Multiple sclerosis and quality of life: The role of cognitive impairment on quality of life in people with multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS), a chronic disease of the central nervous system (CNS), affects functional ability and quality of life (QoL). Depression, fatigue, and disability status are among the many factors that have been shown to impact QoL in people with MS, but the extent to which MS-related cognitive impairment is related to QoL is understudied in the literature. OBJECTIVE: The purpose of this study was to determine relevant predictors of QoL from a wide list of symptoms including physical disability, and a multi-dimensional computerized cognitive assessment battery (CAB), depression, fatigue, and demographic variables (including employment status). In addition, the unique predictive power of cognitive impairment on QoL was explored in relation to other common factors of disease impact. METHODS: 171 people with MS (PwMS) were evaluated with a computerized assessment battery (CAB), EDSS examination, and validated Patient Reported Outcome (PRO) measures (Multiple Sclerosis Impact Scale, MSIS-29; Beck Depression Inventory - Second Edition BDI-2; and the Modified Fatigue Impact Scale, MFIS). RESULTS: 171 PwMS were included [Age: 46.02 years ± 9.85, 124 (72.5%) female]. Depression and fatigue scores were highly correlated with MSIS-29. EDSS, unemployment, memory, executive functioning, and motor skills were moderately correlated with MSIS-29. Predictors of QoL were EDSS, depression, fatigue, executive functioning, and attention. Attention and executive functioning were predictive of QoL even after controlling for demographic variables, fatigue, depression, and physical disability status. CONCLUSION: Findings indicate the need for comprehensive and quantified evaluation of all factors associated with disease burden, which will ultimately serve to improve the QoL in PwMS through more targeted and patient-centered care.

Sequential gains and losses during gambling feedback: Differential effects in time-frequency delta and theta measures.

One critical aspect of reward-feedback is the impact of local outcome history-how past experiences with choices and outcomes influences current behavior and neural activity. Yet, prior event-related potential work in this area has been contentious. This study contributes to this field by using time-frequency measures to better isolate constituent processes. Specifically, we identify how theta and delta are differentially sensitive to local outcome history. Participants completed a binary monetary choice task while we collected EEG data. Unbeknownst to them, trial outcomes were manipulated into pre-determined sequences, ranging from one to eight gains or losses in a row. Analyses were arranged by sequence establishment (first 2 trials of a sequence) and continuation (prolonged sequences of 3-8 trials). During the establishment of a sequence, delta activity to gains and losses were virtually identical on the first (change) trial, demonstrating marked divergence only on the second trial. This difference grew throughout the continuation period, as delta activity was sustained with accruing gains but declined with multiple losses. Theta activity, conversely, demonstrated a maximal loss-gain difference on the change trial but was insensitive to the establishment of a new sequence. Differential theta activity between outcomes decreased as sequences continued, with theta activity increasing over accruing gains and remaining stable over losses. Results indicate that delta-gain and theta-loss signals are relatively stable across sequential outcomes. Furthermore, theta is most sensitive to loss-gain differences on the initial change trial, while delta is more sensitive to gain-loss differences with the continuation of a sequence.

Adolescents and young adults with neurofibromatosis type 1: A descriptive study of adaptive functioning.

Neurofibromatosis type 1 (NF1) is a genetic syndrome affecting about 1 in 3500 individuals; many of those affected have plexiform neurofibroma (pNF) tumors and associated symptoms and complications. Furthermore, learning and attention problems, as well as deficits in adaptive functioning, are common, often beginning in early childhood. This study aimed to describe adaptive functioning and to examine relationships between adaptive functioning and cognitive and academic variables and level of independence among adolescents and young adults (AYA) with NF1 and pNF tumors. Fifty-five AYA aged 16-31 years participated in a series of neuropsychological evaluations while parents completed the Vineland Adaptive Behavior Scales (VABS-II) as part of a larger natural history study. Over one-third (35%) of AYA were neither in school nor employed. Mean VABS-II daily living and socialization scores were low average while mean Verbal and Performance IQ scores were average. VABS-II scores were positively correlated with processing speed, executive functioning, and working memory scores. Verbal IQ was the only significant predictor of work/school status. Identification of the correlates and predictors of adaptive functioning and life achievement can help guide healthcare providers with the early identification of risk factors and possible areas for intervention.

Prospective Memory in Service Members with Mild Traumatic Brain Injury.

INTRODUCTION: Prospective memory (PM) is the ability to remember the intention to perform an action in the future. Following mild traumatic brain injury (mTBI), the brain structures supporting such PM may be compromised. PM is essential for remembering activities specific to TBI survivors that promote recovery, such as following doctors' orders, taking necessary medications, completing physical rehabilitation exercises, and maintaining supportive social relationships. Since the year 2000, more than 315,897 US Service Members are reported to have sustained an mTBI1, yet little has been done to address possible PM concerns. Therefore, identifying impaired PM and interventions that may ameliorate such deficits is important. The primary aim of this study was to determine whether task encoding using implementation intentions leads to better PM performance than encoding using rote rehearsal in Service Members with mTBI (n = 35) or with bodily injuries but no TBI (n = 8) at baseline and 6 months later. MATERIALS AND METHOD: Participants were randomized to one of the two encoding conditions. They were asked to remember to complete a series of four tasks over the course of a 2-hour event-related potential session and to contact a staff member during a specified 2-hour window later that day. PM performance was assessed based on completion of each task at the appropriate time. IRB approval was obtained from The Catholic University of America, Walter Reed National Military Medical Center, and Ft. Belvoir Community Hospital. RESULTS: Service Members with mTBI using implementation intentions outperformed those using rote rehearsal. The effect of injury type and the interaction between encoding condition and injury type did not yield differences that were statistically significant. CONCLUSIONS: The results suggest that implementation intentions may be a useful PM remediation strategy for those who have sustained mTBI. Future research should validate these findings in a larger sample.

Effects of reward context on feedback processing as indexed by time-frequency analysis.

The role of reward context has been investigated as an important factor in feedback processing. Previous work has demonstrated that the amplitude of the feedback negativity (FN) depends on the value of the outcome relative to the range of possible outcomes in a given context, not the objective value of the outcome. However, some research has shown that the FN does not scale with loss magnitude in loss-only contexts, suggesting that some contexts do not show a pattern of context dependence. Methodologically, time-frequency decomposition techniques have proven useful for isolating time-domain ERP activity as separable processes indexed in delta (< 3 Hz) and theta (3-7 Hz). Thus, the current study assessed the role of context in a modified gambling feedback task using time-frequency analysis to better isolate the underlying processes. Results revealed that theta was more context dependent and reflected a binary evaluation of bad versus good outcomes in the gain and even contexts. Delta was more context independent: good outcomes scaled linearly with reward magnitude and good-bad differences scaled with context valence. Our findings reveal that theta and delta are differentially sensitive to context and that context valence may play a critical role in determining how the brain processes feedback.

Utilizing time-frequency amplitude and phase synchrony measure to assess feedback processing in a gambling task.

The neurophysiological mechanisms involved in the evaluation of performance feedback have been widely studied in the ERP literature over the past twenty years, but understanding has been limited by the use of traditional time-domain amplitude analytic approaches. Gambling outcome valence has been identified as an important factor modulating event-related potential (ERP) components, most notably the feedback negativity (FN). Recent work employing time-frequency analysis has shown that processes indexed by the FN are confounded in the time-domain and can be better represented as separable feedback-related processes in the theta (3-7 Hz) and delta (0-3 Hz) frequency bands. In addition to time-frequency amplitude analysis, phase synchrony measures have begun to further our understanding of performance evaluation by revealing how feedback information is processed within and between various brain regions. The current study aimed to provide an integrative assessment of time-frequency amplitude, inter-trial phase synchrony, and inter-channel phase synchrony changes following monetary feedback in a gambling task. Results revealed that time-frequency amplitude activity explained separable loss and gain processes confounded in the time-domain. Furthermore, phase synchrony measures explained unique variance above and beyond amplitude measures and demonstrated enhanced functional integration between medial prefrontal and bilateral frontal, motor, and occipital regions for loss relative to gain feedback. These findings demonstrate the utility of assessing time-frequency amplitude, inter-trial phase synchrony, and inter-channel phase synchrony together to better elucidate the neurophysiology of feedback processing.

Anxiety and feedback processing in a gambling task: Contributions of time-frequency theta and delta.

The feedback negativity (FN) event-related potential (ERP) is widely studied during gambling feedback tasks. However, research on FN and anxiety is minimal and the findings are mixed. To clarify these discrepancies, the current study (N = 238) used time-frequency analysis to disentangle overlapping contributions of delta (0-3 Hz) and theta (3-7 Hz) to feedback processing in a clinically anxious sample, with severity assessed through general worry and physiological arousal scales. Greater general worry showed enhanced delta- and theta-FN broadly across both gain and loss conditions, with theta-FN stronger for losses. Regressions indicated delta-FN maintained unique effects, accounted for theta, and explained the blunted time domain FN for general worry. Increased delta was also associated with physiological arousal, but the effects were accounted for by general worry. Broadly, anxiety-related alterations in feedback processing can be explained by an overall heightened sensitivity to feedback as represented by enhanced delta-FN in relation to the general worry facet of anxiety.

Expectancy effects in feedback processing are explained primarily by time-frequency delta not theta.

The roles of outcome valence and expectancy in feedback processing have been investigated as important factors modulating event-related potential (ERP) measures including the feedback negativity (FN) and P300, but results have been inconsistent. Recent work from our group has shown that processes underlying the FN and P300 are better represented as separable processes in the theta (3-7Hz) and delta (0-3Hz) ranges using time-frequency analysis. The current study evaluated the modulation of time-domain FN and P300 and time-frequency theta and delta to outcome valence and expectancy in a gambling feedback task paradigm. Results revealed that the FN was sensitive to valence but not expectancy, and that valence effects were driven by loss-sensitive theta and gain-sensitive delta. Alternatively, the P300 was sensitive to the expectedness of outcomes but only for gain trials, and these expectancy differences were explained by time-frequency delta not theta. These results add to a growing body of research showing that time-frequency measures reflect separable processes underlying time-domain components, where theta is more sensitive to primary task features and less sensitive to secondary features while delta is sensitive to primary and more complex, secondary task features.