Categorization of novel animals by patients with Alzheimer's disease and corticobasal degeneration.

We taught a novel animal category by rule-based and similarity-based processes to participants with Alzheimer's disease (AD), corticobasal degeneration (CBD), and healthy age-matched participants. Healthy participants successfully categorized by either process. AD patients' rule-based categorization was impaired, while their similarity-based categorization resembled that of healthy participants. Correlations of AD patients' performance with measures of executive functioning suggested a deficit in the cognitive resources necessary for engaging rule-based categorization. The contribution of limited executive resources to categorization difficulty in AD was further demonstrated in a second experiment in which features determining category membership were of lower salience. CBD patients were relatively impaired at similarity-based processing, suggesting that qualitatively distinct categorization processes can be selectively compromised in patients with focal neurodegenerative diseases. Moreover, AD patients' impaired categorization correlated with performance on a measure of semantic memory, implicating this categorization deficit in AD patients' semantic memory difficulty.

Fear sensitivity and the psychological profile of patients with psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) remain a poorly understood phenomenon for both patients and their physicians. Recent work has begun to focus on the possible psychological underpinnings of this diagnosis, but few studies have focused on specific emotional pathologies. This study sought to investigate the impact of a specific emotional measure: self-reported fear sensitivity. Three patient groups (patients with PNES, patients with epilepsy, and healthy volunteers) were administered the Modified Fear Survey Schedule, along with other neuropsychological batteries. As expected, the PNES and epilepsy cohorts demonstrated elevated levels of depression, anxiety, and comorbid psychiatric conditions. The PNES group independently exhibited a statistically significant higher level of fear sensitivity compared with both patients with epilepsy and healthy volunteers. This fear-specific trait was independent of other comorbid psychological factors or psychiatric conditions. These results suggest that patients with PNES exhibit disproportionately elevated fear sensitivity on self-report measures when compared with patients with epilepsy. This finding may reflect an elevated internal "setpoint" for appraising the intensity of emotional settings.

Object perception impairments predict instrumental activities of daily living dependence in Alzheimer's disease.

This study examined the contribution of object perception and spatial localization to functional dependence among Alzheimer's disease (AD) patients. Forty patients with probable AD completed measures assessing verbal recognition memory, working memory, object perception, spatial localization, semantic knowledge, and global cognition. Primary caregivers completed a measure of activities of daily living (ADLs) that included instrumental and basic self-care subscales (i.e., IADLs and BADLs, respectively). Stepwise multiple regressions revealed that global cognition accounted for significant portions of variance among the ADL total, IADL, and BADL scores. However, when global cognition was removed from the model, object perception was the only significant cognitive predictor of the ADL total and IADL subscale scores, accounting for 18.5% and 19.3% of the variance, respectively. When considering multiple cognitive components simultaneously, object perception and the integrity of the inferotemporal cortex is important in the completion of functional abilities in general and IADLs in particular among AD patients.

Earlier onset of Alzheimer disease symptoms in latino individuals compared with anglo individuals.

BACKGROUND: Latino individuals are the largest minority group and the fastest growing population group in the United States, yet there are few studies comparing the clinical features of Alzheimer disease (AD) in this population with those found in Anglo (white non-Latino) patients. OBJECTIVE: To compare the age at AD symptom onset in Latino and Anglo individuals. DESIGN: Cross-sectional assessment using standardized methods to collect and compare age at AD symptom onset, demographic variables, and medical variables. SETTING: Five National Institute on Aging-sponsored Alzheimer's Disease Centers with experience evaluating Spanish-speaking individuals. PATIENTS: We evaluated 119 Latino and 55 Anglo patients who had a diagnosis of AD. MAIN OUTCOME MEASURE: Age at symptom onset. RESULTS: After adjusting for center, sex, and years of education, Latino patients had a mean age at symptom onset 6.8 years earlier (95% confidence interval, 3.5-10.3 years earlier) than Anglo patients. CONCLUSIONS: An earlier age at symptom onset suggests that US mainland Latino individuals may experience an increased burden of AD compared with Anglo individuals. The basis for the younger age at symptom onset remains obscure.

The role of sensory-motor information in object recognition: evidence from category-specific visual agnosia.

The role of sensory-motor representations in object recognition was investigated in experiments involving AD, a patient with mild visual agnosia who was impaired in the recognition of visually presented living as compared to non-living entities. AD named visually presented items for which sensory-motor information was available significantly more reliably than items for which such information was not available; this was true when all items were non-living. Naming of objects from their associated sound was normal. These data suggest that both information about object form computed in the ventral visual system as well as sensory-motor information specifying the manner of manipulation contribute to object recognition.

The neural basis for novel semantic categorization.

We monitored regional cerebral activity with BOLD fMRI during acquisition of a novel semantic category and subsequent categorization of test stimuli by a rule-based strategy or a similarity-based strategy. We observed different patterns of activation in direct comparisons of rule- and similarity-based categorization. During rule-based category acquisition, subjects recruited anterior cingulate, thalamic, and parietal regions to support selective attention to perceptual features, and left inferior frontal cortex to helps maintain rules in working memory. Subsequent rule-based categorization revealed anterior cingulate and parietal activation while judging stimuli whose conformity with the rules was readily apparent, and left inferior frontal recruitment during judgments of stimuli whose conformity was less apparent. By comparison, similarity-based category acquisition showed recruitment of anterior prefrontal and posterior cingulate regions, presumably to support successful retrieval of previously encountered exemplars from long-term memory, and bilateral temporal-parietal activation for perceptual feature integration. Subsequent similarity-based categorization revealed temporal-parietal, posterior cingulate, and anterior prefrontal activation. These findings suggest that large-scale networks support relatively distinct categorization processes during the acquisition and judgment of semantic category knowledge.

Validation of the WMS-III Facial Memory subtest with the Graduate Hospital Facial Memory Test in a sample of right and left anterior temporal lobectomy patients.

A number of studies have shown visuospatial memory deficits following anterior temporal lobectomy (ATL) in the right, nondominant temporal lobe (RATL). The current study examines 26 patients with intractable temporal lobe epilepsy who underwent ATL in either the right (RATL, n = 16) or left temporal lobe (LATL, n = 10) on two tests of facial memory abilities, the Wechsler Memory Scale-III (WMS-III) Faces subtest and the Graduate Hospital Facial Memory Test (FMT). Repeated measures ANOVA on the FMT indicated a significant main effect of side of surgery. The RATL group performed significantly below the LATL group overall. Both groups showed a slight, but non-significant, improvement in performance from pre- to postsurgery on the FMT immediate memory, likely due to practice effects. Repeated measures ANOVA on the WMS-III Faces subtest revealed a significant interaction of group (RATL vs. LATL) by delay (immediate vs. delayed). Overall, the LATL group showed an improvement in recognition scores from immediate to delayed memory, whereas the RATL group performed similarly at both immediate and delayed testing. No effects of surgery were noted on the WMS-III. Following initial data analysis the WMS-III Faces I and II data were re-scored using the scoring suggested by Holdnack and Delis (2003), earlier in this issue. Repeated measures ANOVA revealed a trend toward significance in the three-way interaction of group (RATL vs. LATL) x time of testing (pre- versus postop) x delay (immediate vs. delayed memory). On the Faces I subtest, both the RATL and LATL groups showed a decline from preoperative to postoperative testing. However, on Faces II the LATL group showed an increase in performance from preoperative to postoperative testing, while the RALT group showed a decline in performance from preoperative to postoperative testing. While the FMT appears to be superior to the WMS-III Faces subtest in identifying deficits in facial memory prior to and following RATL, the application of the scoring methodology presented by Holdnack and Delis earlier in this issue does serve to increase the clinical utility of the WMS-III Faces subtest in this population.

Functional MRI predicts post-surgical memory following temporal lobectomy.

Temporal lobectomy is an effective therapy for medically refractory temporal lobe epilepsy (TLE), but may be complicated by amnestic syndromes. Therefore, pre-surgical evaluation to assess the risk/benefit ratio for surgery is required. Intracarotid amobarbital testing (IAT) is currently the most widely used method for assessing pre-surgical memory lateralization, but is relatively invasive. Over the past decade functional MRI (fMRI) has been shown to correlate with IAT for language lateralization, and also for memory lateralization in a small number of patients. This study was carried out to compare fMRI during memory encoding with IAT testing for memory lateralization, and to assess the predictive value of fMRI during memory encoding for post-surgical memory outcome. Thirty-five patients with refractory TLE undergoing pre-surgical evaluation for temporal lobectomy and 30 normal subjects performed a complex visual scene-encoding task during fMRI scanning at 1.5 T using a 10-min protocol. Encoding performance was evaluated with subsequent recognition testing. Twenty-three patients also completed the same task again outside the scanner, an average of 6.9 months following surgery. A region of interest (ROI) analysis was used to quantify activation within hippocampal and a larger mesial temporal lobe ROI consisting of hippocampus, parahippocampus and fusiform gyrus (HPF) as defined by a published template. Normal subjects showed almost symmetrical activation within these ROI. TLE patients showed greater asymmetry. Asymmetry ratios (ARs) from the HPF ROI correlated significantly with memory lateralization by intracarotid amobarbital testing. HPF ARs also correlated significantly with memory outcome, as determined by a change in scene recognition between pre-surgical and post-surgical trials. When absolute activation within the HPF ROI was considered, a significant inverse correlation between activation ipsilateral to temporal lobectomy and memory outcome was observed, with no significant correlation in the contralateral HPF ROI. Although further technical improvements and prospective clinical validation are required, these results suggest that mesial temporal memory activation detected by fMRI during complex visual scene encoding correlates with post-surgical memory outcome and supports the notion that this approach will ultimately contribute to patient management.

Visual processing impairments and decrements in regional brain activity in Alzheimer's disease.

The relationships between intermediate visual processes, involving object and space perception, and regional brain activity using positron emission tomography and single photon emission tomography were investigated in 16 patients with Alzheimer's disease. Significant region specific correlations were found between unfamiliar face matching and cerebral activity in the left occipito-temporal region and middle/inferior temporal regions bilaterally. Letter-word identification correlated significantly with brain activity in the angular gyri and occipital association cortices bilaterally, as well as a broad region of activation in the left hemisphere temporal, parietal and occipital lobes. Additionally, a significant correlation was found between ratings of performance of instrumental activities of daily living and brain activity in occipito-temporal and middle/inferior temporal regions. The present study demonstrates that the neuropathological distribution typically seen in Alzheimer's disease corresponds to impairments in specific aspects of intermediate visual perceptual processing, and it is related to the daily living skills of patients with Alzheimer's disease.

What's in a name: voxel-based morphometric analyses of MRI and naming difficulty in Alzheimer's disease, frontotemporal dementia and corticobasal degeneration.

Confrontation naming is impaired in neurodegenerative conditions like Alzheimer's disease (AD), frontotemporal dementia (FTD) and corticobasal degeneration (CBD). Some behavioural observations suggest a common source of impaired naming across these patient groups, while others find partially unique patterns of naming difficulty. We hypothesized that a large-scale neural network underlies naming, and that patterns of impaired naming in AD, FTD and CBD reflect cortical atrophy that interrupts this network in a manner that is partially shared and partially unique across these patient groups. We tested this hypothesis by correlating naming impairments with voxel-based morphometric (VBM) analyses of cortical atrophy in structural MRIs of 50 patients. We found significant naming deficits in all patient groups. Naming also correlated with lexical retrieval in all patient groups, including subgroups of patients with FTD. VBM analyses showed significant cortical atrophy, which was shared across AD, FTD and CBD patients in the left lateral temporal cortex; this area correlated with naming accuracy in all groups. Left lateral temporal atrophy thus appears to interfere with a lexical retrieval component of naming in AD, FTD and CBD. Impaired naming also correlated with semantic memory and visual perceptual-spatial functioning in specific groups of patients and, correspondingly, naming correlated with cortical atrophy in partially distinct neuroanatomical distributions in AD, FTD, CBD and subgroups of patients with FTD. These partially unique correlation profiles appear to reflect selective interruption of other components of the naming process, including semantic and visual perceptual-spatial functioning. These findings are consistent with the hypothesis that a large-scale neural network supports naming, and that this network is interrupted in several distinct ways in patients with neurodegenerative diseases.

Memory for faces dissociates from memory for location following anterior temporal lobectomy.

It has been suggested that the right and left mesial temporal lobes are specialized for processing different types of information for long-term memory (LTM). Although findings have been consistent in regard to the dominant role of the left mesial temporal lobe (MTL) in verbal memory, the role of the right MTL in non-verbal memory remains debatable. Given the existence of two cortical pathways specialized for processing different types of visuospatial information, we examined whether memory processing for these two types of information might also be differentially localized. The effect of unilateral anterior temporal lobectomy (ATL) was compared for memory for unfamiliar faces and a novel sequence of spatial locations in 86 ATL patients (left ATL (LATL) = 35; right ATL (RATL) = 51) pre- and post-surgery to examine the contributions of right and left MTL structures to LTM for pattern and spatial information. Memory for spatial location was not related to side of ATL or time of testing. On the facial memory task, RATL patients showed impairments relative to LATL patients prior to surgery, which became magnified after surgery. These results extend the proposed dissociation between an occipitotemporal and an occipitoparietal pathway for processing visuospatial information by demonstrating dissociations in LTM systems for these two types of information. Lesions in the right MTL, adjacent to the cortical structures believed to be specialized for facial recognition, specifically impair the memory encoding of new faces, but not spatial locations.

Neural basis for verb processing in Alzheimer's disease: an fMRI study.

Patients with probable Alzheimer's disease (AD) have difficulty understanding verbs. To investigate the neural basis for this deficit, the authors used functional magnetic resonance imaging to examine patterns of neural activation during verb processing in 11 AD patients compared with 16 healthy seniors. Subjects judged the pleasantness of verbs, including MOTION verbs and COGNITION verbs. Healthy seniors and AD patients both activated posterolateral temporal and inferior frontal regions during judgments of verbs. These activations were relatively reduced and somewhat changed in their anatomic distribution in AD patients compared with healthy seniors, particularly for the subcategory of MOTION verbs, but AD patients showed minimal activation in association with COGNITION verbs. These findings imply that poor performance with verbs in AD is due in part to altered activation of the large-scale neural network that supports verb processing.

Whole-brain N-acetylaspartate level and cognitive performance in HIV infection.

BACKGROUND AND PURPOSE: In the brain of HIV-infected patients, proton MR spectroscopic studies are typically used to examine small volumes of tissue with single-voxel methods. Since brain disease is diffuse in patients with HIV, such studies preclude assessment of the true extent of the metabolic burden. To assess this extent, the relationship between global neuronal integrity, reflected by the whole-brain N-acetylaspartate (WBNAA) concentration, was correlated with neuropsychological function and the AIDS dementia complex (ADC) stage score. METHODS: WBNAA levels were compared between 15 HIV-infected patients (seven symptomatic, eight asymptomatic) and 13 age- and sex-matched healthy subjects. The patients' WBNAA level was correlated with cognitive performance, as measured with a battery of eight tests (NPZ-8), including the ADC stage score and four total-memory, mood, motor, and processing speed subtests. RESULTS: WBNAA levels were significantly different between patients and healthy subjects (mean +/- sigma, 11.82 +/- 1.40 and 12.91 +/- 1.03 mmol/L, respectively; P =.032) after we adjusted for age and sex effects. Intermediate negative correlations were found between the WBNAA level, the processing speed subtest score (r = -0.50, P =.03), and the ADC stage score (r = -0.44, P =.05). CONCLUSION: The WBNAA concentration complements brain atrophy data with information about the quality of the remaining neuronal and axonal tissue in patients with HIV infection. In HIV-infected patients, its correlation with processing speed and the ADC score indicates that the latter reflects pathologic deficits, which are extensive throughout the brain.

Categorization of object descriptions in Alzheimer's disease and frontotemporal dementia: limitation in rule-based processing.

Studies of semantic memory in probable Alzheimer's disease (AD) have focused on the degradation of semantic knowledge, but other work in AD suggests an impairment in the semantic categorization processes that operate on this knowledge. We examined the categorization of object descriptions, where semantic category membership judgments were based on rule-based or similarity-based categorization processes. We found that AD patients were selectively limited in their semantic categorization under conditions requiring a rule-based approach. However, AD patients did not differ from healthy seniors under conditions based on judgments of overall similarity. We showed that this was not due to nonspecific or overall task-related difficulty associated with the rule condition by asking the subjects to use similarity-based judgments of perceptually degraded versions of the stimuli. The results of this condition did not differ from other similarity-based judgments but did differ from the rule-based condition in AD. Rule-based judgments of semantic category membership correlated with executive measures of inhibitory control and mental search, but not with measures of episodic memory or overall dementia severity, suggesting a contribution of executive resources to rule-based semantic categorization. Moreover, the pattern of limited rule-based categorization in AD closely resembled the performance profile of patients with frontotemporal dementia, further implying that executive resource limitations underlie AD patients' limited rule-based semantic categorization. These findings suggest that semantic memory difficulty in AD is due in part to a deficit in executive processes that are central to rule-based categorization in semantic memory.

Category-specific medial temporal lobe activation and the consolidation of semantic memory: evidence from fMRI.

Semantic memory consolidation was studied by comparing medial temporal lobe (MTL) fMRI activation to ANIMAL, IMPLEMENT and ABSTRACT nouns in healthy seniors to that of young adults. Relative to healthy seniors, young adults were predicted to show greater MTL activation for IMPLEMENTS, but not ANIMALS, because the ANIMALS category consists of highly intercorrelated and overlapping features that should require less MTL-mediated binding than IMPLEMENTS over a shorter period of time during concept consolidation. ABSTRACT meanings are context-dependent and do not consist of fixed feature sets. Thus it was predicted that ABSTRACT words would not involve age-related feature binding mediated by the MTL. These predictions were confirmed by the results. Our observations are consistent with the hypothesis that the structure of a category influences the consolidation of knowledge in semantic memory.

Neural basis for semantic memory difficulty in Alzheimer's disease: an fMRI study.

Patients with probable Alzheimer's disease are thought to have a semantic memory deficit. We used functional MRI to evaluate the neural basis for impaired semantic memory for ANIMALS and IMPLEMENTS in 11 patients with Alzheimer's disease and 16 healthy seniors. For both categories of knowledge, Alzheimer's disease patients show reduced activation in the left posterolateral temporal-inferior parietal cortex compared with healthy seniors. Activation changes in this heteromodal association region may be related to an impairment of the category-neutral semantic processes involved in integrating feature knowledge that is represented in modality-specific association cortices. We also found increased activation of an area of the left temporal cortex for both categories of knowledge in Alzheimer's disease that was not activated in healthy seniors. Category-specific changes were also seen in Alzheimer's disease compared with healthy seniors that may be related to the neural representation of category-specific feature knowledge represented in semantic memory. For ANIMALS, the left ventral temporal cortex was activated in Alzheimer's disease in an anatomical distribution that was posterior to the left ventral recruitment for this category in healthy seniors. For IMPLEMENTS, frontal-striatal regions were activated in Alzheimer's disease in a manner that was displaced from the locus of recruitment for this category in healthy seniors. Our findings are consistent with a two-component model of semantic memory involving category-neutral processes operating on category- specific knowledge, and both components appear to be compromised in Alzheimer's disease. Components of the large-scale neural network underlying semantic memory may modify themselves to maintain performance in the face of a neurodegenerative disease.

The neural basis for categorization in semantic memory.

We asked young adults to categorize written object descriptions into one of two categories, based on a rule or on overall similarity, while we monitored regional brain activity with functional magnetic resonance imaging (fMRI). We found significantly greater recruitment of left dorsolateral prefrontal cortex for rule-based categorization in direct comparison with similarity-based categorization. Recruitment of right ventral frontal cortex and thalamus was uniquely associated with rule-based categorization as well. These observations lend support to the claim that executive functions such as working memory, inhibitory control, and selective attention contribute to rule-based categorization. Right inferior parietal activation was uniquely associated with similarity-based categorization. This region may play an important role in overall feature configuration that is important for this form of categorization. We found other brain regions recruited for both rule-based and similarity-based categorization: Anterior cingulate cortex may support the implementation of executive functions during situations with competing response alternatives; and left inferior parietal cortex may be related to the integration of feature knowledge about objects represented in modality-specific association cortices. We also administered a degraded-similarity condition where the task of categorizing a written object description was made more difficult by perceptually degrading the stimulus materials. The degraded condition and the rule-based condition, but not the similarity-based condition, were associated with caudate activation. The caudate may support resource demands that are not specific for a particular categorization process. These findings associate partially distinct large-scale neural networks with different forms of categorization in semantic memory.

Visual perceptual functions predict instrumental activities of daily living in patients with dementia.

OBJECTIVE: To assess relations between discrete visual perceptual functions commonly affected in patients with neurodegenerative dementia and the performance of instrumental activities of daily living (IADL). BACKGROUND: Neuropsychologic measures are often used to predict IADL performances in dementia patients. Prior studies have focused on the contribution of higher-level memory and executive deficits to IADL. The relation between visuoperceptual dysfunction and IADL has not been studied systematically. METHODS: Thirty-five elderly patients with neurodegenerative disorders, most diagnosed with probable Alzheimer disease, participated. Patients completed tasks tapping visual perceptual functions believed to be mediated by occipital lobe structures (shape discrimination), posterior inferotemporal regions (face, object form, and written word discrimination), and the dorsolateral parietal lobe (spatial localization). A knowledgeable caregiver rated IADL performance. RESULTS: Object form discrimination, but not other visual perceptual functions, correlated significantly ( = 0.60) with performances of visually based IADL (e.g., misjudging distances, driving, and recognizing familiar people), but not with other IADL, when the variance attributable to dementia severity, language disturbance, and other visual perceptual abilities was controlled. CONCLUSIONS: In contrast to prior investigations that have focused primarily on relations of memory and executive control deficits with IADL in neurologically impaired patients, the results of this study highlight the important contribution of bilateral inferotemporal visual perceptual systems for the performance of IADL in elderly patients with neurodegenerative dementia.

Pseudoword and real word memory in unilateral temporal lobe epilepsy.

Recognition memory for pronounceable pseudowords (PWs), real words, and degraded photographs of unfamiliar faces, was examined in 45 patients with unilateral temporal lobe epilepsy (TLE), before and after Anterior Temporal Lobectomy, to test predictions from two accounts of hemispheric differences in memory functioning: (1) The 'material-specific' account predicts that left TLE (LTLE) patients would be impaired in memory for both familiar (real words) and unfamiliar (PWs) verbal stimuli, while memory for novel complex visual stimuli (unfamiliar faces) would be impaired in right TLE (RTLE) patients. (2) The 'familiarity' account predicts that memory for familiar stimuli (such as words) will be impaired in LTLE patients, while memory for both linguistic and nonlinguistic unfamiliar stimuli should be disrupted in RTLE patients. Results were consistent with the 'material-specific' hypothesis suggesting that both familiar and unfamiliar linguistic stimuli are processed for memory in the left medial temporal lobe (MTL), whereas unfamiliar nonverbal stimuli are processed for memory in the right MTL.

Correlation between percentage of brain parenchymal volume and neurocognitive performance in HIV-infected patients.

BACKGROUND AND PURPOSE: This study was designed to determine whether neuropsychological function in HIV-infected persons is correlated with loss of brain volume (as measured by percentage of brain parenchymal volume [PBV]). We hypothesized that whole-brain parenchymal volume might correlate with neuropsychologic performance, even before overt clinical dysfunction is apparent. METHODS: A computer-assisted segmentation technique with thin section MR imaging was used for 15 patients with HIV infection (seven symptomatic, eight asymptomatic) and for five HIV-negative control participants to quantify whole brain and CSF volumes. To determine the degree of brain atrophy, the PBV relative to that of intracranial content was calculated. Neuropsychological performance was assessed by using a standard battery of eight tests (NPZ-8 test battery). RESULTS: HIV-infected patients had significantly lower NPZ-8 scores (t[18] = 2.26, P <.05) and lower PBV (t[18] = 1.79, P <.01) than those of healthy control participants. With the Spearman rank order correlation coefficients, data analyzed for all 20 study participants (15 HIV-infected patients and five noninfected control participants) showed a significant (r = -0.50, P <.05) negative correlation between PBV and NPZ-8 test battery score. In addition, there was a significant negative correlation between subtest score of motor impairment and PBV (r = -0.69, P <.01) and between AIDS dementia complex score (r = -0.64) and PBV (P <.01). CONCLUSION: These correlations suggest that quantitation of PBV may offer an objective, easily acquired surrogate predictor of neuropsychological impairment and clinically apparent cognitive/motor dysfunction among HIV-infected persons.