Approximately one quarter of 1991 Persian Gulf War Veterans experience cognitive and physiological sequelae that continue to be unexplained by known medical or psychological conditions. Difficulty coming up with words and names, familiar before the war, is a hallmark of the illness. Three Gulf War Syndrome subtypes have been identified and linked to specific war-time chemical exposures. The most functionally impaired veterans belong to the Gulf War Syndrome 2 (Syndrome 2) group, for which subcortical damage due to toxic nerve gas exposure is the suspected cause. Subcortical damage is often associated with specific complex language impairments, and Syndrome 2 veterans have demonstrated poorer vocabulary relative to controls. 11 Syndrome 1, 16 Syndrome 2, 9 Syndrome 3, and 14 age-matched veteran controls from the Seabees Naval Construction Battalion were compared across three measures of complex language. Additionally, functional magnetic resonance imaging (fMRI) was collected during a covert category generation task, and whole-brain functional activity was compared between groups. Results demonstrated that Syndrome 2 veterans performed significantly worse on letter and category fluency relative to Syndrome 1 veterans and controls. They also exhibited reduced activity in the thalamus, putamen, and amygdala, and increased activity in the right hippocampus relative to controls. Syndrome 1 and Syndrome 3 groups tended to show similar, although smaller, differences than the Syndrome 2 group. Hence, these results further demonstrate specific impairments in complex language as well as subcortical and hippocampal involvement in Syndrome 2 veterans. Further research is required to determine the extent of language impairments in this population and the significance of altered neurologic activity in the aforementioned brain regions with the purpose of better characterizing the Gulf War Syndromes.

Although the cortical substrates of verbal working memory are reasonably well understood, less is known about the relative contribution of subcortical structures to verbal working memory. Therefore, in addition to elaboration of a model of verbal working memory by including a specific focus on basal ganglia, the purpose of this study also was to examine potential differences in neural function across the complete process of verbal working memory, from encoding through retrieval. Functional magnetic resonance imaging was used to observe regions of brain activation in neurologically normal participants during a task of verbal working memory. The expected frontal-parietal network was found to be active over the course of the verbal working memory task. The encoding portion of the task engaged left inferior frontal regions and bilateral caudate and thalamus. Bilateral medial thalamus and posterior cingulate regions were engaged during the maintenance phase of the task. Retrieval activated the left inferior frontal sulcus and posterior parietal/occipital regions. Findings are considered in light of current models of verbal working memory and subcortical structures.

Background: People who report mild anomia following stroke often score near or within normal limits on traditional assessments of language. Based on evidence of cognitive influences on linguistic production in people with aphasia, this study examined non-linguistic, cognitive function and its potential influence on word retrieval in individuals with mild anomia. Aims: This study explored the following research questions: Do people with mild anomia have impaired performance on tasks which require (a) automatic vs controlled processing and/or (b) selective attention relative to neurologically typical controls? Methods Procedures: A total of 14 participants with mild anomia and 9 neurologically typical controls were tested using Covert Orienting of Visuospatial Attention Test (COVAT), alone and with linguistic interference, at two interstimulus intervals (ISI) representing automatic and controlled processing. Outcomes Results: Participants with anomia showed significantly slower responses on COVAT alone at 100 ms ISI (automatic processing) compared with controls. The groups did not differ significantly during COVAT alone at 800 ms ISI (controlled processing). Additionally, similar priming patterns were exhibited by both groups on COVAT alone during both interstimulus intervals, indicating an intact validity effect. However, participants with anomia demonstrated significantly delayed response times during the COVAT with linguistic interference, regardless of ISI. Conclusions: Overall, participants with mild anomia demonstrated impairments most notably when interfering stimuli were present, indicating deficits in automatic processing and selective attention. Study results support clinical evaluation of non-linguistic cognitive abilities in individuals reporting anomia who score near or within normal limits on language assessments.

Objective: The purpose of this control study was to assess how visual information interacts with the cognitive processes involved in naming. The impact of subtle alterations in the visual-perceptual integrity of target stimuli on naming was investigated. Methods: Stimuli consisted of 150 black and white line drawings of everyday objects (75 living & 75 non-living). Manipulations of contrast and spatial frequency were made independently during one of two experimental sessions. Session A investigated the effects of 5 levels of contrast (i.e., 1.25%, 2.5%, 5%, 10%, and 20%) on naming. Session B investigated the effects of 6 spatial frequency bandpass filters (i.e., 0.25–0.5; 0.5–01; 1–2; 2–4; 4–8; 8–16 c/deg) on naming. Two neurologically normal adults participated in Session A, two neurologically normal adults participated in Session B, and one neurologically normal adult participated in both (age range = 35–60 years). Results: Significant differences were found between level 1 and levels 3-6 of spatial frequency for latency to name, and differences were found between the lowest two levels and all subsequent levels for accuracy to name. For contrast, there were significant differences between 1.25% contrast and the higher levels (10% & 20%, latency data; 5% & 20%, accuracy data). Discussion: The long-term trajectory of this study is to develop an object naming test for the detection of incipient Alzheimer's disease. In order to achieve this goal, it is important to understand what elements of visual processing are most important in naming in general. This study investigated the influence of spatial frequency and contrast on naming in normal subjects. These pilot data suggest that there is no statistically significant improvement in accuracy and latency to name obtained above and beyond 1–2 c/deg of spatial frequency. The results for the contrast sessions were more ambiguous, and additional data is needed in order to make any conclusions.

BACKGROUND:Mild cognitive impairment (MCI) is often a precursor to Alzheimer disease. Little research has examined the efficacy of cognitive rehabilitation in patients with MCI, and the relevant neural mechanisms have not been explored. The authors previously showed the behavioral efficacy of cognitive rehabilitation using mnemonic strategies for face-name associations in patients with MCI. Here, the authors used functional magnetic resonance imaging (fMRI) to test whether there were training-specific changes in activation and connectivity within memory-related areas. METHODS:A total of 6 patients with amnestic, multidomain MCI underwent pretraining and posttraining fMRI scans, during which they encoded 90 novel face-name pairs and completed a 4-choice recognition memory test immediately after scanning. Patients were taught mnemonic strategies for half the face-name pairs during 3 intervening training sessions. RESULTS:Training-specific effects comprised significantly increased activation within a widespread cerebral cortical network involving medial frontal, parietal, and occipital regions; the left frontal operculum and angular gyrus; and regions in the left lateral temporal cortex. Increased activation common to trained and untrained stimuli was found in a separate network involving inferior frontal, lateral parietal, and occipital cortical regions. Effective connectivity analysis using multivariate, correlation-purged Granger causality analysis revealed generally increased connectivity after training, particularly involving the middle temporal gyrus and foci in the occipital cortex and the precuneus. CONCLUSION:The authors' findings suggest that the effectiveness of explicit-memory training in patients with MCI is associated with training-specific increases in activation and connectivity in a distributed neural system that includes areas involved in explicit memory.

Task-correlated motion artifacts that occur during functional magnetic resonance imaging can be mistaken for brain activity. In this work, a new selective detrending method for reduction of artifacts associated with task-correlated motion (TCM) during speech in event-related functional magnetic resonance imaging is introduced and demonstrated in an overt word generation paradigm. The performance of this new method is compared with that of three existing methods for reducing artifacts because of TCM: (1) motion parameter regression, (2) ignoring images during speech, and (3) detrending time course datasets of signal components related to TCM (deduced from artifact corrupted voxels). The selective detrending method outperforms the other three methods in reducing TCM artifacts and in retaining blood oxygenation level dependent signal.

Five nonfluent aphasia patients participated in a picture-naming treatment that used an intention manipulation (opening a box and pressing a button on a device in the box with the left hand) to initiate naming trials and was designed to re-lateralize word production mechanisms from the left to the right frontal lobe. To test the underlying assumption regarding re-lateralization, patients participated in fMRI of category-member generation before and after treatment. Generally, the four patients who improved during treatment showed reduced frontal activity from pre- to post-treatment fMRI with increasing concentration of activity in the right posterior frontal lobe (motor/premotor cortex, pars opercularis), demonstrating a significant shift in lateraliity toward the right lateral frontal lobe, as predicted. Three of these four patients showed no left frontal activity by completion of treatment, indicating that right posterior lateral frontal activity supported category-member generation. Patients who improved in treatment showed no difference in lateralization of lateral frontal activity from normal controls pre-treatment, but post-treatment, their lateral frontal activity during category-member generation was significantly more right lateralized than that of controls. Patterns of activity pre- and post-treatment suggested increasing efficiency of cortical processing as a result of treatment in the four patients who improved. The one patient who did not improve during treatment showed a leftward shift in lateral frontal lateralization that was significantly different from the four patients who did improve. Neither medial frontal nor posterior perisylvian re-lateralization from immediately pre- to immediately post-treatment images was a necessary condition for significant treatment gains or shift in lateral frontal lateralization. Of the three patients who improved and in whom posterior perisylvian activity could be measured at post-treatment fMRI, all maintained equal or greater amounts of left-hemisphere perisylvian activity as compared to right. This finding is consistent with reviews suggesting both hemispheres are involved in recovery of language in aphasia patients.

The impact of age-related changes in visual-perceptual processing on naming ability has not been reported. The present study investigated the effects of 6 levels of spatial frequency and 6 levels of contrast on accuracy and latency to name objects in 14 young and 13 older neurologically normal adults with intact lexical-semantic functioning. Spatial frequency and contrast manipulations were made independently. Consistent with the hypotheses, variations in these two visual parameters impact naming ability in young and older subjects differently. The results from the spatial frequency-manipulations revealed that, in general, young vs. older subjects are faster and more accurate to name. However, this age-related difference is dependent on the spatial frequency on the image; differences were only seen for images presented at low (e.g., 0.25-1 c/deg) or high (e.g., 8-16 c/deg) spatial frequencies. Contrary to predictions, the results from the contrast manipulations revealed that overall older vs. young adults are more accurate to name. Again, however, differences were only seen for images presented at the lower levels of contrast (i.e., 1.25%). Both age groups had shorter latencies on the second exposure of the contrast-manipulated images, but this possible advantage of exposure was not seen for spatial frequency. Category analyses conducted on the data from this study indicate that older vs. young adults exhibit a stronger nonliving-object advantage for naming spatial frequency-manipulated images. Moreover, the findings suggest that bottom-up visual-perceptual variables integrate with top-down category information in different ways. Potential implications on the aging and naming (and recognition) literature are discussed.

Hemispheric asymmetry reduction in older adults (HAROLD) has been frequently reported in studies of functional brain aging. It is commonly considered to be a plastic brain reorganization that provides compensation for declining unilateral neural efficiency. However, plastic functional alterations may also be associated with neural connectivity changes. Using activation and resting state functional magnetic resonance imaging (fMRI) as well as diffusion tensor imaging (DTI), we examined whether functional and structural connectivity related to prefrontal working memory function is asymmetrically reduced in the two hemispheres of the aging brain; and if yes, whether these asymmetric connectivity declines are correlated with asymmetry reduction in functional activation. With regions of interests defined by verbal working memory activations, it is revealed that although neural connectivity is generally reduced in the aging brain, prefrontal–parietal resting functional connectivity is better preserved in the left hemisphere while prefrontal DTI fiber pathways are better preserved in the right hemisphere. In addition, the laterality change of the functional activation is negatively correlated with that of the resting connectivity and positively correlated with that of the structural connectivity. These results reveal additional aspects of the neuronal alterations of aging and suggest a link between asymmetric connectivity reduction and HAROLD.

AbstractSix individuals with probable Alzheimer’s disease (AD) participated in a phase 1 study employing a repeated measures, parallel baseline design testing the hypothesis that error-free experience during word production practice combined with an acetyl cholinesterase inhibitor would improve confrontation naming ability. While acetyl cholinesterase inhibitors are safe and delay cognition decline associated with AD, improvement over baseline cognition is less evident; clinically significant cognitive deficits persist and progress. Both animal and clinical research strongly implicate acetylcholine in learning, a form of neuroplasticity. In clinical practice, however, people with AD are given cholinergic medications without concomitant systematic/targeted retraining. In this study six participants with probable AD and taking donepezil participated in targeted word production practice using an errorless learning strategy. Results showed that combining behavioral enrichment training and an acetyl cholinesterase inhibitor resulted in significant improvements in verbal confrontation naming of trained items for three of six participants. Differences in baseline dementia severity, living conditions, and medications may have influenced the training response. Detection of substantial treatment effects in 50% of subjects suggests further language treatment studies in AD in combination with an acetyl cholinesterase inhibitor are warranted and provide useful information on inclusion/exclusion criteria for use in subsequent studies. (JINS, 2009, 15, 311–322.)

BACKGROUND: Attention, the processing of one source of information to the exclusion of others, is important for most cognitive processes, including language. Evidence suggests not only that dysfunctional attention mechanisms contribute to language deficits after stroke, but also that orienting attention to a patient's ipsilesional hemispace recruits attention mechanisms in the intact hemisphere and improves language functions in some persons with aphasia. AIMS: The aim of the current research was to offer proof of concept for the strategy of improving picture-naming performance in fluent aphasia by moving stimuli into the left hemispace. It was hypothesised that repeated orientation of attention to the ipsilesional hemispace during picture naming would lead to improved naming accuracy for participants with fluent aphasia. METHODS #ENTITYSTARTX00026; PROCEDURES: Three participants with stable fluent aphasia received daily treatment sessions that consisted of naming simple line drawings presented 45 degrees to the left of body midline on a computer monitor. Naming probes were administered before initiation of the treatment protocol to establish a baseline, and before each treatment session to measure change during treatment. The C statistic was used to establish the stability of baseline performance and to determine whether the slope of the treatment phases differed significantly from the slope of the baseline. OUTCOMES #ENTITYSTARTX00026; RESULTS: Two of the three participants showed significant improvement over baseline performance in the percent correct of naming probes. One participant showed no improvement over baseline accuracy. CONCLUSIONS: Results suggest that engaging right-hemisphere attention mechanisms may improve naming accuracy in some people with fluent aphasia. Findings justify further investigation of this treatment in a larger controlled study.

Relatively few studies have examined the use of cognitive rehabilitation in patients with mild cognitive impairment (MCI), largely due to the assumption that training will not improve functioning in patients with progressive conditions. Face-name association, an ecologically valid task, is both dependent on the explicit memory system and difficult for MCI patients. During three hour-long sessions, eight patients diagnosed with MCI were trained in the use of explicit memory strategies with 45 face-name pairs. For each pair, they were taught to visually identify a facial feature, link a phonological cue to that feature, and recall the associated name. There was significant improvement in recognition accuracy, along with faster reaction times, for trained face-name pairs. Improved accuracy persisted when tested one month after training. Significant, but less, improvement was also found on untrained stimuli, raising the possibility of generalization of training strategies. preliminary results suggest strategy-based cognitive rehabilitation may be beneficial in patients with MCI, though these results must be replicated with a control group to rule out practice effects.

The purpose of this case study was to examine the integrity of cognitive skills, language usage, and language structure components in a patient with corticobasal degeneration (CBD). CBD is a levadopa-nonresponsive, degenerative neurologic movement disorder that is generally accompanied by cognitive (frontal executive dysfunction, dementia) and linguistic (aphasia) disorders. However, no one has reported on social language usage deficits in cases of CBD. The reported frontal executive dysfunction found in CBD led us to expect social language usage deficits in the present case study. Consistent with the literature, the patient demonstrated motor, cognitive (severe apraxia, frontal executive deficits, dementia), and linguistic deficits (aphasia). However she also demonstrated significantly abnormal social language usage previously unreported in the literature.

Twenty-three chronic nonfluent aphasia patients with moderate or severe word-finding impairments and 11 with profound word-finding impairments received two novel picture-naming treatments. The intention treatment initiated picture-naming trials with a complex left-hand movement and was designed to enhance right frontal participation during word retrieval. The attention treatment required patients to view visual stimuli for picture-naming trials in their left hemispace and was designed to enhance right posterior perisylvian participation during word retrieval. Because the intention treatment addressed action mechanisms and nonfluent aphasia reflects difficulty initiating or maintaining action (i.e., language output), it was hypothesized that intention component of the treatment would enhance re-acquisition of picture naming more than the attention component. Patients with moderate and severe word-finding impairment showed gains with both treatments but greater incremental improvement from one treatment phase to the next with the intention than the attention treatment. Thus, the hypothesis that intention component would be a more active constituent than the attention component was confirmed for these patients. Patients with profound word-finding impairment showed some improvement with both treatments but no differential effects for the intention treatment. Almost all patients who showed treatment gains on either treatment also demonstrated generalization from trained to untrained items. (JINS, 2007, 13, 582–594.)