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.

Varied performance of picture description task as a screening tool across MCI subtypes.

A picture description task is a component of Miro Health's platform for self-administration of neurobehavioral assessments. Picture description has been used as a screening tool for identification of individuals with Alzheimer's disease and mild cognitive impairment (MCI), but currently requires in-person administration and scoring by someone with access to and familiarity with a scoring rubric. The Miro Health implementation allows broader use of this assessment through self-administration and automated processing, analysis, and scoring to deliver clinically useful quantifications of the users' speech production, vocal characteristics, and language. Picture description responses were collected from 62 healthy controls (HC), and 33 participants with MCI: 18 with amnestic MCI (aMCI) and 15 with non-amnestic MCI (naMCI). Speech and language features and contrasts between pairs of features were evaluated for differences in their distributions in the participant subgroups. Picture description features were selected and combined using penalized logistic regression to form risk scores for classification of HC versus MCI as well as HC versus specific MCI subtypes. A picture-description based risk score distinguishes MCI and HC with an area under the receiver operator curve (AUROC) of 0.74. When contrasting specific subtypes of MCI and HC, the classifiers have an AUROC of 0.88 for aMCI versus HC and and AUROC of 0.61 for naMCI versus HC. Tests of association of individual features or contrasts of pairs of features with HC versus aMCI identified 20 features with p-values below 5e-3 and False Discovery Rates (FDRs) at or below 0.113, and 61 contrasts with p-values below 5e-4 and FDRs at or below 0.132. Findings suggest that performance of picture description as a screening tool for MCI detection will vary greatly by MCI subtype or by the proportion of various subtypes in an undifferentiated MCI population.

Validation of a Mobile, Sensor-based Neurobehavioral Assessment With Digital Signal Processing and Machine-learning Analytics.

BACKGROUND: The Miro Health Mobile Assessment Platform consists of self-administered neurobehavioral and cognitive assessments that measure behaviors typically measured by specialized clinicians. OBJECTIVE: To evaluate the Miro Health Mobile Assessment Platform's concurrent validity, test-retest reliability, and mild cognitive impairment (MCI) classification performance. METHOD: Sixty study participants were evaluated with Miro Health version V.2. Healthy controls (HC), amnestic MCI (aMCI), and nonamnestic MCI (naMCI) ages 64-85 were evaluated with version V.3. Additional participants were recruited at Johns Hopkins Hospital to represent clinic patients, with wider ranges of age and diagnosis. In all, 90 HC, 21 aMCI, 17 naMCI, and 15 other cases were evaluated with V.3. Concurrent validity of the Miro Health variables and legacy neuropsychological test scores was assessed with Spearman correlations. Reliability was quantified with the scores' intraclass correlations. A machine-learning algorithm combined Miro Health variable scores into a Risk score to differentiate HC from MCI or MCI subtypes. RESULTS: In HC, correlations of Miro Health variables with legacy test scores ranged 0.27-0.68. Test-retest reliabilities ranged 0.25-0.79, with minimal learning effects. The Risk score differentiated individuals with aMCI from HC with an area under the receiver operator curve (AUROC) of 0.97; naMCI from HC with an AUROC of 0.80; combined MCI from HC with an AUROC of 0.89; and aMCI from naMCI with an AUROC of 0.83. CONCLUSION: The Miro Health Mobile Assessment Platform provides valid and reliable assessment of neurobehavioral and cognitive status, effectively distinguishes between HC and MCI, and differentiates aMCI from naMCI.

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.

Neural substrates of spontaneous narrative production in focal neurodegenerative disease.

Conversational storytelling integrates diverse cognitive and socio-emotional abilities that critically differ across neurodegenerative disease groups. Storytelling patterns may have diagnostic relevance and predict anatomic changes. The present study employed mixed methods discourse and quantitative analyses to delineate patterns of storytelling across focal neurodegenerative disease groups, and to clarify the neuroanatomical contributions to common storytelling characteristics. Transcripts of spontaneous social interactions of 46 participants (15 behavioral variant frontotemporal dementia (bvFTD), 7 semantic variant primary progressive aphasia (svPPA), 12 Alzheimer's disease (AD), and 12 healthy older normal controls (NC)) were analyzed for storytelling frequency and characteristics, and videos of the interactions were rated for patients' level of social attentiveness. Compared to controls, svPPAs told more stories and autobiographical stories, and perseverated on aspects of self during the interaction, whereas ADs told fewer autobiographical stories than NCs. svPPAs and bvFTDs were rated as less attentive to social cues. Aspects of storytelling were related to diverse cognitive and socio-emotional functions, and voxel-based anatomic analysis of structural magnetic resonance imaging revealed that temporal organization, narrative evaluations patterns, and social attentiveness correlated with atrophy corresponding to known intrinsic connectivity networks, including the default mode, limbic, salience, and stable task control networks. Differences in spontaneous storytelling among neurodegenerative groups elucidated diverse cognitive, socio-emotional, and neural contributions to narrative production, with implications for diagnostic screening and therapeutic intervention.

Automated MRI-based classification of primary progressive aphasia variants.

Degeneration of language regions in the dominant hemisphere can result in primary progressive aphasia (PPA), a clinical syndrome characterized by progressive deficits in speech and/or language function. Recent studies have identified three variants of PPA: progressive non-fluent aphasia (PNFA), semantic dementia (SD) and logopenic progressive aphasia (LPA). Each variant is associated with characteristic linguistic features, distinct patterns of brain atrophy, and different likelihoods of particular underlying pathogenic processes, which makes correct differential diagnosis highly clinically relevant. Evaluation of linguistic behavior can be challenging for non-specialists, and neuroimaging findings in single subjects are often difficult to evaluate by eye. We investigated the utility of automated structural MR image analysis to discriminate PPA variants (N=86) from each other and from normal controls (N=115). T1 images were preprocessed to obtain modulated grey matter (GM) images. Feature selection was performed with principal components analysis (PCA) on GM images as well as images of lateralized atrophy. PC coefficients were classified with linear support vector machines, and a cross-validation scheme was used to obtain accuracy rates for generalization to novel cases. The overall mean accuracy in discriminating between pairs of groups was 92.2%. For one pair of groups, PNFA and SD, we also investigated the utility of including several linguistic variables as features. Models with both imaging and linguistic features performed better than models with only imaging or only linguistic features. These results suggest that automated methods could assist in the differential diagnosis of PPA variants, enabling therapies to be targeted to likely underlying etiologies.

Detecting sarcasm from paralinguistic cues: anatomic and cognitive correlates in neurodegenerative disease.

While sarcasm can be conveyed solely through contextual cues such as counterfactual or echoic statements, face-to-face sarcastic speech may be characterized by specific paralinguistic features that alert the listener to interpret the utterance as ironic or critical, even in the absence of contextual information. We investigated the neuroanatomy underlying failure to understand sarcasm from dynamic vocal and facial paralinguistic cues. Ninety subjects (20 frontotemporal dementia, 11 semantic dementia [SemD], 4 progressive non-fluent aphasia, 27 Alzheimer's disease, 6 corticobasal degeneration, 9 progressive supranuclear palsy, 13 healthy older controls) were tested using the Social Inference - Minimal subtest of The Awareness of Social Inference Test (TASIT). Subjects watched brief videos depicting sincere or sarcastic communication and answered yes-no questions about the speaker's intended meaning. All groups interpreted Sincere (SIN) items normally, and only the SemD group was impaired on the Simple Sarcasm (SSR) condition. Patients failing the SSR performed more poorly on dynamic emotion recognition tasks and had more neuropsychiatric disturbances, but had better verbal and visuospatial working memory than patients who comprehended sarcasm. Voxel-based morphometry analysis of SSR scores in SPM5 demonstrated that poorer sarcasm comprehension was predicted by smaller volume in bilateral posterior parahippocampi (PHc), temporal poles, and R medial frontal pole (pFWE<0.05). This study provides lesion data suggesting that the PHc may be involved in recognizing a paralinguistic speech profile as abnormal, leading to interpretive processing by the temporal poles and right medial frontal pole that identifies the social context as sarcastic, and recognizes the speaker's paradoxical intentions.

Structural anatomy of empathy in neurodegenerative disease.

Empathy is a complex social behaviour mediated by a network of brain structures. Recently, several functional imaging studies have investigated the neural basis of empathy, but few corroborative human lesion studies exist. Severe empathy loss is a common feature of frontotemporal lobar degeneration (FTLD), and is also seen in other neurodegenerative diseases. In this study, the neuroanatomic basis of empathy was investigated in 123 patients with FTLD, Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy using the Interpersonal Reactivity Index (IRI). IRI Empathic Concern and Perspective taking scores were correlated with structural MRI brain volume using voxel-based morphometry. Voxels in the right temporal pole, the right fusiform gyrus, the right caudate and right subcallosal gyrus correlated significantly with total empathy score (P < 0.05 after whole-brain correction for multiple comparisons). Empathy score correlated positively with the volume of right temporal structures in semantic dementia, and with subcallosal gyrus volume in frontotemporal dementia. These findings are consistent with previous research suggesting that a primarily right frontotemporal network of brain regions is involved in emotion processing, and highlights the roles of the right temporal pole and inferior frontal/striatal regions in regulating complex social interactions. This is the first large-scale lesion study to investigate the neural basis of empathy using correlational analytic methods. The results suggest that the right anterior temporal and medial frontal regions are essential for real-life empathic behaviour.

Multiple cognitive deficits in amnestic mild cognitive impairment.

OBJECTIVE: To determine if more widespread cognitive deficits are present in a narrowly defined group of patients with the amnestic form of mild cognitive impairment (MCI). METHODS: From a larger sample of patients clinically diagnosed as meeting the criteria of Petersen et al. for amnestic MCI, we selected 22 subjects who had Clinical Dementia Rating scores of zero on all domains besides memory and orientation. These MCI subjects with presumably isolated memory impairments were compared to 35 age-matched normal controls and 33 very mild Alzheimer's disease (AD) patients on a battery of neuropsychological tests. RESULT: In addition to the expected deficits in episodic memory, the amnestic MCI group performed less well than the controls but better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Over half the amnestic MCI group (vs. none of the normal controls) scored at least 1 standard deviation below control means on 4 or more of the nonmemory cognitive tasks. CONCLUSIONS: Isolated memory impairment may be fairly uncommon in clinically diagnosed amnestic MCI patients, even when the criteria for amnestic MCI are fairly narrow. Additional cognitive impairments are likely to include fluency and executive functioning. These more diffuse deficits argue for comprehensive cognitive assessments, even when the patient and family are reporting only memory decline, and are consistent with the increase in attention paid to the heterogeneity of MCI.

Brain activation patterns during memory of cognitive agency.

Agency is the awareness that one's own self is the agent or author of an action, a thought, or a feeling. The implicit memory that one's self was the originator of a cognitive event - the sense of cognitive agency - has not yet been fully explored in terms of relevant neural systems. In this functional magnetic resonance imaging (fMRI) study, we examined brain activation patterns differentiating memory for the source of previously self-generated vs. experimenter-presented word items from a sentence completion paradigm designed to be emotionally neutral and semantically constrained in content. Accurate memory for the source of self-generated vs. externally-presented word items resulted in activation of dorsal medial prefrontal cortex (mPFC) bilaterally, supporting an emerging body of work that indicates a key role for this region in self-referential processing. Our data extend the function of mPFC into the domain of memory and the accurate retrieval of the sense of cognitive agency under conditions where agency was encoded implicitly.