In daily social interactions, we need to be able to navigate efficiently through our social environment. According to Dennett (1971), explaining and predicting others' behavior with reference to ...mental states (adopting the
) allows efficient social interaction. Today we also routinely interact with artificial agents: from Apple's
to GPS navigation systems. In the near future, we might start casually interacting with robots. This paper addresses the question of whether adopting the intentional stance can also occur with respect to artificial agents. We propose a new tool to explore if people adopt the intentional stance toward an artificial agent (humanoid robot). The tool consists in a questionnaire that probes participants' stance by requiring them to choose the likelihood of an explanation (mentalistic vs. mechanistic) of a behavior of a robot iCub depicted in a naturalistic scenario (a sequence of photographs). The results of the first study conducted with this questionnaire showed that although the explanations were somewhat biased toward the mechanistic stance, a substantial number of mentalistic explanations were also given. This suggests that it is possible to induce adoption of the intentional stance toward artificial agents, at least in some contexts.
Objective
To establish a fully automated, robust imaging marker for cerebral small vessel disease (SVD) and related cognitive impairment that is easy to implement, reflects disease burden, and is ...strongly associated with processing speed, the predominantly affected cognitive domain in SVD.
Methods
We developed a novel magnetic resonance imaging marker based on diffusion tensor imaging, skeletonization of white matter tracts, and histogram analysis. The marker (peak width of skeletonized mean diffusivity PSMD) was assessed along with conventional SVD imaging markers. We first evaluated associations with processing speed in patients with genetically defined SVD (n = 113). Next, we validated our findings in independent samples of inherited SVD (n = 57), sporadic SVD (n = 444), and memory clinic patients with SVD (n = 105). The new marker was further applied to healthy controls (n = 241) and to patients with Alzheimer's disease (n = 153). We further conducted a longitudinal analysis and interscanner reproducibility study.
Results
PSMD was associated with processing speed in all study samples with SVD (p‐values between 2.8 × 10−3 and 1.8 × 10−10). PSMD explained most of the variance in processing speed (R2 ranging from 8.8% to 46%) and consistently outperformed conventional imaging markers (white matter hyperintensity volume, lacune volume, and brain volume) in multiple regression analyses. Increases in PSMD were linked to vascular but not to neurodegenerative disease. In longitudinal analysis, PSMD captured SVD progression better than other imaging markers.
Interpretation
PSMD is a new, fully automated, and robust imaging marker for SVD. PSMD can easily be applied to large samples and may be of great utility for both research studies and clinical use. Ann Neurol 2016;80:581–592.
Diffusion tensor imaging detects early tissue alterations in Alzheimer's disease and cerebral small vessel disease (SVD). However, the origin of diffusion alterations in SVD is largely unknown.
To ...gain further insight, we applied free water (FW) imaging to patients with genetically defined SVD (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy CADASIL, n = 57), sporadic SVD (n = 444), and healthy controls (n = 28). We modeled freely diffusing water in the extracellular space (FW) and measures reflecting fiber structure (tissue compartment). We tested associations between these measures and clinical status (processing speed and disability).
Diffusion alterations in SVD were mostly driven by increased FW and less by tissue compartment alterations. Among imaging markers, FW showed the strongest association with clinical status (R2 up to 34%, P < .0001). Findings were consistent across patients with CADASIL and sporadic SVD.
Diffusion alterations and clinical status in SVD are largely determined by extracellular fluid increase rather than alterations of white matter fiber organization.
•Diffusion alterations in small vessel disease are mostly driven by free water.•White matter fiber organization seems relatively preserved.•Increased free water is strongly associated with clinical deficits.•Consistent results across genetically defined and sporadic small vessel disease.
The prospect of improving or maintaining cognitive functioning has provoked a steadily increasing number of cognitive training interventions over the last years, especially for clinical and elderly ...populations. However, there are discrepancies between the findings of the studies. One of the reasons behind these heterogeneous findings is that there are vast inter-individual differences in how people benefit from the training and in the extent that training-related gains are transferred to other untrained tasks and domains. In this paper, we address the value of incorporating neural measures to cognitive training studies in order to fully understand the mechanisms leading to inter-individual differences in training gains and their generalizability to other tasks. Our perspective is that it is necessary to collect multimodal neural measures in the pre- and post-training phase, which can enable us to understand the factors contributing to successful training outcomes. More importantly, this understanding can enable us to predict who will benefit from different types of interventions, thereby allowing the development of individually tailored intervention programs.
Cortical superficial siderosis (cSS) has emerged as a clinically relevant imaging feature of cerebral amyloid angiopathy (CAA). However, it remains unknown whether cSS is also present in ...nonamyloid-associated small vessel disease and whether patients with cSS differ in terms of other small vessel disease imaging features.
Three hundred sixty-four CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) patients, 372 population-based controls, and 100 CAA patients with cSS (fulfilling the modified Boston criteria for possible/probable CAA) were included. cSS and cerebral microbleeds were visually rated on T2*-weighted magnetic resonance imaging. White matter hyperintensities were segmented on fluid-attenauted inversion recovery images, and their spatial distribution was compared between groups using colocalization analysis. Cerebral microbleeds location was determined in an observer-independent way using an atlas in standard space.
cSS was absent in CADASIL and present in only 2 population-based controls (0.5%). Cerebral microbleeds were present in 64% of CAA patients with cSS, 34% of patients with CADASIL, and 12% of population-based controls. Among patients with cerebral microbleeds, lobar location was found in 95% of CAA patients with cSS, 48% of CADASIL patients, and 69% of population-based controls. The spatial distribution of white matter hyperintensities was comparable between CAA with cSS and CADASIL as indicated by high colocalization coefficients.
cSS was absent in CADASIL, whereas other small vessel disease imaging features were similar to CAA patients with cSS. Our findings suggest that cSS in combination with other small vessel disease imaging markers is highly indicative of CAA.
Neurofilament light chain (NfL) is a blood marker for neuroaxonal damage. We assessed the association between serum NfL and cerebral small vessel disease (SVD), which is highly prevalent in elderly ...individuals and a major cause of stroke and vascular cognitive impairment.
Using a cross-sectional design, we studied 53 and 439 patients with genetically defined SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy CADASIL) and sporadic SVD, respectively, as well as 93 healthy controls. Serum NfL was measured by an ultrasensitive single-molecule array assay. We quantified magnetic resonance imaging (MRI) markers of SVD, i.e., white matter hyperintensity volume, lacune volume, brain volume, microbleed count, and mean diffusivity obtained from diffusion tensor imaging. Clinical characterization included neuropsychological testing in both SVD samples. CADASIL patients were further characterized for focal neurological deficits (National Institutes of Health stroke scale NIHSS) and disability (modified Rankin scale mRS).
Serum NfL levels were elevated in both SVD samples (
<1e-05 compared with controls) and associated with all SVD MRI markers. The strongest association was found for mean diffusivity (CADASIL, R
=0.52,
=1.2e-09; sporadic SVD, R
=0.21,
<1e-15). Serum NfL levels were independently related to processing speed performance (CADASIL, R
=0.27,
=7.6e-05; sporadic SVD, R
=0.06,
=4.8e-08), focal neurological symptoms (CADASIL, NIHSS,
=4.2e-05) and disability (CADASIL, mRS,
=3.0e-06).
We found serum NfL levels to be associated with both imaging and clinical features of SVD. Serum NfL might complement MRI markers in assessing SVD burden. Importantly, SVD needs to be considered when interpreting serum NfL levels in the context of other age-related diseases.
Introduction: Progressive cognitive decline is the cardinal behavioral symptom in most dementia-causing diseases such as Alzheimer’s disease. While most well-established measures for cognition might ...not fit tomorrow’s decentralized remote clinical trials, digital cognitive assessments will gain importance. We present the evaluation of a novel digital speech biomarker for cognition (SB-C) following the Digital Medicine Society’s V3 framework: verification, analytical validation, and clinical validation. Methods: Evaluation was done in two independent clinical samples: the Dutch DeepSpA (N = 69 subjective cognitive impairment SCI, N = 52 mild cognitive impairment MCI, and N = 13 dementia) and the Scottish SPeAk datasets (N = 25, healthy controls). For validation, two anchor scores were used: the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) scale. Results: Verification: The SB-C could be reliably extracted for both languages using an automatic speech processing pipeline. Analytical Validation: In both languages, the SB-C was strongly correlated with MMSE scores. Clinical Validation: The SB-C significantly differed between clinical groups (including MCI and dementia), was strongly correlated with the CDR, and could track the clinically meaningful decline. Conclusion: Our results suggest that the ki:e SB-C is an objective, scalable, and reliable indicator of cognitive decline, fit for purpose as a remote assessment in clinical early dementia trials.
Using digital technology for neuropsychological assessment is gaining popularity in both clinical and research settings. Digital neuropsychology offers many benefits over the traditional paper‐pencil ...assessments; however, their comparability requires further validation. The aim of this study was to compare a digital, tablet‐based Trail Making Test to the standard paper version. In a within‐subject design, 108 healthy adults completed both digital and paper Trail Making Test in a counterbalanced order. Each participant also performed other tasks measuring core executive abilities (inhibition, working memory, and flexibility) on the tablet. Our findings indicated that the Trail Making Test performance on the two different modalities correlated significantly. Furthermore, correlations of Trail Making Test performance with other cognitive tasks revealed that digital Trail Making Test is comparable with the paper version. However, the modality had a significant effect on Trail Making Test performance; that is, participants were generally faster on the digital platform. Taken together, our findings suggest that with new normative data, traditional Trail Making Test can be adapted successfully to a digital platform.
Digitalization in neuropsychology offers many benefits over traditional paper‐pencil assessments; however, their comparability requires further validation. Our results demonstrated that the digital Trail Making Tests measure the same cognitive abilities as the paper Trail Making Tests and they are comparable. However, our findings also indicated that digital and paper‐pencil Trail Making Tests are not parallel to each other and digitalization requires new normative data.
Objective: There is a need for novel biomarkers that can indicate disease state, project disease progression, or assess response to treatment for amyotrophic lateral sclerosis (ALS) and associated ...neurodegenerative diseases such as frontotemporal dementia (FTD). Digital biomarkers are especially promising as they can be collected non-invasively and at low burden for patients. Speech biomarkers have the potential to objectively measure cognitive, motor as well as respiratory symptoms at low-cost and in a remote fashion using widely available technology such as telephone calls. Methods: The PROSA study aims to develop and evaluate low-burden frequent prognostic digital speech biomarkers. The main goal is to create a single, easy-to-perform battery that serves as a valid and reliable proxy for cognitive, respiratory, and motor domains in ALS and FTD. The study will be a multicenter 12-months observational study aiming to include 75 ALS and 75 FTD patients as well as 50 healthy controls and build on three established longitudinal cohorts: DANCER, DESCRIBE-ALS and DESCRIBE-FTD. In addition to the extensive clinical phenotyping in DESCRIBE, PROSA collects a comprehensive speech protocol in fully remote and automated fashion over the telephone at four time points. This longitudinal speech data, together with gold standard measures, will allow advanced speech analysis using artificial intelligence for the development of speech-based phenotypes of ALS and FTD patients measuring cognitive, motor and respiratory symptoms. Conclusion: Speech-based phenotypes can be used to develop diagnostic and prognostic models predicting clinical change. Results are expected to have implications for future clinical trial stratification as well as supporting innovative trial designs in ALS and FTD.
The fate of subcortical diffusion-weighted imaging (DWI) lesions in stroke patients is highly variable, ranging from complete tissue loss to no visible lesion on follow-up. Little is known about ...within-lesion heterogeneity and its relevance for stroke outcome. Patients with subcortical stroke and recruited through the prospective DEDEMAS study (NCT01334749) were examined at baseline (n = 45), six months (n = 45), and three years (n = 28) post-stroke. We performed high-resolution structural MRI including DWI. Tissue fate was determined voxel-wise using fully automated tissue segmentation. Within-lesion heterogeneity at baseline was assessed by free water diffusion imaging measures. The majority of DWI lesions (66%) showed cavitation on six months follow-up but the proportion of tissue turning into a cavity was small (9 ± 13.5% of the DWI lesion). On average, 69 ± 25% of the initial lesion resolved without any visually apparent signal abnormality. The extent of cavitation at six months post-stroke was independently associated with clinical outcome, i.e. modified Rankin scale score at six months (OR = 4.71, p = 0.005). DWI lesion size and the free water-corrected tissue mean diffusivity at baseline independently predicted cavitation. In conclusion, the proportion of cavitating tissue is typically small, but relevant for clinical outcome. Within-lesion heterogeneity at baseline on advanced diffusion imaging is predictive of tissue fate.
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