Understanding, Assessing and Treating Prospective Memory Dysfunctions in Traumatic Brain Injury Patients

Our capacity to shape and direct our future behaviour is of fundamental importance in the development, pursuit, and maintenance of independence and autonomy from early childhood to late adulthood. A cognitive ability required for those functions is prospective memory (PM), which is the ability to form and remember to prospectively perform the intended action. Researchers have extensively focused on PM impairment in patients with traumatic brain injury (TBI). However, there has been limited research into the assessment and treatment of PM impairment in TBI patients. Reliable and valid tests with normative data are necessary for health professionals working with people with PM impairments. This chapter reviews the principal findings on PM impairment in TBI patients, and the main procedures used to assess and rehabilitate PM

Cognitive flexibility in verbal and nonverbal domains and decision making in anorexia nervosa patients: a pilot study

<p>Abstract</p> <p>Background</p> <p>This paper aimed to investigate cognitive rigidity and decision making impairments in patients diagnosed with Anorexia Nervosa Restrictive type (AN-R), assessing also verbal components.</p> <p>Methods</p> <p>Thirty patients with AN-R were compared with thirty age-matched healthy controls (HC). All participants completed a comprehensive neuropsychological battery comprised of the Trail Making Test, Wisconsin Card Sorting Test, Hayling Sentence Completion Task, and the Iowa Gambling Task. The Beck Depression Inventory was administered to evaluate depressive symptomatology. The influence of both illness duration and neuropsychological variables was considered. Body Mass Index (BMI), years of education, and depression severity were considered as covariates in statistical analyses.</p> <p>Results</p> <p>The AN-R group showed poorer performance on all neuropsychological tests. There was a positive correlation between illness duration and the Hayling Sentence Completion Task Net score, and number of completion answers in part B. There was a partial effect of years of education and BMI on neuropsychological test performance. Response inhibition processes and verbal fluency impairment were not associated with BMI and years of education, but were associated with depression severity.</p> <p>Conclusions</p> <p>These data provide evidence that patients with AN-R have cognitive rigidity in both verbal and non-verbal domains. The role of the impairment on verbal domains should be considered in treatment. Further research is warranted to better understand the relationship between illness state and cognitive rigidity and impaired decision-making.</p

Neurocognitive Effects of Repetitive Transcranial Magnetic Stimulation in Adolescents with Major Depressive Disorder

Objectives: It is estimated that 30–40% of adolescents with major depressive disorder (MDD) do not receive full benefit from current antidepressant therapies. Repetitive transcranial magnetic stimulation (rTMS) is a novel therapy approved by the US Food and Drug Administration to treat adults with MDD. Research suggests rTMS is not associated with adverse neurocognitive effects in adult populations; however, there is no documentation of its neurocognitive effects in adolescents. This is a secondary post hoc analysis of neurocognitive outcome in adolescents who were treated with open-label rTMS in two separate studies. Methods: Eighteen patients (mean age, 16.2 ± 1.1 years; 11 females, 7 males) with MDD who failed to adequately respond to at least one antidepressant agent were enrolled in the study. Fourteen patients completed all 30 rTMS treatments (5 days/week, 120% of motor threshold, 10 Hz, 3,000 stimulations per session) applied to the left dorsolateral prefrontal cortex. Depression was rated using the Children’s Depression Rating Scale-Revised. Neurocognitive evaluation was performed at baseline and after completion of 30 rTMS treatments with the Children’s Auditory Verbal Learning Test (CAVLT) and Delis–Kaplan Executive Function System Trail Making Test. Results: Over the course of 30 rTMS treatments, adolescents showed a substantial decrease in depression severity. Commensurate with improvement in depressive symptoms was a statistically significant improvement in memory and delayed verbal recall. Other learning and memory indices and executive function remained intact. Neither participants nor their family members reported clinically meaningful changes in neurocognitive function. Conclusion: These preliminary findings suggest rTMS does not adversely impact neurocognitive functioning in adolescents and may provide subtle enhancement of verbal memory as measured by the CAVLT. Further controlled investigations with larger sample sizes and rigorous trial designs are warranted to confirm and extend these findings

Anterior cingulate gamma-aminobutyric acid concentrations and electroconvulsive therapy

Objective The anticonvulsant hypothesis posits that ECT’s mechanism of action is related to enhancement of endogenous anticonvulsant brain mechanisms. Results of prior studies investigating the role of the inhibitory neurotransmitter gamma‐aminobutyric acid (“GABA+”, GABA and coedited macromolecules) in the pathophysiology and treatment of depression remain inconclusive. The aim of our study was to investigate treatment‐responsive changes of GABA+ in subjects with a depressive episode receiving electroconvulsive therapy (ECT). Methods In total, 41 depressed subjects (DEP) and 35 healthy controls (HC) were recruited at two independent sites in Norway and the USA. MEGA‐PRESS was used for investigation of GABA+ in the anterior cingulate cortex. We assessed longitudinal and cross‐sectional differences between DEP and HC, as well as the relationship between GABA+ change and change in depression severity and number of ECTs. We also assessed longitudinal differences in cognitive performance and GABA+ levels. Results Depressive episode did not show a difference in GABA+ relative to HC (t71 = −0.36, p = .72) or in longitudinal analysis (t36 = 0.97, p = .34). Remitters and nonremitters did not show longitudinal (t36 = 1.12, p = .27) or cross‐sectional differences in GABA+. GABA+ levels were not related to changes in antidepressant response (t35 = 1.12, p = .27) or treatment number (t36 = 0.05, p = .96). An association between cognitive performance and GABA+ levels was found in DEP that completed cognitive effortful testing (t18 = 2.4, p = .03). Conclusion Our results failed to support GABA as a marker for depression and abnormal mood state and provide no support for the anticonvulsant hypothesis of ECT. ECT‐induced change in GABA concentrations may be related to change in cognitive function.publishedVersio

Transposon activation mutagenesis as a screening tool for identifying resistance to cancer therapeutics

Background: The development of resistance to chemotherapies represents a significant barrier to successful cancer treatment. Resistance mechanisms are complex, can involve diverse and often unexpected cellular processes, and can vary with both the underlying genetic lesion and the origin or type of tumor. For these reasons developing experimental strategies that could be used to understand, identify and predict mechanisms of resistance in different malignant cells would be a major advance. Methods: Here we describe a gain-of-function forward genetic approach for identifying mechanisms of resistance. This approach uses a modified piggyBac transposon to generate libraries of mutagenized cells, each containing transposon insertions that randomly activate nearby gene expression. Genes of interest are identified using next-gen high-throughput sequencing and barcode multiplexing is used to reduce experimental cost. Results: Using this approach we successfully identify genes involved in paclitaxel resistance in a variety of cancer cell lines, including the multidrug transporter ABCB1, a previously identified major paclitaxel resistance gene. Analysis of co-occurring transposons integration sites in single cell clone allows for the identification of genes that might act cooperatively to produce drug resistance a level of information not accessible using RNAi or ORF expression screening approaches. Conclusion: We have developed a powerful pipeline to systematically discover drug resistance in mammalian cells in vitro. This cost-effective approach can be readily applied to different cell lines, to identify canonical or context specific resistance mechanisms. Its ability to probe complex genetic context and non-coding genomic elements as well as cooperative resistance events makes it a good complement to RNAi or ORF expression based screens

Different methods for reproducing time, different results

One of the most widely used tasks for investigating psychological time, time reproduction, requires from participants the reproduction of the duration of a previously presented stimulus. Although prior studies have investigated the effects of different cognitive processes on time reproduction performance, no studies have looked into the effects of different reproduction methods on these performances. In the present study, participants were randomly assigned to one of three reproduction methods, which included (a) just pressing at the end of the interval, (b) pressing to start and stop the interval, and (c) maintaining continuous pressing during the interval. The study revealed that the three reproduction methods were not equivalent, with the method involving keypresses to start and stop the reproduction showing the highest accuracy, and the method of continuous press generating less variability

Different methods for reproducing time, different results

One of the most widely used tasks for investigating psychological time, time reproduction, requires from participants the reproduction of the duration of a previously presented stimulus. Although prior studies have investigated the effects of different cognitive processes on time reproduction performance, no studies have looked into the effects of different reproduction methods on these performances. In the present study, participants were randomly assigned to one of three reproduction methods, which included (a) just pressing at the end of the interval, (b) pressing to start and stop the interval, and (c) maintaining continuous pressing during the interval. The study revealed that the three reproduction methods were not equivalent, with the method involving keypresses to start and stop the reproduction showing the highest accuracy, and the method of continuous press generating less variability. -- Keywords : Time perception . Time reproduction . Method comparison . Motor response