e., difficulty planning and/or executing movements toward contralesional stimuli). Conceptualizations of Input and Output neglect have varied considerably. We provide a novel summary of the terminology, measurement approaches, and neural correlates of these subtypes. A protocol detailing our systematic scoping review strategy is registered on the Open Science Framework (https://osf.io/bvtxf/). For feasibility and greater comparability across studies, we limited our inclusion criteria to tasks focused on visual stimuli and upper-limb movements. A total of 110 articles were included in the review. Subtyping tasks were categorized based on whether they mainly manipulated aspects of the input (i.e., congruence of visual input with motor output, presence of visual input) or the output (i.e., modality, goal, or direction of output) to produce an Input-Output subtype dissociation. We used our review results to identify four main critiques of this literature: 1) lack of consistency/clarity in conceptual models; 2) methodological issues of dissociating Input and Output subtypes; 3) a need for updated neural theories; and 4) barriers to clinical application. We discuss the lessons learned from this subtyping dimension that can be applied to future research on neglect subtype assessment and treatment.

Internal consistency and reliability of the lifetime and modified current cognitive activity questionnaires and their association with cognitive performance: a six-year follow up of the Brain in Motion study.

INTRODUCTION: Cognitive activity questionnaires could provide insight into neurocognitive reserve. The Lifetime Cognitive Activities Questionnaire (LCAQ) assesses cognitive activities at four stages of life. The Modified Current Cognitive Activities Questionnaire (CCAQ) assesses current cognitive activities. We examined the construct validity, internal consistency, test-retest reliability, and stability of these questionnaires throughout the Brain in Motion (BIM) study and their relationship with cognitive performance. METHODS: The LCAQ, Montreal Cognitive Assessment (MoCA), and neuropsychological battery were administered at the initial pre-intervention and six-year follow-up. The CCAQ was administered at five timepoints. Construct validity of the CCAQ/LCAQ was assessed using proxies of cognitive engagement (educational attainment and the North American Adult Reading Test [NAART]). Cronbach alpha analysis determined internal consistency. LCAQ reliability was established by comparing the pre-intervention and six-year follow-up. CCAQ reliability was determined by comparing both pre-intervention assessments, correlations throughout BIM determined stability. A multiple linear regression investigated the associations between cognitive engagement and cognitive domains derived from a principal component analysis. RESULTS: MoCA scores at the initial pre-intervention (27.49 ± 1.46) and six-year follow up (26.53 ± 2.08). The LCAQ and CCAQ correlated with educational attainment and the NAART. The LCAQ (n = 266) produced an alpha of 0.90 (20 items). The CCAQ (n = 261) resulted in an alpha of 0.71 (25 items). LCAQ scores (n = 94) at the initial pre-intervention and six-year follow-up were correlated. CCAQ (n = 94) scores at the initial pre-intervention correlated with scores at all five other timepoints. The multiple linear regression revealed associations between the CCAQ and verbal memory/attention. The NAART was associated with processing speed, concept formation, and verbal memory/attention. CONCLUSIONS: In the absence of cognitive decline, these questionnaires exhibit significant construct validity, internal consistency, test-retest reliability, and the CCAQ displayed stability. The NAART and CCAQ were associated with neuropsychological performance. Our findings support future use of these questionnaires and exemplify the neuroprotective role of cognitive engagement.

Investigating premotor reaching biases after prism adaptation.

Prism adaptation (PA) is both a visuomotor learning task and potential treatment for spatial neglect after stroke. While PA's aftereffects can improve neglect symptoms, therapeutic benefits vary across individuals, possibly due to differences in neglect subtypes. Neglect symptoms can be described along an information processing pathway, yielding perceptual (input) and premotor (output) neglect subtypes. There is some evidence that PA mainly benefits persons with premotor neglect. We investigated whether PA modulates the premotor stage of information processing by examining whether PA could induce a premotor bias in healthy adults. We measured perceptual and premotor biases using a speeded reach task that compares the initiation time of leftward and rightward reaches to lateralized targets from different hand start positions. Using a randomized mixed experimental design, 30 right-handed healthy adults completed this speeded reach task before and after either left-shifting (n = 15) or right-shifting (n = 15) PA. As hypothesized, left-shifting PA speeded initiation time specifically for reaches in the rightward direction, regardless of target location (p = .02, ηp2 = .18), suggesting that PA induced a premotor bias in the direction of the prism aftereffect. These findings have implications for PA's underlying mechanisms, which can inform visuomotor learning theories and PA's use as a treatment for spatial neglect.

Age-related changes to electroencephalographic markers of visuomotor error processing and learning in prism adaptation.

Aging is associated with changes in cognitive function, including declines in learning, memory, and executive function. Prism adaptation (PA) is a useful paradigm to measure changes in explicit and implicit mechanisms of visuo-motor learning with age, but the neural correlates are not well understood. In the present study, we used PA to investigate visuo-motor learning and error processing in older adults. Twenty older adults (56-85 yrs) and 20 younger adults (18-33 yrs) underwent a goal-oriented reaching task while wearing prism goggles as continuous EEG was recorded to examine neural correlates of error detection. We examined behavioural measures of PA, as well as ERP components previously found associated with the early and late phases of adaptation to visual distortion caused by the prism goggles. Our results indicate important age-related behavioural and neurophysiological differences. Older adults reached more slowly than younger adults but showed the same accuracy throughout the prism exposure. Older adults also displayed larger aftereffects, indicating preserved visuomotor adaptation. EEG results indicated similar initial error processing in older and younger adults, as measured by the feedback error related negativity (FRN). As seen previously in young adults, the P3a and P3b declined over the prism exposure phase in both groups. Older adults displayed reduced P3a amplitude compared to the younger group in the early phase of adaptation, however, suggesting reduced attentional orienting. Finally, the older group exhibited a greater P3b amplitude compared to the younger group in the later phases of adaptation, potentially a marker of enhanced context updating underlying spatial realignment, leading to their larger aftereffect. Implications for age-related learning differences and clinical applications are discussed.

Executive Function Poststroke: Concepts, Recovery, and Interventions.

Executive function is frequently impaired among people who have sustained stroke. This review provides an overview of definitions, concepts, and measures. The review also summarizes current best evidence examining executive function impairment and recovery trajectories after stroke, correlates of change over time, and emerging intervention research. Finally, this review provides recommendations for research and clinical practices, as well as priorities for future executive function research.

Olfactory Function and Diffusion Tensor Imaging as Markers of Mild Cognitive Impairment in Early Stages of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder that is typified by motor signs and symptoms but can also lead to significant cognitive impairment and dementia Parkinson's Disease Dementia (PDD). While dementia is considered a nonmotor feature of PD that typically occurs later, individuals with PD may experience mild cognitive impairment (PD-MCI) earlier in the disease course. Olfactory deficit (OD) is considered another nonmotor symptom of PD and often presents even before the motor signs and diagnosis of PD. We examined potential links among cognitive impairment, olfactory functioning, and white matter integrity of olfactory brain regions in persons with early-stage PD. Cognitive tests were used to establish groups with PD-MCI and with normal cognition (PD-NC). Olfactory functioning was examined using the University of Pennsylvania Smell Identification Test (UPSIT) while the white matter integrity of the anterior olfactory structures (AOS) was examined using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) analysis. Those with PD-MCI demonstrated poorer olfactory functioning and abnormalities based on all DTI parameters in the AOS, relative to PD-NC individuals. OD and microstructural changes in the AOS of individuals with PD may serve as additional biological markers of PD-MCI.

Cognitive Training to Enhance Aphasia Therapy (Co-TrEAT): A Feasibility Study.

Persons with aphasia (PWA) often have deficits in cognitive domains such as working memory (WM), which are negatively correlated with recovery, and studies have targeted WM deficits in aphasia therapy. To our knowledge, however, no study has examined the efficacy of multi-modal training which includes both WM training and targeted language therapy. This pilot project examined the feasibility and preliminary efficacy of combining WM training and naming therapy to treat post-stroke PWA. Chronic PWA were randomly assigned to either the a) Phonological Components Analysis (PCA) and WM intervention (WMI) condition (i.e., a computerized adaptive dual n-back task), or b) PCA and active control condition (WMC). Participants received face-to-face PCA therapy 3 times/week for 5 weeks, and simultaneously engaged in WM training or the active control condition five times/week, independently at home. Six PWA were enrolled, 3 in each condition. Feasibility metrics were excellent for protocol compliance, retention rate and lack of adverse events. Recruitment was less successful, with insufficient participants for group analyses. Participants in the WMI (but not the WMC) condition demonstrated a clinically significant (i.e., > 5 points) improvement on the Western Aphasia Battery- Aphasia Quotient (WAB-R AQ) and Boston Naming Test after therapy. Given the small sample size, the performance of two individuals, matched on age, education, naming accuracy pre-treatment, WAB-R AQ and WM abilities was compared. Participant WMI-3 demonstrated a notable increase in WM training performance over the course of therapy; WMC-2 was the matched control. After therapy, WMI-3's naming accuracy for the treated words improved from 30 to 90% (compared to 30-50% for WMC-2) with a 7-point WAB-R AQ increase (compared to 3 for WMC-2). Improvements were also found for WMI-3 but not for WMC-2 on ratings of communicative effectiveness, confidence and some conversation parameters in discourse. This feasibility study demonstrated excellent results for most aspects of Co-TrEAT. Recruitment rate, hampered by limited resources, must be addressed in future trials; remotely delivered aphasia therapy may be a possible solution. Although no firm conclusions can be drawn, the case studies suggest that WM training has the potential to improve language and communication outcomes when combined with aphasia therapy.

Older adults with lower working memory capacity benefit from transcranial direct current stimulation when combined with working memory training: A preliminary study.

Aging is a very diverse process: successful agers retain most cognitive functioning, while others experience mild to severe cognitive decline. This decline may eventually negatively impact one's everyday activities. Therefore, scientists must develop approaches to counteract or, at least, slow down the negative change in cognitive performance of aging individuals. Combining cognitive training and transcranial direct current stimulation (tDCS) is a promising approach that capitalizes on the plasticity of brain networks. However, the efficacy of combined methods depends on individual characteristics, such as the cognitive and emotional state of the individual entering the training program. In this report, we explored the effectiveness of working memory training, combined with tDCS to the right dorsolateral prefrontal cortex (DLPFC), to manipulate working memory performance in older individuals. We hypothesized that individuals with lower working memory capacity would benefit the most from the combined regimen. Thirty older adults took part in a 5-day combined regimen. Before and after the training, we evaluated participants' working memory performance with five working memory tasks. We found that individual characteristics influenced the outcome of combined cognitive training and tDCS regimens, with the intervention selectively benefiting old-old adults with lower working memory capacity. Future work should consider developing individualized treatments by considering individual differences in cognitive profiles.

Managing Fatigue in Parkinson's Disease: Protocol for a Pilot Randomized Controlled Trial.

Background. Fatigue is a disabling symptom of Parkinson's disease (PD). Managing Fatigue: A Six-Week Energy Conservation Intervention was developed to improve the occupational performance of people with fatigue. Efficacy of this program has not been established in PD. Purpose. This study will assess feasibility of the Managing Fatigue: Individual Program (MFIP) delivered via videoconference, the Randomized Controlled Trial (RCT) protocol, and the preliminary effectiveness of the MFIP. Methods. A mixed-methods approach nested in a pilot RCT, randomizing 54 participants 1:1 to usual care or MFIP arms, will be employed to evaluate the feasibility and preliminary effectiveness of MFIP. Qualitative and quantitative data will be collected simultaneously. Implications. Results will identify evidence for establishing protocol requirements for a full-scale RCT. Knowledge of the effectiveness of the one-to-one videoconference delivery format of the program has the potential to enhance the accessibility and the quality of care of the PD population.

Program of Rehabilitative Exercise and Education to Avert Vascular Events After Non-Disabling Stroke or Transient Ischemic Attack (PREVENT Trial): A Randomized Controlled Trial.

BACKGROUND: Non-disabling stroke (NDS) and transient ischemic attack (TIA) herald the possibility of future, more debilitating vascular events. Evidence is conflicting about potency of exercise and education in reducing risk factors for second stroke. METHODS: Three-site, single-blinded, randomized controlled trial with 184 participants <3 months of NDS or TIA (mean age, 65 years; 66% male) randomized to usual care (UC) or UC + 12-week program of exercise and education (PREVENT). Primary (resting systolic blood pressure) and secondary outcomes (diastolic blood pressure [DBPrest], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], TC/HDL, triglycerides, fasting glucose, and body mass index) were assessed at baseline, post-intervention, and 6- and 12-month follow-up. Peak oxygen consumption (VO2peak) was measured at baseline, post-intervention, 12-month assessments. RESULTS: Significant between-group differences at post-intervention favored PREVENT group over UC: DBPrest (mean difference [MD]: -3.2 mmHg, 95% confidence interval [CI]: -6.3, -.2, P = .04) and LDL-C (MD: -.31 mmol/L, 95% CI: -.42, -.20, P = .02). Trends of improvement in PREVENT group were noted in several variables between baseline and 6-month follow-up but not sustained at 12-month follow-up. Of note, VO2 peak did not change over time in either group. CONCLUSION: Impact of PREVENT on vascular risk factor reduction was more modest than anticipated, possibly because several outcome variables approximated normative values at baseline and training intensity may have been sub-optimal. Further investigation is warranted to determine when exercise and education programs are viable adjuncts to pharmaceutical management for reduction of risk factors for second stroke.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: #NCT00885456.

Can prism adaptation effects generalize to wheelchair maneuvering?

BACKGROUND: While prism adaptation (PA) has been recognized as a promising tool for treating spatial neglect, implementation as a standard treatment in clinical care has been lagging. Limited evidence for the generalization of after-effects to everyday activities has been a barrier towards implementation. OBJECTIVES: This study examined whether a home-friendly standardized PA protocol (Peg-the-Mole, PTM) induces after-effects that can transfer to wheelchair maneuvering. We also examined the impact of using constant (1 starting hand position) or variable (3 starting hand positions) training conditions on the transfer of after-effects to wheelchair maneuvering. METHODS: Sixty participants were randomly assigned to one of four PTM conditions: 1) prisms/constant training; 2) prisms/variable training; 3) sham goggles/constant training; 4) sham goggles/variable training. RESULTS: The use of PTM with rightward shifting prisms induced after-effects on proprioceptive and visual pointing outcome tasks. Groups using PTM with prism goggles showed a leftward shift in their position within a wheelchair course and a reduction in the number of right-sided collisions. The training condition did not have an impact on the transfer of after-effects to wheelchair driving. CONCLUSION: PTM is a clinically appealing PA protocol that induces after-effects that can transfer to an everyday activity relevant to patients with neglect.

Impact of tDCS on working memory training is enhanced by strategy instructions in individuals with low working memory capacity.

Interventions to improve working memory, e.g. by combining task rehearsal and non-invasive brain stimulation, are gaining popularity. Many factors, however, affect the outcome of these interventions. We hypothesize that working memory capacity at baseline predicts how an individual performs on a working memory task, by setting limits on the benefit derived from tDCS when combined with strategy instructions; specifically, we hypothesize that individuals with low capacity will benefit the most. Eighty-four participants underwent two sessions of an adaptive working memory task (n-back) on two consecutive days. Participants were split into four independent groups (SHAM vs ACTIVE stimulation and STRATEGY vs no STRATEGY instructions). For the purpose of analysis, individuals were divided based on their baseline working memory capacity. Results support our prediction that the combination of tDCS and strategy instructions is particularly beneficial in low capacity individuals. Our findings contribute to a better understanding of factors affecting the outcome of tDCS when used in conjunction with cognitive training to improve working memory. Moreover, our results have implications for training regimens, e.g., by designing interventions predicated on baseline cognitive abilities, or focusing on strategy development for specific attentional skills.

Role of aging and working memory in performance on a naturalistic visual search task.

Studying age-related changes in working memory (WM) and visual search can provide insights into mechanisms of visuospatial attention. In visual search, WM is used to remember previously inspected objects/locations and to maintain a mental representation of the target to guide the search. We sought to extend this work, using aging as a case of reduced WM capacity. The present study tested whether various domains of WM would predict visual search performance in both young (n = 47; aged 18-35 yrs) and older (n = 48; aged 55-78) adults. Participants completed executive and domain-specific WM measures, and a naturalistic visual search task with (single) feature and triple-conjunction (three-feature) search conditions. We also varied the WM load requirements of the search task by manipulating whether a reference picture of the target (i.e., target template) was displayed during the search, or whether participants needed to search from memory. In both age groups, participants with better visuospatial executive WM were faster to locate complex search targets. Working memory storage capacity predicted search performance regardless of target complexity; however, visuospatial storage capacity was more predictive for young adults, whereas verbal storage capacity was more predictive for older adults. Displaying a target template during search diminished the involvement of WM in search performance, but this effect was primarily observed in young adults. Age-specific interactions between WM and visual search abilities are discussed in the context of mechanisms of visuospatial attention and how they may vary across the lifespan.

Current clinical practice in the screening and diagnosis of spatial neglect post-stroke: Findings from a multidisciplinary international survey.

Spatial neglect has profound implications for quality of life after stroke, yet we lack consensus for screening/diagnosing this heterogeneous syndrome. Our first step in a multi-stage research programme aimed to determine which neglect tests are used (within four categories: cognitive, functional, neurological and neuroimaging/neuromodulation), by which stroke clinicians, in which countries, and whether choice is by professional autonomy or institutional policy. 454 clinicians responded to an online survey: 12 professions (e.g., 39% were occupational therapists) from 33 countries (e.g., 38% from the UK). Multifactorial logistic regression suggested inter-professional differences but fewer differences between countries (Italy was an outlier). Cognitive tests were used by 82% (particularly by psychologists, cancellation and drawing were most popular); 80% used functional assessments (physiotherapists were most likely). 20% (mainly physicians, from Italy) used neuroimaging/ neuromodulation. Professionals largely reported clinical autonomy in their choices. Respondents agreed on the need for a combined approach to screening and further training. This study raises awareness of the translation gap between theory and practice. These findings lay an important foundation to subsequent collaborative action between clinicians, researchers and stroke survivors to reach consensus on screening and diagnostic measures. The immediate next step is a review of the measures' psychometric properties.

Ankle-foot orthoses improve walking but do not reduce dual-task costs after stroke.

BACKGROUND: Cognitive-motor interference, as measured by dual-task walking (performing a mental task while walking), affects many clinical populations. Ankle-foot orthoses (AFOs) are lower-leg splints prescribed to provide stability to the foot and ankle, as well as prevent foot drop, a gait deficit common after stroke. AFO use has been shown to improve gait parameters such as speed and step time, which are often negatively impacted by dual-task walking. OBJECTIVES: Our objective was to establish whether AFOs could protect against cognitive-motor interference, as measured by dual-task walking, following post-stroke hemiplegia. METHODS: A total of 21 individuals with post-stroke hemiplegia that use an AFO completed a dual-task walking paradigm in the form of a 2 (walking with vs. without a concurrent cognitive task) by 2 (walking with vs. without an AFO) repeated-measures design. Changes to both motor and cognitive performance were analyzed. RESULTS: The results suggest that the use of an AFO improves gait overall in both single- and dual-task walking, particularly with respect to stride regularity, but there were no interactions to suggest that AFOs reduce the cognitive-motor dual-task costs themselves. A lack of differences in cognitive performance during dual-task walking with and without the AFO suggests that the AFO's benefit to motor performance cannot be attributed to task prioritization. CONCLUSIONS: These data support the use of AFOs to improve certain gait parameters for post-stroke hemiplegia, but AFOs do not appear to protect against cognitive-motor interference during dual-task walking. Future research should pursue alternate therapeutics for ameliorating task-specific declines under cognitively demanding circumstances.

Genetic Risk, Vascular Function, and Subjective Cognitive Complaints Predict Objective Cognitive Function in Healthy Older Adults: Results From the Brain in Motion Study.

Aging is associated with subjective memory complaints. Approximately half of those with subjective memory complaints have objective cognitive impairment. Previous studies have provided evidence of an association between genetic risk for Alzheimer's disease (AD) and dementia progression. Also, aging is a significant risk factor for vascular pathology that may underlie at least some of the cognitive changes. This study investigates the relative contribution of subjective cognitive complaints (SCC), vascular function, and genetic risk for dementia in predicting objective cognitive performance. Multiple regression and relative importance analysis were used to investigate the relative contribution of vascular function, self-reported SCC, and dementia genetic risk, in predicting objective cognition in a sample of 238 healthy community-dwelling older adults. Age, sex, premorbid cognitive abilities, subjective verbal memory complaints, higher cerebrovascular blood flow during submaximal exercise, and certain dementia risk alleles were significant predictors of worse objective verbal memory performance (p < 0.001, R 2 = 35.2-36.4%). Using relative importance analysis, subjective verbal memory complaints, and certain dementia risk alleles contributed more variance than cerebrovascular measures. These results suggest that age-related changes in memory in healthy older adults can be predicted by subjective memory complaints, genetic risk, and to a lesser extent, cerebrovascular function.

BRAINSTORMING: A study protocol for a randomised double-blind clinical trial to assess the impact of concurrent brain stimulation (tDCS) and working memory training on cognitive performance in Acquired Brain Injury (ABI).

BACKGROUND: Acquired Brain Injury (ABI) admissions have an incidence of 385 per 100,000 of the population in the UK, and as brain injury often involves the frontal networks, cognitive domains affected are likely to be executive control, working memory, and problem-solving deficits, resulting in difficulty with everyday activities. The above observations make working memory, and related constructs such as attention and executive functioning attractive targets for neurorehabilitation. We propose a combined home-based rehabilitation protocol involving the concurrent administration of a working memory training program (adaptive N-back task) with non-invasive transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex to promote long-lasting modification of brain areas underlying working memory function. METHOD: Patients with a working memory deficit will be recruited and assigned to two age-matched groups receiving working memory training for 2 weeks: an active group, receiving tDCS (2 mA for 20 min), and a control group, receiving sham stimulation. After the end of the first 2 weeks, both groups will continue the working memory training for three more weeks. Outcome measures will be recorded at timepoints throughout the intervention, including baseline, after the 2 weeks of stimulation, at the end of the working memory training regimen and 1 month after the completion of the training. DISCUSSION: The aim of the study is to assess if non-invasive tDCS stimulation has an impact on performance and benefits of a working memory training regimen. Specifically, we will examine the impact of brain stimulation on training gains, if changes in gains would last, and whether changes in training performance transfer to other cognitive domains. Furthermore, we will explore whether training improvements impact on everyday life activities and how the home-based training regimen is received by participants, with the view to develop an effective home healthcare tool that could enhance working memory and daily functioning. TRIAL REGISTRATION: This study was registered with clinicaltrials.gov: NCT04010149 on July 8, 2019.