Longitudinal functional alterations in asymptomatic women at risk for Alzheimer's disease.

PURPOSE: The authors sought to determine whether known alterations of brain function in normal individuals who are at high risk for Alzheimer's disease (AD) worsen or stay the same after a significant interval of time. METHODS: The authors used functional magnetic resonance imaging (fMRI) to observe cortical activation during confrontation naming in 14 women with high AD risk and 10 with low risk, based on family history and apolipoprotein-E4 allele status. They repeated the identical scan protocol in the same patients after 4 years. RESULTS: fMRI activation in high-AD-risk participants was found to be further diverged from that of their low-AD-risk counterparts over this period. CONCLUSION: fMRI may report on the presence and progression of neuropathology in the ventral temporal cortex or in functionally connected regions in presymptomatic AD.

Women at risk for AD show increased parietal activation during a fluency task.

BACKGROUND: Imaging studies have shown disparities in resting metabolism and in functional activation between cognitively normal individuals at high and low risk for AD. A recent study has shown increased parietal activation in high-risk subjects during a paired associates recall task, which the authors postulated might overlap activation typically observed in verbal fluency. OBJECTIVE: To determine whether parietal activation is altered in a letter fluency task in cognitively normal individuals at high risk for AD. METHODS: fMRI was used to compare cortical activation between two groups of cognitively normal women differing in their risk for developing AD. A letter fluency task was used, which activates left frontal and parietal regions. The risk groups differed in family history of AD and APOE allele status but were matched in age, education, and measures of cognitive performance. Average age of the study participants was 53 years. RESULTS: The regional patterns of brain activation were similar between groups and similar to patterns observed by other investigators. However, the high-risk group showed significantly increased activation in the left parietal region despite identical letter fluency performance between risk groups. CONCLUSIONS: Cognitively normal individuals at high risk for AD show increased brain activation in the left parietal region with letter fluency, a region adjacent to that observed by others using a recall task. This convergence of results indicates disruption of functional circuits involving the left parietal lobe in asymptomatic individuals at increased risk for AD.

Differences in functional magnetic resonance imaging activation by category in a visual confrontation naming task.

OBJECTIVE: Cortical processing involved in seemingly similar tasks may differ in important ways. The authors mapped cortical regions engaged in a commonly performed picture naming task, seeking differences by semantic category. Functional magnetic resonance imaging was used during presentation of standardized line drawings in 18 healthy right-handed female participants, comparing living versus nonliving entities. During visual naming, across categories there was strong activation of left frontal (BA45/47), bilateral temporo-occipital junction (BA19), and inferior temporal regions (BA36/37). Activation of right inferior temporal cortex (BA19 and BA37) was greater during naming of living versus nonliving category items. No category differences in activation strength in the left temporal lobe were observed. The authors conclude that visual semantic operations may involve visual association cortex in the right temporal lobe in women.

Neural substrates of facial emotion processing using fMRI.

We identified human brain regions involved in the perception of sad, frightened, happy, angry, and neutral facial expressions using functional magnetic resonance imaging (fMRI). Twenty-one healthy right-handed adult volunteers (11 men, 10 women; aged 18-45; mean age 21.6 years) participated in four separate runs, one for each of the four emotions. Participants viewed blocks of emotionally expressive faces alternating with blocks of neutral faces and scrambled images. In comparison with scrambled images, neutral faces activated the fusiform gyri, the right lateral occipital gyrus, the right superior temporal sulcus, the inferior frontal gyri, and the amygdala/entorhinal cortex. In comparisons of emotional and neutral faces, we found that (1) emotional faces elicit increased activation in a subset of cortical regions involved in neutral face processing and in areas not activated by neutral faces; (2) differences in activation as a function of emotion category were most evident in the frontal lobes; (3) men showed a differential neural response depending upon the emotion expressed but women did not.

Channel-consistency following unilateral stroke: an examination of patient communications across verbal and nonverbal domains.

One way in which the dyadic communicative process can go awry is for one or both parties to send channel-inconsistent communications - communications in which the verbal and nonverbal elements are not matched in emotional valence (e.g., uttering positive words with a frown). We hypothesized that unilateral stroke patients would be likely to send such messages. Given the verbal impairments typically associated with left hemisphere damage (LHD), e.g., agrammatism, and the nonverbal impairments typically associated with right hemisphere damage (RHD), we expected LHD and RHD patients to send messages in which the impaired channel was perceived as inconsistent with the unimpaired channel. Ten LHD, 11 RHD and six normal control patients were videotaped while engaging in social interaction. Observers made judgments about the valence of the patients' (1) words (based on transcripts of the interactions), and (2) facial expressions (based on soundless videos of the interactions). Analysis of word-face difference scores revealed a significant linear trend, with messages of LHD patients judged more positive in facial expression than in verbal content, messages of RHD patients judged more positive in verbal content than in facial expression, and messages of control patients judged channel-consistent (similar in valence across facial and verbal channels).

Short-term neuropsychological outcome following Gamma Knife radiosurgery for arteriovenous malformations: a preliminary report.

This study investigated the effect of Gamma Knife radiosurgery for the treatment of arteriovenous malformations (AVMs) on neuropsychological functioning. We examined neuropsychological performance in 10 patients before and after radiosurgical treatment with the Leksell cobalt-60 Gamma Knife unit. The patients included 7 right-handed women and 3 right-handed men. Three patients had left hemisphere AVMs, 4 had right hemisphere AVMs, and 3 had midline AVMs. Each patient was given neuropsychological testing within 1 week before Gamma Knife radiosurgery. Testing was repeated an average of 11.4 months after treatment. There were no statistically significant differences between pre- and postradiosurgical neuropsychological test scores on any measure. Pretreatment AVM diameter as measured on magnetic resonance scans ranged from 1.6 to 6.5 cm. After treatment, 2 AVMs disappeared, 4 decreased slightly in size, and 4 remained unchanged. We conclude that Gamma Knife radiotherapy in this sample of patients was neither detrimental nor beneficial to neuropsychological functioning.

Altered brain activation in cognitively intact individuals at high risk for Alzheimer's disease.

OBJECTIVE: To determine whether brain function is altered in cognitively normal individuals at high risk for AD several years before the typical age at onset for this illness. BACKGROUND: Neuropathologic alterations in AD precede cognitive impairment by several years. It is unknown whether functional alterations in neural circuitry accompany these neuropathologic changes, and if so, whether they may be detectable before onset of symptoms. METHODS: We used functional MRI to compare cortical activation between two groups of cognitively normal women differing only in their risk for developing AD. Visual naming and letter fluency tasks were used to activate brain areas subserving object and face recognition, previously described sites of hypometabolism and neuropathologic alteration in AD. The risk groups differed in family history of AD and apolipoprotein E allele status, but were matched in age, education, and measures of cognitive performance. Average age of the study participants was 52 years. RESULTS: The regional patterns of brain activation were similar between groups. However, the high risk group showed areas of significantly reduced activation in the mid- and posterior inferotemporal regions bilaterally during both tasks despite identical naming and letter fluency performance. CONCLUSIONS: Cognitively normal individuals at high risk for AD demonstrate decreased brain activation in key areas engaged during naming and fluency tasks. Decreased activation in the high risk group may be a consequence of the presence of subclinical neuropathology in the inferotemporal region or in the inputs to that region. If so, these findings provide evidence of a window of opportunity for disease-modifying treatment before the onset of symptomatic AD.

Observer liking of unilateral stroke patients.

OBJECTIVE: To examine observers' initial affective impressions of unilateral stroke patients, based on exposure to the patients' verbal and nonverbal behavior. Given the linguistic deficits associated with left hemisphere damage (LHD), the authors expected affective judgments based on exposure to patients' utterances to be reduced for patients with LHD. Given the nonverbal deficits associated with right hemisphere damage (RHD), the authors expected affective judgments based on exposure to patients' facial expressions to be reduced for patients with RHD. METHOD: Ten patients with LHD, 11 patients with RHD, and seven normal control (NC) patients were videotaped while engaging in social interaction. Observers read transcripts of the interactions and made judgments about how much they liked the patients. They then watched soundless videotapes and made similar liking judgments. This reflected a 3 (patient group) x 2 (coding modality) mixed factorial design. RESULTS: A 2 x 3 analysis of variance yielded a significant interaction. When liking judgments were based on utterances, patients with LHD were liked less than patients with RHD and NC patients. When liking judgments were based on facial expressions, patients with RHD were liked less than patients with LHD and NC patients. CONCLUSIONS: The verbal behavior of patients with LHD and the nonverbal behavior of patients with RHD may affect others' impressions of them, and consequently put these patients at interpersonal risk.

Personality and social competency following unilateral stroke.

Neuropsychological research indicates that the left hemisphere plays a dominant role in verbal production and processing, while the right hemisphere plays a dominant role in nonverbal production and processing. This study sought to examine the effects of such differential hemispheric specialization on personality and social competency. Ten left hemisphere damaged (LHD) stroke patients, 11 right hemisphere damaged (RHD) stroke patients, and 7 neurologically normal (NHD) patients were videotaped while engaging in social interaction with their spouse and an interviewer. Segments of the interactions were independently coded by two observers. Patients and spouses were rated with respect to their level of social competency and the extent to which they were characterized by 10 personality adjectives (e.g., outgoing, warm). Ratings for the personality items were summed to create an aggregate score. Analysis of these scores revealed both LHD and RHD patients to have lower (i.e., more negative) mean scores than NHD patients, suggesting that stroke patients as a whole were seen as socially impaired. Analysis of the socially competent item revealed particular LHD deficits; LHD patients were seen as less socially competent than both RHD and NHD patients. Spouses of LHD, RHD, and NHD patients, in contrast, did not differ in observer-rated social behavior.

Cortical activation in confrontation naming.

Functional magnetic resonance imaging was used to detect cortical activation in the right and left perisylvian cortex of seven young adult right-handed volunteers in response to a letter fluency task and to a visual naming task using standardized line drawings. Both letter fluency and visual naming activated left dorsolateral prefrontal cortex (Brodmann's areas 6, 9, 44 and 45). Only visual naming activated area 37 (a cortical region with strong connections to visual association areas), visual association area 19, and areas 39 and 21 previously shown to activate with auditory semantic tasks. This study supports a role for area 37 as participant in a visual lexicosemantic processing network which may otherwise overlap the auditorysemantic network.

Prosodic characteristics of speech pre- and post-right hemisphere stroke.

Case-control studies have shown right hemisphere specialization in the production of intonation in speech. We examined spontaneous prosody in audiotapes of interviews with a 77-year-old right-handed woman recorded 6 months before and 6 weeks after she suffered a stroke affecting the right frontotemporo-parietal regions and the right basal ganglia. Post-stroke, the patient had a normal Mini-Mental Status Examination Score of 29, hemispatial neglect, and impairments in the comprehension of facial expression and prosody. Self-rated mood was within normal limits. We compared beginning, peak, and ending fundamental frequencies (fo) in breath groups, the timing of these fo changes, rate of speech, pause duration, and breath-group duration. We found that post-stroke, the patient had a more restricted fo contour, no changes in the timing of peak fo, an increased rate of speech, less variability in pause duration, and no changes in breath-group duration.

Spontaneous gestures following right hemisphere infarct.

Neurobehavioral studies of gesturing have been largely limited to left hemisphere damaged (LHD) patients. We compared spontaneous gesturing in seven right hemisphere damaged (RHD) patients, seven LHD patients, and seven normal controls (NHD) during videotaped interviews. Two judges coded symbolic, expressive, grooming, and fidgeting gestures in 120 10-sec intervals of videotape per patient. We found that RHD patients made significantly more total gestures and grooming gestures with the hand ipsilateral to their lesion than did LHD patients. Furthermore, RHD patients made more total and grooming gestures with their right hand than NHD subjects did with either hand. There were no differences in gesture production between the right and left hands of NHD patients. These results suggest that RHD produces enhanced gesturing, particularly involving grooming behavior.

Right hemisphere facial expressivity during natural conversation.

Most studies of facial expressivity in patients with focal brain lesions have examined the ability to produce emotional expression in laboratory settings using various experimental paradigms. In this study, we compared facial expressivity in right hemisphere damaged patients (RHD), left hemisphere damaged patients (LHD), and normal controls (NHD) during videotaped semistructured interviews with the patient and spouse in their home. Three research assistants rated 120 10-sec segments of videotape per patient on a 7-point expressivity scale. We found that RHD patients showed reduced facial expressivity in comparison to both LHD and NHD subjects during spontaneous conversation. In particular, RHD patients demonstrated significantly less smiling and laughter than LHD patients and normal controls. These findings were not a general feature of communicative competence in RHD patients as discourse production equaled that of normal controls. These results support the hypothesis that the right hemisphere mediates facial expressivity during spontaneous social interaction.

Differential impact of right and left hemisphere lesions on facial emotion and object imagery.

Thirty-six patients with unilateral hemispheric lesions of the right hemisphere (RHD), left hemisphere (LHD), or no neurologic disease were evaluated on two tasks of visual imagery: one involved imagery for facial emotions and the other involved imagery for common objects. As a group, the RHD patients were more impaired on the emotional than the object imagery task, whereas the LHD patients showed the opposite pattern. Individual case analyses suggested that the RHD group consisted of different behavioural subtypes. One patient with a right inferior occipito-temporal lesion had a facial emotion imagery generation defect, other RHD patients displayed a facial affect agnosia (being impaired on emotional imagery and emotional perceptual tasks), while other RHD patients had perceptual defects with sparing of imagery performance. A final RHD group was globally impaired across all imagery and perceptual tasks. These findings support the hypothesis that the right hemisphere may contain a 'lexicon' of facial emotions. Furthermore, these findings argue against current views that it is exclusively the left or right hemisphere that mediates visual imagery. Rather, hemispheric asymmetries in imagery performance are to some extent material-representation specific and may arise when (a) the representations of objects/events to be imaged are differentially represented in the hemispheres, and/or (b) when the operations acting on these imaged events are differentially lateralized.

Phonolexical agraphia. Superimposition of acquired lexical agraphia on developmental phonological dysgraphia.

Study of neuropsychological sequelae of a focal acquired brain lesion may bring out and help delineate the features of a compensated developmental language disorder and its anatomical substrate. A left-handed man with a history of phonological developmental dyslexia and dysgraphia learned in early adulthood to read and write using a lexical system. Following a small posterior right parietal infarct when aged 56 yrs he developed a severe agraphia displaying features of phonological dysgraphia with impaired segmentation and features of lexical agraphia. Writing was severely impaired for all classes of word and nonword stimuli but his errors did not resemble those attributable to a deficit in the system responsible for the short-term storage of the graphemic representation of a word (graphemic output buffer). These observations imply that an acquired lexical agraphia has been superimposed on his developmental phonological dysgraphia, resulting in a combined or 'phonolexical' agraphia.

The role of the right hemisphere in emotional communication.

Previous research has established that patients with right hemisphere damage (RHD) are impaired in the comprehension of emotional prosody and facial expression. There are several explanations for this impairment. It may reflect defective acoustic and visuospatial analysis, disruption of nonverbal communicative representations, or a disturbance in the comprehension of emotional meaning. In order to examine these hypotheses, we asked RHD patients, left hemisphere damaged patients (LHD) and normal controls (NC) to judge the emotional content of sentences describing nonverbal expressions, and sentences describing emotional situations. We found that RHD subjects performed normally in their ability to infer the emotion conveyed by sentences describing situations. However, RHD patients were impaired in relation to both LHD and NC in the capacity to judge the emotional content of sentences depicting facial, prosodic, and gestural expressions, suggesting a disruption of nonverbal communicative representations.

Human neuropsychology and the concept of culture.

American anthropology is distinguished by a four-fields approach in which biological, cultural, archaeological, and linguistic dimensions of behavior are examined in evolutionary and cross-cultural perspective. Nevertheless, assumptions of mind-body dualism pervade scholarly thinking in anthropology and have prevented the development of a truly integrated science of human experience. This dualism is most exemplified by the lack of consideration of the role of the brain in both "physical" and "mental" processes, including phenomena labeled as cultural. In this paper, I review neural mechanisms of learning, communication, and emotion, and discuss the implications of these findings for culture theory.

Neuropsychological functioning in hemiparkinsonism.

A standardized neuropsychological battery including measures of intellectual cognitive, memory, attention-concentration, language, abstraction and mental flexibility, and sensory and motor functions was administered to 21 hemiparkinsonian patients (14 with right side and 7 with left side symptoms) and 17 controls matched for age and education. Patients were impaired in all functions except sensory. For motor functions, impairment was ipsilateral to the side of symptoms. For cognitive functions, right side symptoms were associated with verbal deficits whereas left side symptoms were associated with spatial deficits. Thus, a pattern of neuropsychological deficits consistent with the lateralization of motor symptoms may appear in the early stages of the disease.

The effects of right and left hemiparkinsonism on prosody.

Recent studies show right hemisphere dominance in the mediation of emotional prosody and left hemisphere contribution to linguistic prosody in patients with cortical injury. The present study investigated emotional and linguistic functions of prosody as well as facial and musical processing in 21 patients with lateralized subcortical disease. Fourteen right hemiparkinsonians (RPD) and 7 left hemiparkinsonians (LPD) were compared to 17 normal controls (NC). Patients were impaired on receptive and expressive tests of emotional and linguistic prosody. Patients were also selectively impaired on emotional processing of facial stimuli and in the musical processing of pitch and tonal memory, though not timber. These findings suggest that monotone speech reported in PD is of multimodal origins and may involve dysfunction in neural centers involved in emotional and linguistic processing. There were no differences between RPD and LPD groups in the pattern of deficits, suggesting bilateral involvement in emotional processing at the subcortical level.