White matter tract injury and cognitive impairment in human immunodeficiency virus–infected individuals

Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4 = 529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.

Detecting consciousness in a total locked-in syndrome: An active event-related paradigm

Total locked-in syndrome is characterized by tetraplegia, anarthria and paralysis of eye motility. In this study, consciousness was detected in a 21-year-old woman who presented a total locked-in syndrome after a basilar artery thrombosis (49 days post-injury) using an active event-related paradigm. The patient was presented sequences of names containing the patient's own name and other names. The patient was instructed to count her own name or to count another target name. Similar to 4 age- and gender-matched healthy controls, the P3 response recorded for the voluntarily counted own name was larger than while passively listening. This P3 response was observed 14 days before the first behavioral signs of consciousness. This study shows that our active event-related paradigm allowed to identify voluntary brain activity in a patient who would behaviorally be diagnosed as comatose.

Contemporary Food Matters?: A Review Essay

Animal, Vegetable, Miracle: A Year of Food Life Barbara Kingsolver (with Steven L. Hopp & Camille Kingsolver) New York, Harper Perennial, 2007. 370 pp., £4.99 (pbk), ISBN 9780060852559 Stuffed and ...

Youth sport volunteering: developing social capital?

Identifying mild cognitive impairment at baseline in the Ginkgo Evaluation of Memory (GEM) study

To identify, characterize and compare the frequency of mild cognitive impairment (MCI) subtypes at baseline in a large, late-life cohort (n = 3063) recruited into a dementia prevention trial.

Motor Speech Disorders

Acquired dysarthria in conversation: Identifying sources of understandability problems

Background : Acquired progressive dysarthria is traditionally assessed, rated, and researched using measures of speech perception and intelligibility. The focus is commonly on the individual with dysarthria and how speech deviates from a normative range. A complementary approach is to consider the features and consequences of dysarthric speech as it is produced as a turn‐at‐talk in everyday interaction and in particular the ways in which this talk may be identified by its recipient as problematic to understand. Aims : To investigate how dysarthric turns‐at‐talk in everyday conversation may be problematic to understand. Further, to describe how recipients of dysarthric talk identify the source of problematic understandings to the dysarthric speaker. Methods & Procedures : Video data of natural conversation from two dyads were selected for this paper. The dyads were video‐recorded at home, at 3‐monthly intervals, over a maximum period of 18 months. Using the methods of conversation analysis a collection of sequences was identified and transcribed. The sequences were analysed with reference to how the recipients of dysarthric talk, through the use of other‐initiations of repair, identified some element of that talk as problematic. Outcomes & Results : This work shows how a recipient of a dysarthric talk turn in everyday conversation goes about displaying the problematicity of that turn to its speaker. Whilst displaying that a problem exists with a prior turn, the recipient may have difficulty in knowing what that problem actually is. Conclusions & Implications : It is proposed that clinicians and researchers should consider the effects of dysarthric speech in interaction. Specifically, the nature of dysarthric troubles and the practices used to signal understanding problems as they occur in everyday interaction should be fully explored. This consideration may have relevance for clinical assessment and intervention.

Genetic diversity in Blastomyces dermatitidis: implications for PCR detection in clinical and environmental samples

Blastomycosis is a serious and potentially fatal infection caused by the thermally dimorphic fungus Blastomyces dermatitidis. Polymerase chain reaction (PCR) assays targeting the BAD-1 virulence gene promoter have been developed to aid in the detection of the pathogen in clinical and environmental samples. However, little is known regarding the genetic diversity of B. dermatitidis and how this might affect the performance characteristics of these assays. We explored the genetic relatedness of 106 clinical and environmental isolates of B. dermatitidis using a previously described rDNA PCR restriction fragment length polymorphism (RFLP) assay. In addition, we looked for polymorphisms in the promoter region upstream of BAD-1. RFLP analysis showed that all isolates fell into one of five genotypic groups, designated A through E. Genotypic groups A and B predominated, comprising 50/106 (47.2%) and 51/106 (48.1%) of isolates, respectively. Three of 106 (2.8%) isolates were genotype C. Genotypes D and E represented novel genotypes and were each associated with single clinical isolates. PCR of the BAD-1 promoter revealed significant size differences among amplification products. Fifty-one of 106 isolates (50/50 RFLP genotypic group A and 1/51 genotypic group B) had amplicons of 663-bp, nearly twice the size of the expected product. Sequence analysis of amplification products from 17 representative isolates revealed four haplotypes and showed that the size disparity was due to two large insertions. Because these insertions were present in a high percentage of isolates, the utility of the PCR assays for diagnostic purposes could be affected. However, the novel RFLP genotypes and multiple BAD-1 haplotypes may prove useful as markers in population genetic studies.

The semantic relatedness of cue–intention pairings influences event-based prospective memory failures in older adults with HIV infection

HIV infection and aging are each independently associated with prospective memory (ProM) impairment, which increases the risk of poor functional outcomes, including medication non-adherence. The incidence and prevalence of HIV infection among older adults has increased in recent years, thereby raising questions about the combined effects of these risk factors on ProM. In the present study, 118 participants were classified into four groups on the basis of HIV serostatus and age (i.e., <or=40 years and >or=50 years). Results showed significant additive effects of HIV and aging on event-based ProM, with the greatest deficits evident in the older HIV+ group, even after controlling for other demographic factors and potential medical and psychiatric confounds. Event-based ProM impairment was particularly apparent in the older HIV+ group on trials for which the retrieval cue and intention were not semantically related. Worse performance on the semantically unrelated cue-intention trials was associated with executive dysfunction, older age, and histories of immunocompromise in the older HIV+ cohort. These data suggest that older HIV-infected adults are significantly less proficient at engaging the strategic encoding and retrieval processes required to a execute a future intention when the cue is unrelated to the intended action, perhaps secondary to greater neuropathological burden in the prefrontostriatal systems critical to optimal ProM functioning.

HIV-associated deficits in action (verb) generation may reflect astrocytosis

Commensurate with the hypothesized neural dissociation between verb and noun generation, research in HIV infection shows that, relative to noun fluency, action (verb) fluency is disproportionately impaired, more strongly related to executive dysfunction, and more sensitive to declines in everyday functioning. However, whether the neurobiological correlates of HIV-associated deficits in verb and noun generation are separable have not heretofore been investigated. The present study examined the biomarker correlates of action and noun fluency in 74 participants with HIV infection. Biomarkers of viral burden, neuroaxonal damage, macrophage activation, neuroprotection, inflammation, and astrocytosis were measured in plasma and cerebrospinal fluid (CSF). Deficits in action, but not noun generation, were significantly associated with higher CSF levels of S100beta, a marker of astrocyte activation, even after controlling for antiretroviral therapy, current immune compromise, and general cognitive impairment. Concurrent validity for the frontal systems hypothesis of verb generation was provided by post hoc analyses demonstrating that S100beta was also associated with measures of executive functions, but not semantic memory or psychomotor speed. Overall, these findings suggest that HIV-associated impairment in action fluency, and executive dysfunction more generally, may reflect astrocytosis (i.e., elevated S100beta). Complementing the literature in HIV and other clinical populations with frontal systems involvement, these data also support the possible neurobiological dissociation of noun and verb generation.