Background: Postoperative delirium may manifest in the immediate post-anaesthesia care period. Such episodes appear to be predictive of further episodes of inpatient delirium and associated adverse outcomes. Frontal electroencephalogram (EEG) findings of suppression patterns and low proprietary index values have been associated with postoperative delirium and poor outcomes. However, the efficacy of titrating anaesthesia to proprietary index targets for preventing delirium remains contentious. We aim to assess the efficacy of two strategies which we hypothesise could prevent post-anaesthesia care unit (PACU) delirium by maximising the alpha oscillation observed in frontal EEG channels during the maintenance and emergence phases of anaesthesia. Methods: This is a 2 × 2 factorial, double-blind, stratified, randomised control trial of 600 patients. Eligible patients are those aged 60 years or over who are undergoing non-cardiac, non-intracranial, volatile-based anaesthesia of expected duration of more than 2 h. Patients will be stratified by pre-operative cognitive status, surgery type and site. For the maintenance phase of anaesthesia, patients will be randomised (1:1) to an alpha power-maximisation anaesthesia titration strategy versus standard care avoiding suppression patterns in the EEG. For the emergence phase of anaesthesia, patients will be randomised (1:1) to early cessation of volatile anaesthesia and emergence from an intravenous infusion of propofol versus standard emergence from volatile anaesthesia only. The primary study outcomes are the power of the frontal alpha oscillation during the maintenance and emergence phases of anaesthesia. Our main clinical outcome of interest is PACU delirium. Discussion: This is a largely exploratory study; the extent to which EEG signatures can be modified by titration of pharmacological agents is not known. The underlying concept is maximisation of anaesthetic efficacy by individualised drug titration to a clearly defined EEG feature. The interventions are already clinically used strategies in anaesthetic practice, but have not been formally evaluated. The addition of propofol during the emergence phase of volatile-based general anaesthesia is known to reduce emergence delirium in children; however, the efficacy of this strategy in older patients is not known. Trial registration: Australian and New Zealand Clinical Trial Registry, ID: 12617001354370. Registered on 27/09/2017.

Purpose This study investigated whether participation in aerobic exercise enhances the effects of aphasia therapy, and the degree to which basal serum brain-derived neurotropic factor (BDNF) concentrations fluctuate after the beginning of aerobic exercise or stretching activities in individuals with poststroke aphasia. Methods The study used a single-subject, multiple-baseline design. Seven individuals with chronic poststroke aphasia participated in 2 Blocks of aphasia therapy: aphasia therapy alone (Block 1), followed by aphasia therapy with the addition of aerobic activity via bicycle ergometer (n = 5) or stretching (n = 2) (Block 2). Serum BDNF concentrations from blood draws were analyzed in 4 participants who exercised and in 1 participant who stretched. Findings Three of the five exercise participants demonstrated larger Tau-U effects when aphasia therapy was paired with aerobic exercise, whereas 1 of the 2 stretching participants demonstrated a larger effect size when aphasia therapy was paired with stretching. Group-level comparisons revealed a greater overall increase in effect size in the aerobic exercise group, as indicated by differences in Tau-U weighted means. BDNF data showed that all 4 exercise participants demonstrated a decrease in BDNF concentrations during the first 6 weeks of exercise and an increase in BDNF levels near or at baseline during the last 6 weeks of exercise. The stretching participant did not show the same pattern. Implications Additional research is needed to understand the mechanism of effect and to identify the factors that mediate response to exercise interventions, specifically the optimal dose of exercise and timing of language intervention with exercise. ClinicalTrials.gov identifier: NCT01113879.

Blood Oxygen Level Dependent (BOLD) functional MRI is a complex neurovascular signal whose magnitude depends on baseline physiological factors such as cerebral blood flow (CBF). Because baseline CBF varies across the brain and is altered with aging, the interpretation of stand-alone aging-related BOLD changes can be misleading. The primary objective of this study was to develop a methodology that combines task fMRI and arterial spin labeling (ASL) techniques to sensitize task-induced BOLD activity by covarying out the baseline physiology (i.e., CBF) in an aging model. We recruited 11 younger and 13 older healthy participants who underwent ASL and an overt language fMRI task (semantic category member generation). We measured in-scanner language performance to investigate the effect of BOLD sensitization on BOLD-behavior relationships. The results demonstrate that our correction approach is effective at enhancing the specificity and sensitivity of the BOLD signal in both groups. In addition, the correction strengthens the statistical association between task BOLD activity and behavioral performance. Although CBF has inherent age dependence, our results show that retaining the age factor within CBF aides in greater sensitization of task fMRI signals. From a cognitive standpoint, compared to young adults, the older participants showed a delayed domain-general language-related task activity possibly due to compromised vessel compliance. Further, assessment of functional evolution of corrected BOLD activity revealed biphasic BOLD dynamics in both groups where BOLD deactivation may reflect greater semantic demand or increased premium on domain general executive functioning in response to task difficulty. Although it was promising to note that the predictability of behavior using the proposed methodology outperforms other methodologies (i.e., no correction and normalization by division), and provides moderate stability and adequate power, further work with a larger cohort and other task designs is necessary to improve the stability of predicting associated behavior. In summary, we recommend correction of task fMRI signals by covarying out baseline CBF especially when comparing groups with different neurovascular properties. Given that ASL and BOLD fMRI are well established and widely employed techniques, our proposed multi-modal methodology can be readily implemented into data processing pipelines to obtain more accurate BOLD activation maps.

Purpose: Motivation is a complex phenomenon that can influence a person's ability to make progress in treatment. We sought to understand how motivation is currently measured and utilized in aphasia rehabilitation by identifying treatment studies that (1) include measurement of motivation and (2) use motivation to predict treatment response. Method: A scoping review was conducted by systematically searching PubMed, CINAHL, EBSCO, Ovid MEDLINE, and APA PsycInfo using the following search terms: (measurement OR treatment OR rehabilitation OR predict∗) AND (motiv∗ OR engagement OR adherence OR compliance) AND (aphasia OR dysphasia). Results: Two studies met our inclusion criteria. Motivation was measured differently across studies. No studies used motivation to predict treatment outcomes. Discussion/Conclusions: Despite the importance of motivation in aphasia rehabilitation success, studies that include its measurement are sparse. Additional research is needed and should include development of measurement tools and evaluation of the predictive value of motivation on treatment outcomes.

Objective: Advanced age poses an increased risk for cognitive impairment, and therefore, poor knowledge regarding the risks associated with COVID-19 may confer vulnerability. We administered a COVID-19 Knowledge Questionnaire to older persons to evaluate the association between knowledge regarding public health recommendations, and cognitive status as measured by the Montreal Cognitive Assessment (MoCA). Method: Ninety-nine participants completed a 22-item questionnaire about COVID-19 symptoms, risks, and protective strategies, and they also completed the MoCA. Associations between knowledge and cognitive status were examined via Spearman correlations. Results: The mean (SD) age of participants was 72.6 (7.6) years, and MoCA scores averaged 23.4 (4.5) points. Higher MoCA total scores were significantly (p <.001) correlated with a greater number of correct questionnaire responses. Higher Orientation and Memory Index scores were moderately associated with an increased number of correct responses (p <.001), with the Executive Index exhibiting a significant albeit weaker association. MoCA Index scores assessing attention, language, and visuospatial functioning were not significantly associated with COVID-19 knowledge. Conclusions: Given the rapid transmission rate of the SARS CoV-2 infections, COVID knowledge lapses will likely have deleterious repercussions. Public health messages should ensure effective acquisition and retention of COVID specific information, especially in cognitively compromised older adults.

Stroke-related tissue damage within lesioned brain areas is topologically non-uniform and has underlying tissue composition changes that may have important implications for rehabilitation. However, we know of no uniformly accepted, objective non-invasive methodology to identify pericavitational areas within the chronic stroke lesion. To fill this gap, we propose a novel magnetic resonance imaging (MRI) methodology to objectively quantify the lesion core and surrounding pericavitational perimeter, which we call tissue integrity gradation via T2w T1w ratio (TIGR). TIGR uses standard T1-weighted (T1w) and T2-weighted (T2w) anatomical images routinely collected in the clinical setting. TIGR maps are analyzed with relation to subject-specific gray matter and cerebrospinal fluid thresholds and binned to create a false colormap of tissue damage within the stroke lesion, and these are further categorized into low-, medium-, and high-damage areas. We validate TIGR by showing that the cerebral blood flow within the lesion reduces with greater tissue damage (p = 0.005). We further show that a significant task activity can be detected in pericavitational areas and that medium-damage areas contain a significantly lower magnitude of hemodynamic response function than the adjacent damaged areas (p < 0.0001). We also demonstrate the feasibility of using TIGR maps to extract multivariate brain–behavior relationships (p < 0.05) and show general agreement in location compared to binary lesion, T1w-only, and T2w-only maps but that the extent of brain behavior maps may depend on signal sensitivity as denoted by the sparseness coefficient (p < 0.0001). Finally, we show the feasibility of quantifying TIGR in early and late subacute stroke phases, where higher-damage areas were smaller in size (p = 0.002) and that lesioned voxels transition from lower to higher damage with increasing time post-stroke (p = 0.004). We conclude that TIGR is able to (1) identify tissue damage gradient within the stroke lesion across different post-stroke timepoints and (2) more objectively delineate lesion core from pericavitational areas wherein such areas demonstrate reasonable and expected physiological and functional impairments. Importantly, because T1w and T2w scans are routinely collected in the clinic, TIGR maps can be readily incorporated in clinical settings without additional imaging costs or patient burden to facilitate decision processes related to rehabilitation planning.

The last 25 years have seen profound changes in neurocognitive rehabilitation that continue to motivate its evolution. Although the concept of nervous system plasticity was discussed by William James (1890), the foundation for experience-based plasticity had not reached the critical empirical mass to seriously impact rehabilitation research until after 1992. The objective of this review is to describe how the emergence of neural plasticity has changed neurocognitive rehabilitation research. Method: The important developments included (a) introduction of a widely available tool that could measure brain plasticity (i.e., functional MRI); (b) development of new structural imaging techniques that could define limits of and opportunities for neural plasticity; (c) deployment of noninvasive brain stimulation to leverage neural plasticity for rehabilitation; (d) growth of a literature indicating that exercise has positively impacts neural plasticity, especially for older persons; and (e) enhancement of neural plasticity by creating interventions that generalize beyond the boundaries of treatment activities. Given the massive literature, each of these areas is developed by example. Results: The expanding influence of neural plasticity has provided new models and tools for neurocognitive rehabilitation in neural injuries and disorders, as well as methods for measuring neural plasticity and predicting its limits and opportunities. Early clinical trials have provided very encouraging results. Conclusion: Now that neural plasticity has gained a firm foothold, it will continue to influence the evolution of neurocognitive rehabilitation research for the next 25 years and advance rehabilitation for neural injuries and disease.

Embodied cognition offers an approach to word meaning firmly grounded in action and perception. A strong prediction of embodied cognition is that sensorimotor simulation is a necessary component of lexical-semantic representation. One semantic distinction where motor imagery is likely to play a key role involves the representation of manufactured artefacts. Many questions remain with respect to the scope of embodied cognition. One dominant unresolved issue is the extent to which motor enactment is necessary for representing and generating words with high motor salience. We investigated lesion correlates of manipulable relative to nonmanipulable name generation (e.g., name a school supply; name a mountain range) in patients with nonfluent aphasia (N = 14). Lesion volumes within motor (BA4, where BA = Brodmann area) and premotor (BA6) cortices were not predictive of category discrepancies. Lesion symptom mapping linked impairment for manipulable objects to polymodal convergence zones and to projections of the left, primary visual cortex specialized for motion perception (MT/V5+). Lesions to motor and premotor cortex were not predictive of manipulability impairment. This lesion correlation is incompatible with an embodied perspective premised on necessity of motor cortex for the enactment and subsequent production of motor-related words. These findings instead support a graded or "soft" approach to embodied cognition premised on an ancillary role of modality-specific cortical regions in enriching modality-neutral representations. We discuss a dynamic, hybrid approach to the neurobiology of semantic memory integrating both embodied and disembodied components.

Given the profound impact of language impairment after stroke (aphasia), neuroplasticity research is garnering considerable attention as means for eventually improving aphasia treatments and how they are delivered. Functional and structural neuroimaging studies indicate that aphasia treatments can recruit both residual and new neural mechanisms to improve language function and that neuroimaging modalities may hold promise in predicting treatment outcome. In relatively small clinical trials, both non-invasive brain stimulation and behavioural manipulations targeting activation or suppression of specific cortices can improve aphasia treatment outcomes. Recent language interventions that employ principles consistent with inducing neuroplasticity also are showing improved performance for both trained and novel items and contexts. While knowledge is rapidly accumulating, larger trials emphasising how to select optimal paradigms for individualised aphasia treatment are needed. Finally, a model of how to incorporate the growing knowledge into clinical practice could help to focus future research.

BACKGROUND: Frailty is associated with adverse perioperative outcomes including major morbidity, mortality, and increased length of stay. We sought to elucidate the role that a preoperatively assessed Mini-Cog can play in assessing the risk of adverse perioperative outcomes in a population at high risk of frailty. METHODS: In this retrospective case-control study, patients who were >60 years of age, nonambulatory, or had >5 documented medications were preoperatively assessed for handgrip strength, walking speed, and Mini-Cog score. The Emory University Clinical Data Warehouse was then used to extract this information and other perioperative data elements and outcomes data. RESULTS: Data were available for 1132 patients undergoing a wide variety of surgical procedures. For the subset of 747 patients with data for observed-to-expected length of stay, an abnormal Mini-Cog was associated with an increased odds of observed-to-expected >1 (odds ratio, 1.52; 95% CI, 1.05-2.19; P =.025). There was no association of abnormal Mini-Cog with intensive care unit length of stay >3 days (P =.182) discharge to home with self-care (P =.873) or risk of readmission (P =.104). Decreased baseline hemoglobin was associated with increased risk of 2 of the 4 outcomes studied. CONCLUSIONS: In a high-risk pool of patients, Mini-Cog may not be sensitive enough to detect significant differences for most adverse outcomes. Further work is needed to assess whether cognitive screens with greater resolution are of value in this context and to compare tools for assessing overall frailty status.