NEW FRONTIERS IN THE COGNITIVE ASSESSMENT OF AMYOTROPHIC LATERAL SCLEROSIS: BRAIN COMPUTER INTERFACE AND EYE TRACKING

Background: Over the last 20 years, cognitive and behavioural alterations in amyotrophic lateral sclerosis (ALS) have been recognized as an integral part of the disease. A proportion of patients present with a full-blown frontotemporal dementia syndrome, while selective cognitive changes are more commonly found, especially regarding frontal-executive abilities. Moreover, recent studies have highlighted a broader cognitive involvement in this population, concerning language and social cognition. Despite the increased awareness of ALS as a multisystem disorder and the importance of an accurate cognitive evaluation of these patients, the traditional neuropsychological \u2018paper and pencil\u2019 tools do not compensate for patients\u2019 physical disability and can not be adequately used in the moderate-advanced stages of the disease. Objective: To investigate the use of P300-based Brain Computer Interface (BCI) and Eye Tracking (ET) technology for the administration of motor-verbal free cognitive measures in ALS. Materials and Methods: 34 patients diagnosed with ALS and 30 healthy subjects have been recruited. All participants underwent the BCI and ET-based neuropsychological assessment, together with three traditional cognitive screening tools (Frontal Assessment Battery - FAB; Montreal Cognitive Assessment \u2013 MoCA; Working Memory subtest of the Brief Assessment of Cognition in Schizophrenia), two psychological questionnaires (Beck Depression Inventory - BDI; State-Trate Anxiety Inventory - STAI-Y) and a usability questionnaire. For patients, also respiratory examination was performed, and the Frontal Behavioural Inventory - FBI was carried out with caregivers. Results: Significant correlations were observed between the traditional cognitive measures and the BCI- and ET-based neuropsychological assessment, mainly concerning accuracy and time-related variables in the ALS patients sample. Patients provided comparable rates than controls with regard to the BCI and ET usability. Conclusions: The developed motor-verbal free neuropsychological battery allows a longitudinal cognitive assessment during the course of the disease, also when traditional measures are not fully administrable, providing relevant information for clinical practice and ethical issues. Further work will be aimed at refining the developed system and enlarging the cognitive spectrum investigated

Studies on the impact of assistive communication devices on the quality of life of patients with amyotrophic lateral sclerosis

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2016Amyotrophic Lateral Sclerosis (ALS) is a progressive neuromuscular disease with rapid and generalized degeneration of motor neurons. Patients with ALS experiment a relentless decline in functions that affect performance of most activities of daily living (ADL), such as speaking, eating, walking or writing. For this reason, dependence on caregivers grows as the disease progresses. Management of the respiratory system is one of the main concerns of medical support, since respiratory failure is the most common cause of death in ALS. Due to increasing muscle weakness, most patients experience dramatic decrease of speech intelligibility and difficulties in using upper limbs (UL) for writing. There is growing evidence that mild cognitive impairment is common in ALS, but most patients are self-conscious of their difficulties in communicating and, in very severe stages, locked-in syndrome can occur. When no other resources than speech and writing are used to assist communication, patients are deprived of expressing needs or feelings, making decisions and keeping social relationships. Further, caregivers feel increased dependence due to difficulties in communication with others and get frustrated about difficulties in understanding partners’ needs. Support for communication is then very important to improve quality of life of both patients and caregivers; however, this has been poorly investigated in ALS. Assistive communication devices (ACD) can support patients by providing a diversity of tools for communication, as they progressively lose speech. ALS, in common with other degenerative conditions, introduces an additional challenge for the field of ACD: as the disease progresses, technologies must adapt to different conditions of the user. In early stages, patients may need speech synthesis in a mobile device, if dysarthria is one of the initial symptoms, or keyboard modifications, as weakness in UL increases. When upper limbs’ dysfunction is high, different input technologies may be adapted to capture voluntary control (for example, eye-tracking devices). Despite the enormous advances in the field of Assistive Technologies, in the last decade, difficulties in clinical support for the use of assistive communication devices (ACD) persist. Among the main reasons for these difficulties are lack of assessment tools to evaluate communication needs and determine proper input devices and to indicate changes over disease progression, and absence of clinical evidence that ACD has relevant impact on the quality of life of affected patients. For this set of reasons, support with communication tools is delayed to stages where patients are severely disabled. Often in these stages, patients face additional clinical complications and increased dependence on their caregivers’ decisions, which increase the difficulty in adaptation to new communication tools. This thesis addresses the role of assistive technologies in the quality of life of early-affected patients with ALS. Also, it includes the study of assessment tools that can improve longitudinal evaluation of communication needs of patients with ALS. We longitudinally evaluated a group of 30 patients with bulbar-onset ALS and 17 caregivers, during 2 to 29 months. Patients were assessed during their regular clinical appointments, in the Hospital de Santa Maria-Centro Hospitalar Lisboa_Norte. Evaluation of patients was based on validated instruments for assessing the Quality of Life (QoL) of patients and caregivers, and on methodologies for recording communication and measuring its performance (including speech, handwriting and typing). We tested the impact of early support with ACD on the QoL of patients with ALS, using a randomized, prospective, longitudinal design. Patients were able to learn and improve their skills to use communication tools based on electronic assistive devices. We found a positive impact of ACD in psychological and wellbeing domains of quality of life in patients, as well as in the support and psychological domains in caregivers. We also studied performance of communication (words per minute) using UL. Performance in handwriting may decline faster than performance in typing, supporting the idea that the use of touchscreen-based ACD supports communication for longer than handwriting. From longitudinal recordings of speech and typing activity we could observe that ACD can support tools to detect early markers of bulbar and UL dysfunction in ALS. Methodologies that were used in this research for recording and assessing function in communication can be replicated in the home environment and form part of the original contributions of this research. Implementation of remote monitoring tools in daily use of ACD, based on these methodologies, is discussed. Considering those patients who receive late support for the use of ACD, lack of time or daily support to learn how to control complex input devices may hinder its use. We developed a novel device to explore the detection and control of various residual movements, based on sensors of accelerometry, electromyography and force, as input signals for communication. The aim of this input device was to develop a tool to explore new communication channels in patients with generalized muscle weakness. This research contributed with novel tools from the Engineering field to the study of assistive communication in patients with ALS. Methodologies that were developed in this work can be further applied to the study of the impact of ACD in other neurodegenerative diseases that affect speech and motor control of UL

The use of P300-based BCIs in amyotrophic lateral sclerosis : from augmentative and alternative communication to cognitive assessment

The use of augmentative and alternative communication (AAC) tools in patients with amyotrophic lateral sclerosis (ALS), as effective means to compensate for the progressive loss of verbal and gestural communication, has been deeply investigated in the recent literature. The development of advanced AAC systems, such as eye-tracking (ET) and brain-computer interface (BCI) devices, allowed to bypass the important motor difficulties present in ALS patients. In particular, BCIs could be used in moderate to severe stages of the disease, since they do not require preserved ocular-motor ability, which is necessary for ET applications. Furthermore, some studies have proved the reliability of BCIs, regardless of the severity of the disease and the level of physical decline. However, the use of BCI in ALS patients still shows some limitations, related to both technical and neuropsychological issues. In particular, a range of cognitive deficits in most ALS patients have been observed. At the moment, no effective verbal-motor free measures are available for the evaluation of ALS patients\u2019 cognitive integrity; BCIs could offer a new possibility to administer cognitive tasks without the need of verbal or motor responses, as highlighted by preliminary studies in this field. In this review, we outline the essential features of BCIs systems, considering advantages and challenges of these tools with regard to ALS patients and the main applications developed in this field. We then outline the main findings with regard to cognitive deficits observed in ALS and some preliminary attempts to evaluate them by means of BCIs. The definition of specific cognitive profiles could help to draw flexible approaches tailored on patients\u2019 needs. It could improve BCIs efficacy and reduce patients\u2019 efforts. Finally, we handle the open question, represented by the use of BCIs with totally locked in patients, who seem unable to reliably learn to use such tool

Multichannel Characterization of Brain Activity in Neurological Impairments

Hundreds of millions of people worldwide suffer from various neurological and psychiatric disorders. A better understanding of the underlying neurophysiology and mechanisms for these disorders can lead to improved diagnostic techniques and treatments. The objective of this dissertation is to create a novel characterization of multichannel EEG activity for selected neurological and psychiatric disorders based on available datasets. Specifically, this work provides spatial, spectral, and temporal characterizations of brain activity differences between patients/animal models and healthy controls, with focus on modern techniques that quantify cortical connectivity, which is widely believed to be abnormal in such disorders. Exploring the functional brain networks in these patients can provide a better understanding of the pathophysiology and brain network integrity of the respective disorders. This can allow for the assessment of neural mechanism deficits and possibly lead to developing a model for enhancement in the biology of neural interactions in these patients. This unique electrophysiological information may also contribute to the development of target drugs, novel treatments, and genetic studies. Moreover, the outcomes not only provide potential biomarkers for the diagnosis of respective disorders but also can serve as biofeedback for neurotherapy and also development of more sophisticated BCIs

User-centered design in brain–computer interfaces — a case study

The array of available brain–computer interface (BCI) paradigms has continued to grow, and so has the corresponding set of machine learning methods which are at the core of BCI systems. The latter have evolved to provide more robust data analysis solutions, and as a consequence the proportion of healthy BCI users who can use a BCI successfully is growing. With this development the chances have increased that the needs and abilities of specific patients, the end-users, can be covered by an existing BCI approach. However, most end-users who have experienced the use of a BCI system at all have encountered a single paradigm only. This paradigm is typically the one that is being tested in the study that the end-user happens to be enrolled in, along with other end-users. Though this corresponds to the preferred study arrangement for basic research, it does not ensure that the end-user experiences a working BCI. In this study, a different approach was taken; that of a user-centered design. It is the prevailing process in traditional assistive technology. Given an individual user with a particular clinical profile, several available BCI approaches are tested and – if necessary – adapted to him/her until a suitable BCI system is found

P300-Based Brain–Computer Interface Communication: Evaluation and Follow-up in Amyotrophic Lateral Sclerosis

To describe results of training and 1-year follow-up of brain-communication in a larger group of early and middle stage amyotrophic lateral sclerosis (ALS) patients using a P300-based brain–computer interface (BCI), and to investigate the relationship between clinical status, age and BCI performance. A group of 21 ALS patients were tested with a BCI-system using two-dimensional cursor movements. A four choice visual paradigm was employed to training and test the brain-communication abilities. The task consisted of reaching with the cursor one out of four icons representing four basic needs. Five patients performed a follow-up test 1 year later. The clinical severity in all patients were assessed with a battery of clinical tests. A comparable control group of nine healthy subjects was employed to investigate performance differences. Nineteen patients and nine healthy subjects were able to achieve good and excellent cursor movements' control, acquiring at least communication abilities above chance level; during follow-up the patients maintained their BCI-skill. We found mild cognitive impairments in the ALS group which may be attributed to motor deficiencies, while no relevant correlation has been found between clinical data and BCI performance. A positive correlation between age and the BCI-skill in patients was found. Time since training acquisition and clinical status did not affect the patients brain-communication skill at early and middle stage of the disease. A brain-communication tool can be used in most ALS patients at early and middle stage of the disease before entering the locked-in stage

Evaluating Person-Centered Factors Associated with Brain-Computer Interface Access to a Commercial Augmentative and Alternative Communication Device

Purpose: Brain-computer interface (BCI) techniques may provide a link between an individual’s neurological activity and communication device control, which circumvents the requirement for individuals to possess a reliable form of physical movement for augmentative and alternative communication (AAC) device access. However, while BCI technology is rapidly progressing in the laboratory setting, BCI developments are advancing largely without consideration of established AAC best practices, which are crucial for effective clinical implementation of BCI technology. For instance, BCI research largely utilize custom made software and display paradigms and view BCI as a ‘one size fits all’ solution. That BCI is a one size fits all solution contrasts with AAC best practice, which seek to pair an individual to an AAC device that matches their current and future profile, communication needs, and preferences. Therefore, to bring BCI research further in line with existing AAC best practices this dissertation work aims to evaluate initial and recurring person-centered factors associated with learning of motor execution-based BCI switch for accessing a commercial AAC row-column scanning paradigm. Method: Four individuals with a diagnosis of amyotrophic lateral sclerosis (ALS) completed 12 BCI training sessions in which they made letter selections during an automatic row-column scanning pattern from a 7x5 grid. Neural signals utilized for BCI selection control were generated by motor execution during target letter highlighting. For comparison, three individuals without neurological impairment completed three BCI training sessions. During each session, participants completed approximately 20 minutes of online BCI. To assess person-centered factors associated with BCI performance and longitudinal device learning, participants completed both initial and recurring assessment measures. Initial assessment measures of an individual’s unique profile prior to BCI training included evaluation of neural signals utilized for BCI control (i.e., maximum event related synchronization amplitude (ERS), maximum event related synchronization amplitude minus predicted noise floor, and event related synchronization minus desynchronization difference; ERS-ERD), along with screening of cognitive factors, physical motor abilities, and motor imagery skills via the ALS-Cognitive Behavioral Screen, BCI screener (Pitt & Brumberg, 2018b), ALS-Functional Rating Scale, Bimanual Fine Motor Function, and Manual Ability Classification System. Recurring measures were taken during each BCI training session to evaluate changes associated with longitudinal BCI performance, and included measures of fatigue, motivation, time since last meal, device satisfaction, level of frustration with device control, mental and physical effort, and overall ease of device control. Results: Three out of four participants demonstrated either BCI performance in the range of neurotypical peers, or an improving BCI learning trajectory across sessions. However, while BCI learning trajectories for row-column scanning BCI device were variable both between and within participants for those with ALS, findings indicate that approximately five sessions were needed to generally characterize an individual’s learning trajectory during motor execution-based BCI trials. Regarding participant profiles, cognitive screening revealed that the two participants presenting with a suspicion for cognitive impairment achieved the highest levels of BCI accuracy, with their increased levels of performance being possibly supported by largely unimpaired motor skills. In addition, while scores for the cognitive section of the BCI screener were high, the two participants who did not demonstrate a consistent learning trajectory each missed one point in the area of attention and working memory, and one point in the area of cognitive motor learning and abstract problem solving. As expected, prior to BCI use, the greatest amplitude for each neurophysiological measure was generally associated with the highest levels of BCI accuracy. However, this finding was not consistent across sessions as the participant demonstrating the lowest amplitudes prior to BCI performance presented with the highest amplitudes during BCI control. Furthermore, when evaluating neurophysiological measures across sessions, a significant correlation between left hand peak ERS and BCI performance was identified for one participant. Finally, ERS-ERD measure remained highest for the participant achieving the highest level of BCI accuracy and was significantly correlated to BCI performance for the participant achieving the second highest BCI performance levels. For recurring number scale-based recurring measures: 1) ratings of motivation were high for all participants with ALS. However, motivation ratings significantly decreased across sessions for two participants, 2) while satisfaction ratings were positively correlated to BCI performance for two participants, satisfaction ratings for the other two participants were primarily driven by perceived levels of frustration, and 3) mental effort ratings significantly decreased across sessions for one participant along with improved BCI performance, and overall mental effort ratings showed a moderate negative trend with BCI performance for two participants. Conclusion: Overall findings support that (motor) imagery-based BCI switch access to a commercial AAC row-column scanning paradigm may be feasible for individuals with ALS, and that clinical decisions regarding BCI suitability may be informed through approximately 5 BCI training sessions, when using motor execution as a BCI control strategy. Furthermore, while generalization of findings is limited due to the small sample size, results provide multiple directions to help facilitate BCI’s clinical transition by informing BCI assessment and intervention procedures. Regarding BCI assessment, findings provide early guidelines governing the length of device trials for BCI paradigms based on motor execution, and support 1) ideally beginning BCI intervention before severe deterioration of physical motor abilities to facilitate BCI access across the disease course, facilitate BCI success, and support those with cognitive impairments, 2) further research into the development of BCI specific assessment tools, including neurophysiological measures of ERS and ERS-ERD difference to help standardize procedures for identifying factors related to BCI control. Findings relevant to BCI intervention include 1) incorporation of communication tasks beyond copy spelling to support sustained levels of BCI motivation, 2) incorporating a range of recurring person-centered measures in evaluating BCI trial outcomes including performance accuracy, levels of satisfaction, multiple measures of fatigue, and levels of frustration due to potentially differing definitions of fatigue, and differences in factors driving levels of BCI satisfaction 3) supporting more natural levels of mental effort during the establishment of BCI control

Improving the P300-Based Brain-Computer Interface by Examining the Role of Psychological Factors on Performance

The effects of neurodegenerative diseases such as amyotrophic-lateral sclerosis (ALS) eventually render those suffering from the illness unable to communicate, leaving their cognitive function relatively unharmed and causing them to be “locked-in” to their own body. With this primary function compromised there has been an increased need for assistive communication methods such as brain-computer interfaces (BCIs). Unlike several augmentative or alternative communication methods (AACs), BCIs do not require any muscular control, which makes this method ideal for people with ALS. The wealth of BCI research focuses mainly on increasing BCI performance through improving stimulus processing and manipulating paradigms. Recent research has suggested a need for studies focused on harnessing psychological qualities of BCI users, such as motivation, mood, emotion, and depression, in order to increase BCI performance through working with the user. The present studies address important issues related to P300-BCI performance: 1) the impact of mood, emotion, motivation, and depression on BCI performance were examined independently; and 2) pleasant, unpleasant, and neutral emotions were induced in order to determine the influence of emotion on BCI performance. By exploring psychological mechanisms that influence BCI performance, further insight can be gained on the best methods for improving BCI performance and increasing the number of potential BCI users. The results from Study 1 did not reveal a significant relationship between any of the four psychological factors and BCI performance. Since previous research has found a significant impact of motivation and mood on BCI performance, it may be the case that these factors only impact performance for some individuals. As this is the first study to directly investigate the impact of emotion and depression on BCI performance, future research should continue to explore these relationships. The results from Study 2 were inconclusive for the pleasant condition, since it appears the pleasant emotion manipulation was unsuccessful. The findings indicate that unpleasant emotions do not have a significant impact on BCI performance. This result is promising since it indicates that individuals should still be able to use the BCI system to communicate, even when they are experiencing unpleasant emotions. Future research should further explore the impact of pleasant emotions on BCI performance