Supervised, Self-Administered Tablet-Based Cognitive Assessment in Neurodegenerative Disorders and Stroke.

INTRODUCTION: As the population ages, the prevalence of cognitive impairment is expanding. Given the recent pandemic, there is a need for remote testing modalities to assess cognitive deficits in individuals with neurological disorders. Self-administered, remote, tablet-based cognitive assessments would be clinically valuable if they can detect and classify cognitive deficits as effectively as traditional in-person neuropsychological testing. METHODS: We tested whether the Miro application, a tablet-based neurocognitive platform, measured the same cognitive domains as traditional pencil-and-paper neuropsychological tests. Seventy-nine patients were recruited and then randomized to either undergo pencil-and-paper or tablet testing first. Twenty-nine age-matched healthy controls completed the tablet-based assessments. We identified Pearson correlations between Miro tablet-based modules and corresponding neuropsychological tests in patients and compared scores of patients with neurological disorders with those of healthy controls using t tests. RESULTS: Statistically significant Pearson correlations between the neuropsychological tests and their tablet equivalents were found for all domains with moderate (r > 0.3) or strong (r > 0.7) correlations in 16 of 17 tests (p < 0.05). All tablet-based subtests differentiated healthy controls from neurologically impaired patients by t tests except for the spatial span forward and finger tapping modules. Participants reported enjoyment of the tablet-based testing, denied that it provoked anxiety, and noted no preference between modalities. CONCLUSIONS: This tablet-based application was found to be widely acceptable to participants. This study supports the validity of these tablet-based assessments in the differentiation of healthy controls from patients with neurocognitive deficits in a variety of cognitive domains and across multiple neurological disease etiologies.

Disruptions of the Human Connectome Associated With Hemispatial Neglect.

BACKGROUND AND OBJECTIVES: Hemispatial neglect is a heterogeneous and complex disorder that can be classified by frame of reference for "left" vs "right," including viewer-centered neglect (VCN, affecting the contralesional side of the view), stimulus-centered neglect (SCN, affecting the contralesional side of the stimulus, irrespective of its location with respect to the viewer), or both. We investigated the effect of acute stroke lesions on the connectivity of neural networks that underlie VCN or SCN. METHODS: A total of 174 patients within 48 hours of acute right hemispheric infarct underwent a detailed hemispatial neglect assessment that included oral reading, scene copy, line cancellation, gap detection, horizontal line bisection tests, and MRI. Each patient's connectivity map was generated. We performed a linear association analysis between network connectivity strength and continuous measures of neglect to identify lesion-induced disconnections associated with the presence or severity of VCN and SCN. Results were corrected for multiple comparisons. RESULTS: About 42% of the participants with right hemisphere stroke had at least one type of neglect. The presence of any type of neglect was associated with lesions to tracts connecting the right inferior parietal cortex, orbitofrontal cortex, and right thalamus to other right-hemispheric structures. VCN only was strongly associated with tracts connecting the right putamen to other brain regions and tracts connecting right frontal regions with other brain regions. The presence of both types of neglect was most strongly associated with tracts connecting the right inferior and superior parietal cortex to other brain regions and those connecting left or right mesial temporal cortex to other brain regions. DISCUSSION: Our study provides new evidence for the specific white matter tracts where disruption can cause hemispatial neglect in a relatively large number of participants and homogeneous time after onset. We obtained MRI and behavioral testing acutely, before the opportunity for rehabilitation or substantial recovery. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that damage to specific white matter tracts identified on MRI are associated with the presence of neglect following right hemispheric stroke.

Overlapping and dissociable brain activations for fluid intelligence and executive functions.

Cognitive enhancement interventions aimed at boosting human fluid intelligence (gf) have targeted executive functions (EFs), such as updating, inhibition, and switching, in the context of transfer-inducing cognitive training. However, even though the link between EFs and gf has been demonstrated at the psychometric level, their neurofunctional overlap has not been quantitatively investigated. Identifying whether and how EFs and gf might share neural activation patterns could provide important insights into the overall hierarchical organization of human higher-order cognition, as well as suggest specific targets for interventions aimed at maximizing cognitive transfer. We present the results of a quantitative meta-analysis of the available fMRI and PET literature on EFs and gf in humans, showing the similarity between gf and (i) the overall global EF network, as well as (ii) specific maps for updating, switching, and inhibition. Results highlight a higher degree of similarity between gf and updating (80% overlap) compared with gf and inhibition (34%), and gf and switching (17%). Moreover, three brain regions activated for both gf and each of the three EFs also were identified, located in the left middle frontal gyrus, left inferior parietal lobule, and anterior cingulate cortex. Finally, resting-state functional connectivity analysis on two independent fMRI datasets showed the preferential behavioural correlation and anatomical overlap between updating and gf. These findings confirm a close link between gf and EFs, with implications for brain stimulation and cognitive training interventions.

A Virtual, Randomized, Control Trial of a Digital Therapeutic for Speech, Language, and Cognitive Intervention in Post-stroke Persons With Aphasia.

Background: Post-stroke aphasia is a chronic condition that impacts people's daily functioning and communication for many years after a stroke. Even though these individuals require sustained rehabilitation, they face extra burdens to access care due to shortages in qualified clinicians, insurance limitations and geographic access. There is a need to research alternative means to access intervention remotely, such as in the case of this study using a digital therapeutic. Objective: To assess the feasibility and clinical efficacy of a virtual speech, language, and cognitive digital therapeutic for individuals with post-stroke aphasia relative to standard of care. Methods: Thirty two participants completed the study (experimental: average age 59.8 years, 7 female, 10 male, average education: 15.8 years, time post-stroke: 53 months, 15 right handed, 2 left handed; control: average age 64.2 years, 7 female, 8 male, average education: 15.3 years, time post-stroke: 36.1 months, 14 right handed, 1 left handed). Patients in the experimental group received 10 weeks of treatment using a digital therapeutic, Constant Therapy-Research (CT-R), for speech, language, and cognitive therapy, which provides evidence-based, targeted therapy with immediate feedback for users that adjusts therapy difficulty based on their performance. Patients in the control group completed standard of care (SOC) speech-language pathology workbook pages. Results: This study provides Class II evidence that with the starting baseline WAB-AQ score, adjusted by -0.69 for every year of age, and by 0.122 for every month since stroke, participants in the CT-R group had WAB-AQ scores 6.43 higher than the workbook group at the end of treatment. Additionally, secondary outcome measures included the WAB-Language Quotient, WAB-Cognitive Quotient, Brief Test of Adult Cognition by Telephone (BTACT), and Stroke and Aphasia Quality of Life Scale 39 (SAQOL-39), with significant changes in BTACT verbal fluency subtest and the SAQOL-39 communication and energy scores for both groups. Conclusions: Overall, this study demonstrates the feasibility of a fully virtual trial for patients with post-stroke aphasia, especially given the ongoing COVID19 pandemic, as well as a safe, tolerable, and efficacious digital therapeutic for language/cognitive rehabilitation. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04488029.

An Efficient Bedside Measure Yields Prognostic Implications for Language Recovery in Acute Stroke Patients.

BACKGROUND: It is estimated that ∼30% of stroke survivors have aphasia, a language disorder resulting from damage to left-hemisphere language networks. In acute care settings, efficient identification of aphasia is critical, but there is a paucity of efficient bedside assessments. OBJECTIVE: To determine whether objective measures on a picture description task administered within 48 hours post stroke (a) predict language recovery, (b) estimate left-hemisphere lesion volume and location, and (c) correlate with other bedside language assessments. METHOD: Behavioral data were scored at acute and chronic time points. Neuroimaging data were used to determine associations between the picture description task, other language assessments, and lesion volume and location. RESULTS: Acute content units, age, and total lesion volume predicted communication recovery; F3,18 = 3.98, P = 0.024; r = 0.40. Significant correlations were found between the picture description task and lesion volume and location. Picture description outcomes were also associated with other clinical language assessments. DISCUSSION: This picture description task quickly predicted the language performance (communication recovery and outcome) for patients who suffered a left-hemisphere stroke. Picture description task measures correlated with damage in the left hemisphere and with other, more time-consuming and cumbersome language assessments that are typically administered acutely at bedside. CONCLUSION: The predictive value of this picture description task and correlations with existing language assessments substantiate the clinical importance of a reliable yet rapid bedside measure for acute stroke patients that can be administered by a variety of health care professionals.

Closing the Digital Divide in Speech, Language, and Cognitive Therapy: Cohort Study of the Factors Associated With Technology Usage for Rehabilitation.

BACKGROUND: For stroke, traumatic brain injury (TBI), and other neurologic conditions associated with speech-language disorders, speech and language therapy is the standard of care for promoting recovery. However, barriers such as clinician time constraints and insurance reimbursement can inhibit a patient's ability to receive the support needed to optimize functional gain. Although digital rehabilitation has the potential to increase access to therapy by allowing patients to practice at home, the clinical and demographic characteristics that impact a patient's level of engagement with technology-based therapy are currently unknown. OBJECTIVE: This study aimed to evaluate whether the level of engagement with digital therapy differs by various patient characteristics, including age, gender, diagnosis, time from disease onset, and geographic location (urban vs rural). METHODS: Data for patients with stroke or TBI that initiated the use of Constant Therapy, a remotely delivered, cloud-based rehabilitation program for patients with speech-language disorders, were retrospectively analyzed. Only data from therapeutic sessions completed at home were included. The following three activity metrics were evaluated: (1) the number of active weeks of therapy, (2) the average number of active therapy days per week, and (3) the total number of therapeutic sessions completed during the first 20 weeks of program access. An active day or week was defined as having at least one completed therapeutic session. Separate multiple linear regression models were performed with each activity measure as the dependent variable and all available patient demographics as model covariates. RESULTS: Data for 2850 patients with stroke or TBI were analyzed, with the average patient completing 8.6 weeks of therapy at a frequency of 1.5 days per week. Contrary to known barriers to technological adoption, older patients were more active during their first 20 weeks of program access, with those aged 51 to 70 years completing 5.01 more sessions than patients aged 50 years or younger (P=.04). Similarly, patients living in a rural area, who face greater barriers to clinic access, were more digitally engaged than their urban counterparts, with rural patients completing 11.54 more (P=.001) sessions during their first 20 weeks of access, after controlling for other model covariates. CONCLUSIONS: An evaluation of real-world data demonstrated that patients with stroke and TBI use digital therapy frequently for cognitive and language rehabilitation at home. Usage was higher in areas with limited access to clinical services and was unaffected by typical barriers to technological adoption, such as age. These findings will help guide the direction of future research in digital rehabilitation therapy, including the impact of demographics on recovery outcomes and the design of large, randomized controlled trials.

Influence of age, lesion volume, and damage to dorsal versus ventral streams to viewer- and stimulus-centered hemispatial neglect in acute right hemisphere stroke.

We studied 156 individuals with acute, right hemisphere ischemic stroke on a battery of hemispatial neglect tests to distinguish between viewer-centered and stimulus-centered neglect and MRI diffusion weighted imaging. We identified the relative contributions of age, total lesion volume, and damage to subcortical and cortical grey matter regions as well as white matter tracts to both the severity and presence of significant viewer-centered and stimulus-centered neglect, using multivariable regression tests. We found that age, volume of lesion, and percent damage to the regions of interest were each independently associated with the severity of viewer-centered neglect (r2 = .31; p < .0001). However, only age (t = 3.20; p = .002) and percent damage to the angular gyrus (t = 2.63, p = .010), a dorsal stream area, predicted severity of viewer-centered neglect independently of the other variables. The same variables predicted the presence of significant viewer-centered neglect. In contrast, these variables did not significantly predict the severity of stimulus-centered neglect. However, we found that percent damage to ventral stream regions of interest (middle temporal gyrus, inferior temporal gyrus, fusiform gyrus, inferior frontal occipital gyrus, sagittal stratum, along with total infarct volume were associated with the presence of significant stimulus-centered neglect (pseudo r2 = .70, p < .0004). Only percent damage to right inferior temporal gyrus predicted stimulus-centered neglect independently of the other variables (p = .018).

Right hemisphere ventral stream for emotional prosody identification: Evidence from acute stroke.

OBJECTIVE: To determine whether right ventral stream and limbic structures (including posterior superior temporal gyrus [STG], STG, temporal pole, inferior frontal gyrus pars orbitalis, orbitofrontal cortex, amygdala, anterior cingulate, gyrus, and the sagittal stratum) are implicated in emotional prosody identification. METHODS: Patients with MRI scans within 48 hours of unilateral right hemisphere ischemic stroke were enrolled. Participants were presented with 24 sentences with neutral semantic content spoken with happy, sad, angry, afraid, surprised, or bored prosody and chose which emotion the speaker was feeling based on tone of voice. Multivariable linear regression was used to identify individual predictors of emotional prosody identification accuracy from a model, including percent damage to proposed right hemisphere structures, age, education, and lesion volume across all emotions (overall emotion identification) and 6 individual emotions. Patterns of recovery were also examined at the chronic stage. RESULTS: The overall emotion identification model was significant (adjusted r 2 = 0.52; p = 0.043); greater damage to right posterior STG (p = 0.038) and older age (p = 0.009) were individual predictors of impairment. The model for recognition of fear was also significant (adjusted r 2 = 0.77; p = 0.002), with greater damage to right amygdala (p = 0.047), older age (p < 0.001), and less education (p = 0.005) as individual predictors. Over half of patients with chronic stroke had residual impairments. CONCLUSIONS: Right posterior STG in the right hemisphere ventral stream is critical for emotion identification in speech. Patients with stroke with damage to this area should be assessed for emotion identification impairment.

Distinguishing logopenic from semantic & nonfluent variant primary progressive aphasia: Patterns of linguistic and behavioral correlations.

While language characteristics of logopenic variant primary progressive aphasia (lvPPA) are well-defined, behavioral characteristics are less understood. We investigated correlations between language and behavioral scores across three variants of primary progressive aphasia (PPA) and found language performance and behavioral disturbances are correlated in lvPPA, but not other PPA subtypes. Results suggest that unlike other PPA variants, patients diagnosed with lvPPA do not develop negative behaviors until language deficits are severe. This is consistent with the underlying neuropathology of lvPPA, Alzheimer's Disease. Such findings are crucial to clinical prognosis, especially when considering the progressive nature of this disease.

Stealing Cookies in the Twenty-First Century: Measures of Spoken Narrative in Healthy Versus Speakers With Aphasia.

Purpose Our goal was to evaluate an updated version of the "Cookie Theft" picture by obtaining norms based on picture descriptions by healthy controls for total content units (CUs), syllables per CU, and the ratio of left-right CUs. In addition, we aimed to compare these measures from healthy controls to picture descriptions obtained from individuals with poststroke aphasia and primary progressive aphasia (PPA) to assess whether these measures can capture impairments in content and efficiency of communication. Method Using an updated version of this picture, we analyzed descriptions from 50 healthy controls to develop norms for numbers of syllables, total CUs, syllables per CU, and left-right CU. We provide preliminary data from 44 individuals with aphasia (19 with poststroke aphasia and 25 with PPA). Results A total of 96 CUs were established based on the written transcriptions of spoken picture descriptions of the 50 control participants. There was a significant effect of group on total CUs, syllables, syllables per CU, and left-right CUs. The poststroke participants produced significantly fewer total CU and syllables than those with PPA. Each aphasic group produced significantly fewer total CUs, fewer syllables, more syllables per CU, and lower left-right CUs (indicating a right-sided bias) compared to controls. Conclusions Results show that the measures of numbers of syllables, total CUs, syllables per CU, and left-right CUs can distinguish language output of individuals with aphasia from controls and capture impairments in content and efficiency of communication. A limitation of this study is that we evaluated only 44 individuals with aphasia. In the future, we will evaluate other measures, such as CUs per minute, lexical variability, grammaticality, and ratio of nouns to verbs. Supplemental Material https://doi.org/10.23641/asha.7015223.

Atrophy in Distributed Networks Predicts Cognition in Alzheimer's Disease and Type 2 Diabetes.

BACKGROUND: Alzheimer's disease (AD) and type 2 diabetes (T2DM) are common causes of cognitive decline among older adults and share strong epidemiological links. Distinct patterns of cortical atrophy are observed in AD and T2DM, but robust comparisons between structure-function relationships across these two disease states are lacking. OBJECTIVE: To compare how atrophy within distributed brain networks is related to cognition across the spectrum of cognitive aging. METHODS: The relationship between structural MRI changes and cognition was studied in 22 mild-to-moderate AD, 28 T2DM, and 27 healthy participants. Cortical thickness measurements were obtained from networks of interest (NOIs) matching the limbic, default, and frontoparietal resting-state networks. Composite cognitive scores capturing domains of global cognition, memory, and executive function were created. Associations between cognitive scores and the NOIs were assessed using linear regression, with age as a covariate. Within-network General Linear Model (GLM) analysis was run in Freesurfer 6.0 to visualize differences in patterns of cortical atrophy related to cognitive function in each group. A secondary analysis examined hemispheric differences in each group. RESULTS: Across all groups, cortical atrophy within the limbic NOI was significantly correlated with Global Cognition (p = 0.009) and Memory Composite (p = 0.002). Within-network GLM analysis and hemispheric analysis revealed qualitatively different patterns of atrophy contributing to cognitive dysfunction between AD and T2DM. CONCLUSION: Brain network atrophy is related to cognitive function across AD, T2DM, and healthy participants. Differences in cortical atrophy patterns were seen between AD and T2DM, highlighting neuropathological differences.

Leukoaraiosis is independently associated with naming outcome in poststroke aphasia.

OBJECTIVE: To test the hypothesis that severity of leukoaraiosis in the noninfarcted hemisphere at onset is associated with poorer language outcome after poststroke aphasia independently of volume of infarct, damage to 3 critical language areas (left inferior frontal gyrus, superior longitudinal fasciculus, and superior temporal gyrus), comorbid conditions, and time since stroke. METHODS: In this cross-sectional study, we evaluated naming outcome (>3 months after stroke) in 42 individuals who initially had aphasia after stroke. We rated leukoaraiosis in the right hemisphere 1 to 4 weeks from onset of stroke using the Cardiovascular Health Study rating scale. We evaluated associations between severity of leukoaraiosis and each measure of naming using Spearman correlations and evaluated the independent contributions of leukoaraiosis, lesion volume, months since onset, comorbid conditions, and damage to critical nodes of the language network on language outcomes using logistic regression. We also evaluated associations between dichotomously defined leukoaraiosis and language outcomes using χ2 tests. RESULTS: Severity of leukoaraiosis at onset correlated with object naming (ρ = -0.56, p = 0.0008) and word fluency (ρ = -0.37, p = 0.01) outcomes. Severe leukoaraiosis was associated with failure to achieve the highest quartile of object naming and word fluency. Severity of leukoaraiosis was associated with degree of naming outcome with the use of both measures after controlling for lesion volume, months since stroke, comorbid conditions, and damage to specific locations. CONCLUSION: Naming outcome after poststroke aphasia is influenced by the initial severity of right hemisphere leukoaraiosis independently of other variables. Degree of recovery from aphasia may depend on the integrity of the noninfarcted brain tissue.

Selective impairments in components of affective prosody in neurologically impaired individuals.

The intent and feelings of the speaker are often conveyed less by what they say than by how they say it, in terms of the affective prosody - modulations in pitch, loudness, rate, and rhythm of the speech to convey emotion. Here we propose a cognitive architecture of the perceptual, cognitive, and motor processes underlying recognition and generation of affective prosody. We developed the architecture on the basis of the computational demands of the task, and obtained evidence for various components by identifying neurologically impaired patients with relatively specific deficits in one component. We report analysis of performance across tasks of recognizing and producing affective prosody by four patients (three with right hemisphere stroke and one with frontotemporal dementia). Their distinct patterns of performance across tasks and quality of their abnormal performance provides preliminary evidence that some of the components of the proposed architecture can be selectively impaired by focal brain damage.

Right Hemisphere Regions Critical for Expression of Emotion Through Prosody.

Impaired expression of emotion through pitch, loudness, rate, and rhythm of speech (affective prosody) is common and disabling after right hemisphere (RH) stroke. These deficits impede all social interactions. Previous studies have identified cortical areas associated with impairments of expression, recognition, or repetition of affective prosody, but have not identified critical white matter tracts. We hypothesized that: (1) differences across patients in specific acoustic features correlate with listener judgment of affective prosody and (2) these differences are associated with infarcts of specific RH gray and white matter regions. To test these hypotheses, 41 acute ischemic RH stroke patients had MRI diffusion weighted imaging and described a picture. Affective prosody of picture descriptions was rated by 21 healthy volunteers. We identified percent damage (lesion load) to each of seven regions of interest previously associated with expression of affective prosody and two control areas that have been associated with recognition but not expression of prosody. We identified acoustic features that correlated with listener ratings of prosody (hereafter "prosody acoustic measures") with Spearman correlations and linear regression. We then identified demographic variables and brain regions where lesion load independently predicted the lowest quartile of each of the "prosody acoustic measures" using logistic regression. We found that listener ratings of prosody positively correlated with four acoustic measures. Furthermore, the lowest quartile of each of these four "prosody acoustic measures" was predicted by sex, age, lesion volume, and percent damage to the seven regions of interest. Lesion load in pars opercularis, supramarginal gyrus, or associated white matter tracts (and not control regions) predicted lowest quartile of the four "prosody acoustic measures" in logistic regression. Results indicate that listener perception of reduced affective prosody after RH stroke is due to reduction in specific acoustic features caused by infarct in right pars opercularis or supramarginal gyrus, or associated white matter tracts.

Predicting recovery in acute poststroke aphasia.

OBJECTIVE: Many stroke patients show remarkable recovery of language after initial severe impairment, but it is difficult to predict which patients will show good recovery. We aimed to identify patient and lesion characteristics that together predict the best naming outcome in 4 studies. METHODS: We report 2 longitudinal studies that identified 2 variables at onset that were strongly associated with good recovery of naming (the most common residual deficit in aphasia) in the first 6 months after stroke: damage to left posterior superior temporal gyrus (pSTG) and/or superior longitudinal fasciculus/arcuate fasciculus (SLF/AF), and selective serotonin reuptake inhibitor (SSRI) use. We then tested these variables in 2 independent cohorts of chronic left hemisphere stroke patients, using chi-square tests and multivariate logistic regression for dichotomous outcomes and t tests for continuous outcomes. RESULTS: Lesion load in left pSTG and SLF/AF was associated with poorer naming outcome. Preservation of these areas and use of SSRIs were associated with naming recovery, independent of lesion volume, time since stroke, and depression. Patients with damage to these critical areas showed better naming outcome if they took SSRIs for 3 months after stroke. Those with preservation of these critical areas achieved good recovery of naming regardless of SSRI use. INTERPRETATION: Lesion load in left pSTG and SLF/AF at onset predicts later naming performance. Although based on a small number of patients, our preliminary results suggest outcome might be modulated by SSRIs, but these associations need to be confirmed in a larger randomized controlled trial. Ann Neurol 2018;83:612-622.

Regional Brain Dysfunction Associated with Semantic Errors in Comprehension.

Here we illustrate how investigation of individuals acutely after stroke, before structure/function reorganization through recovery or rehabilitation, can be helpful in answering questions about the role of specific brain regions in language functions. Although there is converging evidence from a variety of sources that the left posterior-superior temporal gyrus plays some role in spoken word comprehension, its precise role in this function has not been established. We hypothesized that this region is essential for distinguishing between semantically related words, because it is critical for linking the spoken word to the complete semantic representation. We tested this hypothesis in 127 individuals with 48 hours of acute ischemic stroke, before the opportunity for reorganization or recovery. We identified tissue dysfunction (acute infarct and/or hypoperfusion) in gray and white matter parcels of the left hemisphere, and we evaluated the association between rate of semantic errors in a word-picture verification tasks and extent of tissue dysfunction in each region. We found that after correcting for lesion volume and multiple comparisons, the rate of semantic errors correlated with the extent of tissue dysfunction in left posterior-superior temporal gyrus and retrolenticular white matter.

An update on medications and noninvasive brain stimulation to augment language rehabilitation in post-stroke aphasia.

INTRODUCTION: Aphasia is among the most debilitating outcomes of stroke. Aphasia is a language disorder occurring in 10-30% of stroke survivors. Speech and Language Therapy (SLT) is the gold standard, mainstay treatment for aphasia, but gains from SLT may be incomplete. Pharmaceutical and noninvasive brain stimulation (NIBS) techniques may augment the effectiveness of SLT. Areas covered: Herein reviewed are studies of the safety and efficacy of these adjunctive interventions for aphasia, including randomized placebo-controlled and open-label trials, as well as case series from Pubmed, using search terms 'pharmacological,' 'tDCS' or 'TMS' combined with 'aphasia' and 'stroke.' Expert commentary: Relatively small studies have included participants with a range of aphasia types and severities, using inconsistent interventions and outcome measures. Results to-date have provided promising, but weak to moderate evidence that medications and/or NIBS can augment the effects of SLT for improving language outcomes. We end with recommendations for future approaches to studying these interventions, with multicenter, double-blind, randomized controlled trials.

Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits.

BACKGROUND: Type-2 diabetes mellitus (T2DM) accelerates cognitive aging and increases risk of Alzheimer's disease. Rodent models of T2DM show altered synaptic plasticity associated with reduced learning and memory. Humans with T2DM also show cognitive deficits, including reduced learning and memory, but the relationship of these impairments to the efficacy of neuroplastic mechanisms has never been assessed. OBJECTIVE: Our primary objective was to compare mechanisms of cortical plasticity in humans with and without T2DM. Our secondary objective was to relate plasticity measures to standard measures of cognition. METHODS: A prospective cross-sectional cohort study was conducted on 21 adults with T2DM and 15 demographically-similar non-diabetic controls. Long-term potentiation-like plasticity was assessed in primary motor cortex by comparing the amplitude of motor evoked potentials (MEPs) from single-pulse transcranial magnetic stimulation before and after intermittent theta-burst stimulation (iTBS). Plasticity measures were compared between groups and related to neuropsychological scores. RESULTS: In T2DM, iTBS-induced modulation of MEPs was significantly less than controls, even after controlling for potential confounds. Furthermore, in T2DM, modulation of MEPs 10-min post-iTBS was significantly correlated with Rey Auditory Verbal Learning Task (RAVLT) performance. CONCLUSION: Humans with T2DM show abnormal cortico-motor plasticity that is correlated with reduced verbal learning. Since iTBS after-effects and the RAVLT are both NMDA receptor-dependent measures, their relationship in T2DM may reflect brain-wide alterations in the efficacy of NMDA receptors. These findings offer novel mechanistic insights into the brain consequences of T2DM and provide a reliable means to monitor brain health and evaluate the efficacy of clinical interventions.

Optimal number of pulses as outcome measures of neuronavigated transcranial magnetic stimulation.

OBJECTIVE: Identify the optimal number of pulses necessary to achieve reliable measures of motor evoked potentials (MEPs) in transcranial magnetic stimulation (TMS) studies. METHODS: Retrospective data was obtained from 54 healthy volunteers (30 men, mean age 61.7±13.1years) who as part of prior studies had completed three blocks of 30 consecutive TMS stimuli using neuronavigation. Data from four protocols were assessed: single-pulse TMS for measures of amplitude and latency of MEPs; paired-pulse TMS for short-interval intracortical inhibition (sICI) and intracortical facilitation (ICF); and single-pulse TMS to assess the effects of intermittent theta burst stimulation (iTBS). Two statistical methods were used: an internal consistency analysis and probability of inclusion in the 95% confidence interval (CI) around the mean MEPs amplitude. RESULTS: For single-pulse TMS, the minimum number of pulses needed to achieve reliable amplitude and latency MEPs measures was 21 and 23, respectively. For paired-pulse TMS, the minimum number of pulses needed to achieve reliable sICI and ICF measures was 20 and 25, respectively. Finally, the minimum number of pulses needed to achieve reliable amplitude and latency MEPs measures after iTBS was 22 and 23, respectively. CONCLUSIONS: This study provides guidelines regarding the minimum number of pulses needed to achieve reliable MEPs measurements in various study protocols using neuronavigated TMS. SIGNIFICANCE: Results from this study have the potential to increase the reliability and quality of future neuronavigated TMS studies.

Preserved processing of musical structure in a person with agrammatic aphasia.

Evidence for shared processing of structure (or syntax) in language and in music conflicts with neuropsychological dissociations between the two. However, while harmonic structural processing can be impaired in patients with spared linguistic syntactic abilities (Peretz, I. (1993). Auditory atonalia for melodies. Cognitive Neuropsychology, 10, 21-56. doi:10.1080/02643299308253455), evidence for the opposite dissociation-preserved harmonic processing despite agrammatism-is largely lacking. Here, we report one such case: HV, a former musician with Broca's aphasia and agrammatic speech, was impaired in making linguistic, but not musical, acceptability judgments. Similarly, she showed no sensitivity to linguistic structure, but normal sensitivity to musical structure, in implicit priming tasks. To our knowledge, this is the first non-anecdotal report of a patient with agrammatic aphasia demonstrating preserved harmonic processing abilities, supporting claims that aspects of musical and linguistic structure rely on distinct neural mechanisms.