PubMed Health⌕ Search

Biomedical subjects

A R McIntosh

Publications and source records attributed to A R McIntosh.

At least 19 recordsLinked to original sources
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

B16 melanoma cell arrest in the mouse liver induces nitric oxide release and sinusoidal cytotoxicity: a natural hepatic defense against metastasis.

The formation of liver metastases involves interactions between intravascular cancer cells and the hepatic microvasculature. Here we provide evidence that the arrest of intravascular B16F1 melanoma cells in the liver induces a rapid local release of nitric oxide (NO) that causes apoptosis of the melanoma cells and inhibits their subsequent development into hepatic metastases. B16F1 melanoma cells (5 x 10(5)) labeled with fluorescent microspheres were injected into the portal circulation of C57BL/6 mice. The production of NO in vivo was detected by electron paramagnetic resonance spectroscopy ex vivo using an exogenous NO-trapping agent. A burst of NO was observed in liver samples examined immediately after tumor cell injection. The relative electron paramagnetic resonance signal intensity was 667 +/- 143 units in mice injected with tumor cells versus 28 +/- 5 units after saline injection (P < 0.001). Two-thirds of cells arrested in the sinusoids compared with the terminal portal venules (TPVs). By double labeling of B16F1 cells with fluorescent microspheres and a TdT-mediated UTP end labeling assay, we determined that the melanoma cells underwent apoptosis from 4-24 h after arrest. The mean rate of apoptosis was 2-fold greater in the sinusoids than in the TPVs at 4, 8, and 24 h after injection (P < 0.05-0.01). Apoptotic cells accounted for 15.9 +/- 0.8% of tumor cells located in the sinusoids and 7.1 +/- 0.9% of tumor cells in the TPVs. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester completely blocked the NO burst (P < 0.001) and inhibited the apoptosis of B16F1 cells in the sinusoids by 77%. However, the rate of tumor cell apoptosis in the TPVs was not changed. There were 5-fold more metastatic nodules in the livers of N(G)-nitro-L-arginine methyl ester-treated mice (P < 0.05). The inactive enantiomer N(G)-nitro-D-arginine methyl ester had no effect on the initial NO burst or on apoptosis of tumor cells in vivo. Both annexin V phosphatidylserine plasma membrane labeling and DNA end labeling of apoptotic cells were demonstrated after a 5-min exposure (a time equivalent to the initial transient NO induction in vivo) of B16F1 cells to a NO donor in vitro. These results identify the existence of a natural defense mechanism against cancer metastasis whereby the arrest of tumor cells in the liver induces endogenous NO release, leading to sinusoidal tumor cell killing and reduced hepatic metastasis formation.

Animals↗
PubMed2000

Reactivation of encoding-related brain activity during memory retrieval.

Neuronal models predict that retrieval of specific event information reactivates brain regions that were active during encoding of this information. Consistent with this prediction, this positron-emission tomography study showed that remembering that visual words had been paired with sounds at encoding activated some of the auditory brain regions that were engaged during encoding. After word-sound encoding, activation of auditory brain regions was also observed during visual word recognition when there was no demand to retrieve auditory information. Collectively, these observations suggest that information about the auditory components of multisensory event information is stored in auditory responsive cortex and reactivated at retrieval, in keeping with classical ideas about "redintegration, " that is, the power of part of an encoded stimulus complex to evoke the whole experience.

Adult↗
PubMed2000

Neural correlates of semantic associative encoding in episodic memory.

Associations between individual items are the basic building blocks of learning and memory. Functional neuroimaging has now made it possible to study neural correlates of such associations. The present PET study examined three associative encoding conditions differing in the number of words (0, 1, or 2) semantically related to a third word representing the name of a semantic category. A recall task consisting in the presentation of the category names as cues for retrieving the other two members of the triads followed each encoding condition. As expected, retrieval performance increased as the number of semantic exemplars at encoding increased (10%, 43%, 70% items recalled, respectively). A first analysis (partial least squares, PLS) of the PET data identified task-related patterns of activity for associative encoding and cued-recall tasks. A second analysis identified brain regions whose activity was modulated by the number of semantic exemplars at encoding. Some of the task-related brain regions also showed modulated activity by semantic relatedness and consisted in the left inferior prefrontal cortex, right medial temporal lobe, fusiform gyrus and inferior temporal gyrus bilaterally. Some of these regions showed greater activity when words in a triad were unrelated, whereas others did so when the three words were semantically related. These regions have been consistently reported in previous functional neuroimaging studies of associative encoding and may constitute key structures in association formation.

Adult↗
PubMed2000

Large scale neurocognitive networks underlying episodic memory.

Large-scale networks of brain regions are believed to mediate cognitive processes, including episodic memory. Analyses of regional differences in brain activity, measured by functional neuroimaging, have begun to identify putative components of these networks. To more fully characterize neurocognitive networks, however, it is necessary to use analytical methods that quantify neural network interactions. Here, we used positron emission tomography (PET) to measure brain activity during initial encoding and subsequent recognition of sentences and pictures. For each type of material, three recognition conditions were included which varied with respect to target density (0%, 50%, 100%). Analysis of large-scale activity patterns identified a collection of foci whose activity distinguished the processing of sentences vs. pictures. A second pattern, which showed strong prefrontal cortex involvement, distinguished the type of cognitive process (encoding or retrieval). For both pictures and sentences, the manipulation of target density was associated with minor activation changes. Instead, it was found to relate to systematic changes of functional connections between material-specific regions and several other brain regions, including medial temporal, right prefrontal and parietal regions. These findings provide evidence for large-scale neural interactions between material-specific and process-specific neural substrates of episodic encoding and retrieval.

Adult↗
PubMed2000

The effects of divided attention on encoding- and retrieval-related brain activity: A PET study of younger and older adults.

Divided attention (DA) disrupts episodic encoding, but has little effect on episodic retrieval. Furthermore, normal aging is associated with episodic memory impairments, and when young adults are made to encode information under DA conditions, their memory performance is reduced and resembles that of old adults working under full attention (FA) conditions. Together, these results suggest a common neurocognitive mechanism by which aging and DA during encoding disrupt memory performance. In the current study, we used PET to investigate younger and older adults' brain activity during encoding and retrieval under FA and DA conditions. In FA conditions, the old adults showed reduced activity in prefrontal regions that younger adults activated preferentially during encoding or retrieval, as well as increased activity in prefrontal regions young adults did not activate. These results indicate that prefrontal functional specificity of episodic memory is reduced by aging. During encoding, DA reduced memory performance, and reduced brain activity in left-prefrontal and medial-temporal lobe regions for both age groups, indicating that DA during encoding interferes with encoding processes that lead to better memory performance. During retrieval, memory performance and retrieval-related brain activity were relatively immune to DA for both age groups, suggesting that DA during retrieval does not interfere with the brain systems necessary for successful retrieval. Finally, left inferior prefrontal activity was reduced similarly by aging and by DA during encoding, suggesting that the behavioral correspondence between these effects is the result of a reduced ability to engage in elaborate encoding operations.

Adult↗
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

Interactions of prefrontal cortex in relation to awareness in sensory learning.

In an associative learning paradigm, human subjects could be divided based on whether they were aware that one tone predicted a visual event and another did not. Only aware subjects acquired a differential behavioral response to the tones. Regional cerebral blood flow in left prefrontal cortex showed learning-related changes only in aware subjects. Left prefrontal cortex also showed changes in functional connectivity with contralateral prefrontal cortex, sensory association cortices, and cerebellum. Several of the interacting areas correlated with aware subjects' behavior. These results suggest cerebral processes underlying awareness are mediated through interactions of large-scale neurocognitive systems.

Acoustic Stimulation↗
PubMed1999

Brain SPECT imaging and left hemispatial neglect covaried using partial least squares: the Sunnybrook Stroke study.

Hemispatial neglect, characterized as failure to attend to contralesional space, is hypothesized by current neuroanatomical models to result from damage to a network involving the frontal, parietal, and cingulate cortices, basal ganglia, and thalamus. This study investigated this model of neglect in 81 right hemisphere-damaged acute stroke patients using 99mTc-HMPAO single photon emission-computed tomography (SPECT). In order to exploit the inherent collinearity of SPECT regional brain ratios, a novel statistical technique, partial least squares (PLS), was utilized. It makes use of high correlations to identify biologically relevant patterns of brain activity. Averaged ipsilesional cerebellar ratios from 152 brain segments were covaried with performance on subtests of the Sunnybrook Neglect Battery. In this patient sample, the most influential region identified by PLS corresponded to the area surrounding the right temporal-parietal-occipital (TPO) junction that included the right lateral occipital, temporal, and inferior parietal lobes. Hypoperfusion in the medial frontal cortex, including the anterior cingulate, also emerged as significantly associated with more severe neglect. Thus, hypoperfusion in only two of the five hypothesized network regions emerged as significantly associated with hemispatial neglect on SPECT imaging. This work converges with structural imaging studies to suggest that damage to the TPO junction, not just the parietal lobe, may be the critical region for hemispatial neglect. Our study demonstrated the utility of PLS for analyzing functional imaging and behavioral data sets in a clinical population in relation to current neuroanatomical models of neglect.

Aged↗
PubMed1999

Positron emission tomography correlations in and beyond medial temporal lobes.

This article discusses the potential usefulness of brain/ behavior correlational analyses in functional neuroimaging studies of memory, and how such analyses can illuminate the role of medial temporal lobes (MTL) and the hippocampus in episodic and declarative memory processes such as encoding and retrieval. Reanalysis of the results of four previously reported positron emission tomography (PET) studies yielded evidence of both positive and negative between-subjects correlations between recognition-memory accuracy and regional blood flow. The sites of these correlations were in MTL regions as well as in other cortical and subcortical areas, including frontal lobes (Brodmann areas 6, 9, 10, 11, and 47), temporal lobes (BAs 21, 22, and 38), insula, fusiform gyrus, and cuneus/precuneus. These findings were discussed with respect to issues such as localization of the correlation sites, the distinction between brain sites revealed by brain/cognition correlational analyses ("how" sites) and those yielded by cognitive subtraction methods ("what" sites), the tendency of the "how" sites in MTL to occur in the left hemisphere, the tendency of other "how" sites to occur in one or the other hemisphere, rather than bilaterally, and the meaning and "reality" of both brain/behavior correlations and task-related activations. Because of the known incidence of false-positives, all neuroimaging data, including those involving the localization of "what" and "how" memory sites in MTL and other brain regions, need to be interpreted cautiously, and findings of individual studies should not be overinterpreted.

Brain↗
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↗
PubMed1998

Understanding neural interactions in learning and memory using functional neuroimaging.

Neuroimaging methods such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) provide a unique opportunity to explore activity across the entire human brain in many different behaviors. An important additional feature is the ability to examine interacting neural systems using methods that focus on the covariances of activity. Two of these methods, partial least squares and structural equation modeling, are presented with specific examples. Shifting prefrontal and limbic interactions were observed in a working memory task for faces. In an episodic memory retrieval study, the activity of right prefrontal cortex was related to either memory search or successful retrieval depending on its interactions with other brain regions. This latter observation implies that regional activity must be evaluated within the neural context in which it occurs. The general hypothesis that learning and memory are emergent properties of network interactions is discussed, emphasizing that a region can play a different role across many functions and that role is governed by its interactions with anatomically related regions.

Animals↗
PubMed1998

Functional network differences in schizophrenia: a rCBF study of semantic processing.

Studies of regional cerebral blood flow in patients with schizophrenia have led to the idea that dysfunctional neurocircuitry may play a role in patients' cognitive deficits. The present PET study was designed to explore this idea by comparing the functional neural networks associated with semantic processing for patients and normal controls through structural equation modeling (path analysis). The patients showed significantly different neural interactions among frontal regions, between the frontal and temporal cortices, and between the frontal lobe and anterior cingulate than controls. These discrepancies were especially striking given there were minimal group differences in task performance. Results suggest that schizophrenia involves a neural abnormality that is evident in functional networks during cognitive performance.

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

Functional clustering: identifying strongly interactive brain regions in neuroimaging data.

Brain imaging data are generally used to determine which brain regions are most active in an experimental paradigm or in a group of subjects. Theoretical considerations suggest that it would also be of interest to know which set of brain regions are most interactive in a given task or group of subjects. A subset of regions that are much more strongly interactive among themselves than with the rest of the brain is called here a functional cluster. Functional clustering can be assessed by calculating for each subset of brain regions a measure, the cluster index, obtained by dividing the statistical dependence within the subset by that between the subset and rest of the brain. A cluster index value near 1 indicates a homogeneous system, while a high cluster index indicates that a subset of brain regions forms a distinct functional cluster. Within a functional cluster, individual brain regions are ranked at the center or at the periphery according to their statistical dependence with the rest of that cluster. The applicability of this approach has been tested on PET data obtained from normal and schizophrenic subjects performing a set of cognitive tasks. Analysis of the data reveals evidence of functional clustering. A comparative evaluation of which regions are more peripheral or more central suggests distinct differences between the two groups of subjects. We consider the applicability of this analysis to data obtained with imaging modalities offering higher temporal resolution than PET.

Adult↗
PubMed1998

Mapping neural interactivity onto regional activity: an analysis of semantic processing and response mode interactions.

Neuroimaging studies of cognition have typically been designed to identify brain regions that are active during a cognitive process. However, identifying how brain regions interact may be equally important. In a recent study we found that the pattern of activation associated with a semantic task differed depending on how subjects made a response, suggesting that there was an interaction between the neural systems underlying response mode and semantic processing (J. M. Jennings et al., 1997, NeuroImage 5, 229-239). This result raises two important questions, which we examined here: (1) How did the regions underlying semantic performance influence one another, or interact, to produce a different pattern of activation in each case? (2) What can be learned about the neurobiology of semantic processing when different regions are identified as a function of response? We addressed these questions using structural equation modeling. This technique produced functional network models representing the effect of different regions on each other during the semantic task for each response. A common network of regions associated with semantic processing was observed and included the left inferior frontal and left superior temporal cortices, with other regions brought into that network depending on response (e.g., right middle frontal). Moreover, changes in the influences among these regions across response condition predicted the pattern of activation found previously. These results show how an arbitrary response can affect the neural pathways associated with a cognitive process, likely due to the parallel and reentrant organization of the brain, and emphasize the importance of examining functional connections when studying cognition.

Adult↗