End-to-end Learning for Image-based Detection of Molecular Alterations in Digital Pathology

Current approaches for classification of whole slide images (WSI) in digital pathology predominantly utilize a two-stage learning pipeline. The first stage identifies areas of interest (e.g. tumor tissue), while the second stage processes cropped tiles from these areas in a supervised fashion. During inference, a large number of tiles are combined into a unified prediction for the entire slide. A major drawback of such approaches is the requirement for task-specific auxiliary labels which are not acquired in clinical routine. We propose a novel learning pipeline for WSI classification that is trainable end-to-end and does not require any auxiliary annotations. We apply our approach to predict molecular alterations for a number of different use-cases, including detection of microsatellite instability in colorectal tumors and prediction of specific mutations for colon, lung, and breast cancer cases from The Cancer Genome Atlas. Results reach AUC scores of up to 94% and are shown to be competitive with state of the art two-stage pipelines. We believe our approach can facilitate future research in digital pathology and contribute to solve a large range of problems around the prediction of cancer phenotypes, hopefully enabling personalized therapies for more patients in future.Comment: MICCAI 2022; 8.5 Pages, 4 Figure

Influence of sublexical frequencies on the speech production in aphasia and apraxia of speech

The aim of this study was to evaluate the influence of sublexical frequencies on the speech production of patients with apraxia of speech and patients with a phonological disorder. Recent studies have discussed syllable frequency as an important parameter which influences phonetically and / or phonologically disturbed speech. In the current investigation frequencies for the units syllable, phoneme, biphoneme, onset and rhyme were evaluated. The focus of our analysis was how the frequencies of the target units relate to those of the units realised by the patients. The results are discussed with regard to the pathomechanisms underlying of apraxia of speech and phonological impairment

In Time with the Beat: Entrainment in Patients with Phonological Impairment, Apraxia of Speech, and Parkinson’s Disease

In the present study, we investigated if individuals with neurogenic speech sound impairments of three types, Parkinson’s dysarthria, apraxia of speech, and aphasic phonological impairment, accommodate their speech to the natural speech rhythm of an auditory model, and if so, whether the effect is more significant after hearing metrically regular sentences as compared to those with an irregular pattern. This question builds on theories of rhythmic entrainment, assuming that sensorimotor predictions of upcoming events allow humans to synchronize their actions with an external rhythm. To investigate entrainment effects, we conducted a sentence completion task relating participants’ response latencies to the spoken rhythm of the prime heard immediately before. A further research question was if the perceived rhythm interacts with the rhythm of the participants’ own productions, i.e., the trochaic or iambic stress pattern of disyllabic target words. For a control group of healthy speakers, our study revealed evidence for entrainment when trochaic target words were preceded by regularly stressed prime sentences. Persons with Parkinson’s dysarthria showed a pattern similar to that of the healthy individuals. For the patient groups with apraxia of speech and with phonological impairment, considerably longer response latencies with differing patterns were observed. Trochaic target words were initiated with significantly shorter latencies, whereas the metrical regularity of prime sentences had no consistent impact on response latencies and did not interact with the stress pattern of the target words to be produced. The absence of an entrainment in these patients may be explained by the more severe difficulties in initiating speech at all. We discuss the results in terms of clinical implications for diagnostics and therapy in neurogenic speech disorders. View Full-Tex

Assessing the treatment effects in apraxia of speech: introduction and evaluation of the Modified Diadochokinesis Test

Background: The number of reliable and valid instruments to measure the effects of therapy in apraxia of speech (AoS) is limited. Aims: To evaluate the newly developed Modified Diadochokinesis Test (MDT), which is a task to assess the effects of rate and rhythm therapies for AoS in a multiple baseline across behaviours design. Methods: The consistency, accuracy and fluency of speech of 24 adults with AoS and 12 unaffected speakers matched for age, gender and educational level were assessed using the MDT. The reliability and validity of the instrument were considered and outcomes compared with those obtained with existing tests. Results: The results revealed that MDT had a strong internal consistency. Scores were influenced by syllable structure complexity, while distinctive features of articulation had no measurable effect. The testretest and intra- and inter-rater reliabilities were shown to be adequate, and the discriminant validity was good. For convergent validity different outcomes were found: apart from one correlation, the scores on tests assessing functional communication and AoS correlated significantly with the MDT outcome measures. The spontaneous speech phonology measure of the Aachen Aphasia Test (AAT) correlated significantly with the MDT outcome measures, but no correlations were found for the repetition subtest and the spontaneous speech articulation/prosody measure of the AAT. Conclusions & Implications: The study shows that the MDT has adequate psychometric properties, implying that it can be used to measure changes in speech motor control during treatment for apraxia of speech. The results demonstrate the validity and utility of the instrument as a supplement to speech tasks in assessing speech improvement aimed at the level of planning and programming of speech

Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

Schizotypy and Behavioural Adjustment and the Role of Neuroticism

In the present study the relationship between behavioural adjustment following cognitive conflict and schizotypy was investigated using a Stroop colour naming paradigm. Previous research has found deficits with behavioural adjustment in schizophrenia patients. Based on these findings, we hypothesized that individual differences in schizotypy, a personality trait reflecting the subclinical expression of the schizophrenia phenotype, would be associated with behavioural adjustment. Additionally, we investigated whether such a relationship would be explained by individual differences in neuroticism, a non-specific measure of negative trait emotionality known to be correlated with schizotypy. 106 healthy volunteers (mean age: 25.1, 60% females) took part. Post-conflict adjustment was measured in a computer-based version of the Stroop paradigm. Schizotypy was assessed using the Schizotypal Personality Questionnaire (SPQ) and Neuroticism using the NEO-FFI. We found a negative correlation between schizotypy and post-conflict adjustment (r = -.30, p<.01); this relationship remained significant when controlling for effects of neuroticism. Regression analysis revealed that particularly the subscale No Close Friends drove the effect. Previous findings of deficits in cognitive control in schizophrenia patients were extended to the subclinical personality expression of the schizophrenia phenotype and found to be specific to schizotypal traits over and above the effects of negative emotionality

Association of schizotypy with striatocortical functional connectivity and its asymmetry in healthy adults

Altered striatocortical functional connectivity has been suggested to be a trait marker of schizophrenia spectrum disorders, including schizotypal personality. In the present study, we examined the association between schizotypal personality traits and striatocortical functional connectivity in a sample of healthy adults. The German version of the Schizotypal Personality Questionnaire was obtained from N=111 participants recruited from the general public. Resting-state functional magnetic resonance imaging scans were acquired at 3T. Six striatal seed regions in each hemisphere were defined and striatocortical resting-state functional connectivity (rsFC) as well as its lateralization indices was calculated. Regression analysis showed that schizotypy scores, especially from the positive dimension, were positively correlated with rsFC between ventral striatum and frontal cortex and negatively associated with rsFC between dorsal striatum and posterior cingulate. No significant associations were found between negative dimension schizotypy and striatocortical rsFC. We also found positive correlations between schizotypy total scores and lateralization index of right dorsal caudate and right rostral putamen. In conclusion, the present study extends previous evidence of altered striatocortical rsFC in the schizophrenia spectrum. The observed associations resemble in part the alterations observed in psychotic patients and their relatives, providing support for dimensionality from schizotypal personality to the clinical disorder. Hum Brain Mapp 39:288-299, 2018. (c) 2017 Wiley Periodicals, Inc

The Three Models of Emotional Intelligence and Performance in a Hot and Cool go/no-go Task in Undergraduate Students

Emotional intelligence (EI), or the ability to perceive, use, understand and regulate emotions, appears to be helpful in the performance of “hot” (i.e., emotionally laden) cognitive tasks when using performance-based ability models, but not when using self-report EI models. The aim of this study is to analyze the relationship between EI (as measured through a performance-based ability test, a self-report mixed test and a self-report ability test) and cognitive control ability during the performance of hot and “cool” (i.e., non-emotionally laden) “go/no-go” tasks. An experimental design was used for this study in which 187 undergraduate students (25% men) with a mean age of 21.93 years (standard deviation [SD] = 3.8) completed the three EI tests of interest (Mayer-Salovey-Caruso Emotional Intelligence Test [MSCEIT], Trait Meta-Mood Scale [TMMS] and Emotional Quotient Inventory–Short Form [EQi:S]) as well as go/no-go tasks using faces and geometric figures as stimuli. The results provide evidence for negative associations between the “managing” branch of EI measured through the performance-based ability test of EI and the cognitive control index of the hot go/no-go task, although similar evidence was not found when using the cool task. Further, the present study failed to observe consistent results when using the self-report EI instruments. These findings are discussed in terms of both the validity and implications of the various EI models.This research was supported in part by the projects Innovation and Development Agency of Andalusia, Spain (SEJ-07325), and the Spanish Ministry of Economy (PSI2012-37490)

Relationships between neuropsychological and antisaccade measures in multiple sclerosis patients

Background: The Stroop test is frequently used to assess deficits in inhibitory control in people with multiple sclerosis (MS). This test has limitations and antisaccade eye movements, that also measure inhibitory control, may be an alternative to Stroop.Objectives: The aim of this study was twofold: (i) to investigate if the performance in the antisaccade task is altered in patients with MS and (ii) to investigate the correlation between performances in neuropsychological tests, the Stroop test and the antisaccade task.Methods: We measured antisaccades (AS) parameters with an infrared eye tracker (SMIRED 250 Hz) using a standard AS paradigm. A total of 38 subjects diagnosed with MS and 38 age and gender matched controls participated in this study. Neuropsychological measures were obtained from the MS group.Results: Patients with MS have higher error rates and prolonged latency than controls in the antisaccade task. There was a consistent association between the Stroop performance and AS latency. Stroop performance but not AS latency was associated with other neuropsychological measures in which the MS group showed deficits.Conclusions: Our findings suggest that AS may be a selective and independent measure to investigate inhibitory control in patients with MS. More studies are necessary to confirm our results and to describe brain correlates associated with impaired performance in the antisaccade task in people diagnosed with MS.The Vision Rehabilitation Lab and Antonio Filipe Macedo receive or received funding from Shamir Optical Industry Lt, Portugal, from grants PTDC/DTP-EPI/0412/2012 (Prevalence and Costs of Visual Impairment in Portugal) and UID/FIS/04650/2013 (Framework of the Strategic Funding granted to Centre of Physics at Minho University). Multiple Sclerosis Association "Todos com a Esclerose Multiple" paid the salary of Marisa Borges Ferreira. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Linking cognitive measures of response inhibition and reward sensitivity to trait impulsivity

Impulsivity is regarded as a multifaceted construct that comprises two dimensions: rapid-response impulsivity and reward-delay impulsivity. It is unclear, however, which aspects of trait impulsivity, as assessed by self-report measures are related to rapid-response impulsivity and/or to reward-delay impulsivity, as different results have been reported in studies using both self-report and cognitive measures. This study aimed to directly relate self-report measures of impulsivity to cognitive measures of impulsivity in individuals at low- or high-levels on two impulsivity dimensions, specifically rapid-response impulsivity and reward-delay impulsivity. Participants were classified into high- or low-impulsivity groups based on (1) level of rapid-response impulsivity (determined by BIS-11 Motor subscale scores); (2) level of reward-delay impulsivity (determined by BIS/BAS subscale scores); and (3) a combination of rapid-response impulsivity and reward-delay impulsivity levels. Impulsivity was assessed using Go/No-Go, Stop-Signal and Delay-Discounting tasks and self-report measures. The high rapid-response impulsivity group showed significantly higher reward-delay impulsivity on both, the Delay-Discounting tasks and on self-report measures assessing reward-delay impulsivity, than the low-risk group. Based on the level of reward-delay impulsivity, the high reward-delay impulsivity group scored significantly higher on task-based (cognitive) and self-report measures assessing rapid-response inhibition than the low reward-delay impulsivity group. Combining both dimensions of impulsivity showed that the high-impulsivity group performed significantly worse in rapid-response paradigms and temporally discounted significantly more impulsively than the low-impulsivity group. Thus, combined impulsivity factors provide better assessment of impulsivity than each dimension alone. In conclusion, robust differences in impulsivity can be identified in non-clinical young adults