Memory encoding and retrieval in the aging brain.

Decline in episodic memory, the encoding and retrieval of autobiographical events, is a hallmark of normal cognitive aging. Although the primary causes of this decline remain elusive, event-related brain potential (ERP) studies have contributed to an understanding of age-related episodic memory failure. These data reveal that, although the retrieval-based episodic memory (EM) effect does not differ dramatically between young and older adults, the acquisition-related data suggest a decline in episodic encoding (i.e., semantic elaboration) with increasing age. We conclude that, at the current state of knowledge, encoding deficiencies are more important than retrieval deficits in understanding the causes of episodic memory decline in the older adult.     

CD45 Isoform Expression in Autoimmune Myasthenia Gravis

In myasthenia gravis (MG), humoral and cellular immune mechanisms are involved in the autoimmune pathogenesis. In this study, we investigated the role of the CD45 molecule in MG, having recently reported an association in multiple sclerosis. CD45, a protein-tyrosine phophatase receptor type C (PTPRC), is essential for both thymic selection and peripheral activation of T and B cells. Our aims were to determine (a) the prevalence of a functional mutation in the CD45 gene (exon 4 77C &#77 G; prevalence analysis), and (b) the distribution of memory (CD45RO+) and naïve (CD45RA+) T cells in the peripheral blood (subset analysis). T cells from 78 patients with generalised MG were stained with monoclonal antibodies against CD45RO, CD45RA, CD4 and CD8 and quantified by four-colour flow cytometry. The control panel for the prevalence analysis (a) consisted of 303 healthy individuals. (b) From those, 67 age- and sex-matched probands were randomly selected as controls for the subset analysis. Patients were stratified according to their MG onset age, thymic pathology and immunosuppressive treatment. Statistical analysis was performed by Fisher's exact test, asymptotic &#104 2 test, the two-sided Mann-Whitney test and Spearman's correlation coefficient. As a result, the 77C &#77 G mutation in exon 4 of the CD45 gene was found in 1 of 78 patients versus none of the 303 controls. Thus, no association was detected with this single nucleotide polymorphism in MG patients overall. Surprisingly, however, ratios of CD45RO+ to CD45RA+ T cells were lower among CD8+ T cells from patients with late-onset MG ( P =0.023). Thymoma patients also showed a similar trend among CD4+ and CD8+ T-cells, as expected. These differences were not related to immunosuppressive drug treatment or thymectomy (in the 67 informative patients). Since there is no other evidence for increased thymopoiesis in late-onset MG, we propose an altered subset balance in the circulation.     

Modified Response Elaboration Training: A systematic extension with replications

Background: Response Elaboration Training (RET; Kearns, 1985 Kearns, K. P. 1985. “Response elaboration training for patient initiated utterances”. In Clinical aphasiology, Edited by: Brookshire, R. H. 196–204. Minneapolis, MN: BRK.  [Google Scholar]) has been found to consistently result in increased production of content in discourse with persons with aphasia. Positive treatment effects have been reported for persons representing a variety of aphasia types and severities. RET was modified for application with persons with acquired apraxia of speech and aphasia and positive outcomes were also associated with the modified treatment (Wambaugh & Martinez, 2000 Wambaugh, J. L. and Martinez, A. L. 2000. Effects of rate and rhythm control treatment on consonant production accuracy in apraxia of speech. Aphasiology, 14: 851–871. [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). Although RET has received systematic study, its stimulus generalisation effects are not well understood.

Aims: This investigation was designed to measure the stimulus generalisation effects of modified RET (M-RET) in a variety of conditions as well as to further study the effects of M-RET applied to a personal recount condition.

Methods & Procedures: Multiple baseline designs (across behaviours and participants) were utilised to examine treatment effects. Treatment was applied sequentially to picture sets and a personal recount condition with six persons with chronic aphasia. Production of correct information units (CIUs) was measured in the following conditions: (1) discourse production in response to sets of trained and untrained pictures, (2) home conversations, and (3) production of discourse in structured tasks. Formal measures of functional communication were also completed prior to and following treatment.

Outcomes & Results: Increases in production of CIUs in response to pictures were observed for 11 of the 12 applications of M-RET to picture sets. Response generalisation to untrained picture sets was associated with M-RET applied to pictures sets; increases were slight and were greater for untrained sets that were probed more frequently. Maintenance of gains was generally strong for the participants with nonfluent aphasia, but was minimal for the participant with fluent aphasia. Gains were not evident for M-RET applied to personal recounts; only one participant evidenced changes possibly associated with treatment in the personal recount condition. Improvements in structured discourse samples and a functional communication measure were observed for the majority of the participants following treatment. Lack of compliance in completion of recordings of home conversations limited the utility of that measure.

Conclusions: M-RET applied to pictures resulted in improvements in production of content in treated and untreated picture conditions for the majority of the participants. Treatment effects extended to additional outcome measures. Although some positive changes were observed for the participant with fluent aphasia, maintenance was problematic. Application of M-RET to a personal recount condition was not associated with improved performance for most of the participants.     

Clonal accumulation of activated CD8+ T cells in the central nervous system during the early phase of neuroborreliosis

Borrelia burgdorferi may cause an acute infection of the central nervous system (CNS) that rarely leads to chronic disease. To characterize host immunity to B. burgdorferi in humans, we performed serial T cell receptor (TCR) variable beta (TCRBV) chain analyses in blood and cerebrospinal fluid (CSF) samples from 10 patients with acute neuroborreliosis. In most patients, we found significant differences in TCRBV expression between CSF and peripheral blood T cells, predominantly involving CD8(+) T cells. T cells that accumulated in the CSF had a memory phenotype and expressed high levels of C-C chemokine receptor 5 and CD69. Serial studies demonstrated that CD8(+) T cell accumulation decreased continuously after resolution of the infection. In 2 patients, serial analysis of the TCR-alpha and -beta chain sequences revealed that overexpression of TCRBV in CSF was caused by extensive clonal expansion of CD8(+) T cells. Our findings support the role of CD8(+) T cells during the early host defense against spirochete infection of the CNS.     

Is resting anterior EEG alpha asymmetry a trait marker for depression? Findings for healthy adults and clinically depressed patients

Several lines of evidence suggest that asymmetric anterior brain activation is related to affective style, linking left hemisphere activation to positive affect and right hemisphere activation to negative affect. However, previous reports of left frontal hypoactivation in depressed patients were not confirmed in recent studies. This study evaluated additional characteristics of resting EEG alpha (8-13 Hz) asymmetry in 15 clinically depressed patients and 22 healthy adults by recording EEG activity on two separate occasions, 2-4 weeks apart. Across both sessions, group differences in anterior EEG asymmetry were compatible with the original hypothesis. However, groups differed in temporal stability of anterior EEG asymmetry, which was retest reliable in controls but not depressed patients. In contrast, temporal stability of posterior EEG asymmetry was acceptable in both groups. Increased variability of anterior EEG asymmetry may be a characteristic feature for depression, and, if so, this would challenge the notion that anterior EEG alpha asymmetry is a trait marker for depression.