Biomedical subjects

C L Grady

Publications and source records attributed to C L Grady.

At least 19 recordsLinked to original sources

PubMed2001

"What" and "where" in the human auditory system.

The extent to which sound identification and sound localization depend on specialized auditory pathways was examined by using functional magnetic resonance imaging and event-related brain potentials. Participants performed an S1-S2 match-to-sample task in which S1 differed from S2 in its pitch and/or location. In the pitch task, participants indicated whether S2 was lower, identical, or higher in pitch than S1. In the location task, participants were asked to localize S2 relative to S1 (i.e., leftward, same, or rightward). Relative to location, pitch processing generated greater activation in auditory cortex and the inferior frontal gyrus. Conversely, identifying the location of S2 relative to S1 generated greater activation in posterior temporal cortex, parietal cortex, and the superior frontal sulcus. Differential task-related effects on event-related brain potentials (ERPs) were seen in anterior and posterior brain regions beginning at 300 ms poststimulus and lasting for several hundred milliseconds. The converging evidence from two independent measurements of dissociable brain activity during identification and localization of identical stimuli provides strong support for specialized auditory streams in the human brain. These findings are analogous to the "what" and "where" segregation of visual information processing, and suggest that a similar functional organization exists for processing information from the auditory modality.

Acoustic Stimulation↗

PubMed2001

An examination of the effects of stimulus type, encoding task, and functional connectivity on the role of right prefrontal cortex in recognition memory.

Right anterior prefrontal cortex and other brain areas are active during memory retrieval but the role of prefrontal cortex and how it interacts with these other regions to mediate memory function remain unclear. To explore these issues we used positron emission tomography to examine the effects of stimulus material and encoding task on brain activity during visual recognition, assessing both task-related changes and functional connectivity. Words and pictures of objects were encoded using perceptual and semantic strategies, resulting in better memory for semantically encoded items. There was no significant effect of prior encoding strategy on brain activity during recognition. Right anterior prefrontal cortex was equally active during recognition of both types of stimuli irrespective of initial encoding strategy. Regions whose activity was positively correlated with activity in right anterior prefrontal cortex included widespread areas of prefrontal and inferior temporal cortices bilaterally. Activity in this entire network of regions was negatively correlated with recognition accuracy of semantically encoded items. These results suggest that initial encoding task has little impact on the set of brain regions that is active during subsequent recognition. Right anterior prefrontal cortex appears to be involved in retrieval mode, reflected in its equivalent activity across conditions differing in both stimulus type and encoding task, and also in retrieval effort, shown by the negative correlation between its functional connectivity and individual differences in recognition accuracy.

Adult↗

PubMed2001

Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease.

To examine functional interactions between prefrontal and medial temporal brain areas during face memory, blood flow was measured in patients with Alzheimer's disease and healthy controls using PET. We hypothesized that controls would show correlated activity between frontal and posterior brain areas, including the medial temporal cortex, whereas patients would not, although frontal activity per se might be spared or even increased compared with controls. We used a delayed match to sample paradigm with delays from 1 to 16 s. There was no change in recognition accuracy with increasing delay in controls, whereas patients showed impaired recognition over all delays that worsened as delay increased. Controls showed increased activity in the bilateral prefrontal and parietal cortex with increasing delay, whereas the patients had increased activity in the right prefrontal, anterior cingulate and left amygdala. Increased activity in the right prefrontal cortex was associated with better memory performance in both groups and activity in the left amygdala was correlated with better performance in the patients. Based on these task and behavioural effects, we examined functional connectivity of the right prefrontal cortex and left amygdala in both groups by determining those areas whose activity was correlated with activity in these regions. In controls, activity in the right prefrontal cortex was positively correlated with blood flow in the left prefrontal cortex, bilateral extrastriate and parietal areas and the right hippocampus. In patients, activity in the right prefrontal cortex was correlated mainly with other prefrontal regions. Areas where activity was correlated with the left amygdala in patients included the bilateral posterior parahippocampal gyri, a number of left prefrontal regions, anterior and posterior cingulate, thalamus, and insula. Controls had a relatively restricted set of regions where activity correlated with the left amygdala, mainly temporal and occipital areas. These results support the idea of a functional disconnection between the prefrontal cortex and the hippocampus in Alzheimer's disease and suggest that memory breakdown in early Alzheimer's disease is related to a reduction in the integrated activity within a distributed network that includes these two areas. The unexpected finding of increased involvement of the amygdala suggests that the patients may have processed the emotional content of the faces to a greater degree than did the controls. Furthermore, the positive association between amygdala activity and memory performance in the patients suggests a possible compensatory role for an emotion-related network of regions.

Aged↗

PubMed2000

Corticolimbic interactions associated with performance on a short-term memory task are modified by age.

Aging has been associated with a decline in memory abilities dependent on hippocampal processing. We investigated whether the functional interactions between the hippocampus and related cortical areas were modified by age. Young and old subjects' brain activity was measured using positron emission tomography (PET) while they performed a short-term memory task (delayed visual discrimination) in which they determined which of two successively presented sine-wave gratings had the highest spatial frequency. Behavioral performance was equal for the two groups. Partial least squares (PLS) analysis of PET images identified a hippocampal voxel whose activity was similarly correlated with performance across groups. Using this voxel as a seed, a second PLS analysis identified cortical regions functionally connected to the hippocampus. Quantification of the neural interactions with structural equation modeling suggested that a different hippocampal network supported performance in the elderly. Unlike the neural network engaged by the young, which included prefrontal cortex Brodmann's area (BA) 10, fusiform gyrus, and posterior cingulate gyrus, the network recruited by the old included more anterior areas, i.e., dorsolateral prefrontal cortex (BA 9/46), middle cingulate gyrus, and caudate nucleus. Recruitment of a distinct corticolimbic network for visual memory in the elderly suggests that age-related neurobiological deterioration not only results in focal changes but also in the modification of large-scale network operations.

Adult↗

PubMed2000

Functional brain imaging and age-related changes in cognition.

There are a number of age-related structural and physiological changes in the brain that could have implications for cognitive function in the elderly. The impact of these age-related changes in the brain on cognition has been studied using neuroimaging to examine brain activity during tasks of memory, perception and attention, and determine how this activity differs between young and older individuals. It has often been found that older individuals utilize different areas of the brain than do young subjects when carrying out the same cognitive task. This has led some researchers to suggest that older persons utilize different functional brain networks, perhaps to compensate for reductions of efficiency in task-related brain areas. However, data collected to date on this issue are still limited, so although the evidence is intriguing, the definitive interpretation of these findings must await further experiments.

Adult↗

PubMed2000

Changes in memory processing with age.

Over the years, a large body of literature has shown that humans display losses in memory with age, but that not all types of memory are affected equally. Similarly, recent evidence from functional neuroimaging experiments has revealed that, depending on the task, older adults can display greater or lesser activity in task-relevant brain areas compared with younger adults. Recent behavioral and neurophysiological experiments are furthering our understanding of the effects of aging on cognition. It appears that some brain changes seen with age may be compensatory.

Adaptation, Physiological↗

PubMed1999

Recruitment of unique neural systems to support visual memory in normal aging.

The performance of many cognitive tasks changes in normal aging [1] [2] [3]. Recent behavioral work has identified some tasks that seem to be performed in an age-invariant manner [4]. To understand the brain mechanisms responsible for this, we combined psychophysical measurements of visual short-term memory with positron emission tomography (PET) in young and old individuals. Participants judged the differences between two visual stimuli, and the memory load was manipulated by interposing a delay between the two stimuli. Both age groups performed the task equally well, but the neural systems supporting performance differed between young and old individuals. Although there was some overlap in the brain regions supporting performance (for example, occipital, temporal and inferior prefrontal cortices, and caudate), the functional interconnections between these common regions were much weaker in old participants. This suggests that the regions were not operating effectively as a network in old individuals. Old participants recruited unique areas, however, including medial temporal and dorsolateral prefrontal cortices. These unique areas were strongly interactive and their activity was related to performance only in old participants. Therefore, these areas may have acted to compensate for reduced interactions between the other brain areas.

Adolescent↗

PubMed1999

Frontotemporal interactions in face encoding and recognition.

Cognition may result from different patterns of neural interactions distributed across the brain. If this is true then across different cognitive tasks different functional interactions should be observed within an anatomical network. To investigate this hypothesis, a network analysis of PET data obtained from a face memory study was conducted. PET scans were obtained while subjects performed face perception, face encoding and face recognition tasks. Partial least squares (PLS) analysis of rCBF was used to identify brain regions that were engaged during these tasks, and anatomically based structural equation modeling (SEM) was used to construct functional models for matching, encoding and recognition. There was some overlap in the functional interactions observed across the three cognitive tasks. In all three tasks, there were positive interactions involving the left occipitotemporal regions. These interactions may represent the perceptual component of the three tasks. Task-specific functional interactions were also observed. During face encoding, there was a bilateral positive influence of occipitotemporal regions on medial temporal regions. In addition, there were positive interhemispheric interactions between middle temporal regions and between limbic regions during encoding. These patterns may reflect the participation of medial temporal cortex in the formation of new memories. In the face recognition task, there was a positive loop in the right hemisphere from occipital cortex to frontal cortex and back from frontal cortex to occipitotemporal cortex. In addition, there was a strong positive input into the right hippocampal region from right occipitotemporal cortex. This pattern of interaction was specific to the recognition task and might represent the process whereby the input faces are compared to the internal representation laid down during encoding, thus enabling recognition.

Adult↗

PubMed1999

Individual differences in PET activation of object perception and attention systems predict face matching accuracy.

We sought to investigate how individual differences in the regional patterns of cerebral blood flow (rCBF) relate to task performance during the perceptual matching of faces. We analyzed rCBF data obtained by PET and H2150 from nine young healthy, right-handed, adult males (mean age 29i3 years) using a statistical model of regional covariance, the Scaled Subprofile Model (SSM). SSM analysis performed on a voxel-basis for scan subtractions comparing face-matching and control tasks extracted two patterns whose subject expression in a multiple regression analysis was highly predictive of task accuracy (R2 = 0.87, p < 0.002). The pattern reflecting this linear combination was principally characterized by higher rCBF in regions of bilateral occipital and occipitotemporal cortex, right orbitofrontal cortex, left thalamus, basal ganglia, midbrain, and cerebellum with relatively lower rCBF in anterior cingulate, regions in bilateral prefrontal and temporal cortex, right thalamus, and right inferior parietal cortex. The results indicate that individual subject differences in face matching performance are specifically associated with the functional interaction of cortical and subcortical brain regions previously implicated in aspects of object perception and visual attentional processing.

Adult↗

PubMed1999

The effects of age on the neural correlates of episodic encoding.

Young and old adults underwent positron emission tomographic scans while encoding pictures of objects and words using three encoding strategies: deep processing (a semantic living/nonliving judgement), shallow processing (size judgement) and intentional learning. Picture memory exceeded word memory in both young and old groups, and there was an age-related decrement only in word recognition. During the encoding tasks three brain activity patterns were found that differentiated stimulus type and the different encoding strategies. The stimulus-specific pattern was characterized by greater activity in extrastriate and medial temporal cortices during picture encoding, and greater activity in left prefrontal and temporal cortices during encoding of words. The older adults showed this pattern to a significantly lesser degree. A pattern distinguishing deep processing from intentional learning of words and pictures was identified, characterized mainly by differences in prefrontal cortex, and this pattern also was of significantly lesser magnitude in the old group. A final pattern identified areas with increased activity during deep processing and intentional learning of pictures, including left prefrontal and bilateral medial temporal regions. There was no group difference in this pattern. These results indicate age-related dysfunction in several encoding networks, with sparing of one specifically involved in more elaborate encoding of pictures. These age-related changes appear to affect verbal memory more than picture memory.

Adult↗

PubMed1999

Premutation female carriers of fragile X syndrome: a pilot study on brain anatomy and metabolism.

OBJECTIVE: It was thought that premutation carriers of fragile X syndrome (FraX) have no neurobiological abnormalities, but there have been no quantitative studies of brain morphometry and metabolism. Thus the authors investigated brain structure and metabolism in premutation carriers of FraX. METHOD: Eight normal IQ, healthy female permutation FraX carriers aged 39 +/- 9 years (mean +/- SD) and 32 age-sex-handedness-matched controls (39 +/- 10 years) were studied; in vivo brain morphometry was measured using volumetric magnetic resonances imaging, and regional cerebral metabolic rates for glucose were measured using positron emission tomography and (18F)-2-fluoro-2-deoxy-D-glucose. RESULTS: Compared with controls, FraX premutation carriers had a significant (1) decrease in volume of whole brain, and caudate and thalamic nuclei bilaterally; (2) increase in volume of hippocampus and peripheral CSF bilaterally, and third ventricle; (3) relative hypometabolism of right parietal, temporal, and occipital association areas; (4) bilateral relative hypermetabolism of hippocampus; (5) relative hypermetabolism of left cerebellum; and (6) difference in right-left asymmetry of the Wernicke and Broca language areas. CONCLUSIONS: Premutation carriers of FraX, as defined by analysis of peripheral lymphocytes, have abnormalities in brain anatomy and metabolism. The biological basis for this is unknown, but most likely it includes tissue heterogeneity for mutation status. The findings may be of relevance to people counseling families with FraX and to understanding other neuropsychiatric disorders which are associated with expansion of triplet repeats and genetic anticipation.

Adult↗

PubMed1998

Neural correlates of the episodic encoding of pictures and words.

A striking characteristic of human memory is that pictures are remembered better than words. We examined the neural correlates of memory for pictures and words in the context of episodic memory encoding to determine material-specific differences in brain activity patterns. To do this, we used positron emission tomography to map the brain regions active during encoding of words and pictures of objects. Encoding was carried out by using three different strategies to explore possible interactions between material specificity and types of processing. Encoding of pictures resulted in greater activity of bilateral visual and medial temporal cortices, compared with encoding words, whereas encoding of words was associated with increased activity in prefrontal and temporoparietal regions related to language function. Each encoding strategy was characterized by a distinctive activity pattern, but these patterns were largely the same for pictures and words. Thus, superior overall memory for pictures may be mediated by more effective and automatic engagement of areas important for visual memory, including medial temporal cortex, whereas the mechanisms underlying specific encoding strategies appear to operate similarly on pictures and words.

Adult↗

PubMed1998

Age-related changes in regional cerebral blood flow during working memory for faces.

Young and old adults underwent positron emission tomography during the performance of a working memory task for faces (delayed match-to-sample), in which the delay between the sample and choice faces was varied from 1 to 21 s. Reaction time was slower and accuracy lower in the old group, but not markedly so. Values of regional cerebral blood flow (rCBF) were analyzed for sustained activity across delay conditions, as well as for changes as delay increased. Many brain regions showed similar activity during these tasks in both young and old adults, including left anterior prefrontal cortex, which had increased rCBF with delay, and ventral extrastriate cortex, which showed decreased rCBF with delay. However, old adults had less activation overall and less modulation of rCBF across delay in right ventrolateral prefrontal cortex than did the young adults. Old adults also showed greater rCBF activation in left dorsolateral prefrontal cortex across all WM delays and increased rCBF at short delays in left occipitoparietal cortex compared to young adults. Activity in many of these regions was differentially related to performance in that it was associated with decreasing response times in the young group and increasing response times in the older individuals. Thus despite the finding that performance on these memory tasks and associated activity in a number of brain areas are relatively preserved in old adults, differences elsewhere in the brain suggest that different strategies or cognitive processes are used by the elderly to maintain memory representations over short periods of time.

Adult↗

PubMed1997

Age-related differences in effective neural connectivity during encoding and recall.

Age-related differences in brain activity may reflect local neural changes in the regions involved or they may reflect a more global transformation of brain function. To investigate this issue, we applied structural equation modeling to the results of a positron emission tomography (PET) study in which young and old adults encoded and recalled word pairs. In the young group there was a shift from positive interactions involving the left prefrontal cortex during encoding to positive interactions involving the right prefrontal cortex during recall, whereas in the old group frontal interactions were mixed during encoding and bilaterally positive during recall. The present results suggest that age-related changes in neural activation are partly due to age-related changes in effective connectivity in the neural network underlying the task.

Adult↗

PubMed1997

Attention-related modulation of activity in primary and secondary auditory cortex.

We investigated the effects of auditory attention on brain activity using functional magnetic resonance imaging. Subjects listened to three word lists, three times each, and were instructed to count the number of times they heard a target word during two of these presentations. For the third, they listened to the words without counting. All subjects showed significant areas of activation in auditory cortex during the listening conditions compared to rest. There was significantly more activation and a larger area of activation, particularly in association cortex, in the left temporal lobe during counting of targets compared to the no-target conditions, with a similar trend in the right hemisphere. These results provide evidence of an attention-related enhancement of both activation magnitude and extent in auditory cortex.

Adult↗

PubMed1997

Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory.

Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease. To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task. Eight control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans. rCBF was measured using H215O and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces. Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated. These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort.

Adult↗

PubMed1997

Age-related differences in neural activity during memory encoding and retrieval: a positron emission tomography study.

Positron emission tomography (PET) was used to compare regional cerebral blood flow (rCBF) in young (mean 26 years) and old (mean 70 years) subjects while they were encoding, recognizing, and recalling word pairs. A multivariate partial-least-squares (PLS) analysis of the data was used to identify age-related neural changes associated with (1) encoding versus retrieval and (2) recognition versus recall. Young subjects showed higher activation than old subjects (1) in left prefrontal and occipito-temporal regions during encoding and (2) in right prefrontal and parietal regions during retrieval. Old subjects showed relatively higher activation than young subjects in several regions, including insular regions during encoding, cuneus/precuneus regions during recognition, and left prefrontal regions during recall. Frontal activity in young subjects was left-lateralized during encoding and right-lateralized during recall [hemispheric encoding/retrieval asymmetry (HERA)], whereas old adults showed little frontal activity during encoding and a more bilateral pattern of frontal activation during retrieval. In young subjects, activation in recall was higher than that in recognition in cerebellar and cingulate regions, whereas recognition showed higher activity in right temporal and parietal regions. In old subjects, the differences in blood flow between recall and recognition were smaller in these regions, yet more pronounced in other regions. Taken together, the results indicate that advanced age is associated with neural changes in the brain systems underlying encoding, recognition, and recall. These changes take two forms: (1) age-related decreases in local regional activity, which may signal less efficient processing by the old, and (2) age-related increases in activity, which may signal functional compensation.

Adult↗

PubMed1997

Frequency variation of a pattern-flash visual stimulus during PET differentially activates brain from striate through frontal cortex.

We evaluate regional cerebral blood flow (rCBF) in 19 healthy elderly subjects, mean age 64 +/- 11 (SD, years), during a passive visual stimulus in which pattern-flash frequency was parametrically manipulated. Using goggles with a grid of red lights imbedded into each lens, we performed five positron emission tomography (PET) H2(15)O water scans on each subject at alternating (left to right eye) flash frequencies of 0, 1, 4, 7, and 14 Hz. We found a biphasic rising and falling rCBF response in the striate cortex (7 Hz peak) and left anterior cingulate (4 Hz peak), 1 Hz activation in left middle temporal gyrus (V5), monotonically increasing rCBF in posterior areas (lateral and inferior visual association areas, Brodmann 18 and 19), and monotonically decreasing rCBF in anterior areas (frontal, cingulate, and superior temporal) predominantly in right hemisphere. We suggest the striate rCBF changes at all frequencies primarily reflect lateral geniculate input, the middle temporal activation at 1 Hz reflects perception of apparent motion, and the posterior extrastriate rCBF monotonic increase represents a neural response to increasing luminance intensity and form and color complexity that occur as pattern-flash frequency increases. The anterior monotonic rCBF decrease may represent active cross-modal functional suppression of brain areas irrelevant for processing the passive visual stimulus. Pattern-flash rCBF responses were highly reproducible (no series effect), more so in posterior than in anterior brain regions. The reproducibility and systematically changing rCBF responses to this passive stimulus suggest that it could be successfully used as a disease probe to evaluate neural function and drug effects in cognitively impaired patients.

Aged↗