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Barry Horwitz

Publications and source records attributed to Barry Horwitz.

16 recordsLinked to original sources
PubMed2005

Discrimination and categorization of speech and non-speech sounds in an MEG delayed-match-to-sample study.

We investigated the perception and categorization of speech (vowels, syllables) and non-speech (tones, tonal contours) stimuli using MEG. In a delayed-match-to-sample paradigm, participants listened to two sounds and decided if they sounded exactly the same or different (auditory discrimination, AUD), or if they belonged to the same or different categories (category discrimination, CAT). Stimuli across the two conditions were identical; the category definitions for each kind of sound were learned in a training session before recording. MEG data were analyzed using an induced wavelet transform method to investigate task-related differences in time-frequency patterns. In auditory cortex, for both AUD and CAT conditions, an alpha (8-13 Hz) band activation enhancement during the delay period was found for all stimulus types. A clear difference between AUD and CAT conditions was observed for the non-speech stimuli in auditory areas and for both speech and non-speech stimuli in frontal areas. The results suggest that alpha band activation in auditory areas is related to both working memory and categorization for new non-speech stimuli. The fact that the dissociation between speech and non-speech occurred in auditory areas, but not frontal areas, points to different categorization mechanisms and networks for newly learned (non-speech) and natural (speech) categories.

Acoustic Stimulation↗
PubMed2005

Investigating the neural basis for functional and effective connectivity. Application to fMRI.

Viewing cognitive functions as mediated by networks has begun to play a central role in interpreting neuroscientific data, and studies evaluating interregional functional and effective connectivity have become staples of the neuroimaging literature. The neurobiological substrates of functional and effective connectivity are, however, uncertain. We have constructed neurobiologically realistic models for visual and auditory object processing with multiple interconnected brain regions that perform delayed match-to-sample (DMS) tasks. We used these models to investigate how neurobiological parameters affect the interregional functional connectivity between functional magnetic resonance imaging (fMRI) time-series. Variability is included in the models as subject-to-subject differences in the strengths of anatomical connections, scan-to-scan changes in the level of attention, and trial-to-trial interactions with non-specific neurons processing noise stimuli. We find that time-series correlations between integrated synaptic activities between the anterior temporal and the prefrontal cortex were larger during the DMS task than during a control task. These results were less clear when the integrated synaptic activity was haemodynamically convolved to generate simulated fMRI activity. As the strength of the model anatomical connectivity between temporal and frontal cortex was weakened, so too was the strength of the corresponding functional connectivity. These results provide a partial validation for using fMRI functional connectivity to assess brain interregional relations.

Auditory Perception↗
PubMed2005

Integrating neuroscientific data across spatiotemporal scales.

A major challenge confronting neuroscientists is associated with the multiple spatial and temporal scales of investigation of neural structure and function. I shall discuss the use of computational neural modeling as one method to bridge some of the different spatial and temporal levels. This approach will be illustrated using large-scale, neurobiologically realistic network models of auditory and visual pattern recognition that relate neuronal dynamics to fMRI data. It will be demonstrated that the models are capable of exhibiting the salient features of both electrophysiological neuronal activities and fMRI values that are in agreement with empirically observed data.

Animals↗
PubMed2004

Resting state brain glucose metabolism is not reduced in normotensive healthy men during aging, after correction for brain atrophy.

Studies using positron emission tomography (PET) have reported that global and regional values for cerebral blood flow and metabolic rates for glucose (CMRglc and rCMRglc) decline with age in humans. We wished to determine if such decreases could have reflected a partial volume effect (PVE) of cerebral atrophy in the elderly, rather than "intrinsic" reductions per gram brain. We used PET to compare rCMRglc, before and after correcting for the PVE, between 13 healthy older men (aged: 55-82 years) and 11 healthy young men (aged: 22-34 years). PET was performed with 18F-fluoro-2-deoxy-d-glucose while the subjects were in the "resting" state (eyes covered and ears plugged with cotton). The PET scans were normalized to a common brain volume after superimposing them on the subjects' tissue segmented magnetic resonance scans. Analysis showed that rCMRglc in the absence of a PVE correction was significantly less in the older group in insular, frontal, superior temporal cortical, and thalamic regions. Statistical significant differences in rCMRglc, however, were absent after the PVE correction. Thus, statistically significant age reductions in regional brain glucose metabolism, corrected for brain atrophy, are not detectable in healthy normotensive men scanned while in the resting state.

Adult↗
PubMed2004

Brain network interactions in auditory, visual and linguistic processing.

In the paper, we discuss the importance of network interactions between brain regions in mediating performance of sensorimotor and cognitive tasks, including those associated with language processing. Functional neuroimaging, especially PET and fMRI, provide data that are obtained essentially simultaneously from much of the brain, and thus are ideal for enabling one to assess interregional functional interactions. Two ways to use these types of data to assess network interactions are presented. First, using PET, we demonstrate that anterior and posterior perisylvian language areas have stronger functional connectivity during spontaneous narrative production than during other less linguistically demanding production tasks. Second, we show how one can use large-scale neural network modeling to relate neural activity to the hemodynamically-based data generated by fMRI and PET. We review two versions of a model of object processing - one for visual and one for auditory objects. The regions comprising the models include primary and secondary sensory cortex, association cortex in the temporal lobe, and prefrontal cortex. Each model incorporates specific assumptions about how neurons in each of these areas function, and how neurons in the different areas are interconnected with each other. Each model is able to perform a delayed match-to-sample task for simple objects (simple shapes for the visual model; tonal contours for the auditory model). We find that the simulated electrical activities in each region are similar to those observed in nonhuman primates performing analogous tasks, and the absolute values of the simulated integrated synaptic activity in each brain region match human fMRI/PET data. Thus, this type of modeling provides a way to understand the neural bases for the sensorimotor and cognitive tasks of interest.

Animals↗
PubMed2004

"What" and "where" in visual working memory: a computational neurodynamical perspective for integrating FMRI and single-neuron data.

Single-neuron recordings, functional magnetic resonance imaging (fMRI) data, and the effects of lesions indicate that the prefrontal cortex (PFC) is involved in some types of working memory and related cognitive processes. Based on these data, two different models of the topographical and functional organization of the PFC have been proposed: organization-by-stimulus-domain, and organization-by-process. In this article, we utilize an integrate-and-fire network to model both single-neuron and fMRI data on short-term memory in order to understand data obtained in topologically different parts of the PFC during working memory tasks. We explicitly model the mechanisms that underlie working memory-related activity during the execution of delay tasks that have a "what"-then-"where" design (with both object and spatial delayed responses within the same trial). The model contains different populations of neurons (as found experimentally) in attractor networks that respond in the delay period to the stimulus object, the stimulus position, and to combinations of both object and position information. The pools are arranged hierarchically and have global inhibition through inhibitory interneurons to implement competition. It is shown that a biasing attentional input to define the current relevant information (object or location) enables the system to select the correct neuronal populations during the delay period in what is a biased competition model of attention. The processes occurring at the AMPA and NMDA synapses are dynamically modeled in the integrate-and-fire implementation to produce realistic spiking dynamics. It is shown that the fMRI data characteristic of the dorsal PFC and linked to spatial processing and manipulation of items can be reproduced in the model by a high level of inhibition, whereas the fMRI data characteristic of the ventral PFC and linked to object processing can be produced by a lower level of inhibition, even though the network is itself topographically homogeneous with no spatial topology of the neurons. This article, thus, not only presents a model for how spatial versus object short-term memory could be implemented in the PFC, but also shows that the fMRI BOLD signal measured during such tasks from different parts of the PFC could reflect a higher level of inhibition dorsally, without this dorsal region necessarily being primarily spatial and the ventral region object-related.

Algorithms↗
PubMed2004

Relating fMRI and PET signals to neural activity by means of large-scale neural models.

This article reviews the four ways by which large-scale, neurobiologically realistic modeling can be used in conjunction with functional neuroimaging data, especially that obtained by functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), to help investigators understand the neural bases for sensorimotor and cognitive functions. The conceptually distinct purposes served are:(1) formulating and implementing specific hypotheses about how neuronal populations mediate a task, which will be illustrated using models of visual and auditory object processing; (2) determining how well an experimental design paradigm or analysis method works, which will be illustrated by examining event-related fMRI; (3) investigating the meaning in neural terms of macro-level concepts, which will be illustrated using functional connectivity; and (4) combining different types of macroscopic data with one another, which will be illustrated using transcranial magnetic stimulation (TMS) and PET.

Brain↗
PubMed2003

Activation of Broca's area during the production of spoken and signed language: a combined cytoarchitectonic mapping and PET analysis.

Broca's area in the inferior frontal gyrus consists of two cytoarchitectonically defined regions-Brodmann areas (BA) 44 and 45. Combining probabilistic maps of these two areas with functional neuroimaging data obtained using PET, it is shown that BA45, not BA44, is activated by both speech and signing during the production of language narratives in bilingual subjects fluent from early childhood in both American Sign Language (ASL) and English when the generation of complex movements and sounds is taken into account. It is BA44, not BA45, that is activated by the generation of complex articulatory movements of oral/laryngeal or limb musculature. The same patterns of activation are found for oral language production in a group of English speaking monolingual subjects. These findings implicate BA45 as the part of Broca's area that is fundamental to the modality-independent aspects of language generation.

Adult↗
PubMed2003

The elusive concept of brain connectivity.

Neurons and neural populations do not function as islands onto themselves. Rather, they interact with other such elements through their afferent and efferent connections in an orchestrated manner so as to enable different sensorimotor and cognitive tasks to be performed. The concept of functional connectivity and the allied notion of effective connectivity were introduced to designate the functional strengths of such interactions. Functional neuroimaging methods, especially PET and fMRI, have been used extensively to evaluate the functional connectivity between different brain regions. After providing a brief historical review of these notions of brain connectivity, I argue that the conceptual formulations of functional and effective connectivity are far from clear. Specifically, the terms functional and effective connectivity are applied to quantities computed on types of functional imaging data (e.g., PET, fMRI, EEG) that vary in spatial, temporal, and other features, using different definitions (even for data of the same modality) and employing different computational algorithms. Until it is understood what each definition means in terms of an underlying neural substrate, comparisons of functional and/or effective connectivity across studies may appear inconsistent and should be performed with great caution.

Brain↗
PubMed2003

Interindividual differences in functional interactions among prefrontal, parietal and parahippocampal regions during working memory.

To clarify the neural systems deployed by individual subjects during working memory (WM), we collected functional neuroimaging data from healthy subjects, and constructed a model of 2-back WM using structural equation modeling (SEM). A group model was constructed, and models for each subject were validated against it. The group model consisted principally of regions in the prefrontal and parietal cortex, with considerable interindividual variance in the single-subject models. To explore this variance, subjects were split into two groups based on performance. Performance level and self-reported strategy scores were used in a correlation analysis against path weights between nodes of individual models. High performers utilized a left hemisphere sub-network involving inferior parietal lobule and Broca's area, whereas lower performers utilized a right hemisphere sub-network with interactions between inferior parietal lobule and dorsolateral prefrontal cortex. Further, we observed an interaction between the parahippocampal formation and the inferior parietal lobule that was related to the different strategies used by the individuals to perform the task. Strategy and performance level appear to be intricately related in this task, with neural systems supporting verbal processing producing better performance than those associated with spatial processing. These results demonstrate that individual behavioral characteristics are reflected in specific neurofunctional patterns at the system level and that these can be captured by analytical techniques such as SEM.

Adult↗
PubMed2003

Relation of corpus callosum and hippocampal size to age in nondemented adults with Down's syndrome.

OBJECTIVE: Aging in Down's syndrome is accompanied by amyloid and neurofibrillary pathology, the regional and laminar distribution of which resembles pathological changes seen in Alzheimer's disease. Previous studies using magnetic resonance imaging (MRI) demonstrated age-related atrophy of medial temporal lobe structures in nondemented older subjects with Down's syndrome, reflecting early allocortical pathology. Corpus callosum atrophy has been established as a marker of neocortical neuronal loss in Alzheimer's disease. This study investigated whether atrophy of the corpus callosum and hippocampus occurs in nondemented subjects with Down's syndrome and compared the degree of age-related atrophy between these structures. METHOD: Hippocampus and corpus callosum measures were obtained from volumetric T(1)-weighted MRI scans of 34 nondemented Down's syndrome adults (mean age=41.6 years, 17 women) and 31 healthy comparison subjects (mean age=41.8 years, 14 women). RESULTS: Down's syndrome subjects had smaller corpus callosum areas and hippocampal volumes relative to age-matched healthy comparison subjects, even after age and total intracranial volume were controlled. There was an age-related decrease of corpus callosum area (most prominent in posterior regions) and hippocampal volume in the Down's syndrome group. The degree of the age effect was comparable between the total corpus callosum and hippocampus, and corpus callosum size was correlated with cognitive performance in the Down's syndrome subjects. There was no correlation between age and corpus callosum or hippocampal size in the comparison group. CONCLUSIONS: Comparable decrease of corpus callosum and hippocampal size with age in nondemented subjects with Down's syndrome suggests that neocortical neuronal alterations accompany allocortical changes in the predementia phase of Down's syndrome.

Adult↗
PubMed2002

fMRI study comparing names versus pictures of objects.

We performed an fMRI one-back recognition study aimed at distinguishing the semantic versus perceptual aspects of how objects and their written forms are processed. There were three types of visually presented items: pictures (schematic drawings of objects); words identifying these objects; and a mixed condition in which pictures were interleaved with words. A semantic decision about object identity was required when pictures were interleaved with words. This condition, contrasted with the other two, invoked a larger signal in multiple areas, including frontal cortex, bilateral occipitotemporal cortex, and the right middle temporal gyrus. We propose that the left occipitotemporal and right temporal activations are indicative of the neural substrate mediating picture-word conversions, whereas the frontal activations reflect the coordinating functions of the central executive.

Adult↗
PubMed2002

Effect of attention on central auditory processing: an fMRI study.

Functional magnetic resonance imaging was used to investigate preattentive and attentional processing of auditory stimuli in 18 right-handed normal volunteers. Responses to trains of 1000-Hz pure tones and infrequent (15%) deviant 1300-Hz tones were characterized while subjects ignored all tones; listened for deviants in the left ear; or listened for deviants in the right ear. Preattentive detection of deviants, associated with the mismatch negativity in electrophysiology, was associated with bilateral temporal lobe activation, with a rightward predominance. Processing of deviant stimuli while attending to either ear produced a more robust and widespread activation of these temporal regions, again with a rightward predominance. Thus, preattentive tone processing appears to be linked to asymmetric activation of a core set of temporal regions in which activity is significantly amplified by selective attention. Extratemporal regions activated by attending to targets in either ear included the anterior cingulate cortex, supramarginal gyrus, and dorsolateral prefrontal cortex.

Acoustic Stimulation↗
PubMed2002

Relation of medial temporal lobe volumes to age and memory function in nondemented adults with Down's syndrome: implications for the prodromal phase of Alzheimer's disease.

OBJECTIVE: In Down's syndrome (trisomy 21), a dementia syndrome occurs that is phenotypically similar to Alzheimer's disease; the initial phase is characterized by memory loss. The authors used an in vivo structural technique in the predementia stage of Alzheimer's disease in adults with Down's syndrome to investigate whether atrophy of medial temporal lobe structures occurs in these subjects and whether volumes of these structures correlate specifically with performance on memory tests. METHOD: The subjects were 34 nondemented Down's syndrome adults (mean age=41.6 years, 17 women and 17 men) and 33 healthy comparison subjects (mean age=41.3, 15 women and 18 men). By using T(1)-weighted magnetic resonance imaging slices taken perpendicular to the Sylvian fissure, volumes of the hippocampus, amygdala, anterior and posterior parahippocampal gyrus, and temporal pole CSF were measured in both hemispheres. These data were normalized to the total intracranial volume. RESULTS: For Down's syndrome, smaller volumes of the right and left amygdala, hippocampus, and posterior parahippocampal gyrus were significantly associated with greater age; this association was not seen in the anterior parahippocampal gyrus. The amygdala and hippocampus volumes were positively correlated with memory measures. For the comparison group, there was no relationship between volume and age in any region. CONCLUSIONS: In the predementia phase of Down's syndrome, significant volume changes in medial temporal lobe structures occur with age and are related to memory. These structures are affected early in Alzheimer's disease in Down's syndrome, and their evaluation may help identify people in the preclinical stages of Alzheimer's disease.

Adult↗
PubMed1992

Effect of Nucleus Basalis Magnocellularis Ablation on Local Brain Glucose Utilization in the Rat: Functional Brain Reorganization.

After unilateral destruction of the nucleus basalis magnocellularis (NBM) in 3-month-old rats, which reduces cholinergic inputs to the ipsilateral frontoparietal neocortex, regional cerebral metabolic rates for glucose (rCMRglc) of denervated cortex are initially reduced, but nearly normalize by 2 weeks. To examine functional reorganization of the brain after unilateral destruction of the NBM, a correlation analysis of rCMRglc was performed on two groups of 16 young rats 2 weeks after stereotaxic ablation of the right NBM with ibotenate or sham surgery. rCMRglc was measured in 117 brain regions of awake rats with the [14C]deoxyglucose method. For each region pair, a partial correlation coefficient was calculated for rCMRglc across animals. Most correlations between cholinergic nuclei of both left and right forebrain (medial septum and diagonal band) and right (66/72, mean increase 0.44) but not left (39/72) frontoparietal cortical regions were larger (P < 0.001) in lesioned rats, as were those between most frontoparietal region pairs (516/630, P < 0.001). These results suggest that, after unilateral NBM ablation, (1) functional interactions are established between the remaining cholinergic forebrain and the deafferented cortex, (2) the neocortex becomes more integrated, and (3) functional reorganization involves both cortical hemispheres. These changes do not correspond to those reported to occur in Alzheimer's disease.

Journal Article↗