Biomedical subjects

Darren R Gitelman

Publications and source records attributed to Darren R Gitelman.

At least 19 recordsLinked to original sources

PubMed2006

Weaker top-down modulation from the left inferior frontal gyrus in children.

Previous studies have shown that developmental changes in the structure and function of prefrontal regions can continue throughout childhood and adolescence. Our recent results suggested a role for the left inferior frontal cortex in modulating task-dependent shifts in effective connectivity when adults focus on orthographic versus phonological aspects of presented words. Specifically, the top-down influence of the inferior frontal cortex determined whether incoming word-form information from the fusiform gyrus would have a greater impact on the parietal areas involved in orthographic processing or temporal areas involved in phonological processing (Bitan, T., Booth, J.R., Choy, J., Burman, D.D., Gitelman, D.R. and Mesulam, M.-M., 2005. Shifts of Effective Connectivity within a Language Network during Rhyming and Spelling. J. Neurosci. 25, 5397-5403.). In the current study, we find that children displayed an identical pattern of task-dependent functional activations within this network. In comparison to adults, however, children had significantly weaker top-down modulatory influences emanating from the inferior frontal area. Adult language processing may thus involve greater top-down cognitive control compared to children, resulting in less interference from task-irrelevant information.

Adult↗

PubMed2006

Orienting attention based on long-term memory experience.

Attentional orienting and memory are intrinsically bound, but their interaction has rarely been investigated. Here we introduce an experimental paradigm using naturalistic scenes to investigate how long-term memory can guide spatial attention and thereby enhance identification of events in the perceptual domain. In the task, stable memories of objects embedded within complex scenes guide spatial orienting. We compared the behavioral effects and neural systems of memory-guided orienting with those in a more traditional attention-orienting task in which transient spatial cues guide attention. Memory-guided attention operated within surprisingly short intervals and conferred reliable and sizeable advantages for detection of objects embedded in scenes. Event-related functional magnetic resonance imaging showed that memory-guided attention involves the interaction between brain areas participating in retrieval of memories for spatial context with the parietal-frontal network for visual spatial orienting. Activity in the hippocampus was specifically engaged in memory-guided spatial attention and correlated with the ensuing behavioral advantage.

Adult↗

PubMed2006

Vasectomy in men with primary progressive aphasia.

OBJECTIVE: To study the frequency of vasectomy in men with primary progressive aphasia (PPA). BACKGROUND: PPA is a dementia syndrome in which aphasia emerges in relative isolation during the initial stages of illness. On the basis of a clinical observation in a patient who dated the onset of symptoms to the period after a vasectomy, and because of the curious sharing of the tau protein exclusively by brain and sperm, vasectomy rates were examined in men with PPA. METHOD: This study used a case control design. Forty-seven men with PPA and 57 men with no cognitive impairment (NC) between 55 and 80 years of age were surveyed about a history of vasectomy. RESULTS: The age-adjusted rate of vasectomy in PPA patients (40%) was higher than in NC (16%, P=0.02). There was a younger age at onset for the patients with vasectomy (58.8 vs. 62.9 y, P=0.03). CONCLUSIONS: Vasectomy may constitute one risk factor for PPA in men. Potential mechanisms mediating risk include vasectomy-induced immune responses to sperm, which shares antigenic epitopes with brain. Antisperm antibodies can also develop in women and become risk factors for PPA.

Aged↗

PubMed2005

Language network specializations: an analysis with parallel task designs and functional magnetic resonance imaging.

Although the classical core regions of the language system (Broca's and Wernicke's areas) were defined over a century ago, it took the advent of functional imaging to sharpen our understanding of how these regions and adjacent parts of the brain are associated with particular aspects of language. One limitation of such studies has been the need to compare results across different subject groups, each performing a different type of language task. Thus, this study was designed to examine overlapping versus segregated brain activations associated with three fundamental language tasks, orthography, phonology and semantics performed by the same subjects during a single experimental session. The results demonstrate a set of primarily left-sided core language regions in ventrolateral frontal, supplementary motor, posterior mid-temporal, occipito-temporal and inferior parietal areas, which were activated for all language tasks. Segregated task-specific activations were demonstrated within the ventrolateral frontal, mid-temporal and inferior parietal areas. Within the inferior frontal cortex (Broca's regional complex), segregated activations were seen for the semantic and phonological tasks. These findings demonstrate both common and task specific activations within the language system.

Adult↗

PubMed2005

Shifts of effective connectivity within a language network during rhyming and spelling.

We used functional magnetic resonance imaging to examine task-specific modulations of effective connectivity within a left-hemisphere language network during spelling and rhyming judgments on visually presented words. We identified sites showing task-specific activations for rhyming in the lateral temporal cortex (LTC) and for spelling in the intraparietal sulcus (IPS). The inferior frontal gyrus (IFG) and fusiform gyrus were engaged by both tasks. Dynamic causal modeling showed that each task preferentially strengthened modulatory influences converging on its task-specific site (LTC for rhyming, IPS for spelling). These remarkably selective and symmetrical findings demonstrate that the nature of the behavioral task dynamically shifts the locus of integration (or convergence) to the network component specialized for that task. Furthermore, they suggest that the role of the task-selective areas is to provide a differential synthesis of incoming information rather than providing differential control signals influencing the activity of other network components. Our findings also showed that switching tasks led to changes in the target area influenced by the IFG, suggesting that the IFG may play a pivotal role in setting the cognitive context for each task. We propose that task-dependent shifts in effective connectivity are likely to be mediated through top-down modulations from the IFG to the task-selective regions in a way that differentially enhances their sensitivity to incoming word-form information.

Adult↗

PubMed2005

The "zoom lens" of focal attention in visual search: changes in aging and Alzheimer's disease.

Visual search for a target in an array of distractors relies upon flexible shifts between global and local modes of attentional processing. Visual search is slowed in patients with Alzheimer's disease (AD), in part due to an increase in the number and duration of eye fixations made en route to a target (Rösler et al., 2000). This phenomenon may represent a compensatory adaptation to a narrowing of the zone of focal attention, necessitating more shifts of gaze in order to attend to the global workspace. Eye fixations were analyzed in two regions of interest (ROIs, central fixation and peripheral target locations) in 9 patients with mild AD, 9 cognitively intact age-matched control subjects, and 9 young controls, while they searched for a target object in a radial array that contained from 1 to 6 stimuli. Contrasted with young subjects, the search strategy of older controls and, to a greater extent, AD patients showed an increase in the average number and duration of peripheral fixations. Reduced efficiency of visual search in AD may be contributed to by reduced ability to dynamically adjust the attentional zoom, coupled with the inability to disengage attention from peripheral targets.

Adult↗

PubMed2005

Taste and olfactory intensity perception changes following left insular stroke.

The authors tested suprathreshold intensity perception of gustatory and olfactory stimuli in a 70-year-old right-handed man following a left posterior insular stroke and compared his results with those of age-matched controls. Both modalities revealed significant differences between left (ipsilateral to lesion) and right (contralateral) ratings of intensity. In both gustation and olfaction, these differences were driven primarily by trends toward increased contralateral sensitivity relative to controls. Intensity changes were most pronounced for unpleasant odors and for tastes perceived strongly as either pleasant (sweet) or unpleasant (salty, bitter). These results show that a left posterior insula lesion may affect taste and olfactory perception similarly by increasing sensitivity contralateral to the lesion. One possible mechanism is release from inhibition at the cortical level.

Aged↗

PubMed2005

Larger deficits in brain networks for response inhibition than for visual selective attention in attention deficit hyperactivity disorder (ADHD).

BACKGROUND: Brain activation differences between 12 control and 12 attention deficit hyperactivity disorder (ADHD) children (9- to 12-year-olds) were examined on two cognitive tasks during functional magnetic resonance imaging (fMRI). METHOD: Visual selective attention was measured with the visual search of a conjunction target (red triangle) in a field of distracters and response inhibition was measured with a go/no-go task. RESULTS: There were limited group differences in the selective attention task, with control children showing significantly greater intensity of activation in a small area of the superior parietal lobule region of interest. There were large group differences in the response inhibition task, with control children showing significantly greater intensity of activation in fronto-striatal regions of interest including the inferior, middle, superior and medial frontal gyri as well as the caudate nucleus and globus pallidus. CONCLUSION: The widespread hypoactivity for the ADHD children on the go/no-go task is consistent with the hypothesis that response inhibition is a specific deficit in attention deficit hyperactivity disorder.

Attention↗

PubMed2005

Simultaneous assessment of motor and language areas with a single functional MR imaging paradigm: feasibility.

The purpose of this study was to test a hybrid multitask paradigm in healthy subjects and in a patient at preoperative functional magnetic resonance (MR) imaging. In this new paradigm, tasks related to different centers of brain function (motor and language) are performed in alternation during a single functional MR imaging examination, without the typical rest period, to improve time efficiency without compromising the quality of activation maps. The institutional review board approved the study, and all participants gave informed prior consent. The study complied with the Health Insurance Portability and Accountability Act. Seven healthy right-handed volunteers (four men, three women; age range, 22-40 years) were studied first. In both individual and group analyses, there was no statistically significant difference in results between assessment with the multitask design and that with the traditional block design. An advantage of the new paradigm was substantial time savings because the subject was engaged during the entire examination. Finally, the multitask design was tested in a patient undergoing preoperative evaluation, with similar results; therefore, use of the multitask design is feasible in a clinical setting.

Adult↗

PubMed2004

Chronic back pain is associated with decreased prefrontal and thalamic gray matter density.

The role of the brain in chronic pain conditions remains speculative. We compared brain morphology of 26 chronic back pain (CBP) patients to matched control subjects, using magnetic resonance imaging brain scan data and automated analysis techniques. CBP patients were divided into neuropathic, exhibiting pain because of sciatic nerve damage, and non-neuropathic groups. Pain-related characteristics were correlated to morphometric measures. Neocortical gray matter volume was compared after skull normalization. Patients with CBP showed 5-11% less neocortical gray matter volume than control subjects. The magnitude of this decrease is equivalent to the gray matter volume lost in 10-20 years of normal aging. The decreased volume was related to pain duration, indicating a 1.3 cm3 loss of gray matter for every year of chronic pain. Regional gray matter density in 17 CBP patients was compared with matched controls using voxel-based morphometry and nonparametric statistics. Gray matter density was reduced in bilateral dorsolateral prefrontal cortex and right thalamus and was strongly related to pain characteristics in a pattern distinct for neuropathic and non-neuropathic CBP. Our results imply that CBP is accompanied by brain atrophy and suggest that the pathophysiology of chronic pain includes thalamocortical processes.

Aging↗

PubMed2004

Priming effects in the fusiform gyrus: changes in neural activity beyond the second presentation.

Repetition priming typically leads to a decrease in the activation of sensory cortical areas upon a second exposure to the same visual stimulus. This effect is thought to reflect more efficient or fluent re-processing of previously seen stimuli so that less neural activity is required. Fluent re-processing has been hypothesized to be a potential link from repetition priming to neural changes associated with visual expertise. To examine this potential connection, the neural correlates of priming were examined across eight stimulus repetitions using functional magnetic resonance imaging. Sizeable regions of bilateral ventral occipito-temporal cortex (including the fusiform gyrus) exhibited reduced responses to the second presentation of a stimulus. Most of these areas displayed no further reduction in response to subsequent repetitions of the same stimuli. Because expertise accrues over many exposures, these areas, while clearly involved in priming, do not exhibit an activity pattern consistent with the development of expertise. In contrast, an area in the right posterior fusiform gyrus exhibited reductions in evoked response that grew in magnitude for stimulus repetitions from the second to the eighth presentations. This region exhibits a pattern of activity consistent with a gradual and cumulative enhancement of the fluency effect across trials, suggesting that it may mediate the link between priming and the development of visual expertise.

Adolescent↗

PubMed2004

Brain-behavior correlation in children depends on the neurocognitive network.

We examined brain-behavior correlations in 12 children (age range 9.3 to 11.7 years) during a selective attention task that required the visual search of a conjunction of features and during a response inhibition task that required the inhibition of a pre-potent response during "no-go" blocks. We found that the association between performance in these tasks and brain activation as measured by functional magnetic resonance imaging (fMRI) depended on the neurocognitive network. Specifically, better performance during the no-go task was associated with greater activation in the response inhibition network including the prefrontal cortex and basal ganglia. In contrast, better performance during the visual search task was associated with less activation in the selective attention network including superior parietal lobule and lateral premotor cortex. These results show that the relation of performance to the magnitude of neural activation is complex and may display differential relationships based on the cognitive domain, anatomical region, and perhaps also developmental stage.

Attention↗

PubMed2004

Neural evidence that vivid imagining can lead to false remembering.

The imperfect nature of memory is highlighted by the regularity with which people fail to remember, or worse, remember something that never happened. We investigated the formation of a particular type of erroneous memory by monitoring brain activity using functional magnetic resonance imaging during the presentation of words and photos. Participants generated a visual image of a common object in response to each word. Subsequently, they sometimes claimed to have seen photos of specific objects they had imagined but not actually seen. In precuneus and inferior parietal regions of the cerebral cortex, activations in response to words were greater when participants subsequently claimed to have seen the corresponding object than when a false memory for that object was not subsequently produced. These findings indicate that brain activity reflecting the engagement of visual imagery can lead to falsely remembering something that was only imagined.

Adolescent↗

PubMed2004

Development of brain mechanisms for processing orthographic and phonologic representations.

Developmental differences in the neurocognitive networks for lexical processing were examined in 15 adults and 15 children (9- to 12-year-olds) using functional magnetic resonance imaging (fMRI). The lexical tasks involved spelling and rhyming judgments in either the visual or auditory modality. These lexical tasks were compared with nonlinguistic control tasks involving judgments of line patterns or tone sequences. The first main finding was that adults showed greater activation than children during the cross-modal lexical tasks in a region proposed to be involved in mapping between orthographic and phonologic representations. The visual rhyming task, which required conversion from orthography to phonology, produced greater activation for adults in the angular gyrus. The auditory spelling task, which required the conversion from phonology to orthography, also produced greater activation for adults in the angular gyrus. The greater activation for adults suggests they may have a more elaborated posterior heteromodal system for mapping between representational systems. The second main finding was that adults showed greater activation than children during the intra-modal lexical tasks in the angular gyrus. The visual spelling and auditory rhyming did not require conversion between orthography and phonology for correct performance but the adults showed greater activation in a system implicated for this mapping. The greater activation for adults suggests that they have more interactive convergence between representational systems during lexical processing.

Acoustic Stimulation↗

PubMed2003

Dissociating explicit and implicit category knowledge with fMRI.

Neuroimaging of healthy volunteers identified separate neural systems supporting the expression of category knowledge depending on whether the learning mode was intentional or incidental. The same visual category was learned either intentionally or implicitly by two separate groupsof participants. During a categorization test, functional magnetic resonance imaging (fMRI) was used to compare brain activity evoked by category members and nonmembers. After implicit learning, when participants had learned the category incidentally, decreased occipital activity was observed for novel categorical stimuli compared with noncategorical stimuli. In contrast, after intentional learning, novel categorical stimuli evoked increased activity in the hippocampus, right prefrontal cortex, left inferior temporal cortex, precuneus, and posterior cingulate. Even though the categorization test was identical in the two conditions, the differences in brain activity indicate differing representations of category knowledge depending on whether the category had been learned intentionally or implicitly.

Brain Mapping↗

PubMed2003

Primary progressive aphasia: PPA and the language network.

Primary Progressive Aphasia (PPA) is a behaviorally focal dementia syndrome with deterioration of language functions but relative preservation of other cognitive domains for at least the first two years of disease. In this study, PPA patients with impaired word finding but intact comprehension of conversational speech and their matched control subjects were examined using voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI). fMRI compared signal changes during phonological and semantic language tasks with those during a control task (matching letters). PPA patients showed longer reaction times and reduced accuracy versus controls on the language tasks, but no performance differences on the control task. VBM demonstrated reduced gray matter in left superior temporal and inferior parietal regions in the PPA group. However, these patients showed a normal pattern of activation within the classical language regions. In addition, PPA patients showed activations, not seen in normals, in fusiform gyrus, precentral gyrus, and intra-parietal sulcus. These activations were found to correlate negatively with measures of naming and task performance. The additional activations in PPA may therefore represent a compensatory spread of language-related neural activity or a failure to suppress activity in areas normally inhibited during language tasks.

Aged↗

PubMed2003

Relation between brain activation and lexical performance.

Functional magnetic resonance imaging (fMRI) was used to determine whether performance on lexical tasks was correlated with cerebral activation patterns. We found that such relationships did exist and that their anatomical distribution reflected the neurocognitive processing routes required by the task. Better performance on intramodal tasks (determining if visual words were spelled the same or if auditory words rhymed) was correlated with more activation in unimodal regions corresponding to the modality of sensory input, namely the fusiform gyrus (BA 37) for written words and the superior temporal gyrus (BA 22) for spoken words. Better performance in tasks requiring cross-modal conversions (determining if auditory words were spelled the same or if visual words rhymed), on the other hand, was correlated with more activation in posterior heteromodal regions, including the supramarginal gyrus (BA 40) and the angular gyrus (BA 39). Better performance in these cross-modal tasks was also correlated with greater activation in unimodal regions corresponding to the target modality of the conversion process (i.e., fusiform gyrus for auditory spelling and superior temporal gyrus for visual rhyming). In contrast, performance on the auditory spelling task was inversely correlated with activation in the superior temporal gyrus possibly reflecting a greater emphasis on the properties of the perceptual input rather than on the relevant transmodal conversions.

Acoustic Stimulation↗

PubMed2003

Cerebral hemispheric specialization for spatial attention: spatial distribution of search-related eye fixations in the absence of neglect.

The "specialization" of the right hemisphere for spatial attention is widely accepted but poorly understood. While several theories have been supported by studies of patients with acute hemispatial neglect, generalizability beyond this population remains unclear. In this study, we compared the predictions of two attention models [Brain 119 (1996) 841; Trans. Am. Neurol. Assoc. 95 (1970) 143] when applied to data obtained from subjects with unilateral right- or left-cerebral lesions, but without clinical evidence of neglect during a visual search task. Both Left Lesion and Right Lesion subjects detected fewer targets in the contralesional hemispace. However, the Right Lesion subjects also made fewer visual fixations and longer saccades in the contralesional hemispace, suggesting a fundamental alteration in the architecture of visual search. The spatial distribution of fixations made by Right Lesion subjects more closely fits the prediction of a "salience" model than of the strict interpretation of a linear "gradient" model. These data support the long-standing notion of right hemisphere dominance for spatial attention, especially for the top-down processes entailed in self-directed visual search, and extend this to lesion patients without clinically evident neglect. A theoretical model based on the salience of extrapersonal space appears useful for understanding alterations of attentional allocation, particularly after recovery from stroke.

Adult↗