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Biomedical subjects

D R Gitelman

Publications and source records attributed to D R Gitelman.

At least 19 recordsLinked to original sources

Neural correlates of rule-based and information-integration visual category learning.

An emerging theory of the neurobiology of category learning postulates that there are separate neural systems supporting the learning of categories based on verbalizeable rules (RB) or through implicit information integration (II). The medial temporal lobe (MTL) is thought to play a crucial role in successful RB categorization, whereas the posterior regions of the caudate are hypothesized to support II categorization. Functional neuroimaging was used to assess activity in these systems during category-learning tasks with category structures designed to afford either RB or II learning. Successful RB categorization was associated with relatively increased activity in the anterior MTL. Successful II categorization was associated with increased activity in the caudate body. The dissociation observed with neuroimaging is consistent with the roles of these systems in memory and dissociations reported in patient populations. Convergent evidence from these approaches consistently reinforces the idea of multiple neural systems supporting category learning.

Adolescent↗

The posterior cingulate and medial prefrontal cortex mediate the anticipatory allocation of spatial attention.

The purpose of this study was to identify brain regions underlying internally generated anticipatory biases toward locations where significant events are expected to occur. Subjects fixated centrally and responded to peripheral targets preceded by a spatially valid (predictive), invalid (misleading), or neutral central cue while undergoing fMRI scanning. In some validly cued trials, reaction time was significantly shorter than in trials with neutral cues, indicating that the cue had successfully induced a spatial redistribution of motivational valence, manifested as expectancy. The largest cue benefits led to selectively greater activations within the posterior cingulate and medial prefrontal cortex. These two areas thus appear to establish a neural interface between attention and motivation. An inverse relationship to cue benefit was seen in the parietal cortex, suggesting that spatial expectancy may entail the inhibition of attention-related areas to reduce distractibility by events at irrelevant locations.

Adult↗

Filtering of distractors during visual search studied by positron emission tomography.

We investigated the sensitivity of brain areas to the presence of filtering operations during overt visual search in crowded displays. Task conditions involved either visual search or predetermined simple eye movements for the detection of target digits. Furthermore, visual displays either contained letter foils that required filtering or contained only target digits. Brain imaging using positron emission tomography showed extensive overlap between areas involved in overt visual search and eye movements. Selective filtering of foils affected visual processing in ventral areas associated with object recognition and in primary visual cortex.

Adult↗

Neural correlates of artificial grammar learning.

Artificial grammar learning (AGL) is a form of nondeclarative memory that involves the nonconscious acquisition of abstract rules. While data from amnesic patients indicate that AGL does not depend on the medial temporal lobe, the neural basis of this type of memory is unknown and was therefore examined using event-related fMRI. Prior to scanning, participants studied letter strings constructed according to an artificial grammar. Participants then made grammaticality judgments about novel grammatical and nongrammatical strings while fMRI data were collected. The participants successfully acquired knowledge of the grammar, as evidenced by correct identification of the grammatical letter strings (57.4% correct; SE 1.9). During grammaticality judgments, widespread increases in activity were observed throughout the occipital, posterior temporal, parietal, and prefrontal cortical areas, reflecting the cognitive demands of the task. More specific analyses contrasting grammatical and nongrammatical strings identified greater activity in left superior occipital cortex and the right fusiform gyrus for grammatical stimuli. Increased activity was also observed in the left superior occipital and left angular gyrus for correct responses compared to incorrect. Comparing activity during grammaticality judgments versus a matched recognition control task again identified greater activation in the left angular gyrus. The network of areas exhibiting increased activity for grammatical stimuli appears to have more in common with studies examining word-form processing or mental calculation than the fluency effects previously reported for nondeclarative memory tasks such as priming and visual categorization. These results suggest that a novel nondeclarative memory mechanism supporting AGL exists in the left superior occipital and inferior parietal cortex.

Adult↗

Electromyography as a recording system for eyeblink conditioning with functional magnetic resonance imaging.

This study was designed to develop a suitable method of recording eyeblink responses while conducting functional magnetic resonance imaging (fMRI). Given the complexity of this behavioral setup outside of the magnet, this study sought to adapt and further optimize an approach to eyeblink conditioning that would be suitable for conducting event-related fMRI experiments. This method involved the acquisition of electromyographic (EMG) signals from the orbicularis oculi of the right eye, which were subsequently amplified and converted into an optical signal outside of the head coil. This optical signal was converted back into an electrical signal once outside the magnet room. Electromyography (EMG)-detected eyeblinks were used to measure responses in a delay eyeblink conditioning paradigm. Our results indicate that: (1) electromyography is a sensitive method for the detection of eyeblinks during fMRI; (2) minimal interactions or artifacts of the EMG signal were created from the magnetic resonance pulse sequence; and (3) no electromyography-related artifacts were detected in the magnetic resonance images. Furthermore, an analysis of the functional data showed areas of activation that have previously been shown in positron emission tomography studies of human eyeblink conditioning. Our results support the strength of this behavioral setup as a suitable method to be used in association with fMRI.

Acoustic Stimulation↗

Impact of signal-to-noise on functional MRI of the human amygdala.

The impact of signal-to-noise (SNR) on fMRI of the amygdala was investigated during a picture encoding task. The SNR value required to observe reliable activation was determined by computer simulations. Blood oxygen level-dependent (BOLD) sensitivity maps were generated to indicate brain regions with sufficient SNR to test the statistical hypotheses. The results showed that the medial aspect of the amygdala had insufficient SNR to detect a 1% peak BOLD signal change for a t-test comparison in a majority of subjects. None of these subjects showed activation in regions with unacceptable SNR values, indicating a low false positive rate. Furthermore, hemispheric asymmetries in the BOLD sensitivity maps mirrored asymmetries in the activation patterns. Impoverished SNR was also found in the basal forebrain and orbitofrontal cortex. These findings emphasize the importance of considering SNR when interpreting fMRI results in the limbic forebrain.

Adult↗

Dynamic allocation of attention in aging and Alzheimer disease: uncoupling of the eye and mind.

CONTEXT: Visual attention can be distributed focally, in the direction of gaze, or globally, throughout the extrapersonal space. Aging, and especially Alzheimer disease (AD), may influence global attention, resulting in shifts of gaze to attend to the global workspace. OBJECTIVE: To determine if subjects who have AD and cognitively intact older subjects shift their gaze more often than young subjects while viewing a dynamic stimulus that emphasizes global attention. DESIGN: Experimental study of eye fixation patterns in response to a simulated driving scene with stationary and moving distractors. SETTING: Urban, medical school, National Institute on Aging-funded Alzheimer's Disease Center. PARTICIPANTS: Thirteen subjects with mild probable AD, 13 age-comparable cognitively intact older control subjects, and 11 young control subjects. MAIN OUTCOME MEASURE: Proportion of eye fixations within and outside of a central region of interest encompassing the "road" surface. RESULTS: Young controls made significantly more eye fixations (mean number of eye fixations, 47.5) than either of the other 2 groups (older controls mean, 33.2; patients with AD mean, 32.2). However, 76% of their fixations remained within the central region of interest. Older controls and subjects with AD made proportionately fewer fixations within this region (48% and 49%, respectively) than young controls and moved their eyes more often to the periphery but did not differ from one another. CONCLUSIONS: Young controls maintain central eye position regardless of peripheral distraction. Older controls move their eyes to the periphery, presumably to widen the window of attention. Subjects with mild AD did not experience an additional disadvantage beyond that associated with aging.

Adult↗

Voxel-based morphometry of herpes simplex encephalitis.

Voxel-based morphometry (VBM) is a powerful tool for analyzing changes in gray or white matter density of the brain. By using an automated segmentation procedure and standardized parametric statistics it avoids biases inherent in operator-dependent morphological operations (J. Ashburner and K. J. Friston, 2000, NeuroImage 11, 805-821). Since its introduction in 1995, VBM has been used to examine anatomical changes in a variety of diseases associated with neurologic and psychiatric dysfunction. Given the power of this technique for discerning subtle anatomical changes, we wanted to assess its performance on brains with gross structural abnormalities. Such results could have implications regarding the difficulties to be faced when examining other types of distorted brains (e.g., brains with changes due to degenerative disease). This report describes the use of VBM for examining individual and group changes in gray matter concentration in five patients who had recovered from herpes simplex encephalitis (HSE) compared with age- and sex-matched controls. Because HSE tends to affect a specific set of brain regions we thought that this would (1) provide an opportunity to assess the anatomical face validity of VBM, (2) allow us to assess the problems of this technique when used on distorted brains, and (3) provide an in vivo demonstration of the gray matter changes due to HSE. We found that, despite problems in normalizing and segmenting these severely distorted brains, VBM was able to identify correctly a number of the regional gray matter abnormalities in HSE. The results, while consistent with the well-known histopathology of the disease, also demonstrate potential difficulties with this method.

Adult↗

Heterogeneity of cingulate contributions to spatial attention.

Functional magnetic resonance imaging was used to investigate activation patterns within the cingulate region during tasks based on spatial attention. Subjects were asked to detect targets which appeared either at the site indicated by a cue or on the opposite side. A "cue effect" was identified by the presence of shorter reaction times to validly than invalidly cued targets, showing that an anticipatory bias had been generated in the direction of the cue. Target detection accuracy was consistently above 90% although cue effects and reaction times displayed substantial variations, from one task session to another. Activation within the anterior cingulate region was seen in 16 of the 26 sessions but showed no correlation with reaction time. Posterior cingulate activation was seen in only 6 of the 26 sessions. However, a random effects analysis showed that the task-related signal change in this region was strongly correlated with the speed of target detection. A post hoc analysis indicated that this correlation was significant only when cue effects were present. No other part of the cerebral cortex displayed significant correlations with reaction times or cue effects. These results suggest that the cingulate component of the attentional network has at least two functionally segregated sectors, an anterior one in BA 24/32 and a posterior cingulo-retrosplenial one in BA 23/29/30. The posterior sector appears to be associated with the speed of detecting spatial targets, especially when attention is under the influence of a cue-induced anticipatory bias. The anterior cingulate focus did not display such a relationship in our tasks and is likely to mediate other aspects of attentional deployment such as performance monitoring, response selection or target identification.

Adult↗

Location- or feature-based targeting of peripheral attention.

Using event-related fMRI we determined the differential effects of feature- versus location-based cues for directing peripheral attention. Pairs of same-color targets appeared on the left and on the right. A predictive cue indicated whether the subsequent targeting of attention would be based on location (left versus right) or color (red versus blue). Subjects had to press a button when the relevant pair of targets (in the cued side of space or of the cued color) were identical in shape. The feature-based cue thus also led to a "global" expectancy of targets on either side of space whereas the location-based cue elicited a more "focal" expectancy limited to one side of space. The right inferior parietal lobule was more active when attention was targeted on the basis of location than of color. There was no difference between left-sided or right-sided attention in this region, indicating that it mediated the targeting to both sides of space. These results show that the right inferior parietal cortex plays a relatively selective role in mediating location-based and spatially focal modes of attentional deployment. Its relatively equal activation for leftward and rightward attentional shifts is also consistent with models of right hemispheric dominance of spatial attention.

Adult↗

Functional specificity of superior parietal mediation of spatial shifting.

Using event-related functional magnetic resonance imaging (fMRI) we determined how brain activity changes when an attended target shifts its location. In the main experiment, a white square could appear at 10 possible eccentricities along the horizontal meridian. It remained on the screen for a variable period of time and then changed location. At any time the stimulus could dim briefly. Subjects had to press a button when the stimulus dimmed. In order to perform this task attention had to be locked onto the target and shift with it. Half of the runs were performed overtly and half covertly. The event of interest consisted of the shift in the location of the attentional target. The state of maintained attention occurring in between the shifts constituted the baseline. The superior parietal gyrus was activated bilaterally in response to attentional shifts. No other area showed a significant response to shifting. On the left side the amplitude of the superior parietal response correlated positively with the distance of the shift. On the right side a significant correlation was present only for overt shifts. In a separate experiment we compared the maintaining of attention at a single spatial location to passive fixation: the frontal eye fields, anterior cingulate, right dorsolateral prefrontal cortex, and inferior parietal lobule were significantly activated, indicating that the absence of a shift-related response in these areas in the main experiment was due to the fact that they were equally activated by maintaining and shifting attention. The response to spatial shifts and the correlation with the distance between the original and the new location points to a specific role of the superior parietal gyrus in shifting the locus of spatial attention.

Adult↗

Hunger selectively modulates corticolimbic activation to food stimuli in humans.

Functional magnetic resonance imaging (fMRI) was used to determine whether visual responses to food in the human amygdala and related corticolimbic structures would be selectively altered by changes in states of hunger. Participants viewed images of motivationally relevant (food) and motivationally irrelevant (tool) objects while undergoing fMRI in alternately hungry and satiated conditions. Food-related visual stimuli elicited greater responses in the amygdala, parahippocampal gyrus. and anterior fusiform gyrus when participants were in a hungry state relative to a satiated state. The state-dependent activation of these brain structures did not generalize to the motivationally irrelevant objects. These results support the hypothesis that the amygdala and associated inferotemporal regions are involved in the integration of subjective interoceptive states with relevant sensory cues processed along the ventral visual stream.

Adult↗

The development of specialized brain systems in reading and oral-language.

Functional magnetic resonance imaging (fMRI) was used to examine differences between children (9-12 years) and adults (21-31 years) in the distribution of brain activation during word processing. Orthographic, phonologic, semantic and syntactic tasks were used in both the auditory and visual modalities. Our two principal results were consistent with the hypothesis that development is characterized by increasing specialization. Our first analysis compared activation in children versus adults separately for each modality. Adults showed more activation than children in the unimodal visual areas of middle temporal gyrus and fusiform gyrus for processing written word forms and in the unimodal auditory areas of superior temporal gyrus for processing spoken word forms. Children showed more activation than adults for written word forms in posterior heteromodal regions (Wernicke's area), presumably for the integration of orthographic and phonologic word forms. Our second analysis compared activation in the visual versus auditory modality separately for children and adults. Children showed primarily overlap of activation in brain regions for the visual and auditory tasks. Adults showed selective activation in the unimodal auditory areas of superior temporal gyrus when processing spoken word forms and selective activation in the unimodal visual areas of middle temporal gyrus and fusiform gyrus when processing written word forms.

Adult↗

Impact of signal-to-noise on functional MRI.

Functional magnetic resonance imaging (fMRI) has recently been adopted as an investigational tool in the field of neuroscience. The signal changes induced by brain activations are small ( approximately 1-2%) at 1.5T. Therefore, the signal-to-noise ratio (SNR) of the time series used to calculate the functional maps is critical. In this study, the minimum SNR required to detect an expected MR signal change is determined using computer simulations for typical fMRI experimental designs. These SNR results are independent of manufacturer, site environment, field strength, coil type, or type of cognitive task used. Sensitivity maps depicting the minimum detectable signal change can be constructed. These sensitivity maps can be used as a mask of the activation map to help remove false positive activations as well as identify regions of the brain where it is not possible to confidently reject the null hypothesis due to a low SNR.

Artifacts↗

Real-time monitoring of eye movements using infrared video-oculography during functional magnetic resonance imaging of the frontal eye fields.

Monitoring eye movements is a critical aspect of experimental design for studies of spatial attention and visual perception. However, obtaining online eye-movement recordings has been technologically difficult during functional magnetic resonance (MR) imaging studies. Previous approaches to monitoring eye movements either have distorted the MR images or have shown MR-related interference in the recordings. We report a technique using long-range infrared video-oculography to record eye movements without causing artifacts in the MR images. Analysis of the MR signal from a phantom obtained with the eye-movement equipment turned on or off confirmed the absence of significant additional noise in the MR time series. Eye movements of three subjects were monitored while they performed tasks of covert and overt shifts of spatial attention. Activation of the frontal eye fields during the covert task was seen even when the eye-movement recordings demonstrated no significant difference in saccadic eye movements between the baseline and the active conditions.

Adult↗

Covert visual spatial orienting and saccades: overlapping neural systems.

We used functional magnetic resonance imaging (fMRI) to investigate the functional anatomical relationship between covert orienting of visual spatial attention and execution of saccadic eye movements. Brain areas engaged by shifting spatial attention covertly and by moving the eyes repetitively toward visual targets were compared and contrasted directly within the same subjects. The two tasks activated highly overlapping neural systems and showed that common parietal and frontal regions are more activated during the covert task than the overt oculomotor condition. The possible nature of the relationship between these two operations is discussed.

Adult↗

Emotional curiosity: modulation of visuospatial attention by arousal is preserved in aging and early-stage Alzheimer's disease.

Previous studies have shown that Alzheimer's disease, even in its early stages, decreases novelty-seeking behaviors (curiosity) and impairs the shifting of spatial attention to extrapersonal targets. In this study, early-stage probable Alzheimer's disease patients (PRAD) and young and aging controls were shown pairs of visual scenes, some of which contained emotionally-arousing material, while eye movements were recorded under free viewing conditions. In all three subject groups, emotionally-arousing scenes attracted more viewing time and also became the preferential target of the initial visual orientation. Our findings suggest that the arousing properties of sensory stimuli may overcome some of the AD-related impairments in the distribution of attention to extrapersonal targets. These results may have implications for interventions aimed at improving the cognitive symptoms of PRAD.

Adult↗

Alterations of visual search strategy in Alzheimer's disease and aging.

Visual search, characterized by eye fixation patterns, was examined in 8 patients with Alzheimer's disease (AD), 8 cognitively intact, age-matched individuals, and 8 young control participants as they searched for a number among a nonlinear array of letters on a large computer screen. Among the 3 groups, target detection accuracy differed and detection time increased linearly. There were more fixations, and fixation duration was significantly longer in the AD patients than in the other 2 groups. These factors contributed to the lengthening of target detection time. This qualitative difference in the architecture of visual search between AD and aging may reflect a specific deficit in the disengagement of visual spatial attention, a prolongation of saccade initiation, or inefficiency in planning a search strategy.

Adult↗