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Biomedical subjects

S Y Bookheimer

Publications and source records attributed to S Y Bookheimer.

At least 19 recordsLinked to original sources
PubMed2001

Functional MRI changes during panic anticipation and imagery exposure.

While undergoing fMRI, six patients with DSM IV diagnosis of panic disorder and six normal controls performed directed imagery of neutral, moderate and high anxiety situations based on an individually determined behavioral hierarchy. Brain activity was compared during high vs neutral anxiety blocks for each group of subjects using SPM99b. Panic patients showed increased activity in inferior frontal cortex, hippocampus and throughout the cingulate both anterior and posterior, extending into the orbitofrontal cortex and encompassing both hemispheres. These areas may constitute the important circuit in the psychopathology of panic disorder. We propose that this pattern of activity may enhance the encoding and retrieval of strong emotional events, facilitating the recapitulation of traumatic experiences and leading to panic disorder in vulnerable individuals.

Adult↗
PubMed2001

Estrogen use and brain metabolic change in older adults. A preliminary report.

Because estrogen may influence brain blood flow and metabolism in older adults, we used positron emission tomography to evaluate cerebral glucose metabolic change in post-menopausal women and men. Women estrogen users (n=4), women non-users (n=8) and men (n=10) were scanned at baseline and two years later. Analyses focused on glucose metabolism in lateral temporal, inferior parietal and posterior cingulate brain regions, previously reported to decline in non-demented older persons. No metabolic differences in cerebral regions of interest were found among groups at baseline. At follow-up, women estrogen users showed significantly increased glucose metabolism in the lateral temporal region, whereas women non-users and men exhibited no significant metabolic change in this region. These findings suggest that estrogen use may protect against regional cerebral metabolic decline in postmenopausal women.

Aged↗
PubMed2001

Unfolding the human hippocampus with high resolution structural and functional MRI.

The hippocampus is a region of the brain that is crucial to memory function. Functional neuroimaging allows for the noninvasive investigation of the neurophysiology of human memory by observing changes in blood flow in the brain. We have developed a technique that employs high-resolution functional magnetic resonance imaging (fMRI) in combination with cortical unfolding to provide activation maps of the hippocampal region that surpass in anatomic and functional detail other methods of in vivo human brain mapping of the medial temporal lobe. We explain the principles behind this method and illustrate its application to a novelty-encoding paradigm.

Brain Mapping↗
PubMed2001

Memory self-appraisal and depressive symptoms in people at genetic risk for Alzheimer's disease.

OBJECTIVES: A previous study found that subjective memory loss in middle-aged and older persons is associated with the major genetic risk for Alzheimer's disease, the apolipoprotein E-4 (APOE-4) allele. No previous study has focused on subjective memory complaints and depressive symptoms in the same subject population at genetic risk for Alzheimer's disease. METHOD: Sixty-six persons (mean age = 64 years, range = 43 to 82 years) without major depression or dementia but with mild age-related memory complaints were rated for severity of depressive symptoms, using the Hamilton Depression Rating Scale, and assessed for the presence of the APOE-4 allele. Severity of subjective memory loss was assessed using the Memory Functioning Questionnaire, which measures four memory domains: frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics usage. RESULTS: Depressive symptoms were significantly associated with subjective memory loss in subjects without the APOE-4 allele, for retrospective functioning (perceived change in memory) and mnemonics usage, but not in APOE-4 carriers. The same significant associations were found when the analysis was limited to the 44 subjects in the mid-age range (55-74 years), wherein APOE-4 confers its greatest effects on risk for Alzheimer's disease. CONCLUSION: These results confirm that mild depressive symptoms are related to subjective memory loss, but for some forms of memory complaint, the relationship holds true only for people without the major known genetic risk for Alzheimer's disease.

Adult↗
PubMed2001

Temporal spatial differences observed by functional MRI and human intraoperative optical imaging.

Pre-operative functional magnetic resonance imaging (fMRI), cortical evoked potentials (EPs) and intraoperative optical imaging of intrinsic signals (iOIS) were employed to relate the temporal-spatial characteristics of sensorimotor responses in human brain. Peripheral somasthetic stimulation (2 s) was provided either by a 110 Hz finger vibrator or transcutaneous median nerve stimulation in eight patients undergoing neurosurgical procedures. Each technique provided unique spatial patterns and temporal response profiles. EPs and iOIS activities were observed over the surface of pre- and post-central gyri (at the level of the superior genu) with very similar spatial distributions. In contrast, fMRI spatial distributions depended upon the model used for statistical correlation analysis. Using a monophasic response model, fMRI primarily localized within the central sulcus and did not demonstrate large signal changes over the pre- and post-central gyri (areas with iOIS/EP activity). However, as initial negative responses were incorporated into the response model, fMRI progressively localized closer to the iOIS and somatosensory EP maps. Temporally, responses to single stimuli differed between the fMRI and iOIS techniques. Using a monophasic model for fMRI analysis, the total fMRI response was delayed by 2--3 s relative to iOIS. As initial negative responses were incorporated in the analysis, the fMRI time course developed temporal characteristics similar to iOIS. Ultimately, when fMRI time courses were examined over pixels co-localizing with iOIS activation (without using statistical correlation analysis), the fMRI temporal profile included an initial decrease in signal (an initial dip) that closely resembled the time course of iOIS response. This is the first study to experimentally co-localize (temporally and spatially) iOIS and fMRI signals in human subjects. The spatial/temporal differences in this study likely reflect the capillary versus venous contributions of iOIS and fMRI, respectively. The temporal/spatial co-localization of the iOIS signal and the fMRI initial dip suggests the initial fMRI dip and the iOIS signal may result from similar physiologic events.

Algorithms↗
PubMed2000

Activation of language cortex with automatic speech tasks.

OBJECTIVE: To identify automatic speech tasks that reliably demonstrate increased regional cerebral blood flow (rCBF) in Broca's and Wernicke's areas of the cortex using PET. BACKGROUND: Localizing language with direct cortical stimulation mapping requires that patients have a stable baseline on tests that engage eloquent cortex. For dysphasic patients or younger children, automatic speech tasks such as counting are often used in lieu of more complex language tests. Evidence from both lesion and neuroimaging studies suggests that these tasks may not adequately engage language cortices. In this study, we examined rCBF during automatic oromotor and speech tasks of varying complexity to identify those eliciting increased CBF in Broca's and Wernicke's areas. METHODS: Eight normal volunteers underwent PET during rest, tongue movements, and three automatic speech tasks: repeating a phoneme sequence, repeating the months of the year, and reciting a memorized prose passage. Images were averaged across subjects and compared across tasks for regional localization and laterality. RESULTS: Whereas all activation tasks produced increased relative CBF in brain regions that correlated with articulation and auditory processing, only the two tasks that used real words (versus phonemes) showed left-lateralized rCBF increases in posterior superior temporal lobe (Wernicke's area), and only the prose repetition task produced left lateralized activity in Broca's area. CONCLUSIONS: Whereas automatic speech typically does not engage language cortex, repeating a memorized prose passage showed unambiguous activation in both Broca's and Wernicke's areas. These results caution against the use of common automatic speech tasks for mapping eloquent cortex and suggest an alternative task for those with poor language abilities or acquired dysphasia who cannot perform standardized language tests reliably.

Adult↗
PubMed2000

Patterns of brain activation in people at risk for Alzheimer's disease.

BACKGROUND: The epsilon4 allele of the apolipoprotein E gene (APOE) is the chief known genetic risk factor for Alzheimer's disease, the most common cause of dementia late in life. To determine the relation between brain responses to tasks requiring memory and the genetic risk of Alzheimer's disease, we performed APOE genotyping and functional magnetic resonance imaging (MRI) of the brain in older persons with intact cognition. METHODS: We studied 30 subjects (age, 47 to 82 years) who were neurologically normal, of whom 16 were carriers of the APOE epsilon4 allele and 14 were homozygous for the APOE epsilon3 allele. The mean age and level of education were similar in the two groups. Patterns of brain activation during functional MRI scanning were determined while subjects memorized and recalled unrelated pairs of words and while subjects rested between such periods. Memory was reassessed in 14 subjects two years later. RESULTS: Both the magnitude and the extent of brain activation during memory-activation tasks in regions affected by Alzheimer's disease, including the left hippocampal, parietal, and prefrontal regions, were greater among the carriers of the APOE epsilon4 allele than among the carriers of the APOE epsilon3 allele. During periods of recall, the carriers of the APOE epsilon4 allele had a greater average increase in signal intensity in the hippocampal region (1.03 percent vs. 0.62 percent, P<0.001) and a greater mean (+/-SD) number of activated regions throughout the brain (15.9+/-6.2 vs. 9.4+/-5.5, P=0.005) than did carriers of the APOE epsilon3 allele. Longitudinal assessment after two years indicated that the degree of base-line brain activation correlated with degree of decline in memory. CONCLUSIONS: Patterns of brain activation during tasks requiring memory differ depending on the genetic risk of Alzheimer's disease and may predict a subsequent decline in memory.

Aged↗
PubMed2000

Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease.

The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.

Aged↗
PubMed2000

Modulating emotional responses: effects of a neocortical network on the limbic system.

Humans share with animals a primitive neural system for processing emotions such as fear and anger. Unlike other animals, humans have the unique ability to control and modulate instinctive emotional reactions through intellectual processes such as reasoning, rationalizing, and labeling our experiences. This study used functional MRI to identify the neural networks underlying this ability. Subjects either matched the affect of one of two faces to that of a simultaneously presented target face (a perceptual task) or identified the affect of a target face by choosing one of two simultaneously presented linguistic labels (an intellectual task). Matching angry or frightened expressions was associated with increased regional cerebral blood flow (rCBF) in the left and right amygdala, the brain's primary fear centers. Labeling these same expressions was associated with a diminished rCBF response in the amygdalae. This decrease correlated with a simultaneous increase in rCBF in the right prefrontal cortex, a neocortical region implicated in regulating emotional responses. These results provide evidence for a network in which higher regions attenuate emotional responses at the most fundamental levels in the brain and suggest a neural basis for modulating emotional experience through interpretation and labeling.

Adult↗
PubMed2000

Methodological issues in pediatric neuroimaging.

The emergence of new technologies to study brain function in vivo has resulted in an explosion of interest in cognitive neuroscience within the last ten years. While most research in functional neuroimaging has been geared toward adult normal volunteers, the development of functional magnetic resonance imaging (fMRI) has made it possible to study neural development in normal children, as well as those with developmental disorders. This technology provides an unprecedented opportunity to expand our knowledge of brain function throughout childhood. A variety of technological, experimental, and practical difficulties are amplified when imaging children. This paper reviews some of the more challenging theoretical and practical concerns and provides suggestions for their management.

Child↗
PubMed2000

Application of cortical unfolding techniques to functional MRI of the human hippocampal region.

We describe a new application of cortical unfolding to high-resolution functional magnetic resonance imaging (fMRI) of the human hippocampal region. This procedure includes techniques to segment and unfold the hippocampus, allowing the fusiform, parahippocampal, perirhinal, entorhinal, subicular, and CA fields to be viewed and compared across subjects. Transformation parameters derived from unfolding high-resolution structural images are applied to coplanar, functional images, yielding two-dimensional "unfolded" activation maps of hippocampi. The application of these unfolding techniques greatly enhances the ability of fMRI to localize and characterize signal changes within the medial temporal lobe. Use of this method on a novelty-encoding paradigm reveals a temporal dissociation between activation along the collateral sulcus and activation in the hippocampus proper.

Adult↗
PubMed2000

Temporal and topographical characterization of language cortices using intraoperative optical intrinsic signals.

We used intraoperative optical imaging of intrinsic signals (iOIS) and electrocortical stimulation mapping (ESM) to compare functionally active brain regions in 10 awake patients undergoing neurosurgical resection. Patients performed two to four tasks, including visual and auditory naming, word discrimination, and/or orofacial movements. All iOIS maps included areas identified by ESM mapping. However, iOIS also revealed topographical specificity dependent on language task. In Broca's area, naming paradigms activated both anterior and posterior inferior frontal gyrus (IFG), while the word discrimination paradigm activated only posterior IFG. In Wernicke's area, object naming produced activations localizing over the inferior and anterior/posterior regions, while the word discrimination task activated superior and anterior cortices. These results may suggest more posterior phonological activation and more anterior semantic activations in Broca's area, and more anterior/superior phonological activation and more posterior/inferior semantic activations in Wernicke's area. Although similar response onset was observed in Broca's and Wernicke's areas, temporal differences were revealed during block paradigm (20-s) activations. In Broca's area, block paradigms yielded a boxcar temporal activation profile (in all tasks) that resembled response profiles observed in motor cortex (with orofacial movements). In contrast, activations in Wernicke's area responded with a more dynamic profile (including early and late peaks) which varied with paradigm performance. Wernicke's area profiles were very similar to response profiles observed in sensory and visual cortex. The differing temporal patterns may therefore reflect unique processing performed by receptive (Wernicke's) and productive (Broca's) language centers. This study is consistent with task-specific semantic and phonologic regions within Broca's and Wernicke's areas and also is the first report of response profile differences dependent on cortical region and language task.

Brain↗
PubMed2000

Remembering episodes: a selective role for the hippocampus during retrieval.

Some memories are linked to a specific time and place, allowing one to re-experience the original event, whereas others are accompanied only by a feeling of familiarity. To uncover the distinct neural bases for these two types of memory, we measured brain activity during memory retrieval using event-related functional magnetic resonance imaging. We show that activity in the hippocampus increased only when retrieval was accompanied by conscious recollection of the learning episode. Hippocampal activity did not increase for items recognized based on familiarity or for unrecognized items. These results indicate that the hippocampus selectively supports the retrieval of episodic memories.

Adult↗
PubMed2000

Optical imaging of bilingual cortical representations. Case report.

The organization of language in the brains of multilingual persons remains controversial. The authors investigated language representations in a proficient bilingual patient by using a novel neuroimaging technique, intraoperative optical imaging of intrinsic signals (iOIS), and a visual object naming task. The results indicate that there are cortical areas that are activated by the use of both English and Spanish languages (superior temporal sulcus, superior and middle temporal gyri, and parts of the supramarginal gyrus). In addition, language-specific areas were identified in the supramarginal (Spanish) and precentral (English) gyri. These results suggest that cortical language representations in bilingual persons may consist of both overlapping and distinct components. Furthermore, this study demonstrates the utility of iOIS in detecting topographical segregation of cognitively distinct cortices.

Adult↗
PubMed1999

Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures.

BACKGROUND: Previous studies have suggested a variety of factors that may be associated with the presence of hippocampal formation (HF) atrophy in patients with complex partial seizures (CPS), including a history of complex or prolonged febrile seizures (FS), age at seizure onset, and epilepsy duration. OBJECTIVE: To determine whether epilepsy duration is related to HF atrophy. METHODS: We performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal onset on video-EEG. None had evidence for an alien tissue lesion or extra-hippocampal seizure onset. All had a history of secondary generalization. Brain structures were drawn on consecutive images and pixel points summed from successive pictures to calculate volumes. RESULTS: Nine patients with a history of complex or prolonged FS had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than did patients without a history of FS. Epilepsy duration had a significant relation to ipsilateral HF volume and ipsilateral/contralateral ratio. In a multivariate analysis, the effect of duration, but not age at onset or scan, was significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration. CONCLUSIONS: A history of FS predicted the severity of HF atrophy in our patients. Age at onset or study was not a significant factor. Epilepsy duration, however, did have a significant effect, suggesting that, after an initial insult, progressive HF damage may occur in patients with persistent seizures.

Adult↗
PubMed1999

(15)O water positron emission tomography in language localization: a study comparing positron emission tomography visual and computerized region of interest analysis with the Wada test.

We compared (15)O water positron emission tomography (PET) auditory and visual confrontational naming activation with an intracarotid amobarbital (Amytal) injection procedure (IAP) for language lateralization in 12 patients with intractable epilepsy. PET scans were evaluated by three raters experienced in functional imaging as well as by a region of interest (ROI) approach. Compared with IAP, raters' positive predictive value for language lateralization ranged from 88 to 91%. ROI analysis had a positive predictive value of 80%. Six patients had surgery; 1 with right-sided IAP language dominance but left-sided PET activation had dysphasia for 6 months after left temporal lobectomy.

Adolescent↗
PubMed1999

Form and content: dissociating syntax and semantics in sentence comprehension.

The distinction between syntax (sentence form) and semantics (sentence meaning) is fundamental to our thinking about language. Whether and where this distinction is represented at the neural level is still a matter of considerable debate. In the present fMRI study, we examined the neural correlates of syntactic and semantic functions using an innovative activation paradigm specifically designed to unequivocally disentangle syntactic from lexicosemantic aspects of sentence processing. Our findings strongly indicate that a part of Broca's area (BA 44, pars opercularis) is critically implicated in processing syntactic information, whereas the lower portion of the left inferior frontal gyrus (BA 47, pars orbitalis) is selectively involved in processing the semantic aspects of a sentence.

Adult↗