Significant Performance Deficits Research Articles

The Bay Area Verbal Learning Test (BAVLT): Normative Data and the Effects of Repeated Testing, Simulated Malingering, and Traumatic Brain Injury

Verbal learning tests (VLTs) are widely used to evaluate memory deficits in neuropsychiatric and developmental disorders. However, their validity has been called into question by studies showing significant differences in VLT scores obtained by different examiners. Here we describe the computerized Bay Area Verbal Learning Test (BAVLT), which minimizes inter-examiner differences by incorporating digital list presentation and automated scoring. In the 10-min BAVLT, a 12-word list is presented on three acquisition trials, followed by a distractor list, immediate recall of the first list, and, after a 30-min delay, delayed recall and recognition. In Experiment 1, we analyzed the performance of 195 participants ranging in age from 18 to 82 years. Acquisition trials showed strong primacy and recency effects, with scores improving over repetitions, particularly for mid-list words. Inter-word intervals (IWIs) increased with successive words recalled. Omnibus scores (summed over all trials except recognition) were influenced by age, education, and sex (women outperformed men). In Experiment 2, we examined BAVLT test-retest reliability in 29 participants tested with different word lists at weekly intervals. High intraclass correlation coefficients were seen for omnibus and acquisition scores, IWIs, and a categorization index reflecting semantic reorganization. Experiment 3 examined the performance of Experiment 2 participants when feigning symptoms of traumatic brain injury. Although 37% of simulated malingerers showed abnormal (p < 0.05) omnibus z-scores, z-score cutoffs were ineffective in discriminating abnormal malingerers from control participants with abnormal scores. In contrast, four malingering indices (recognition scores, primacy/recency effects, learning rate across acquisition trials, and IWIs) discriminated the two groups with 80% sensitivity and 80% specificity. Experiment 4 examined the performance of a small group of patients with mild or severe TBI. Overall, both patient groups performed within the normal range, although significant performance deficits were seen in some patients. The BAVLT improves the speed and replicability of verbal learning assessments while providing comprehensive measures of retrieval timing, semantic organization, and primacy/recency effects that clarify the nature of performance.

The effect of comorbid depression on facial and prosody emotion recognition in first-episode schizophrenia spectrum

BackgroundComorbid depression is common in first-episode schizophrenia spectrum (FES) disorders. Both depression and FES are associated with significant deficits in facial and prosody emotion recognition performance. However, it remains unclear whether people with FES and comorbid depression, compared to those without comorbid depression, have overall poorer emotion recognition, or instead, a different pattern of emotion recognition deficits. The aim of this study was to compare facial and prosody emotion recognition performance between those with and without comorbid depression in FES. MethodsThis study involved secondary analysis of baseline data from a randomized controlled trial of vocational intervention for young people with first-episode psychosis (N=82; age range: 15–25 years). ResultsThose with comorbid depression (n=24) had more accurate recognition of sadness in faces compared to those without comorbid depression. Severity of depressive symptoms was also associated with more accurate recognition of sadness in faces. Such results did not recur for prosody emotion recognition. LimitationsIn addition to the cross-sectional design, limitations of this study include the absence of facial and prosodic recognition of neutral emotions. ConclusionsFindings indicate a mood congruent negative bias in facial emotion recognition in those with comorbid depression and FES, and provide support for cognitive theories of depression that emphasise the role of such biases in the development and maintenance of depression. Longitudinal research is needed to determine whether mood-congruent negative biases are implicated in the development and maintenance of depression in FES, or whether such biases are simply markers of depressed state.

Postural Motor Learning Deficits in People With MS in Spatial but Not Temporal Control of Center of Mass

Background: Multiple sclerosis (MS) is associated with balance deficits resulting in falls and impaired mobility. Although rehabilitation has been recommended to address these balance deficits, the extent to which people with MS can learn and retain improvements in postural responses is unknown. Aim: To determine the ability of people with MS to improve postural control with surface perturbation training. Methods: A total of 24 patients with mild MS and 14 age-matched controls underwent postural control training with a set pattern of continuous, forward-backward, sinusoidal, and surface translations provided by a force platform. Postural control was then tested the following day for retention. The primary outcome measures were the relative phase and center-of-mass (CoM) gain between the body CoM and the platform motion. Results: People with MS demonstrated similar improvements in acquiring and retaining changes in the temporal control of the CoM despite significant deficits in postural motor performance at the baseline. Both MS and control groups learned to anticipate the pattern of forward-backward perturbations, so body CoM shifted from a phase-lag (age-matched controls [CS] = −7.1 ± 1.3; MS = −12.9 ± 1.0) toward a phase-lead (CS = −0.7 ± 1.8; MS = −6.1 ± 1.4) relationship with the surface oscillations. However, MS patients were not able to retain the changes in the spatial control of the CoM acquired during training. Conclusions: People with MS have the capacity to improve use of a feed-forward postural strategy with practice and retain the learned behavior for temporal not spatial control of CoM, despite their significant postural response impairments.

Emotional Intelligence deficits in schizophrenia: The impact of non-social cognition

BackgroundPrevious studies using the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT) revealed significant performance deficits across all areas of Emotional Intelligence (EI) in schizophrenia patients compared to healthy controls. However, none of these studies has investigated a potential influence of non-social cognition on these findings. Methods56 schizophrenia outpatients and 84 control subjects were investigated using the MSCEIT and the Brief Assessment of Cognition in Schizophrenia (BACS). Analyses of covariance were performed with adjustment for the BACS composite score and education. To investigate this issue in more detail, a mediation analysis was conducted. ResultsPatients showed significantly lower EI and non-social cognition levels compared to healthy controls. After adjustment for BACS composite score and education, only the group difference in the “managing emotions” branch and thus in the “strategic” EI part of the MSCEIT remained statistically significant, whereas for all other MSCEIT branches (perceiving, using, understanding emotions) statistical significance was lost. The mediation analysis revealed that the difference between schizophrenia patients and controls regarding the MSCEIT total score was almost fully attributable to the mediating effect of non-social cognition. ConclusionsOur findings suggest that in schizophrenia patients EI is largely influenced by non-social cognitive functioning. Only the “managing emotions” branch was found to be independent of non-social cognition. Consequently, non-social cognitive performance was mainly responsible for the observed differences in EI between schizophrenia patients and controls. This has to be taken into account when interpreting MSCEIT data in this population.

Meta-analysis of executive functioning in ecstasy/polydrug users.

Ecstasy/3,4-methylenedioxymethamphetamine (MDMA) use is proposed to cause damage to serotonergic (5-HT) axons in humans. Therefore, users should show deficits in cognitive processes that rely on serotonin-rich, prefrontal areas of the brain. However, there is inconsistency in findings to support this hypothesis. The aim of the current study was to examine deficits in executive functioning in ecstasy users compared with controls using meta-analysis. We identified k = 39 studies, contributing 89 effect sizes, investigating executive functioning in ecstasy users and polydrug-using controls. We compared function-specific task performance in 1221 current ecstasy users and 1242 drug-using controls, from tasks tapping the executive functions - updating, switching, inhibition and access to long-term memory. The significant main effect demonstrated overall executive dysfunction in ecstasy users [standardized mean difference (SMD) = -0.18, 95% confidence interval (CI) -0.26 to -0.11, Z = 5.05, p < 0.001, I 2 = 82%], with a significant subgroup effect (χ 2 = 22.06, degrees of freedom = 3, p < 0.001, I 2 = 86.4%) demonstrating differential effects across executive functions. Ecstasy users showed significant performance deficits in access (SMD = -0.33, 95% CI -0.46 to -0.19, Z = 4.72, p < 0.001, I 2 = 74%), switching (SMD = -0.19, 95% CI -0.36 to -0.02, Z = 2.16, p < 0.05, I 2 = 85%) and updating (SMD = -0.26, 95% CI -0.37 to -0.15, Z = 4.49, p < 0.001, I 2 = 82%). No differences were observed in inhibitory control. We conclude that this is the most comprehensive analysis of executive function in ecstasy users to date and provides a behavioural correlate of potential serotonergic neurotoxicity.

A Wireless EEG Recording Method for Rat Use inside the Water Maze.

With the continued miniaturisation of portable embedded systems, wireless EEG recording techniques are becoming increasingly prevalent in animal behavioural research. However, in spite of their versatility and portability, they have seldom been used inside water-maze tasks designed for rats. As such, a novel 3D printed implant and waterproof connector is presented, which can facilitate wireless water-maze EEG recordings in freely-moving rats, using a commercial wireless recording system (W32; Multichannel Systems). As well as waterproofing the wireless system, battery, and electrode connector, the implant serves to reduce movement-related artefacts by redistributing movement-related forces away from the electrode connector. This implant/connector was able to successfully record high-quality LFP in the hippocampo-striatal brain regions of rats as they undertook a procedural-learning variant of the double-H water-maze task. Notably, there were no significant performance deficits through its use when compared with a control group across a number of metrics including number of errors and speed of task completion. Taken together, this method can expand the range of measurements that are currently possible in this diverse area of behavioural neuroscience, whilst paving the way for integration with more complex behaviours.

Treatment-Resistant Obsessive-Compulsive Disorder: Neurocognitive and Clinical Correlates

There are a number of studies examining clinical and comorbidity profiles among patients with treatment-resistant obsessive-compulsive disorder (TR-OCD); however, there have been far fewer investigations of neurocognitive function among such patients. Five patients with treatment-refractory obsessive-compulsive symptoms underwent neurocognitive and clinical/personality testing. A number of TR-OCD patients met diagnostic criteria for major axis I disorders (particularly mood and anxiety disorders) as well as clusters A, B, and C personality disorders. TR-OCD patients demonstrated significant performance deficits on neurocognitive tests of visuospatial working memory, visuoconstructive ability, and executive control as well as one test of processing speed, but not a second, relative to healthy normative controls. TR-OCD patients and normative controls did not differ significantly on measures of verbal working memory, sequencing, figure copy organization, inhibitory control, and odor identification. In addition, TR-OCD patients were directly compared to five healthy controls evaluated in our laboratory for a separate unpublished study. TR-OCD patients demonstrated significant performance deficits on tests of visuospatial working memory, information processing speed, and executive control, and obtained substantially higher scores on dimensional measures of social anxiety and depressive symptom severity, but not schizotypal personality features. Group differences of tests of verbal working memory, inhibitory control, and additional tests of executive function were not significant. In summary, patients with TR-OCD presented with comorbid axis I conditions (primarily mood and anxiety disorders) and personality disorders. TR-OCD patients demonstrated deficits on some, but not all, tests of working memory and executive control. Neurocognitive test findings lend partial support to the hypothesis that right hemisphere (particularly dorsolateral-prefrontal, but not orbitofrontal) dysfunction is associated with TR-OCD, and a number of TR-OCD patients met diagnostic criteria for major axis I disorders (particularly mood and anxiety disorders) as well as cluster A, B, and C personality disorders further complicating treatment.

The Effects of Repeated Testing, Simulated Malingering, and Traumatic Brain Injury on Visual Choice Reaction Time.

Choice reaction time (CRT), the time required to discriminate and respond appropriately to different stimuli, is a basic measure of attention and processing speed. Here, we describe the reliability and clinical sensitivity of a new CRT test that presents lateralized visual stimuli and adaptively adjusts stimulus onset asynchronies using a staircase procedure. Experiment 1 investigated the test–retest reliability in three test sessions performed at weekly intervals. Performance in the first test session was accurately predicted from age and computer-use regression functions obtained in a previously studied normative cohort. Central processing time (CentPT), the difference between the CRTs and simple reaction time latencies measured in a separate experiment, accounted for 55% of CRT latency and more than 85% of CRT latency variance. Performance improved significantly across the three test sessions. High intraclass correlation coefficients were seen for CRTs (0.90), CentPTs (0.87), and an omnibus performance measure (0.81) that combined CRT and minimal SOA z-scores. Experiment 2 investigated performance in the same participants when instructed to feign symptoms of traumatic brain injury (TBI): 87% produced abnormal omnibus z-scores. Simulated malingerers showed greater elevations in simple reaction times than CRTs, and hence reduced CentPTs. Latency-consistency z-scores, based on the difference between the CRTs obtained and those predicted based on CentPT latencies, discriminated malingering participants from controls with high sensitivity and specificity. Experiment 3 investigated CRT test performance in military veterans who had suffered combat-related TBI and symptoms of post-traumatic stress disorder, and revealed small but significant deficits in performance in the TBI population. The results indicate that the new CRT test shows high test–retest reliability, can assist in detecting participants performing with suboptimal effort, and is sensitive to the effects of TBI on the speed and accuracy of visual processing.

Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior.

Dendrites are highly complex 3D structures that define neuronal morphology and connectivity and are the predominant sites for synaptic input. Defects in dendritic structure are highly consistent correlates of brain diseases. However, the precise consequences of dendritic structure defects for neuronal function and behavioral performance remain unknown. Here we probe dendritic function by using genetic tools to selectively abolish dendrites in identified Drosophila wing motoneurons without affecting other neuronal properties. We find that these motoneuron dendrites are unexpectedly dispensable for synaptic targeting, qualitatively normal neuronal activity patterns during behavior, and basic behavioral performance. However, significant performance deficits in sophisticated motor behaviors, such as flight altitude control and switching between discrete courtship song elements, scale with the degree of dendritic defect. To our knowledge, our observations provide the first direct evidence that complex dendrite architecture is critically required for fine-tuning and adaptability within robust, evolutionarily constrained behavioral programs that are vital for mating success and survival. We speculate that the observed scaling of performance deficits with the degree of structural defect is consistent with gradual increases in intellectual disability during continuously advancing structural deficiencies in progressive neurological disorders.

Developing situation awareness amongst nursing and paramedicine students utilizing eye tracking technology and video debriefing techniques: A proof of concept paper

ObjectiveThe aims of this quasi-experimental before-and-after study were to first determine whether the use of eye tracking technology combined with video debriefing techniques has the potential to improve the quality of feedback and enhance situation awareness (SA) in simulated settings and second to determine students' satisfaction towards simulated learning. MethodsNursing and paramedicine students from three universities participated in three 8-minute simulation scenarios of acutely deteriorating patients. Eye tracking glasses video recorded the scenarios and tracked right eye movement. On completion, participants were questioned using the Situation Awareness Global Assessment Technique, completed the Satisfaction with Simulation Experience Scale (SSES), and provided textual feedback and received video-based verbal feedback. ResultsParticipants lacked awareness of presenting medical conditions and patient environments and had poor recall of patient vital signs. Significant improvements in SA scores were demonstrated between the first and third scenarios (P = 0.04). Participants reported greater insight into their performance and were satisfied with simulated learning. ConclusionsUse of visual field review techniques appears to enhance the use of realistic simulated practice as a means of addressing significant performance deficits. Eye tracking and point of view recording techniques are feasible and with applicable debriefing techniques could enhance clinical and situated performance.

A modified controlled cortical impact technique to model mild traumatic brain injury mechanics in mice.

For the past 25 years, controlled cortical impact (CCI) has been a useful tool in traumatic brain injury (TBI) research, creating injury patterns that includes primary contusion, neuronal loss, and traumatic axonal damage. However, when CCI was first developed, very little was known on the underlying biomechanics of mild TBI. This paper uses information generated from recent computational models of mild TBI in humans to alter CCI and better reflect the biomechanical conditions of mild TBI. Using a finite element model of CCI in the mouse, we adjusted three primary features of CCI: the speed of the impact to achieve strain rates within the range associated with mild TBI, the shape, and material of the impounder to minimize strain concentrations in the brain, and the impact depth to control the peak deformation that occurred in the cortex and hippocampus. For these modified cortical impact conditions, we observed peak strains and strain rates throughout the brain were significantly reduced and consistent with estimated strains and strain rates observed in human mild TBI. We saw breakdown of the blood–brain barrier but no primary hemorrhage. Moreover, neuronal degeneration, axonal injury, and both astrocytic and microglia reactivity were observed up to 8 days after injury. Significant deficits in rotarod performance appeared early after injury, but we observed no impairment in spatial object recognition or contextual fear conditioning response 5 and 8 days after injury, respectively. Together, these data show that simulating the biomechanical conditions of mild TBI with a modified cortical impact technique produces regions of cellular reactivity and neuronal loss that coincide with only a transient behavioral impairment.

Contribution of auditory working memory to speech understanding in mandarin-speaking cochlear implant users.

PurposeTo investigate how auditory working memory relates to speech perception performance by Mandarin-speaking cochlear implant (CI) users.MethodAuditory working memory and speech perception was measured in Mandarin-speaking CI and normal-hearing (NH) participants. Working memory capacity was measured using forward digit span and backward digit span; working memory efficiency was measured using articulation rate. Speech perception was assessed with: (a) word-in-sentence recognition in quiet, (b) word-in-sentence recognition in speech-shaped steady noise at +5 dB signal-to-noise ratio, (c) Chinese disyllable recognition in quiet, (d) Chinese lexical tone recognition in quiet. Self-reported school rank was also collected regarding performance in schoolwork.ResultsThere was large inter-subject variability in auditory working memory and speech performance for CI participants. Working memory and speech performance were significantly poorer for CI than for NH participants. All three working memory measures were strongly correlated with each other for both CI and NH participants. Partial correlation analyses were performed on the CI data while controlling for demographic variables. Working memory efficiency was significantly correlated only with sentence recognition in quiet when working memory capacity was partialled out. Working memory capacity was correlated with disyllable recognition and school rank when efficiency was partialled out. There was no correlation between working memory and lexical tone recognition in the present CI participants.ConclusionsMandarin-speaking CI users experience significant deficits in auditory working memory and speech performance compared with NH listeners. The present data suggest that auditory working memory may contribute to CI users' difficulties in speech understanding. The present pattern of results with Mandarin-speaking CI users is consistent with previous auditory working memory studies with English-speaking CI users, suggesting that the lexical importance of voice pitch cues (albeit poorly coded by the CI) did not influence the relationship between working memory and speech perception.

Directly observed care: can unannounced standardized patients address a gap in performance measurement?

There are three potential sources of information for evaluating a clinician's performance: documentation, patient report, and directly observed care. Current measures draw on just two of these: data recorded in the medical record and surveys of patients. Neither captures an array of performance characteristics, including clinician attention to symptoms and signs while taking a history or conducting a physical exam, accurate recording in the medical record of information obtained during the encounter, evidence based communication strategies for preventive care counseling, and effective communication behavior. Unannounced Standardized Patients (USPs) have been widely deployed as a research strategy for systematically uncovering significant performance deficits in each of these areas, but have not been adopted for quality improvement. Likely obstacles include concerns about the ethics of sending health professionals sham patients, the technical challenges of the subterfuge, and concerns about the relatively small sample sizes and substantial costs involved. However, the high frequency of significant and remediable performance deficits unmasked by USPs, and the potential to adapt registration and record keeping systems to accommodate their visits, suggest that their selective and purposeful deployment could be a cost effective and powerful strategy for addressing a gap in performance measurement.

In vivo polymerization of poly(3,4-ethylenedioxythiophene) in the living rat hippocampus does not cause a significant loss of performance in a delayed alternation task

After extended implantation times, traditional intracortical neural probes exhibit a foreign-body reaction characterized by a reactive glial sheath that has been associated with increased system impedance and signal deterioration. Previously, we have proposed that the local in vivo polymerization of an electronically and ionically conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), might help to rebuild charge transport pathways across the glial scar between the device and surrounding parenchyma (Richardson-Burns et al 2007 J. Neural Eng. 4 L6–13). The EDOT monomer can be delivered via a microcannula/electrode system into the brain tissue of living animals followed by direct electrochemical polymerization, using the electrode itself as a source of oxidative current. In this study, we investigated the long-term effect of local in vivo PEDOT deposition on hippocampal neural function and histology. Rodent subjects were trained on a hippocampus-dependent task, delayed alternation (DA), and implanted with the microcannula/electrode system in the hippocampus. The animals were divided into four groups with different delay times between the initial surgery and the electrochemical polymerization: (1) control (no polymerization), (2) immediate (polymerization within 5 min of device implantation), (3) early (polymerization within 3–4 weeks after implantation) and (4) late (polymerization 7–8 weeks after polymerization). System impedance at 1 kHz was recorded and the tissue reactions were evaluated by immunohistochemistry. We found that under our deposition conditions, PEDOT typically grew at the tip of the electrode, forming an ∼500 µm cloud in the tissue. This is much larger than the typical width of the glial scar (∼150 µm). After polymerization, the impedance amplitude near the neurologically important frequency of 1 kHz dropped for all the groups; however, there was a time window of 3–4 weeks for an optimal decrease in impedance. For all surgery–polymerization time intervals, the polymerization did not cause significant deficits in performance of the DA task, suggesting that hippocampal function was not impaired by PEDOT deposition. However, GFAP+ and ED-1+ cells were also found at the deposition two weeks after the polymerization, suggesting potential secondary scarring. Therefore, less extensive deposition or milder deposition conditions may be desirable to minimize this scarring while maintaining decreased system impedance.

The contribution of medial prefrontal cortical regions to conditioned inhibition.

Few studies have considered the process by which individuals learn to omit a response, which is an essential aspect of adaptive behavior. Several lines of evidence indicate that two regions of the medial prefrontal cortex have disparate roles in behavioral flexibility. In particular, the prelimbic cortex (PL) is thought to facilitate the generation of a strategy to inhibit a prepotent response, whereas the infralimbic cortex (IL) appears to be more important for maintaining extensively trained inhibitory behaviors. The present experiments were designed to elucidate the contributions of PL and IL to the acquisition and maintenance of Pavlovian conditioned inhibition. In Experiment 1, damage to PL before training in a compound feature negative discrimination task impaired inhibitory learning. By comparison, lesions of IL had little effect. In Experiment 2, lesions of PL or IL occurred after overtraining, and damage to IL significantly impaired subsequent performance in the task, suggesting that this region is involved in the continued expression of Pavlovian conditioned inhibition after thorough training. PL may also be involved in maintaining inhibition, as evidenced by a marginally significant lesion-induced performance deficit. These data support the notion that PL and IL have distinguishable roles in modulating inhibition, while contributing important information about the specific role for PL in acquisition of an inhibitory response and IL in performance.

Inhibition, Executive Function, and Freezing of Gait

Studies suggest that freezing of gait (FoG) in people with Parkinson's disease (PD) is associated with declines in executive function (EF). However, EF is multi-faceted, including three dissociable components: inhibiting prepotent responses, switching between task sets, and updating working memory. This study investigated which aspect of EF is most strongly associated with FoG in PD. Three groups were studied: adults with PD (with and without FoG) and age-matched, healthy adults. All participants completed a battery of cognitive tasks previously shown to discriminate among the three EF components. Participants also completed a turning-in-place task that was scored for FoG by neurologists blind to subjects' self-reported FoG. Compared to both other groups, participants with FoG showed significant performance deficits in tasks associated with inhibitory control, even after accounting for differences in disease severity, but no significant deficits in task-switching or updating working memory. Surprisingly, the strongest effect was an intermittent tendency of participants with FoG to hesitate, and thus miss the response window, on go trials in the Go-Nogo task. The FoG group also made slower responses in the conflict condition of the Stroop task. Physician-rated FoG scores were correlated both with failures to respond on go trials and with failures to inhibit responses on nogo trials in the Go-Nogo task. These results suggest that FoG is associated with a specific inability to appropriately engage and release inhibition, rather than with a general executive deficit.

Fatigue Assessment: Subjective Peer-to-Peer Fatigue Scoring

Fatigue is a complex entity with contributing factors that may include insufficient sleep, circadian dysrhythmia, high workload, extended duty periods, clinical sleep pathology, psychosocial aspects, environmental factors, and many others. It can contribute to significant performance deficits and crucial safety lapses. Despite maximal implementation of accepted techniques and best practices for mitigation strategies, the deployed military rotary-wing (RW) environment must still contend with substantial fatigue-related issues among aircrew. We introduce a novel subjective peer-to-peer fatigue rating system recently demonstrated in a deployed military RW environment. Each pilot provides an anonymous weekly fatigue rating for every other pilot in the unit exclusive of self. Median and variance of the peer ratings for each pilot are recorded by the safety officer and tracked over time. The program allows for a multidimensional external perspective on a pilot's fatigue state, relative function, and degree of coping. Scoring is predicated upon the recognition of a significant deviation from a peer's baseline that may include social and interpersonal interactions or the observation of deficits in duty performance. The research basis for scientific validity and reliability regarding current peer fatigue scoring systems is exiguous. This novel approach may be of merit, particularly among military aircrew in a deployed-type setting with sustained high workload, operational stress, and limited time for supernumerary tasks. An anonymous subjective peer-to-peer fatigue scoring system is worthy of further scientific investigation, particularly warranting studies of reliability and validity.

Cognitive function in children with brain tumors in the first year after diagnosis compared to healthy matched controls

Improved survival of children with brain tumors (BTs) has increased focus on ameliorating morbidity. To reduce the risk of progressive cognitive decline, remedial strategies need to be instituted early, based upon accurate appraisal of need, yet few studies have investigated cognition in BT children early post-diagnosis. The study aims were to investigate cognition in children with primary BTs 1, 6, and 12 months post-diagnosis compared with healthy children, exploring the impact of disease and treatment variables. Forty-eight children aged 2-16 years with primary BTs, referred to a Regional Neurosurgical Unit over the 2-year study period were eligible for enrollment. The "best friends" model was used to recruit matched controls. Cognition was assessed using age-appropriate Wechsler Intelligence scales; Children's Memory Scale; Test of Everyday Attention for Children, and Wechsler Quicktest. Patients with BTs had significantly reduced performance compared to controls early post-diagnosis in tests of Performance IQ, processing speed, verbal and visual memory, and selective attention. Improved performance over 12 months was seen in patients with BTs although also, for some measures, in controls. Significant deficits in cognitive performance were seen one year post-diagnosis for Verbal IQ; processing speed, visual and verbal immediate memory, and selective attention. Infratentorial site, high tumor grade, hydrocephalus, radiotherapy, and chemotherapy were associated with poorer functioning. Early cognitive impairment is present in BT children, sometimes prior to radiotherapy/chemotherapy treatment, and is associated with hydrocephalus, high tumor grade and infratentorial site. Future studies should investigate the role of early rehabilitation in improving cognition.

The Role of Clinical and Instrumented Outcome Measures in Balance Control of Individuals with Multiple Sclerosis

Purpose. The aim of the study was to investigate differences in balance control between individuals with multiple sclerosis (MS) and healthy control subjects using clinical scales and instrumented measures of balance and determine relationships between balance measures, fatigue, and disability levels in individuals with MS with and without a history of falls. Method. Twelve individuals with MS and twelve healthy controls were evaluated using the Berg Balance and Activities-specific Balance Confidence Scales, Modified Clinical Test of Sensory Interaction on Balance, and Limits of Stability Tests as well as Fatigue Severity Scale and Barthel Index. Results. Mildly affected individuals with MS had significant balance performance deficits and poor balance confidence levels (P < 0.05). MS group had higher sway velocities and diminished stability limits (P < 0.05), significant sensory impairments, high fatigue and disability levels (P < 0.05). Sway velocity was a significant predictor of balance performance and the ability to move towards stability limits for the MS group. For the MS-fallers group, those with lower disability levels had faster movement velocities and better balance performance. Conclusion. Implementation of both clinical and instrumented tests of balance is important for the planning and evaluation of treatment outcomes in balance rehabilitation of people with MS.

Mice Null for Calsequestrin 1 Exhibit Deficits in Functional Performance and Sarcoplasmic Reticulum Calcium Handling

In skeletal muscle, the release of calcium (Ca2+) by ryanodine sensitive sarcoplasmic reticulum (SR) Ca2+ release channels (i.e., ryanodine receptors; RyR1s) is the primary determinant of contractile filament activation. Much attention has been focused on calsequestrin (CASQ1) and its role in SR Ca2+ buffering as well as its potential for modulating RyR1, the L-type Ca2+ channel (dihydropyridine receptor, DHPR) and other sarcolemmal channels through sensing luminal [Ca2+]. The genetic ablation of CASQ1 expression results in significant alterations in SR Ca2+ content and SR Ca2+ release especially during prolonged activation. While these findings predict a significant loss-of-function phenotype in vivo, little information on functional status of CASQ1 null mice is available. We examined fast muscle in vivo and in vitro and identified significant deficits in functional performance that indicate an inability to sustain contractile activation. In single CASQ1 null skeletal myofibers we demonstrate a decrease in voltage dependent RyR Ca2+ release with single action potentials and a collapse of the Ca2+ release with repetitive trains. Under voltage clamp, SR Ca2+ release flux and total SR Ca2+ release are significantly reduced in CASQ1 null myofibers. The decrease in peak Ca2+ release flux appears to be solely due to elimination of the slowly decaying component of SR Ca2+ release, whereas the rapidly decaying component of SR Ca2+ release is not altered in either amplitude or time course in CASQ1 null fibers. Finally, intra-SR [Ca2+] during ligand and voltage activation of RyR1 revealed a significant decrease in the SR[Ca2+]free in intact CASQ1 null fibers and a increase in the release and uptake kinetics consistent with a depletion of intra-SR Ca2+ buffering capacity. Taken together we have revealed that the genetic ablation of CASQ1 expression results in significant functional deficits consistent with a decrease in the slowly decaying component of SR Ca2+ release.