Biomedical subjects

Abraham Z Snyder

Publications and source records attributed to Abraham Z Snyder.

At least 19 recordsLinked to original sources

PubMed2006

Coherent spontaneous activity identifies a hippocampal-parietal memory network.

Despite traditional theories emphasizing parietal contributions to spatial attention and sensory-motor integration, functional MRI (fMRI) experiments in normal subjects suggest that specific regions within parietal cortex may also participate in episodic memory. Here we examined correlations in spontaneous blood-oxygenation-level-dependent (BOLD) signal fluctuations in a resting state to identify the network associated with the hippocampal formation (HF) and determine whether parietal regions were elements of that network. In the absence of task, stimuli, or explicit mnemonic demands, robust correlations were observed between activity in the HF and several parietal regions (including precuneus, posterior cingulate, retrosplenial cortex, and bilateral inferior parietal lobule). These HF-correlated regions in parietal cortex were spatially distinct from those correlated with the motion-sensitive MT+ complex. Reanalysis of event-related fMRI studies of recognition memory showed that the regions spontaneously correlated with the HF (but not MT+) were also modulated during directed recollection. These regions showed greater activity to successfully recollected items as compared with other trial types. Together, these results associate specific regions of parietal cortex that are sensitive to successful recollection with the HF.

Adolescent↗

PubMed2006

Attentional selection of moving objects by a serial process.

How does the efficiency of attentional selection depend on the number of attended objects in a display? We measured the channel capacity (CC) of human observers during the attentional tracking of moving targets. The relation between CC and target number was used to estimate target-sampling rate. The sampling rate was halved when the number of targets was doubled, indicating that tracking was accomplished by a mechanism whose processing rate did not vary with target number. Systematically varying the dynamic parameters of the display provided inconclusive evidence for the idea that the time interval between successive samples of the same target increased with target number. These results are consistent with the hypothesis that the selection of multiple moving objects involves a limited capacity processor.

Attention↗

PubMed2006

Separate modulations of human V1 associated with spatial attention and task structure.

Functional magnetic resonance imaging (fMRI) was used while normal human volunteers engaged in simple detection and discrimination tasks, revealing separable modulations of early visual cortex associated with spatial attention and task structure. Both modulations occur even when there is no change in sensory stimulation. The modulation due to spatial attention is present throughout the early visual areas V1, V2, V3, and VP, and varies with the attended location. The task structure activations are strongest in V1 and are greater in regions that represent more peripheral parts of the visual field. Control experiments demonstrate that the task structure activations cannot be attributed to visual, auditory, or somatosensory processing, the motor response for the detection/discrimination judgment, or oculomotor responses such as blinks or saccades. These findings demonstrate that early visual areas are modulated by at least two types of endogenous signals, each with distinct cortical distributions.

Adult↗

PubMed2006

Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems.

On the basis of task-related imaging studies in normal human subjects, it has been suggested that two attention systems exist in the human brain: a bilateral dorsal attention system involved in top-down orienting of attention and a right-lateralized ventral attention system involved in reorienting attention in response to salient sensory stimuli. An important question is whether this functional organization emerges only in response to external attentional demands or is represented more fundamentally in the internal dynamics of brain activity. To address this question, we examine correlations in spontaneous fluctuations of the functional MRI blood oxygen level-dependent signal in the absence of task, stimuli, or explicit attentional demands. We identify a bilateral dorsal attention system and a right-lateralized ventral attention system solely on the basis of spontaneous activity. Further, we observe regions in the prefrontal cortex correlated with both systems, a potential mechanism for mediating the functional interaction between systems. These findings demonstrate that the neuroanatomical substrates of human attention persist in the absence of external events, reflected in the correlation structure of spontaneous activity.

Attention↗

PubMed2005

Coherent spontaneous activity accounts for trial-to-trial variability in human evoked brain responses.

Trial-to-trial variability in the blood oxygen level-dependent (BOLD) response of functional magnetic resonance imaging has been shown to be relevant to human perception and behavior, but the sources of this variability remain unknown. We demonstrate that coherent spontaneous fluctuations in human brain activity account for a significant fraction of the variability in measured event-related BOLD responses and that spontaneous and task-related activity are linearly superimposed in the human brain.

Brain↗

PubMed2005

Neural basis and recovery of spatial attention deficits in spatial neglect.

The syndrome of spatial neglect is typically associated with focal injury to the temporoparietal or ventral frontal cortex. This syndrome shows spontaneous partial recovery, but the neural basis of both spatial neglect and its recovery is largely unknown. We show that spatial attention deficits in neglect (rightward bias and reorienting) after right frontal damage correlate with abnormal activation of structurally intact dorsal and ventral parietal regions that mediate related attentional operations in the normal brain. Furthermore, recovery of these attention deficits correlates with the restoration and rebalancing of activity within these regions. These results support a model of recovery based on the re-weighting of activity within a distributed neuronal architecture, and they show that behavioral deficits depend not only on structural changes at the locus of injury, but also on physiological changes in distant but functionally related brain areas.

Analysis of Variance↗

PubMed2005

Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory.

Alzheimer's disease (AD) and antecedent factors associated with AD were explored using amyloid imaging and unbiased measures of longitudinal atrophy in combination with reanalysis of previous metabolic and functional studies. In total, data from 764 participants were compared across five in vivo imaging methods. Convergence of effects was seen in posterior cortical regions, including posterior cingulate, retrosplenial, and lateral parietal cortex. These regions were active in default states in young adults and also showed amyloid deposition in older adults with AD. At early stages of AD progression, prominent atrophy and metabolic abnormalities emerged in these posterior cortical regions; atrophy in medial temporal regions was also observed. Event-related functional magnetic resonance imaging studies further revealed that these cortical regions are active during successful memory retrieval in young adults. One possibility is that lifetime cerebral metabolism associated with regionally specific default activity predisposes cortical regions to AD-related changes, including amyloid deposition, metabolic disruption, and atrophy. These cortical regions may be part of a network with the medial temporal lobe whose disruption contributes to memory impairment.

Adolescent↗

PubMed2005

Transient BOLD responses at block transitions.

Block-design fMRI responses include sustained components present for the duration of each task block as well as transient components at the beginning and end of each block. Almost all prior block-design fMRI studies have focused on the sustained response components while the transient responses at block transitions have been largely ignored. These transients, therefore, remain poorly characterized. We here present a systematic study of block-transition transient responses obtained using four widely divergent tasks. We characterize transient response topography and examine the extent to which these responses vary across different tasks and between block onset and offset. Our analysis reveals that certain regions show transient responses regardless of task or transition type. However, our analysis also shows that specific task state transitions give rise to transient responses with unique spatial profiles. Relevance of the current findings to studies of exogenous attention, task shifting, and the BOLD overshoot is discussed.

Adult↗

PubMed2005

Cerebellar activity switches hemispheres with cerebral recovery in aphasia.

The right postero-lateral cerebellum participates with the left frontal lobe in the selection and production of words. Using fMRI, we examined whether cerebellar activity switches hemispheres in parallel with recruitment of putative compensatory right homologous frontal regions in post-stroke aphasia. Re-examining the data of Blasi et al. [Blasi, V., Young, A. C., Tansy, A. P., Petersen, S. E., Snyder, A. Z., & Corbetta, M. (2002). Word retrieval learning modulates right frontal cortex in patients with left frontal damage. Neuron, 36(1), 159-170], we asked: (1) if activity in the right cerebellum was disrupted by a left frontal lesion, (2) if activity switched to the left cerebellum, and (3) if activity in the left cerebellum was modulated by learning, as was right frontal cortex. Fourteen age-matched controls and eight mildly aphasic stroke patients participated. Aphasic participants all had lesions due to unilateral left hemisphere stroke at or near Broca's area. Subjects silently performed a word stem completion task with either novel or repeated items. Activity in right cerebellum of aphasic individuals was minimal and was not modulated by learning, as for controls. However, we observed robust learning-related attenuation of the BOLD signal in the left postero-lateral cerebellum consistent with learning-related effects in right frontal cortex. These findings support the hypothesis that right frontal and left cerebellar circuits are likely to be functionally relevant to recovered/residual verbal function.

Adult↗

PubMed2005

The human brain is intrinsically organized into dynamic, anticorrelated functional networks.

During performance of attention-demanding cognitive tasks, certain regions of the brain routinely increase activity, whereas others routinely decrease activity. In this study, we investigate the extent to which this task-related dichotomy is represented intrinsically in the resting human brain through examination of spontaneous fluctuations in the functional MRI blood oxygen level-dependent signal. We identify two diametrically opposed, widely distributed brain networks on the basis of both spontaneous correlations within each network and anticorrelations between networks. One network consists of regions routinely exhibiting task-related activations and the other of regions routinely exhibiting task-related deactivations. This intrinsic organization, featuring the presence of anticorrelated networks in the absence of overt task performance, provides a critical context in which to understand brain function. We suggest that both task-driven neuronal responses and behavior are reflections of this dynamic, ongoing, functional organization of the brain.

Attention↗

PubMed2005

A functional MRI study of preparatory signals for spatial location and objects.

We investigated preparatory signals for spatial location and objects in normal observers using functional magnetic resonance imaging (fMRI). Activity for attention-directing cues was separated from activity for subsequent test arrays containing the target stimulus. Subjects were more accurate in discriminating a target face among distracters when they knew in advance its location (spatial directional cue), as compared to when the target could randomly appear at one of two locations (spatial neutral cue), indicating that the spatial cue was used. Spatially specific activations occurred in a region at the intersection of the ventral intraparietal sulcus and transverse occipital sulcus (vIPS-TOS), which showed significantly stronger activation for rightward- than leftward-directing cues, while other fronto-parietal areas were activated by the cue but did not show spatial specificity. In visual cortex, activity was weak or absent in retinotopic occipital regions following attention-directing cues and this activity was not spatially specific. In a separate task, subject discriminated a target outdoor scene among distracters after the presentation of spatial neutral cues. There was no significant difference in dorsal frontoparietal activity during the face versus scene discrimination task. Also, there was only weak evidence for selective preparatory activity in ventral object-selective regions, although the activation of these regions to the subsequent test array did depend upon which discrimination (face or place) was performed. We conclude first that under certain circumstances, spatial cues that produce strong behavioral effects may modulate parietal-occipital regions in a spatially specific manner without producing similar modulations in retinotopic occipital regions. Second, attentional modulations of object-selective regions in temporal-occipital cortex can occur even though preparatory object-selective modulations of those regions are absent or weak.

Analysis of Variance↗

PubMed2005

The BOLD onset transient: identification of novel functional differences in schizophrenia.

Blood oxygen level dependent (BOLD) signals characteristically exhibit an overshoot (transient signal increase) at the beginning of fMRI task blocks. This onset transient has often been overlooked as an independent measure of neuronal activity, but it may represent unique functional processes. We examined onset transient responses in normal subjects and individuals with schizophrenia performing three cognitive tasks. These analyses revealed a regionally specific and task specific attenuation of the onset transient in individuals with schizophrenia during performance of a working memory task. Furthermore, this attenuation was often not accompanied by a corresponding population difference in the sustained response, and is missed through conventional fMRI analysis techniques. Relevance of these findings to both an interpretation of the onset transient and the pathology of schizophrenia are discussed.

Adult↗

PubMed2005

White matter lesions are prevalent but differentially related with cognition in aging and early Alzheimer disease.

BACKGROUND: White matter lesions (WMLs) are prevalent in nondemented aging and in Alzheimer disease (AD). Their relationship with cognition in the earliest stages of AD is unknown. OBJECTIVE: To assess the relationship between WMLs and cognition in nondemented aging and in early-stage AD. DESIGN: Cross-sectional study. SETTING: Alzheimer Disease Research Center, St Louis, MO. PARTICIPANTS: Participants were nondemented (n = 88) or had very mild (n = 48) or mild (n = 20) AD. MAIN OUTCOME MEASURES: Regression coefficients for deep WMLs and periventricular WMLs (PVWMLs) as predictors of cognition, after controlling for age, educational achievement, brain atrophy, and infarctlike lesions. RESULTS: White matter lesions were present in nondemented aging and in early-stage AD, with no group differences in deep WML burden and a modest PVWML burden increase in the AD group. The prevalence of infarctlike lesions was equivalent between groups. Age and hypertension were related to deep WML burden and PVWML burden. Deep WML burden and PVWML burden were associated with reduced global cognition in AD but not in nondemented aging. A PVWML x AD status interaction for global cognition suggests that the relationship between PVWMLs and cognition is modified by AD. In AD, global cognitive reductions were related to impairments in visual memory, processing speed, and executive function. CONCLUSIONS: White matter lesions are prevalent in nondemented aging and in early-stage AD, and their presence influences cognitive impairment in the earliest stages of AD. Individuals with early-stage AD may be more vulnerable to the cognitive effect of WMLs than nondemented aging individuals with similar WML burden.

Age of Onset↗

PubMed2005

Registration of [18F]FDG microPET and small-animal MRI.

This paper describes a voxel-based method for coregistering microPET [(18)F]FDG emission images and MRI data without the need for fiducial markers. [(18)F]FDG has a well-characterized biodistribution in normal mice and thus may be useful for image registration. Female BALB/c mice were implanted with EMT-6 mouse mammary carcinoma 1 week prior to imaging. Three imaging sessions were performed in which a [(18)F]FDG microPET-R4 emission scan was taken followed by small-animal MRI with and without Gd-based contrast agent. MicroPET and MR images were registered using a voxel-based algorithm that computes rigid-body image transformations based on the alignment of intensity gradients. Registration accuracy was assessed on the basis of dual-modality external fiducial line sources incorporated into the mouse bed. The root mean square (rms) registration errors were 0.74 mm translation and 1.44 degrees rotation without contrast and 0.72 mm translation and 0.89 degrees rotation with contrast. Generally, good registration was evident upon inspection of fused microPET/MR images. Accurate automated, voxel-based microPET-MR image coregistration, utilizing image intensity gradients, is feasible. Our technique requires no manual identification of image features and makes no use of surgically implanted or external fiducial markers or stereotactic apparatus.

Animals↗

PubMed2004

Differing neuropsychological and neuroanatomical correlates of abnormal reading in early-stage semantic dementia and dementia of the Alzheimer type.

Individuals with semantic dementia (SD) were differentiated neuropsychologically from individuals with dementia of the Alzheimer type (DAT) at very mild-to-mild stages (clinical dementia rating 0.5 or 1). A picture naming and recognition memory experiment provided a particularly useful probe for early identification, with SD individuals showing preserved picture recognition memory and impaired naming, and DAT individuals tending to show the reverse dissociation. The identification of an early SD group provided the opportunity to inform models of reading by exploring the influence of isolated lexical semantic impairment on reading regular words. Results demonstrated prolonged latency in both SD and DAT group reading compared to a control group but exaggerated influence of frequency and length only for the SD group. The SD reading pattern was associated with focal atrophy of the left temporal pole. These cognitive-neuroanatomical findings suggest a role for the left temporal pole in lexical/semantic components of reading and demonstrate that cortical thickness differences in the left temporal pole correlate with prolonged latency associated with increased reliance on sublexical components of reading.

Aged↗

PubMed2004

Frontal-hippocampal double dissociation between normal aging and Alzheimer's disease.

Controversy persists regarding whether Alzheimer's disease (AD) is a distinct entity or instead exists on a continuum with nondemented aging. To explore this issue, volumetric analyses of callosal and hippocampal regions were performed on 150 participants aged 18-93 years. Group-level analyses revealed that nondemented age-related differences were greater in anterior than posterior callosal regions and were not augmented by early-stage AD. In contrast, early-stage AD was associated with substantial reduction in hippocampal volume. Examination of the 100 older adults using regression analyses demonstrated age-associated differences in callosal volume that were similar in demented and nondemented individuals. Early-stage AD was again characterized by a marked reduction in hippocampal volume while age alone induced only mild differences in hippocampal volume. As a final analysis, the formal double dissociation was confirmed by comparing the effects of age directly against the effects of dementia. These results suggest a multiple-component model of aging. One process, associated with AD, manifests early and prominently in the medial temporal lobe. A separate process, ubiquitous in aging, affects brain white matter with an anterior-to-posterior gradient and may underlie the executive difficulties common in aging.

Adolescent↗

PubMed2004

Thinning of the cerebral cortex in aging.

The thickness of the cerebral cortex was measured in 106 non-demented participants ranging in age from 18 to 93 years. For each participant, multiple acquisitions of structural T1-weighted magnetic resonance imaging (MRI) scans were averaged to yield high-resolution, high-contrast data sets. Cortical thickness was estimated as the distance between the gray/white boundary and the outer cortical surface, resulting in a continuous estimate across the cortical mantle. Global thinning was apparent by middle age. Men and women showed a similar degree of global thinning, and did not differ in mean thickness in the younger or older groups. Age-associated differences were widespread but demonstrated a patchwork of regional atrophy and sparing. Examination of subsets of the data from independent samples produced highly similar age-associated patterns of atrophy, suggesting that the specific anatomic patterns within the maps were reliable. Certain results, including prominent atrophy of prefrontal cortex and relative sparing of temporal and parahippocampal cortex, converged with previous findings. Other results were unexpected, such as the finding of prominent atrophy in frontal cortex near primary motor cortex and calcarine cortex near primary visual cortex. These findings demonstrate that cortical thinning occurs by middle age and spans widespread cortical regions that include primary as well as association cortex.

Adolescent↗

PubMed2004

Effect of practice on reading performance and brain function.

Word reading is considered a highly over-learned task. If true, then practice should have no effect on its performance or associated functional brain anatomy. We tested this hypothesis in two experiments of skilled readers repeatedly reading the same list of nouns (1 session, 10 runs). In Experiment 1 we used fMRI to monitor the changes in brain activity. In Experiment 2 we recorded voice onset latency reaction times. Neither experiment showed changes as an effect of practice. In a third experiment, Experiment 3, we examined the behavioral effect of prolonged practice on the word association task of verb generation for which reading nouns aloud has served as a control. Both short (1 session, 10 runs) and long term (15 days, 150 runs) effects were noted providing a new perspective on functional anatomical differences between word reading and verb generation previously noted after short periods of practice.

Adult↗