Neural correlates of alerting and orienting impairment in multiple sclerosis patients

Background A considerable percentage of multiple sclerosis patients have attentional impairment, but understanding its neurophysiological basis remains a challenge. The Attention Network Test allows 3 attentional networks to be studied. Previous behavioural studies using this test have shown that the alerting network is impaired in multiple sclerosis. The aim of this study was to identify neurophysiological indexes of the attention impairment in relapsing-remitting multiple sclerosis patients using this test. Results After general slowing had been removed in patients group to isolate the effects of each condition, some behavioral differences between them were obtained. About Contingent Negative Variation, a statistically significant decrement were found in the amplitude for Central and Spatial Cue Conditions for patient group (p<0.05). ANOVAs showed for the patient group a significant latency delay for P1 and N1 components (p<0.05) and a decrease of P3 amplitude for congruent and incongruent stimuli (p<0.01). With regard to correlation analysis, PASAT-3s and SDMT showed significant correlations with behavioral measures of the Attention Network Test (p<0.01) and an ERP parameter (CNV amplitude). Conclusions Behavioral data are highly correlated with the neuropsychological scores and show that the alerting and orienting mechanisms in the patient group were impaired. Reduced amplitude for the Contingent Negative Variation in the patient group suggests that this component could be a physiological marker related to the alerting and orienting impairment in relapsing-remitting multiple sclerosis. P1 and N1 delayed latencies are evidence of the demyelination process that causes impairment in the first steps of the visual sensory processing. Lastly, P3 amplitude shows a general decrease for the pathological group probably indexing a more central impairment. These results suggest that the Attention Network Test give evidence of multiple levels of attention impairment, which could help in the assessment and treatment of relapsing-remitting multiple sclerosis patients.Ministerio de Economía y Competitividad de España PSI2010-16825Asociación NeuroinvestAsociación Sanitaria Virgen Macaren

Microstructural MRI Correlates of Cognitive Impairment in Multiple Sclerosis: The Role of Deep Gray Matter

Although cognitive impairment (CI) is frequently observed in people with multiple sclerosis (pwMS), its pathogenesis is still controversial. Conflicting results emerged concerning the role of microstructural gray matter (GM) damage especially when involving the deep GM structures. In this study, we aimed at evaluating whether differences in cortical and deep GM structures between apparently cognitively normal (ACN) and CI pwMS (36 subjects in total) are present, using an extensive set of diffusion MRI (dMRI) indices and conventional morphometry measures. The results revealed increased anisotropy and restriction over several deep GM structures in CI compared with ACN pwMS, while no changes in volume were present in the same areas. Conversely, reduced anisotropy/restriction values were detected in cortical regions, mostly the pericalcarine cortex and precuneus, combined with reduced thickness of the superior frontal gyrus and insula. Most of the dMRI metrics but none of the morphometric indices correlated with the Symbol Digit Modality Test. These results suggest that deep GM microstructural damage can be a strong anatomical substrate of CI in pwMS and might allow identifying pwMS at higher risk of developing CI

Effect of Exercise Training Intensity on Cognition

A literature review examining the effects of exercise intensity and modality on cognitive performance

Cognitive and Motor Neurobehavioral Relationships in People with Multiple Sclerosis and Healthy Individuals

Even though cognition and motor behavior have been traditionally conceived as independent processes, a growing body of literature supports that motor and cognitive processes are highly interrelated (Hommel et al., 2016; Mirelman et al., 2018). The relative contribution of cognition -or executive control- to motor behavior has been evidenced by means of a behavioral approach (e.g. dual task) and/or a neurophysiological approach (Clark, 2015). In this context, a deeper understanding of the cognitive-motor interference that arises from the dual task performance of a motor and cognitive task is needed, as well as the characterization of cognitive demand in neural oscillatory activity in motor-related cortical regions of the brain. The general aim of this thesis is to examine the interplay between cognitive and motor processes by means of its effect on behavior and neural correlates in people with Multiple Sclerosis and healthy individuals. It will be achieved through the study of the cognitive-motor interference during dual-task performance in people with Multiple Sclerosis and healthy individuals, as well as through the study of oscillatory brain activity potentially associated with the cognitive demand during motor control in a healthy sample. The focus is not only theoretical but also applied since the cognitivemotor interference is evaluated for its applicability to the cognitive functional assessment of people with Multiple Sclerosis

The Role of Premotor Areas in Dual Tasking in Healthy Controls and Persons With Multiple Sclerosis: An fNIRS Imaging Study

Persons with multiple sclerosis (pwMS) experience declines in physical and cognitive abilities and are challenged by dual-tasks. Dual-tasking causes a drop in performance, or what is known as dual-task cost (DTC). This study examined DTC of walking speed (WS) and cognitive performance (CP) in pwMS and healthy controls (HCs) and the effect of dual-tasking on cortical activation of bilateral premotor cortices (PMC) and bilateral supplementary motor area (SMA). Fourteen pwMS and 14 HCs performed three experimental tasks: (1) single cognitive task while standing (SingCog); (2) single walking task (SingWalk); and (3) dual-task (DualT) that included concurrent performance of the SingCog and SingWalk. Six trials were collected for each condition and included measures of cortical activation, WS and CP. WS of pwMS was significantly lower than HC, but neuropsychological (NP) measures were not significantly different. pwMS and HC groups had similar DTC of WS, while DTC of CP was only significant in the MS group; processing speed and visual memory predicted 55% of this DTC. DualT vs. SingWalk recruited more right-PMC activation only in HCs and was associated with better processing speed. DualT vs. SingCog recruited more right-PMC activation and bilateral-SMA activation in both HC and pwMS. Lower baseline WS and worse processing speed measures in pwMS predicted higher recruitment of right-SMA (rSMA) activation suggesting maladaptive recruitment. Lack of significant difference in NP measures between groups does not rule out the influence of cognitive factors on dual-tasking performance and cortical activations in pwMS, which might have a negative impact on quality of life

Neural Contributions to Physical Activity: From the Brain to the Muscle and Back Again

The thesis aims to explore the neural contribution to physical activity. The work is divided into two chapters containing research conducted in Italy, France or both states. The first chapter includes four behavioural studies aimed at evaluating the reciprocal relationship between physical activity and cognition. The second chapter contains two neurophysiological studies aimed at investigating the muscle length and the type of contraction's contribution to the activity of the motor system. Chapter one investigates how motor condition influences cognitive processes and vice versa. Several studies suggested that engaging in physical activity programs elicits a wide range of neural changes. One of those is enhancing cognitive performance (e.g., working memory or information processing speed). On the other side, specific cognitive interventions (e.g., action observation or motor imagery) can ameliorate motor performance. This reciprocal interaction could produce adverse effects if people exceed one of these two activities, which induce a fatiguing state. Chapter two looks into the activity of the corticomotor system as a function of muscle length and type of contraction. After a general introduction exploring previous studies investigating the role of muscle length (in static and dynamic form) on the corticomotor system, the chapter will present two studies. The first study examined the influence of muscle length on neuromuscular function and corticospinal excitability. The second study investigated the difference in primary motor cortex excitability when preparing concentric and eccentric contractions

Assessment of the effects of aerobic fitness on cerebrovascular function in young adults using multiple inversion time arterial spin labelling MRI

The cross-sectional study investigated the effects of aerobic fitness on cerebrovascular function in the healthy brain. We quantified grey matter (GM) cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), in a sample of young adults within a normal fitness range. Based on existing TCD and fMRI evidence, we predicted a positive relationship between fitness and resting GM CBF, and CVR. Exploratory hypotheses that highe

Advanced MRI techniques in the study of cerebellar cortex

The cerebellum (from the Latin "little brain") is the dorsal portion of the metencephalon and is located in the posterior cranial fossa. Although representing only 10% of the total brain volume, it contains more than 50% of the total number of neurons of the central nervous system (CNS). Its organization resembles the one found in the telencephalon, with the presence of a superficial mantle of gray matter (GM) known as the cerebellar cortex, covering the cerebellar white matter (WM) in which three pairs of deep cerebellar GM nuclei are embedded. The number of studies dedicated to the study of the cerebellum and its function has significantly increased during the last years. Nevertheless, although many theories on the cerebellar function have been proposed, to date we still are not able to answer the question about the exact function of this structure. Indeed, the classical theories focused on the role of the cerebellum in fine-tuning for muscle control has been widely reconsidered during the last years, with new hypotheses that have been advanced. These include its role as sensory acquisition device, extending beyond a pure role in motor control and learning, as well as a pivotal role in cognition, with a recognized cerebellar participation in a variety of cognitive functions, ranging from mood control to language, memory, attention and spatial data management. A huge contribution to our understanding of how the cerebellum participates in all these different aspects of motor and non-motor behavior comes from the application of advanced imaging techniques. In particular, Magnetic Resonance Imaging (MRI) can provide a non-invasive evaluation of anatomical integrity, as well as information about functional connections with other brain regions. This thesis is organized as follows: - In Chapter 1 is presented a general introduction to the cerebellar anatomy and functions, with particular reference to the anatomical organization of cerebellar cortex and its connections with the telencephalon - Chapter 2 will contain a general overview about some of the major advanced MRI methods that can be applied to investigate the anatomical integrity and functional status of the cerebellar cortex - In Chapter 3 will be presented a new method to evaluate the anatomy and integrity of cerebellar cortex using ultra-high field MRI scanners - Chapters 4, 5 and 6 will contain data obtained from the application of some of the previously described advanced imaging techniques to the study of cerebellar cortex in neurodegenerative and neuroinflammatory disorders affecting the CNS

Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction

Postoperative cognitive dysfunction (POCD) is serious disorder in the central nervous system common in aged patients after anesthesia. Although its clinical symptoms are well recognized, however, the molecular etiology of the POCD remains unrevealed. Similarly, neither gold standard molecular diagnosis nor effective treatment is available for POCD until the present. Therefore, we aimed to explore the molecular mechanism of this disorder through investigating lncRNAs and mRNAs associated with POCD human patients and investigate their underlying regulatory pathways. In this study, we recruited 200 patients requiring hip or knee replacement surgery. Their neurological functions were assessed at two time points, 1 day before the surgery and 30 days post-surgery. In parallel, serum samples were collected from the participants to analyze lncRNAs and mRNAs differential expression profile between POCD and non-POCD patients using microarray analysis. To further investigate the role differentially expressed mRNA and lncRNAs, Gene Ontology (GO), pathway analyses on mRNAs and lncRNA-mRNA interaction network were performed. As a result, 68 lncRNAs and 115 mRNAs were dysregulated in the POCD group compared to non-POCD group. Among them, the top 10 upregulated lncRNAs and 10 downregulated lncRNAs were listed for enrichment analysis. Interestingly, we found that these lncRNA and mRNA are involved in biological process, molecular function, and cellular component in addition to various signaling pathways, suggesting that the pathogenesis of POCD involves lncRNAs and mRNAs differential expression. Consequently, the genetic dysregulation between the non-POCD and POCD patients participates in the occurrence and development of POCD, and could be served as diagnostic biomarkers and drug targets for POCD treatment

Cognitive-motor interaction in health and disability

Background: Almost all major aspects of daily life revolve around the completion of movements such as locomotion, reaching and grasping. Often these movements are performed in complex and distracting environments with specific goals in mind. Traditionally, habitual motor tasks such as walking have been viewed as unrelated to the cognitive domain; however, there is growing evidence of cognitive-motor interaction (CMI), perhaps associated with the inability to allocate attentional resources during dual tasking and/or damage within shared neural tracts of the brain. Inquiries into the manifestation, mechanisms and implications of CMI are ecologically relevant as we commonly perform tasks concurrently, such as walking and talking on a phone or attempting to recall a shopping list while traversing the grocery store. Moreover, cognitive-motor interactions have been shown to be related to adverse outcomes such as falling in health and disability. It is also apparent that dual tasking can further compound the impairments commonly observed in individuals with neurological disorders. Ultimately, a deeper understanding of CMI could lead to strategies for improving multitasking performance through targeted intervention, training and/or rehabilitation. Specific Aims: The purpose of the current work was to examine a theoretical basis of CMI through the implementation of experimental manipulations based on an individual, environment and task (IET) centered motor control framework. This work is of both theoretical and clinical importance. The primary aim of this analysis was to present an in depth theoretical examination of CMI that to date has not been explicitly performed in any population. By carrying out an analysis of this nature, future studies examining CMI may be better informed in regards to the responsible mechanisms related to particular observations. Additionally, a better understanding of the individual, environmental, and task factors that relate to CMI could help enhance current dual task interventions and rehabilitation techniques. Methods: Three experiments were carried out, with each examining manipulations of the key areas outlined in the IET framework. That is, the foundation of this work was to manipulate task and environmental constraints during dual tasking in multiple clinical populations with neurodegenerative disease or injury and healthy control subjects to provide a comprehensive analysis of the driving factors that lead to altered performance when multitasking. Experiment one aimed to determine the effect of varying environmental complexity (i.e. risk levels) on both task perception and CMI during dual tasking. Participants were asked to simultaneously walk and think in environments with varied difficulty (e.g. narrow walkways, obstacles) to determine how an added environmental stimulus alters dual task performance. Experiment two examined the attentional demands of movement through the use of probe reaction times during different mobility/stability tasks. Participants completed five tasks (sitting, standing, stationary cycling, leaning to stability limits and walking) requiring a range of stability and mobility control while simultaneously responding to randomly presented auditory cues. Experiment three considered the effect of explicit task instructions towards cognitive or motor prioritization and their effect on observed CMI behavior. Participants were asked to walk and think while given instructions on which domain (e.g. cognitive or motor) to prioritize. Results: All three experiments included samples of both healthy individuals and individuals with neurological impairment (e.g. multiple sclerosis and Parkinson's disease) The primary result of the present work was a direct comparison of the attentional capacity model, a neuro-resource based framework of dual tasking, compared to the behaviorally based self-awareness prioritization model. Examining the results from the three experiments as a whole suggests that the capacity model in and of itself may not fully describe the changes to gait and balance during concurrent performance. Contrarily, measures similar to the hazard estimate and postural reserve constructs of the prioritization model commonly displayed congruence with the observed CMI outcomes. Additionally, these relationships were primarily present across all groups, healthy and clinical samples, indicating that the level of physiological and/or cognitive impairment in an individual may be more pertinent to dual task costs than the disease or injury that is the root of those impairments. Conclusions: The current results have worthwhile clinical import. First, they suggest that studies of CMI should consider utilizing methodology that limits task bias in order to get the most valid understanding of prioritization as possible. Moreover, it was determined in the current analysis that in total, the participants tended to adopt a posture second approach for simple motor conditions and later shift this focus towards posture as task difficulty increased. This behavior suggests that cognitive flexibility is present in both the healthy and clinical populations and ultimately could be a target for intervention if possibly unsafe dual task strategies are observed. Additionally, it is of note that overall measures of physiological fall risk, cognition and balance confidence were commonly related to observed DTCs. This suggests that symptoms and not the underlying neurological disorder may drive CMI behavior. Ultimately, the current results serve to provide exciting new evidence in regards to the theoretical underpinnings of CMI