A method for selecting an efficient diagnostic protocol for classification of perceptive and cognitive impairments in neurological patients

"Published in final edited form as: Conf Proc IEEE Eng Med Biol Soc. 2011 ; 2011: 1129–1132. doi:10.1109/IEMBS.2011.6090264."An important and unresolved problem in the assessment of perceptual and cognitive deficits in neurological patients is how to choose from the many existing behavioral tests, a subset that is sufficient for an appropriate diagnosis. This problem has to be dealt with in clinical trials, as well as in rehabilitation settings and often even at bedside in acute care hospitals. The need for efficient, cost effective and accurate diagnostic-evaluations, in the context of clinician time constraints and concerns for patients’ fatigue in long testing sessions, make it imperative to select a set of tests that will provide the best classification of the patient’s deficits. However, the small sample size of the patient population complicates the selection methodology and the potential accuracy of the classifier. We propose a method that allows for ordering tests based on having progressive increases in classification using cross-validation to assess the classification power of the chosen test set. This method applies forward linear regression to find an ordering of the tests with leave-one-out cross-validation to quantify, without biasing to the training set, the classification power of the chosen tests.R01 NS064100 - NINDS NIH HHS; R01NS064100 - NINDS NIH HHSAccepted manuscrip

Executive functions in the elderly with Mild Cognitive Impairment: a systematic review on motor and cognitive inhibition, conflict control and cognitive flexibility

Background: Mild Cognitive Impairment (MCI) is a syndrome characterised by mild cognitive decline, on one or more domains, but which does not compromise daily functions. Several studies have investigated the relationship between MCI and deficit in executive functions (EFs) but, unlike robust evidence in the mnestic domain, the nature of executive deficits in the MCI population remains uncertain. Objectives: This systematic review aims to evaluate EFs in patients with MCI, considering inhibition (motor and cognitive), conflict control and cognitive flexibility. Method: The databases used for the search were PUBMED, PsycINFO, PsycARTICLES and MEDLINE. Eligibility criteria: use of specific paradigms for EFs assessment ("Wisconsin Card Sorting Test", "Stroop Task", "Go/No-Go Task", "Flanker Task"); age over 65, studies published in English. Exclusion criteria: presence of dementia; psychiatric disorders; stroke; cranial trauma; inclusion of participants with MCI in groups with healthy elderly or those with dementia. Results: Fifty-five studies were selected, namely: Stroop Task (N=30), WCST (N=14), Go/No-Go (N=9), Flanker Task (N=2). Results have shown in people with MCI deficits in all the EFs considered. Conclusions: The results of this review support the applicability of the four experimental tasks examined for the study of EFs in people with MCI. These paradigms are useful in research, diagnosis and therapeutic purposes, allowing obtaining an articulated EFs profile that can compromise the daily life in elderly. These EFs are not generally evaluated by standard assessment of MCI, but their evaluation can lead to a better knowledge of MCI and help in the diagnosis and treatment

Multiple sclerosis: Physiological, perceptive and neural responses to exercise intensity

The aim of this work was to investigate physiological, perceptive and neurological responses to exercise intensity in people with multiple sclerosis (PwMS). The thesis begins with reviews of Multiple Sclerosis (MS) and exercise followed by three main studies. The first study explores the within session and test-retest reliability of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) from the resting tibialis anterior (TA) muscle of people with multiple sclerosis (PwMS). MEPs were recorded from 10 PwMS (2male, 8female) in 5 blocks of 5 trials using stimulators configured to fire a single pulse. MEP peak amplitudes (mV) and MEP areas (mV.mS) were measured at 2 durations MEPshort (30ms) and MEPlong (mean 50ms). The size of the first MEP (T1) from each block (mean 5.1) was significantly different to subsequent trials (T2 -T5) for MEPlong (mean 4.5 p 0.05). The testretest intraclass coefficients of correlation (ICC) and their 95% confidence intervals indicated high (>0.80) reliability for both MEParea and MEPpeak. The results showed that consistent, repeatable TMS measures were obtained from the resting TA of PwMS. The second study compared physiological and perceptive measures of PwMS to a group of healthy individuals while performing a symptom-limited graded exercise test (GXT), and through the post-exercise time-course to recovery. 54 PwMS (MSG, mean age 52.8years ± 9.0) and 17 healthy, age-matched controls (CG,mean age 48.9 years ± 5.7) performed a symptom-limited graded exercise test (GXT). Expired air (VO2), heart rate (HR), and differential ratings of perceived exertion (RPE breathing and RPE legs) were recorded during exercise, and HR and RPE (breathing and legs) during the recovery period. There were no significant differences in any baseline measure except RPEleg (MSG mean1.1±1.2; CG 0.2 ±0.4 p <0.05). During the GXT MS group means (±SD) failed to reach any criterion measure considered to represent peak performance. The control group mean exercise measures reached recognised criteria for peak testing on two measures; mean heart rate of within ± 10 beats of age predicted HRmax, mean RER value greater than 1.10. Significant differences existed between groups in all peak measures (mean MSG VO2 peak 20.1±6.4, mean CG VO2 peak 27.8 ±6.8; mean MSG HRpeak 140.1±24.8, mean CG HRpeak 167.7± 9.4; mean MSG RPE breathing 5.1±1.7, mean CG RPE breathing 6.8± 2.3; mean MS watts 97.4±35.2, mean CG watts 161.8 ± 43.4 p 0.05). There were no significant effects on the peak measures of variables when weighted by MS classification (RR-MS, SP-MS and PP- MS). There were differences between group recovery values for RPEleg at 10 mins (mean MSG 1.8 ±1.2, mean CG 1.0±1.1 p<0.05) and Temp°C at 3mins (mean MSG 36.5± 0.5, mean CG 36.9± 0.6 p<0.05) and 10mins (mean MSG 36.4±0.4, mean CG 37.0±0.3p<0.05) post-exercise. MS HR remained marginally above preexercise HR values at 10 minutes post-exercise. Differential measures of RPE for both groups recovered to pre-exercise values at 5 mins (±SD). During maximal exertion, it was observed that PwMS irrespective of disease classification, or years from onset were neither limited by their heart rate, nor their breathing, but that leg fatigue or lack of central drive to the lower limb was the reason for their inability to continue. In the third study, the physiological perceptive and central responses of PwMS were explored during exercise at low and high intensity, and through the timecourse to recovery. Participants performed 2 exercise training (ET) sessions where they performed 20 minutes of exercise on a cycle ergometer at 45% (ET45) and 60% (ET60) relative to peak watts determined during a GXT. 12 MSG and 9 CG completed the 2 exercise sessions. Repeated measures ANOVA revealed no significant differences in groups’baseline measures of HR, Temp°C, RPEbr, RPEleg or TMS measures between-groups or between-sessions. When comparing groups during ET45, measures of all variables were similar, except for RPE leg at 14mins,(mean MSG 3.3 ±1.1, CG 2.1±1.2 p<0.05). During ET60 MSG HR was higher from 14mins (mean 107.8bpm ±12.6 bpm, CG 136.8 bpm ±13.8 p<0.05). When comparing the results of MSG ET45 and ET60, during the 35 minute postexercise phase MSG HR recovered to pre-exercise values at 10 mins (mean HR 71.4bpm ±12.7, baseline 63.8 bpm ±9.8 p>0.05) after ET45, while post-ET60 HR failed to recover before session-end (mean HR 83 bpm ±11.3, baseline 64.6 bpm ±8.2, p<0.05). TMS measures were significantly depressed after both training sessions. Mean MEP size were 71% ±38% of pre-exercise levels at 30 secs post-ET45 (p<0.05) and 52% ±17.8% post ET60 at 2 minutes (p<0.05). Post-ET45 MEPs recovered to pre-exercise values at 10mins while post-ET-60 MEPs recovered at 20 mins. MEP latency and MEPρeriph were unchanged. Following ET60 we observed a strong negative relationship between Temp°C and MEPs (r=-.65, p=0.023). The investigation revealed significant, intensity-dependent, physiological and perceptive differences, during exercise and through the time-course to recovery. Analysis of responses to post-exercise TMS revealed a significant depression in corticospinal excitability, with a clear intensity-dependent difference in the depth and duration of MEP depression. In addition, an inverse relationship was found between internal body temperature and corticospinal excitability. The results may offer further guidance to clinicians for the provision of safe, appropriate and effective exercise prescription to PwMS

Non Invasive Tools for Early Detection of Autism Spectrum Disorders

Autism Spectrum Disorders (ASDs) describe a set of neurodevelopmental disorders. ASD represents a significant public health problem. Currently, ASDs are not diagnosed before the 2nd year of life but an early identification of ASDs would be crucial as interventions are much more effective than specific therapies starting in later childhood. To this aim, cheap an contact-less automatic approaches recently aroused great clinical interest. Among them, the cry and the movements of the newborn, both involving the central nervous system, are proposed as possible indicators of neurological disorders. This PhD work is a first step towards solving this challenging problem. An integrated system is presented enabling the recording of audio (crying) and video (movements) data of the newborn, their automatic analysis with innovative techniques for the extraction of clinically relevant parameters and their classification with data mining techniques. New robust algorithms were developed for the selection of the voiced parts of the cry signal, the estimation of acoustic parameters based on the wavelet transform and the analysis of the infant’s general movements (GMs) through a new body model for segmentation and 2D reconstruction. In addition to a thorough literature review this thesis presents the state of the art on these topics that shows that no studies exist concerning normative ranges for newborn infant cry in the first 6 months of life nor the correlation between cry and movements. Through the new automatic methods a population of control infants (“low-risk”, LR) was compared to a group of “high-risk” (HR) infants, i.e. siblings of children already diagnosed with ASD. A subset of LR infants clinically diagnosed as newborns with Typical Development (TD) and one affected by ASD were compared. The results show that the selected acoustic parameters allow good differentiation between the two groups. This result provides new perspectives both diagnostic and therapeutic

A Novel Intervention Approach Focusing on Social Communicative Functioning in Patients with Schizophrenia Spectrum Disorder: Effects of a Specific Speech-Gesture Training on Quality of Life and Neural Processing

Dysfunctional social communication is one of the most stable characteristics in patients with schizophrenia that severely affects quality of life. Interpreting abstract speech and integrating nonverbal information is particularly affected. Considering the difficulty to treat communication dysfunctions with usual intervention, we investigated the possibility to improve quality of life and co-verbal gesture processing in patients with schizophrenia by applying a multimodal speech-gesture (MSG) training. In the MSG training, we offered eight sessions (60 min each) including perceptive and expressive tasks as well as meta-learning elements and transfer exercises to 29 patients with schizophrenia spectrum disorder (SSD). Patients were randomized to a waiting-first group (N=20) or a training-first group (N=9), and were compared to healthy controls (N=17). Outcomes were quality of life and related changes in the neural processing of abstract speech-gesture information, which were measured pre-post training through standardized psychological questionnaires and functional Magnetic Resonance Imaging, respectively. Pre-training, patients showed reduced quality of life as compared to controls but improved significantly during the training. Strikingly, this improvement was correlated with neural activation changes in the middle temporal gyrus for the processing of abstract multimodal content. Improvement during training, self-report measures and ratings of relatives confirmed the MSG-related changes. Together, we provide first promising results of a novel multimodal speech-gesture training for patients with schizophrenia. We could link training induced changes in speech-gesture processing to changes in quality of life, demonstrating the relevance of intact communication skills and gesture processing for well-being

Models and Analysis of Vocal Emissions for Biomedical Applications

The MAVEBA Workshop proceedings, held on a biannual basis, collect the scientific papers presented both as oral and poster contributions, during the conference. The main subjects are: development of theoretical and mechanical models as an aid to the study of main phonatory dysfunctions, as well as the biomedical engineering methods for the analysis of voice signals and images, as a support to clinical diagnosis and classification of vocal pathologies

Visual strategies underpinning social cognition in traumatic brain injury

Impairments in social cognition after traumatic brain injury (TBI) are well documented but poorly understood (McDonald, 2013). Deficits in emotion perception, particularly facial affect recognition, are frequently reported in the literature (Babbage et al., 2011; Knox & Douglas, 2009), as well as mentalizing impairments and difficulty in understanding sincere and sarcastic exchanges (Channon, Pellijeff & Rule, 2005). To fully understand social impairments, both low-level and high-level processes must be explored. Few studies have focused on low-level perceptual processes in regards to facial affect recognition after TBI, and those that do typically use static social stimuli which lack ecological validity (Alves, 2013). This thesis employed eyetracking technology to explore the visual strategies underpinning the processing of contemporary static and dynamic social cognition tasks in a group of 18 TBI participants and 18 age, gender and education matched controls. The group affected by TBI scored significantly lower on the Movie for the Assessment of Social Cognition (MASC; Dziobek, et al., 2006), the Amsterdam Dynamic Facial Expression Set (ADFES; van der Schalk, Hawk, Fischer & Doosje, 2009), and The Assessment of Social Inference Test (McDonald et al., 2003). These findings suggest that, across a range of reliable assessments, individuals with TBI displayed significant social cognition deficits, including emotion perception and theory of mind, thus presenting strong evidence that social cognition is altered post-TBI. Impairments were not related to low-level visual processing as measured through eye-tracking metrics. This important insight suggests that social cognition changes post-TBI is likely associated with impairments in higher-level cognitive functioning. Interestingly, the group with TBI did display some aberrant fixation patterns in response to one static and one dynamic task but gaze patterns were similar between the groups on the remaining tasks. These non-uniform results warrant further exploration of low-level alterations post-TBI. Findings are discussed in reference to academic and clinical implications

Understanding Mother’s Perceptions on Assessment And Educational Programming for Their Children With Cerebral Visual Impairment

Brain-based visual impairment is the leading cause of visual impairment in early childhood populations in the developed world and its contribution to childhood visual impairment is increasing (Bosch et al., 2014; Dutton & Bax, 2010; Hoyt, 2007; Kong et al., 2012; Kran et al., 2019). In order to meet the needs of this population, comprehensive assessment that includes information from families and caregivers, pediatric ophthalmologists, neurodevelopmental specialists, vision professionals, and education teams is crucial for academic and functional success (Lueck & Dutton, 2015). Family input during the special education process and the transfer of knowledge from the clinical to the educational setting that the parent provides is also vital for this population. While parent participation is a mandated feature of special education programming development, parents of children with special needs (including those with visual disability) do not always participate to the extent the law presumes. The purpose of this qualitative multiple case study was to examine the experiences of 3 participants who are mothers of children with this visual impairment, bounded together by their shared experiences at a large children’s hospital in a city in the United States and participation in their children’s special education programming. The researcher explored the experiences of participants in both the clinical and educational environments and ultimately their feelings on the adequacy and effectiveness of their children’s educational programming relative to their visual disability. The results from this study revealed valuable information on the multitude of roles that mothers play across the physical, social, and emotional spaces in the lives of their children. Since comprehensive assessment and specific programming is crucial for the success of students with CVI, the results of this study helped to construct a more comprehensive picture of the outcomes of clinical and educational assessment and opportunities for collaboration with parents and families of children with CVI. It also provided a better understanding of the challenges families face, lack of resources on CVI, and a lack of qualified personnel in the field