Bilateral basal ganglia activity in verbal working memory.

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.

Activation and effective connectivity changes following explicit-memory training for face-name pairs in patients with mild cognitive impairment: a pilot study.

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.

Age effects on visual-perceptual processing and confrontation naming.

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.

Regional changes in word-production laterality after a naming treatment designed to produce a rightward shift in frontal activity.

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.

Asymmetric connectivity reduction and its relationship to "HAROLD" in aging brain.

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.

Explicit memory training leads to improved memory for face-name pairs in patients with mild cognitive impairment: results of a pilot investigation.

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.

Functional MRI of language in aphasia: a review of the literature and the methodological challenges.

Animal analogue studies show that damaged adult brains reorganize to accommodate compromised functions. In the human arena, functional magnetic resonance imaging (fMRI) and other functional neuroimaging techniques have been used to study reorganization of language substrates in aphasia. The resulting controversy regarding whether the right or the left hemisphere supports language recovery and treatment progress must be reframed. A more appropriate question is when left-hemisphere mechanisms and when right-hemisphere mechanisms support recovery of language functions. Small lesions generally lead to good recoveries supported by left-hemisphere mechanisms. However, when too much language eloquent cortex is damaged, right-hemisphere structures may provide the better substrate for recovery of language. Some studies suggest that recovery is particularly supported by homologues of damaged left-hemisphere structures. Evidence also suggests that under some circumstances, activity in both the left and right hemispheres can interfere with recovery of function. Further research will be needed to address these issues. However, daunting methodological problems must be managed to maximize the yield of future fMRI research in aphasia, especially in the area of language production. In this review, we cover six challenges for imaging language functions in aphasia with fMRI, with an emphasis on language production: (1) selection of a baseline task, (2) structure of language production trials, (3) mitigation of motion-related artifacts, (4) the use of stimulus onset versus response onset in fMRI analyses, (5) use of trials with correct responses and errors in analyses, and (6) reliability and stability of fMRI images across sessions. However, this list of methodological challenges is not exhaustive. Once methodology is advanced, knowledge from conceptually driven fMRI studies can be used to develop theoretically driven, mechanism-based treatments that will result in more effective therapy and to identify the best patient candidates for specific treatments. While the promise of fMRI in the study of aphasia is great, there is much work to be done before this technique will be a useful clinical tool.

Treatment of naming in nonfluent aphasia through manipulation of intention and attention: a phase 1 comparison of two novel treatments.

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.

Why consider impaired social language usage in a case of corticobasal degeneration?

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.

Treatment of word-finding deficits in fluent aphasia through the manipulation of spatial attention: Preliminary findings.

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.

Neural substrates of syntactic mapping treatment: an fMRI study of two cases.

Two patients (G01, J02) with chronic nonfluent aphasia and sentence production deficits received syntactic mapping treatment to improve sentence production. The patients had dramatically different outcomes in that improved syntax production generalized to nontreatment tasks for G01, but not for JO2. To learn how treatment influenced the neural substrates for syntax production, both patients underwent pre- and posttreatment functional magnetic resonance imaging (fMRI) of sentence generation. G01 showed more robust activity posttreatment than pretreatment in Broca's area; ventral temporal activity decreased slightly from pre- to posttreatment. Comparison of J02's pretreatment and posttreatment images revealed little change, although activity was more diffuse pre- than posttreatment. Findings suggest that for G01, rehabilitation led to engagement of an area (Broca's area) used minimally during the pretreatment scan, whereas for J02, rehabilitation may have led to more efficient use of areas already involved in sentence generation during the pretreatment scan. fMRI findings are discussed in the context of sentence-production outcome and generalization.

Eyeblink classical conditioning to auditory and olfactory stimuli: performance among older adults with and without the apolipoprotein E epsilon 4 allele.

Patients with Alzheimer's disease (AD) demonstrate slowed acquisition of the conditioned response (CR) in eyeblink classical conditioning paradigms (EBCC), although it is unknown how early in the course of the disease CR acquisition is affected. This study investigated whether changes in the rate of CR acquisition were apparent in nondemented older adults at greater genetic risk for developing AD (i.e., carriers of the apolipoprotein E [APOE] epsilon 4 allele). Both epsilon 4+ and epsilon 4- participants demonstrated CR acquisition to auditory and olfactory CSs; however, rate of acquisition to the olfactory CS was significantly slower in epsilon 4+ persons. Both groups acquired the CR to an auditory CS at the same rate. Results support olfactory compromise in the earliest stages of the AD disease process. ((c) 2005 APA, all rights reserved).

Role of the right and left hemispheres in recovery of function during treatment of intention in aphasia.

Two patients with residual nonfluent aphasia after ischemic stroke received an intention treatment that was designed to shift intention and language production mechanisms from the frontal lobe of the damaged left hemisphere to the right frontal lobe. Consistent with experimental hypotheses, the first patient showed improvement on the intention treatment but not on a similar attention treatment. In addition, in keeping with experimental hypotheses, the patient showed a shift of activity to right presupplementary motor area and the right lateral frontal lobe from pre- to post-intention treatment functional magnetic resonance imaging (fMRI) of language production. In contrast, the second patient showed improvement on both the intention and attention treatments. During pre-treatment fMRI, she already showed lateralization of intention and language production mechanisms to the right hemisphere that continued into post-intention treatment imaging. From pre- to post-treatment fMRI of language production, both patients demonstrated increased activity in the posterior perisylvian cortex, although this activity was lateralized to left-hemisphere language areas in the second but not the first patient. The fact that the first patient's lesion encompassed almost all of the dominant basal ganglia and thalamus whereas the second patient's lesion spared these structures suggests that the dominant basal ganglia could play a role in spontaneous reorganization of language production functions to the right hemisphere. Implications regarding the theoretical framework for the intention treatment are discussed.

Comparison of baseline conditions to investigate syntactic production using functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) in humans has revealed increases in brain activity associated with various mental activities that are task-dependent. However, changes in brain activity have been dependent on baseline as well as experimental tasks. In the present study, fMRI was applied to investigate the most appropriate baseline task, picture naming or passive viewing of nonsense objects, to isolate syntactic processes related to 14.7-s blocks of silent sentence generation in 10 neurologically normal adults. The aim of this comparison was to determine the most suitable baseline task for the purpose of elucidating changes in the neural substrates of sentence generation following therapy for syntax production problems. Use of naming but not passive object viewing as a baseline task obscured activity in Broca's area, a region previously shown to be involved in syntactic processing. These results suggest that passive viewing of nonsense objects serves as a more appropriate baseline comparison than object naming for investigating sentence processing.

Left and right basal ganglia and frontal activity during language generation: contributions to lexical, semantic, and phonological processes.

fMRI was used to determine the frontal, basal ganglia, and thalamic structures engaged by three facets of language generation: lexical status of generated items, the use of semantic vs. phonological information during language generation, and rate of generation. During fMRI, 21 neurologically normal subjects performed four tasks: generation of nonsense syllables given beginning and ending consonant blends, generation of words given a rhyming word, generation of words given a semantic category at a fast rate (matched to the rate of nonsense syllable generation), and generation of words given a semantic category at a slow rate (matched to the rate of generating of rhyming words). Components of a left pre-SMA-dorsal caudate nucleus-ventral anterior thalamic loop were active during word generation from rhyming or category cues but not during nonsense syllable generation. Findings indicate that this loop is involved in retrieving words from pre-existing lexical stores. Relatively diffuse activity in the right basal ganglia (caudate nucleus and putamen) also was found during word-generation tasks but not during nonsense syllable generation. Given the relative absence of right frontal activity during the word generation tasks, we suggest that the right basal ganglia activity serves to suppress right frontal activity, preventing right frontal structures from interfering with language production. Current findings establish roles for the left and the right basal ganglia in word generation. Hypotheses are discussed for future research to help refine our understanding of basal ganglia functions in language generation.