Biomedical subjects

Anthony R McIntosh

Publications and source records attributed to Anthony R McIntosh.

At least 19 recordsLinked to original sources

PubMed2006

Two distinct functional networks for successful resolution of proactive interference.

In proactive interference (PI) paradigms, previous learning impairs the acquisition of new, related information. In rats, efficient resolution of PI relies on cholinergic modulation from the basal forebrain (BF). To test whether humans resolve PI using a functional network dependent on the medial septum/diagonal band of Broca (MS/DB) nuclei of the BF, we analyzed functional magnetic resonance imaging signal recorded while human participants learned to respond to baseline color paired associates and then additional pairs that interfered with the baseline pairs. Multivariate, partial least-squares analysis supported a MS/DB-dependent functional network: MS/DB activity covaried with activity in areas important to selective attention, including intraparietal sulcus, and memory that are direct cholinergic efferents of the MS/DB, including the hippocampus, as well as the ventrolateral prefrontal cortex, implicated in PI resolution. This network was associated with effective PI-resolution behavior. A second network also correlated with PI resolution but appearing not to be driven by the MS/DB, included the lateral orbitofrontal cortex. Patients with compromised BF function did not engage the MS/DB-dependent network reliably; instead their PI-resolution behavior was well explained by the second network. Thus, 2 functional networks may underly a single cognitive function; when the MS/DB-dependent attention/memory integration network is compromised, an alternate network is available to maintain normal levels of performance.

Alcoholism↗

PubMed2006

Clustered functional MRI of overt speech production.

To investigate the neural network of overt speech production, event-related fMRI was performed in 9 young healthy adult volunteers. A clustered image acquisition technique was chosen to minimize speech-related movement artifacts. Functional images were acquired during the production of oral movements and of speech of increasing complexity (isolated vowel as well as monosyllabic and trisyllabic utterances). This imaging technique and behavioral task enabled depiction of the articulo-phonologic network of speech production from the supplementary motor area at the cranial end to the red nucleus at the caudal end. Speaking a single vowel and performing simple oral movements involved very similar activation of the cortical and subcortical motor systems. More complex, polysyllabic utterances were associated with additional activation in the bilateral cerebellum, reflecting increased demand on speech motor control, and additional activation in the bilateral temporal cortex, reflecting the stronger involvement of phonologic processing.

Acoustic Stimulation↗

PubMed2006

Testing effective connectivity changes with structural equation modeling: what does a bad model tell us?

Structural equation modeling (SEM) is a statistical method that can assess changes in effective connectivity across tasks or between groups. In its initial application to neuroimaging data, anatomical connectivity provided the constraints to decompose interregional covariances to estimate effective connections. There have been concerns expressed, however, with the validity of interpreting effective connections for a model that does not adequately fit the data. We sought to address this concern by creating two population networks with different patterns of effective connectivity, extracting three samples sizes (N = 100, 60, 20), and then assessing whether the ability to detect effective connectivity differences depended on absolute model fit. Four scenarios were assessed: (1) elimination of a region showing no task differences; (2) elimination of connections with no task differences; (3) elimination of connections that carried task differences, but could be expressed through alternative indirect routes; (4) elimination of connections that carried task differences, and could not be expressed through indirect routes. We were able to detect task differences in all four cases, despite poor absolute model fit. In scenario 3, total effects captured the overall task differences even though the direct effect was no longer present. In scenario 4, task differences that were included in the model remained, but the missing effect was not expressed. In conclusion, it seems that when independent information (e.g., anatomical connectivity) is used to define the causal structure in SEM, inferences about task- or group-dependent changes are valid regardless of absolute model fit.

Algorithms↗

PubMed2006

Linking associative and serial list memory: Pairs versus triples.

Paired associates and serial list memory are typically investigated separately. An "isolation principle" (J. B. Caplan, 2005) was proposed to explain behavior in both paradigms by using a single model, in which serial list and paired associates memory differ only in how isolated pairs of items are from interference from other studied items. In the present study, 2 experiments identify a critical dissociation between the 2 paradigms, challenging this unified account. Specifically, forward and backward probes were highly correlated for pairs and less so for short lists (triples). The authors asked whether the isolation principle could quantitatively accommodate this type of dissociation. A simulation confirmed that a single model incorporating the isolation principle can adequately explain this and other dissociations, supporting the common processes view.

Adolescent↗

PubMed2006

Age-related changes in brain activity across the adult lifespan.

A number of theories have emerged to explain the well-studied changes in memory that occur with age. Many of these theories invoke mechanisms that have the potential to affect multiple cognitive domains, in addition to memory. Such mechanisms include alterations in attentional or inhibitory function, or dysfunction of specific brain areas, such as the frontal lobes. To gain insight into these mechanisms, we used functional magnetic resonance imaging to examine brain activity during encoding and recognition tasks in young, middle-aged, and older adults to identify correlations between age and brain activity across the various tasks. The goal was to see whether these correlations were task-specific or common across tasks, and to determine whether age differences emerged in a linear fashion over the adult years. Across all memory tasks, at both encoding and recognition, linear increases of activity with age were found in areas normally decreased during task performance (e.g., medial frontal and parietal regions), whereas activity in regions with task-related activation (e.g., dorsolateral prefrontal cortex) decreased with age. These results suggest that there is a gradual, age-related reduction in the ability to suspend non-task-related or "default-mode" activity and engage areas for carrying out memory tasks. Such an alteration in the balance between default-mode and task-related activity could account for increased vulnerability to distraction from irrelevant information, and thereby affect multiple cognitive domains.

Adult↗

PubMed2005

Modulation of effective connectivity by cognitive demand in phonological verbal fluency.

Verbal fluency is a classic neuropsychological measure of language production. Phonological verbal fluency involves the generation of words beginning with a specified letter, and its functional neuroanatomy is comprised of a distributed network of regions which is modulated by cognitive load. In order to investigate the functional relationship of these regions, the effective connectivity was analyzed with covariance structural equation modeling under conditions of varying cognitive load. Significant path coefficients were evident between the anterior cingulate, left middle frontal gyrus, and precuneus. The left middle frontal gyrus showed a facilitory projection to the precuneus which had a suppressive influence on anterior cingulate activation. With increasing cognitive demand, the left middle frontal projection to the precuneus became suppressive, and the path coefficient from the precuneus to the anterior cingulate showed a marked diminution in strength. The path analysis suggests that the lead-in process for letter verbal fluency may primarily involve an orthographic visual strategy. The marked changes in path coefficients with the increased cognitive load may reflect the greater demands placed on executive function. The significant changes in path coefficient values with increased cognitive demand indicate the importance of accounting for task difficulty not only in the interpretation of brain activation maps but also for effective connectivity measurements.

Adult↗

PubMed2005

Parallel networks operating across attentional deployment and motion processing: a multi-seed partial least squares fMRI study.

Anticipatory deployment of attention may operate through networks of brain areas that modulate the representations of to-be-attended items in advance of their occurrence through top-down control. Luks and Simpson (2004) (Luks, T.L., Simpson, G.V., 2004. Preparatory deployment of attention to motion activates higher order motion-processing brain regions. NeuroImage 22, 1515-1522) found activations in both control areas and sensory areas during anticipatory deployment of attention to visual motion in the absence of stimuli. In the present follow-up analysis, we tested which network activity during anticipatory deployment of attention is functionally connected with task-related network activity during subsequent selective processing of motion stimuli. Following a cue (anticipatory phase), participants monitored a sequence of complex motion stimuli for a target motion pattern (task phase). We analyzed fMR signal using a partial least squares analysis with previously identified cue- and motion-related voxels as seed regions. The method identified two networks that covaried with the activity of seed regions during the cue and motion-stimulus-processing phases of the task. We suggest that the first network, involving ventral intraparietal sulcus, superior parietal lobule and motor areas, is related to anticipatory and sustained visuomotor attention. Operating in parallel to this visuomotor attention network, there is a second network, involving visual occipital areas, frontal areas as well as angular and supramarginal gyri, that may underlie anticipatory and sustained visual attention processes.

Adult↗

PubMed2005

The Talairach coordinate of a point in the MNI space: how to interpret it.

To perform group studies using functional imaging data, the individual brain images are usually transformed into a common coordinate space. The two most widely used spaces in the neuroscience community are the Talairach space and the Montreal Neurological Institute (MNI) space. The Talairach coordinate system has become the standard reference for reporting the brain locations in scientific publication, even when the data have been spatially transformed into different brain templates (e.g., MNI space). When expressed in terms of individual subjects, the mapping of a coordinate in MNI space to the Talairach space generates distinct coordinates for different subjects. In this paper, we describe two approaches to derive the Talairach coordinates from the MNI space, which is based on the ICBM152 template from the International Consortium of Brain Mapping. One approach is the Talairach Method of Piecewise Linear Scaling (TMPLS) as implemented in the AFNI software package; and the other is a template-matching approach using the linear transformation in SPM99. The uncertainty measurements of the mapping results are presented. This may allow researchers to better interpret results reporting in the Talairach coordinates obtained from the MNI space. This study also examines the discrepancy between the derived Talairach coordinates and those obtained from the mni2tal script, a tool commonly used by the neuroimaging community. Large discrepancies are found in the inferior regions, superior frontal and occipital regions.

Adult↗

PubMed2005

Task-related activity in prefrontal cortex and its relation to recognition memory performance in young and old adults.

Older adults often have more widespread prefrontal cortex (PFC) activation during memory retrieval tasks, compared to young adults, particularly in the left hemisphere. Recruitment of additional frontal activity in older adults has been attributed by some researchers to compensation, perhaps for reduced activity elsewhere in the brain, whereas others have described it as a non-selective response that may be due to a failure to inhibit these PFC regions. To address further the impact of PFC activity on memory in older adults, we used PET to measure brain activity during recognition memory tasks. Both young and old adults showed increased activity during recognition, compared to a control task, in bilateral PFC. Young adults showed greater activation of left hippocampus and lateral temporal cortex during recognition, whereas older adults showed greater activity in the right inferior frontal gyrus. Age differences also were seen in correlations between brain activity and memory performance. There were positive correlations between activity in the right parahippocampal gyrus and recognition performance in young adults, whereas positive correlations between activity in PFC and performance were found only in older adults. These positive correlations included the right inferior PFC region where older adults had greater activation. Activity in this right PFC region was negatively correlated with medial temporal activity in both groups. These results provide further evidence for age-specific patterns of brain activity underlying memory performance and are consistent with the idea that PFC assumes a larger role in supporting successful recognition memory with increasing age. The negative correlation between activity in PFC and medial temporal regions, as well as the age differences in how these regions were related to behavior, suggest that those older individuals who recruit PFC to a greater degree may do so as a compensatory response to reductions in medial temporal regions.

Adult↗

PubMed2005

Age-related reorganization of encoding networks directly influences subsequent recognition memory.

Functional magnetic resonance imaging was used to link performance-related brain activity during two word encoding tasks to subsequent recognition for those words in young and older adults. There were no significant group differences in performance during encoding, but the young subjects performed better than the older at the recognition task. Performance-related brain networks strongly differed between the two groups. In young subjects, there were two networks associated with performance, one related to encoding (mainly involving premotor and parietal brain regions) and the other to recognition (involving middle frontal, and lateral and medial temporal regions), whereas the network for older subjects (including prefrontal, premotor, lateral and medial temporal regions) was associated both with encoding and recognition. Areas in this network strongly overlapped with those supporting recognition in the young subjects (e.g., medial temporal lobe), suggesting that older subjects may have recruited these areas to maintain performance during encoding. However, this reorganization of brain networks appears to have come at the cost of subsequent recognition.

Adult↗

PubMed2005

The relation between brain activity during memory tasks and years of education in young and older adults.

Higher education is associated with less age-related decline in cognitive function, but the mechanism of this protective effect is unknown. The authors examined the effect of age on the relation between education and brain activity by correlating years of education with activity measured using functional MRI during memory tasks in young and older adults. In young adults, education was negatively correlated with frontal activity, whereas in older adults, education was positively correlated with frontal activity. Medial temporal activity was associated with more education in young adults but less education in older adults. This suggests that the frontal cortex is engaged by older adults, particularly by the highly educated, as an alternative network that may be engaged to aid cognitive function.

Adult↗

PubMed2005

The role of anterior cingulate cortex in working memory is shaped by functional connectivity.

The anterior cingulate (AC) cortex seems to be similarly engaged by attentional and memory processes. We tested the hypothesis that this common activation is best explained by changes in the regions interacting (functionally connected) with AC. Subjects were tested on two variants of a 2-back working memory task: a standard version with strong attentional demands, and a cued version that more strongly promoted memory retrieval. AC activation, measured with functional MRI, was found in both tasks, although more sustained in the standard condition. The regions functionally connected to the AC, and the relation of these activity patterns to memory performance, were completely different across tasks. In the standard task, the pattern related to a speed-accuracy tradeoff, whereas the connectivity pattern unique to the cued task related only to better accuracy. By virtue of these changing patterns of functional connectivity, the contribution of AC to attention- and memory-driven performance was similarly changed.

Adult↗

PubMed2004

Time course of changes in brain activity and functional connectivity associated with long-term adaptation to a rotational transformation.

The purpose of this study was to examine the time course of changes in cerebral activity and functional connectivity during long-term adaptation to a visuomotor transformation. Positron emission tomography was used to measure changes in brain activity as subjects tracked a target under the influence of a rotational transformation that distorted visual feedback. The experiment was 1 week long and consisted of two scanning sessions (obtained on days 2 and 7), aimed at examining early and late stages of learning. On average, visuomotor adaptation was achieved within 3 days. During early stages of adaptation, better performance was associated with greater activity in brain areas related to attention including bilateral dorso- and ventrolateral prefrontal cortices, frontal eye fields, and the human homologue of area MT. However, as adaptation proceeded, improvements in performance were associated with greater activity in motor regions such as the left (contralateral) sensorimotor cortex, bilateral anterior cerebellum, left cingulate motor area, right putamen, and a nonmotor region within the middle temporal gyrus. This learning-specific shift in brain activity was associated with a progressive change in the functional connectivity of these regions toward the end of the first session. Interestingly, only the functional connections between the anterior cerebellum, left middle temporal gyrus, and left sensorimotor cortex remained strong once visuomotor adaptation was achieved. Our findings suggest that visuomotor adaptation is not only reflected in persistent changes in activity in motor-related regions, but also in the strengthening and maintenance of specific functional connections.

Adaptation, Physiological↗

PubMed2004

An integrative MEG-fMRI study of the primary somatosensory cortex using cross-modal correspondence analysis.

We develop a novel approach of cross-modal correspondence analysis (CMCA) to address whether brain activities observed in magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) represent a common neuronal subpopulation, and if so, which frequency band obtained by MEG best fits the common brain areas. Fourteen adults were investigated by whole-head MEG using a single equivalent current dipole (ECD) and synthetic aperture magnetometry (SAM) approaches and by fMRI at 1.5 T using linear time-invariant modeling to generate statistical maps. The same somatosensory stimulus sequences consisting of tactile impulses to the right sided: digit 1, digit 4 and lower lip were used in both neuroimaging modalities. To evaluate the reproducibility of MEG and fMRI results, one subject was measured repeatedly. Despite different MEG dipole locations and locations of maximum activation in SAM and fMRI, CMCA revealed a common subpopulation of the primary somatosensory cortex, which displays a clear homuncular organization. MEG activity in the frequency range between 30 and 60 Hz, followed by the ranges of 20-30 and 60-100 Hz, explained best the defined subrepresentation given by both MEG and fMRI. These findings have important implications for improving and understanding of the biophysics underlying both neuroimaging techniques, and for determining the best strategy to combine MEG and fMRI data to study the spatiotemporal nature of brain activity.

Adult↗

PubMed2004

Improving permutation test power for group analysis of spatially filtered MEG data.

Non-parametric statistical methods, such as permutation, are flexible tools to analyze data when the population distribution is not known. With minimal assumptions and better statistical power compared to the parametric tests, permutation tests have recently been applied to the spatially filtered magnetoencephalography (MEG) data for group analysis. To perform permutation tests on neuroimaging data, an empirical maximal null distribution has to be found, which is free from any activated voxels, to determine the threshold to classify the voxels as active at a given probability level. An iterative procedure is used to determine the distribution by computing the null distribution, which is recomputed when a possible activated voxel is found within the current distributions. Besides the high computational costs associated with this approach, there is no guarantee that all activated voxels are excluded when constructing the maximal null distribution, which may reduce the statistical power. In this study, we propose a novel way to construct the maximal null distribution from the data of the resting period. The approach is tested on the MEG data from a somatosensory experiment, and demonstrated that the approach could improve the power of the permutation test while reducing the computational cost at the same time.

Adult↗

PubMed2004

Characterizing spatial and temporal features of autobiographical memory retrieval networks: a partial least squares approach.

Conway (Conway, M.A., 1992. A structural model of autobiographical memory. In: Conway, M.A., Spinnler, H., Wagenaar, W.A. (Eds.), Theoretical Perspectives on Autobiological Memory. Kluwer Academic Publishers, Dordrecht, The Netherlands, pp. 167-194) proposed that two types of autobiographical memories (AMs) exist within a hierarchical AM system: unique, specific events and repeated, general memories. There is little research on whether retrieval of these AMs relies on different neural substrates. To investigate this issue, we used a multivariate image analysis technique, spatiotemporal partial least squares (PLS), to identify distributed patterns of activity most related to AM tasks that we have found to be associated with a medial and left-lateralized network. Using PLS, specific and general memories were more strongly associated with different parts of this retrieval network. Specific AM retrieval was associated more with activation of regions involved in imagery in episodic memory, including the left precuneus, left superior parietal lobule and right cuneus, whereas general AM retrieval was associated with activation of the right inferior temporal gyrus, right medial frontal cortex, and left thalamus. These two patterns emerged at different lags after stimulus onset, with the general AM pattern peaking between 2 and 6 s, and the specific AM pattern between 6 and 8 s. These lag differences are consistent with Conway's theory which posits that general AMs are the preferred level of entry to the AM system. A seed PLS analysis revealed that the regions functionally connected to the hippocampus during retrieval did not differentiate specific from general AM retrieval, which confirms our earlier univariate analysis indicating that some aspects of the memory retrieval network are shared by these memories.

Adult↗

PubMed2004

The functional neuroanatomy of episodic and semantic autobiographical remembering: a prospective functional MRI study.

Autobiographical memory comprises episodic and semantic components mediated by dissociable states of consciousness, one promoting the experience of the self at a specific moment in the past, and the other involving self-knowledge that does not require ''mental time travel.'' These components can be difficult to dissociate using retrospective autobiographical stimuli collection. In this study, we manipulated the episodic/semantic distinction within prospectively collected autobiographical stimuli. Over several months, participants made recordings documenting specific episodes, repeated episodes, and world knowledge. These recordings were later played back to participants during scanning with functional MRI. The results indicated overlapping but distinct patterns of brain activity corresponding to episodic and semantic autobiographical memory. Both episodic and semantic autobiographical memory engaged the left anteromedial prefrontal cortex associated with self-reference, but the episodic condition did so to a greater degree. The episodic condition uniquely engaged the medial temporal, posterior cingulate, and diencephalic regions associated with remote memory recovery. Whereas the episodic condition engaged the right temporo-parietal cortex involved in reconstruction of spatial context and attentional orienting, the semantic condition engaged the left temporo-parietal and parieto-frontal systems involved in egocentric spatial processing and top-down attentional control. Episodic recollection was also associated with suppression of emotional paralimbic regions. These findings support a functional neuroanatomical dissociation between episodic and semantic autobiographical memory, providing concordance to amnesic syndromes with disproportionate impairment in one of these two forms of autobiographical memory.

Adult↗

PubMed2003

Direct activation of the ventral striatum in anticipation of aversive stimuli.

The brain "reward" system, centered on the limbic ventral striatum, plays a critical role in the response to pleasure and pain. The ventral striatum is activated in animal and human studies during anticipation of appetitive/pleasurable events, but its role in aversive/painful events is less clear. Here we present data from three human fMRI studies based on aversive conditioning using unpleasant cutaneous electrical stimulation and show that the ventral striatum is reliably activated. This activation is observed during anticipation and is not a consequence of relief after the aversive event. Further, the ventral striatum is activated in anticipation regardless of whether there is an opportunity to avoid the aversive stimulus or not. Our data suggest that the ventral striatum, a crucial element of the brain "reward" system, is directly activated in anticipation of aversive stimuli.

Adult↗