Using fMR adaptation, we studied the effects of aging on the neural processing of passively viewed naturalistic pictures composed of a prominent object against a background scene. Spatially distinct neural regions showing specific patterns of adaptation to objects, background scenes, and contextual integration (binding) were identified in young adults. Older adults did not show adaptation responses corresponding to binding in the medial-temporal areas. They also showed an adaptation deficit for objects whereby their lateral occipital complex (LOC) did not adapt to repeated objects in the context of a changing background. The LOC could be activated, however, when objects were presented without a background. Moreover, the adaptation deficit for objects viewed against backgrounds was reversed when elderly subjects were asked to attend to objects while viewing these complex pictures. These findings suggest that the elderly have difficulty with simultaneous processing of objects and backgrounds that, in turn, could contribute to deficient contextual binding.

OBJECTIVE: Working memory, a critical cognitive capacity that is affected in schizophrenia, can be divided into maintenance and manipulation processes. Previous behavioral research suggested that manipulation is more affected than maintenance in patients with chronic schizophrenia. In this study of first-episode schizophrenia patients, the authors evaluated the extent to which the two working memory processes are affected early in the course of schizophrenia. METHOD: Study subjects were 11 first-episode schizophrenia patients and 11 matched healthy comparison subjects. Each group performed two verbal working memory tasks while undergoing functional magnetic resonance imaging. One task required maintenance of information; the other required manipulation of information in addition to maintenance. RESULTS: Under behaviorally matched conditions, both groups activated a predominantly left-sided frontal-parietal network. The manipulation plus maintenance task elicited activation of greater magnitude and spatial extent. With both tasks, patients showed less bilateral dorsolateral prefrontal cortex activation and greater ventrolateral prefrontal cortex activation, relative to the comparison subjects. A group-by-task interaction was observed for activation at the left dorsolateral and ventrolateral prefrontal cortex. The increase in activation when patients engaged in the manipulation plus maintenance task was disproportionately less in the dorsolateral prefrontal cortex and greater in the ventrolateral prefrontal cortex. CONCLUSIONS: These functional neuroanatomical findings add support to earlier suggestions that manipulation of information is selectively more affected than maintenance of information in persons with schizophrenia. They also suggest the presence of interacting regions of dysfunctional and compensatory prefrontal responses in the dorsolateral and ventrolateral prefrontal cortex, respectively, that are more prominent when information is manipulated. This disrupted prefrontal network is present relatively early in the course of schizophrenia.

Working memory is an important mental capacity that is compromised following sleep deprivation (SD). To understand how working memory load interacts with state to influence brain activation in load-sensitive regions, and the extent to which SD-related changes are common across different loads, we used fMRI to study twelve healthy subjects following 24 h of SD using a verbal n-back task with three load levels. Performance decline was observed by way of reduced accuracy and slower response times following SD. The left prefrontal region and thalamus showed load dependent activity modulation that interacted with state. The right parietal and anterior medial frontal regions showed load dependent changes in activity as well as an effect of state. The anterior cingulate and occipital regions showed activation that displayed state effects that were independent of working memory load. These findings represent a step toward identifying how different brain regions exhibit varying vulnerability to the deleterious effects of SD on working memory.

Several lines of evidence suggest the importance of phonological working memory (PWM) in language acquisition. We investigated the neural correlates of PWM in young adults who were under compelling social pressure to be bilingual. Equal bilinguals had high proficiency in English and Chinese as measured by a standardized examination, whereas unequal bilinguals were proficient in English but not Chinese. Both groups were matched on several measures of nonverbal intelligence and working memory. In-scanner behavioral results did not show between-group differences. Of the regions showing load-dependent increments in activation, the left insula showed greater activation in equal bilinguals. Unequal bilinguals showed greater task-related deactivation in the anterior medial frontal region and greater anterior cingulate activation. Although unequal bilinguals kept apace with equal bilinguals in the simple PWM task, the differential cortical activations suggest that more optimal engagement of PWM in the latter may correlate with better second-language attainment.

Previous work has suggested that object and place processing are neuroanatomically dissociated in ventral visual areas under conditions of passive viewing. It has also been shown that the hippocampus and parahippocampal gyrus mediate the integration of objects with background scenes in functional imaging studies, but only when encoding or retrieval processes have been directed toward the relevant stimuli. Using functional magnetic resonance adaptation, we demonstrated that object, background scene, and contextual integration of selectively repeated objects and background scenes could be dissociated during the passive viewing of naturalistic pictures involving object-scene pairings. Specifically, bilateral fusiform areas showed adaptation to object repetition, regardless of whether the associated scene was novel or repeated, suggesting sensitivity to object processing. Bilateral parahippocampal regions showed adaptation to background scene repetition, regardless of whether the focal object was novel or repeated, suggesting selectivity for background scene processing. Finally, bilateral parahippocampal regions distinct from those involved in scene processing and the right hippocampus showed adaptation only when the unique pairing of object with background scene was repeated, suggesting that these regions perform binding operations.

Prior work has shown that when responses to incidentally encoded words are sorted, subsequently remembered words elicit greater left prefrontal BOLD signal change relative to forgotten words. Similarly, low-frequency words elicit greater activation than high-frequency words in the same left prefrontal regions, contributing to their better subsequent memorability. This study examined the relative contribution of encoding and retrieval processes to the correct recognition of target words. A mixture of high- and low-frequency words was incidentally encoded. Scanning was performed at encoding as well as during retrieval. During encoding, greater activation in the left prefrontal and anterior cingulate regions predicted a higher proportion of hits for low-frequency words. However, data acquired during recognition showed that word frequency did not modulate activation in any of the areas tracking successful recognition. This result demonstrates that under some circumstances, the recognition of studied words is determined purely by processes that are active during encoding. In contrast to the finding for hits, activation associated with correctly rejected foils was modulated by word frequency, being higher for high-frequency words in the left lateral parietal and anterior prefrontal regions. These findings were replicated in two further experiments, one in which the number of test items at recognition was doubled and another where encoding strength for high-frequency words was varied (once vs. 10 times). These results indicate that word frequency modulates activity in the left lateral parietal and anterior prefrontal regions contingent on whether the item involved is correctly recognized as a target or a foil. This observation is consistent with a dual process account of episodic memory.

Event-related fMRI was used to evaluate the effect of printed word frequency on the subsequent recognition of words incidentally encoded while 16 healthy right-handed volunteers performed living/nonliving judgments. Semantic judgment took longer for low-frequency words. These words were more accurately recognized than high-frequency words at later testing. Low-frequency words were also associated with relatively greater left prefrontal, left fusiform gyrus, and anterior cingulate activation. Words that were subsequently recognized were associated with greater activation in the left prefrontal region compared to those that were forgotten. These findings suggest the specific brain regions where less commonly encountered words are processed in a manner that facilitates their subsequent recognition.

We determined the reproducibility of both the direction and the effect size of the word frequency effect (WFE) as it relates to associative semantic judgments. Sixteen volunteers were scanned twice. At the group level of analysis, signal change and voxel counting could both reproducibly detect the existence of a WFE. However, signal change data showed less intersession variation, particularly in the left inferior frontal gyrus. The effect size of WFE was well reproduced only with signal change measurements. In consideration of the signal change data, statistical threshold did not have a major effect on the detection or determination of the effect size. In general, while the direction of the WFE was reasonably reproducible at the individual level, the effect size was far less well reproduced. These findings suggest that with existing techniques, fMRI may be used to track changes in brain activation stemming from improvement in language proficiency at the group level but not at the individual level.

The effect of word repetition within and across languages was studied in English-Chinese bilinguals who read rapidly presented word pairs in a block design and an event-related fMRI study. Relatively less increase in MR signal was observed when the second word in a pair was identical in meaning to the first. This occurred in the English-only and mixed-languages conditions. Repetition-induced reductions in BOLD signal change were found in the left lateral prefrontal and lateral temporal regions in both types of conditions in the block experiment, suggesting that processing in these regions is sensitive to semantic features present in words and characters, and that part of the semantic neuronal networks serving English and Chinese is shared. In addition, these regions showed greater absolute signal change in the mixed-languages trials relative to the English-only trials. These findings were mostly replicated in an event-related experiment. Together, the experiments suggest that while the networks for Chinese and English word processing have shared components, there are also components that may be language specific.

We investigated the extent of hemodynamic recovery following the paired presentation of either identical or different faces at two different inter-stimulus intervals (ISI). Signal recovery was consistently better at an ISI of 6 sec compared to 3 sec. Significantly less signal recovery was associated with identical faces compared to different faces in bilateral mid-fusiform and right prefrontal regions but not in the calcarine and posterior fusiform regions. Repetition suppression effects contributed significantly to incomplete signal recovery in a region-specific manner. Simulations using empirically derived data suggest that experiments with shorter ISI (average 4.5-6.0 sec) are as sensitive as experiments with intermediate ISI (average 9 sec) in detecting response differences if experimental duration is equivalent. However, designs using intermediate ISI may be more appropriate if the expected difference in responses is small and if the number of suitable stimuli is limited.

This review examines how blood oxygen level-dependent functional magnetic resonance imaging (fMRI) may be harnessed to study the brain when it engages in language processing tasks. This method makes clinical and scientific contributions to understanding language function. Issues such as the lateralisation of language function, brain plasticity in health, ageing and neurological disease, and as well as how 2 different languages are processed, may all be evaluated by fMRI.

The effect of word frequency on semantic processing was characterized by studying two groups of right-handed participants using fMRI. Stimuli were presented in blocks of either high frequency or low frequency word triplets where a sample word appeared above a pair of test words. One group (n = 8) made semantic judgments by selecting the word from the test pair that was more closely associated with the sample. Stimulus triplets were designed such that relatedness between sample and "correct" items was obvious. The other group (n = 8) read the words silently without making any semantic decision and pressed a button on completing the reading of each triplet. Semantic judgments while no less accurate, were associated with greater left prefrontal BOLD signal change when they involved low frequency words, whereas there was no reliable effect of word frequency in the reading condition. These findings suggest that retrieval effort modulates left prefrontal activity when deliberate access to semantics is required.

Objective: To document how right hemisphere language dominance in neurologically normal right-handed individuals affects lateralization of face encoding and level of performance in neuropsychological tests. Methods: Three healthy right-handed adults with predominantly right hemisphere language activation during single-word or sentence-level processing were identified from 210 consecutive right-handed subjects studied using blood oxygenation level-dependent contrast fMRI. These three study subjects (S1 to S3) underwent a second scanning session where they performed word and face encoding. Their functional scans were contrasted with those obtained from six healthy control subjects (C1 to C6) with left hemisphere language dominance. Psychometric tests were performed on the study subjects. Results: Right hemisphere-dominant language activation was reproduced in the second scanning session in the three study subjects. The extent to which the lateralization of face encoding was reversed varied. Right hemisphere language was associated with lower (but within normal) verbal IQ compared with performance IQ in two of three volunteers. Verbal and nonverbal memory scores were normal and did not differ appreciably. Conclusion: Right hemisphere-dominant language in healthy dextrals exists but is rare. The extent to which face encoding is reversed in these individuals is variable. Cognitive function does not appear to be significantly compromised even though some psychometric test scores are asymmetric in favor of nonverbal performance when the reversal of lateralization of face and word memory is not complete.