Primary melanotic tumors of the nervous system: a consecutive case series.

BACKGROUND AND PURPOSE: Primary melanotic tumors of the nervous system (PMTNS) are thought to be an exceedingly rare group of tumors not captured by tumor registries. We aimed to determine relative incidence, clinical presentation, diagnostic findings, patient management, and outcome. METHODS: We retrospectively searched the database of the Section of Neuro-Oncology at the Yale Cancer Center for patients with primary or metastatic melanotic lesions of the nervous system. For patients with PMTNS, we recorded demographic data, clinical presentation, histopathological and imaging findings, therapy, and outcome. RESULTS: A total of 116 patients with melanotic lesions were identified, including four patients with PMTNS. The relative incidence of PMTNS was therefore calculated as 3.4%. Histology of PMTNS patients revealed melanocytoma in three patients and psammomatous melanotic schwannoma in one patient. Symptoms were non-specific and attributed to tumor mass effect. Magnetic resonance imaging showed hyperintensity on pre-contrast T1-weighted imaging, hypointensity on T2-weighted imaging, and homogenous contrast enhancement in all PMTNS patients. Definitive diagnosis was based on tissue analysis, with detection of melanin-containing cells on conventional histology and S100-positivity on immunohistochemistry. Molecular analysis for GNAQQ209L mutation assisted in establishing diagnosis when only small amounts of tissue were available. Aggressive surgical treatment showed favorable outcomes in all cases; radiation therapy was used for residual or relapsed disease. The median follow-up was 7.5 ± 5 years, and all patients were alive on the day of database closure. CONCLUSION: Primary melanotic tumors of the nervous system are rare nervous system tumors. Outcome appears excellent, and complete surgical resection may form the basis for favorable outcome. Radiation therapy may represent a therapeutic approach for residual or relapsed disease.

Hippocampal size anomalies in a community-based cohort with childhood-onset epilepsy.

OBJECTIVES: Epidemiologic evidence suggests the natural history of refractory mesial temporal lobe epilepsy is complicated, yet little is known about the hippocampus from the nontertiary center perspective. METHODS: In a community-based cohort, individuals with nonsyndromic focal epilepsy with onset <16 years and controls had research MRI scans. Hippocampal (HC) volumes were manually measured, corrected for total brain volume, and converted to Z scores (Z(HC)) based on the controls' values. Volumes in cases and controls were compared. RESULTS: Average volumes were not significantly different in cases with unknown cause (n = 117) relative to controls (n = 63). The group with structural and other conditions (n = 23) had significantly smaller volumes. Asymmetry (larger/smaller HC) did not vary among the 3 groups. Hippocampal variances were significantly larger in each epilepsy group relative to controls. In the unknown cause group, 25 (21%) had extreme() values: 15 (13%) with Z(HC) >1.96; 10 (9%) with Z(HC) <-1.96. By contrast, 2/63 (3%) controls had extreme values (p = 0.001). Within the unknown cause group, temporal lobe epilepsy (TLE) cases were more likely to have extreme hippocampal volumes than non-TLE (31% vs 15%, p = 0.03). Extreme volumes were generally interpreted as normal visually. These anomalies were not associated with seizure remission or pharmacoresistance. CONCLUSIONS: Classic mesial TLE with hippocampal sclerosis is an uncommon finding in the general population. Volume anomalies, both large and small, are often bilateral. The significance of these findings is unclear; however, speculations regarding preexisting hippocampal pathology (e.g., dysplasia) as a factor in TLE and other neocortical epilepsies have been made by others.

MR imaging of familial Creutzfeldt-Jakob disease: a blinded and controlled study.

BACKGROUND AND PURPOSE: The E200K mutation of the PRNP (prion protein) gene is the most common cause of familial Creutzfeldt-Jakob disease (fCJD), which has imaging and clinical features that are similar to the sporadic form. The purpose of this study was to conduct a controlled and blinded evaluation of the sensitivity and specificity of MR imaging in this unique population. MATERIALS AND METHODS: We compared the MR imaging characteristics of 15 early stage familial CJD patients (age, 60 +/- 7 years) with a group of 22 healthy subjects from the same families (age, 61 +/- 8 years). MR imaging included diffusion-weighted imaging (DWI), T2-weighted fast spin-echo imaging, and a fluid-attenuated inversion recovery (FLAIR) sequence. The scans were rated for abnormalities by an experienced neuroradiologist blind to diagnosis, group assignment, age, and sex. RESULTS: Thirteen of 15 fCJD subjects had abnormal MR imaging. FLAIR signal intensity abnormality in the caudate or putamen nuclei demonstrated a sensitivity of 87% and specificity of 91%. DWI abnormality in the caudate nucleus showed a sensitivity of 73% and a specificity of 100%. Abnormalities in the thalamus (6 patients), cingulate gyrus (6 patients), frontal lobes (4 patients), and occipital lobes (3 patients) were best detected with DWI. No signal intensity abnormalities were demonstrated in the cerebellum. T2-weighted and T1-weighted sequences were uninformative. CONCLUSIONS: FLAIR and DWI abnormalities in the caudate nucleus and putamen offer the best sensitivity and specificity for diagnosing fCJD. Our findings support recent recommendations that MR imaging should be added to the diagnostic evaluation of CJD.

Delayed leukoencephalopathy with stroke-like presentation in chemotherapy recipients.

BACKGROUND: A transient leukoencephalopathy mimicking cerebrovascular accident has been described as a complication of chemotherapy, most commonly in recipients of intrathecal methotrexate for childhood leukaemia. Recently published neuroimaging data suggest a common pathophysiology associated with a variety of chemotherapy agents and modes of administration. METHODS: We reviewed the medical literature for single reports and case series of patients presenting with stroke-like episodes while receiving systemic or intrathecal chemotherapy. We only included studies providing detailed neuroimaging data. Patients with cerebrovascular accidents were excluded. RESULTS: We identified 27 reports of toxic leukoencephalopathy in patients treated with methotrexate (intrathecal, systemic), 5-fluorouracil and its derivative carmofur, and capecitabine. Diffusion weighted imaging (DWI) of all patients revealed well demarcated hyperintense lesions within the subcortical white matter of the cerebral hemispheres and the corpus callosum, corresponding to areas of decreased proton diffusion on apparent diffusion coefficient (ADC) maps (available in 21/27 patients). Lesions exceeded the confines of adjacent vascular territories. Complete resolution of symptoms within 1-4 days was accompanied by normalisation of ADC abnormalities. However, fluid attenuated inversion recovery (FLAIR) sequences frequently revealed persistent white matter abnormalities. CONCLUSIONS: Several pathophysiological models of delayed leukoencephalopathy after exposure to intrathecal or systemic chemotherapy have been proposed. DWI findings in this cohort are indicative of cytotoxic oedema within cerebral white matter and lend support to an at least partially reversible metabolic derangement as the basis for this syndrome.

Diffusion-weighted MRI correlates of subacute methotrexate-related neurotoxicity.

OBJECTIVES: A delayed stroke-like leukoencephalopathy has been observed in patients receiving methotrexate (MTX) for childhood leukemia. Diffusion-weighted MRI (DWI) may help to distinguish between ischemic stroke and chemotherapy-related leukoencephalopathy. Although conventional MRI correlates have been described for this stroke-like syndrome, DWI data are largely unavailable. Our objective is to present a retrospective analysis of the DWI findings in four patients who suffered subacute neurotoxicity after intrathecal MTX. DESIGN: We reviewed the medical records of four patients, who were seen by us between July 2000 and February 2004 for sudden onset of a central neurological syndrome within days of intrathecal MTX. Patients underwent standardized MRI within 48 h of symptom onset; MRI included DWI and apparent diffusion coefficient (ADC) maps. RESULTS: DWI of all patients revealed well-demarcated hyperintense lesions within the subcortical white matter corresponding to areas of restricted proton diffusion on ADC maps. Lesions exceeded the confines of adjacent vascular territories. Complete resolution of symptoms within 1-4 days was accompanied by normalization of ADC abnormalities. CONCLUSIONS: DWI findings in this cohort seem to reflect cytotoxic edema within cerebral white matter suggesting a reversible metabolic derangement, rather than ischemia, as the basis for this syndrome.

Functional MR imaging of regional brain activation associated with the affective experience of pain.

OBJECTIVE: Current models propose that the experience of pain includes both sensory and affective components. Our purpose was to use functional MR imaging to determine areas of the brain engaged by the affective dimension of pain. SUBJECTS AND METHODS: Twelve healthy adults underwent functional MR imaging using a gradient-echo echoplanar technique while a cold pressor test, consisting of cold and pain tasks, was applied first to one foot and then to the other. The cold task involved the application of cold water (14-20 degrees C) that was not at a painful level. For the pain task, the water temperature was then lowered to a painful temperature (8-14 degrees C) and subsequently to the pain threshold (3-8 degrees C). Images acquired at room temperature before the cold and pain tasks served as a baseline task. Composite maps of brain activation were generated by comparing the baseline task with the cold task and the cold task with the pain task. The significance of signal changes was estimated by randomization of individual activation maps. RESULTS: Cold-related activation (p < 0.01) was found in the postcentral gyrus bilaterally, laterally, and inferiorly to the primary motor-sensory area of the foot and at a site near the second somatosensory site. Activation also occurred in the frontal lobe (the bilateral middle frontal gyri and the right inferior frontal gyrus), the left anterior insula, the left thalamus, and the superior aspect of the anterior cingulate gyrus (seen at one slice location). Pain-related activation (p < 0.01) included the anterior cingulate gyrus (seen at four slice locations); the superior frontal gyrus, especially on the right; and the right cuneus. CONCLUSION: Compared with the basic sensory processing of pain, the affective dimension of pain activates a cortical network that includes the right superior frontal gyrus, the right cuneus, and a large area of the anterior cingulate gyrus.

The functional neural architecture of components of attention in language-processing tasks.

Using functional magnetic resonance imaging we examined three important dimensions of attentional control (selective attention, divided attention, and executive function) in 25 neurologically normal, right-handed men and women, using tasks involving the perception and processing of printed words, spoken words, or both. In the context of language-processing manipulations: selective attention resulted in increased activation at left hemisphere parietal sites as well as at inferior frontal sites, divided attention resulted in additional increases in activation at these same left hemisphere sites and was also uniquely associated with increased activation of homologous sites in the right hemisphere, and executive function (measured during a complex task requiring sequential decision-making) resulted in increased activation at frontal sites relative to all other conditions. Our findings provide support for the belief that specific functional aspects of attentional control in language processing involve widely distributed but distinctive cortical systems, with mechanisms associated with the control of perceptual selectivity involving primarily parietal and inferior frontal sites and executive function engaging specific sites in frontal cortex.

Functional magnetic resonance imaging of cocaine craving.

OBJECTIVE: Identification of brain activity associated with craving is important for understanding the neurobiology of addiction. METHOD: Brain activity was measured in cocaine addicts and healthy subjects by functional magnetic resonance imaging (fMRI) while the subjects watched videotapes designed to elicit happy feelings, sad feelings, or the desire to use cocaine. The subjects indicated the onset of drug craving or emotional response, allowing comparison of groups before and after such feelings. RESULTS: Robust activation of the anterior cingulate was evident in patients watching cocaine-cue tapes but not in patients watching happy or sad tapes or in healthy subjects under any condition. Anterior cingulate activation preceded the reported onset of craving and was evident in patients who did not report craving. In contrast, patients showed less activation than healthy subjects during the cocaine-cue tapes in areas of the frontal lobes. After the reported onset of craving, cocaine-dependent subjects showed greater activity than healthy subjects in regions that are more active in healthy subjects when they watch sad tapes than when they watch happy tapes, suggesting a physiologic link between cocaine-cue responses and normal dysphoric states. Dynamic aspects of regional brain activations, but not the location of activations, were abnormal in cocaine-dependent subjects watching sad tapes, suggesting more general affective dysregulation. Patients showed low activation of sensory areas during initial viewing of all videotapes, suggesting generalized alteration in neuroresponsiveness. CONCLUSIONS: Cocaine cues lead to abnormally high cingulate and low frontal lobe activation in cocaine addicts. Addicts also show more general abnormalities in affect-related brain activation.

Contribution of the anteromedial temporal lobes to the evaluation of facial emotion.

Amygdala damage can result in impairments in evaluating facial expressions largely specific to fear. In contrast, right-hemisphere cortical lesions result in a more global deficit in facial emotion evaluation. This study addressed these 2 contrasting findings by investigating amygdala and adjacent cortical contributions to the evaluation of facial emotion in 12 patients with right and 11 patients with left unilateral anteromedial temporal lobectomy (RTL and LTL, respectively) and 23 normal controls. RTL but not LTL patients revealed impaired intensity ratings that included but were not exclusive to fear, with the most severe deficits confined to expressions related to affective states of withdrawal-avoidance. This suggests that affective hemispheric specializations in cortical function may extend to subcortical limbic regions. In addition, the right amygdala and adjacent cortex may be part of a neural circuit representing facial expressions of withdrawal.

Network analysis of brain activations in working memory: behavior and age relationships.

Forty-six middle-aged female subjects were scanned using functional Magnetic Resonance Imaging (fMRI) during performance of three distinct stages of a working memory task-encoding, rehearsal, and recognition-for both printed pseudowords and visual forms. An expanse of areas, involving the inferior frontal, parietal, and extrastriate cortex, was active in response to stimuli during both the encoding and recognition periods. Additional increases during memory recognition were seen in right prefrontal regions, replicating a now-common finding [for reviews, see Fletcher et al. (1997) Trends Neurosci 20:213-218; MacLeod et al. (1998) NeuroImage 7:41-48], and broadly supporting the Hemispheric Encoding/Retrieval Asymmetry hypothesis [Tulving et al. (1994) Proc Natl Acad Sci USA 91:2016-2020]. Notably, this asymmetry was not qualified by the type of material being processed. A few sites demonstrated higher activity levels during the rehearsal period, in the absence of any new stimuli, including the medial extrastriate, precuneus, and the medial temporal lobe. Further analyses examined relationships among subjects' brain activations, age, and behavioral scores on working memory tests, acquired outside the scanner. Correlations between brain scores and behavior scores indicated that activations in a number of areas, mainly frontal, were associated with performance. A multivariate analysis, Partial Least Squares [McIntosh et al. (1996) NeuroImage 3:143-157, (1997) Hum Brain Map 5:323-327], was then used to extract component effects from this large set of univariate correlations. Results indicated that better memory performance outside the scanner was associated with higher activity at specific sites within the frontal and, additionally, the medial temporal lobes. Analysis of age effects revealed that younger subjects tended to activate more than older subjects in areas of extrastriate cortex, medial frontal cortex, and the right medial temporal lobe; older subjects tended to activate more than younger subjects in the insular cortex, right inferior temporal lobe, and right inferior frontal gyrus. These results extend recent reports indicating that these regions are specifically involved in the memory impairments seen with aging.

Preliminary evidence of improved verbal working memory performance and normalization of task-related frontal lobe activation in schizophrenia following cognitive exercises.

OBJECTIVE: The authors' goal was to evaluate the possibility of treating brain and behavioral aspects of verbal memory dysfunction in patients with schizophrenia through cognitive exercises. METHOD: Eight patients did daily verbal memory exercises that became progressively more difficult over a 10-week training period. Memory performance and regional brain activations during a verbal memory task were assessed before and after these exercises. RESULTS: Verbal but not nonverbal memory performance improved after training; three patients made substantial gains, and five showed little change. Performance gains were correlated with increases in task-related activation of the left inferior frontal cortex. One patient given 5 extra weeks of training 6 weeks after the initial training period showed maintenance of initial performance gains 6 weeks after training, further improvement after the second period of training, and normalization of task-related activation of the left inferior frontal cortex. CONCLUSIONS: Verbal memory deficits can be ameliorated by memory exercises in some patients with schizophrenia. Performance improvements are associated with increased task-related activation of the same brain region that is activated during verbal memory tasks in healthy individuals.

Cerebral activation during multiplication: a functional MR imaging study of number processing.

BACKGROUND AND PURPOSE: Current models of brain function propose that number processing involves the interaction of different neuronal networks. Our purpose was to use functional MR (fMR) imaging to elucidate the brain regions engaged by multiplication. METHODS: Eighteen adults underwent fMR imaging while performing matching, multiplication, and control tasks. For each task, three or four single-digit or low-value double-digit numbers were presented serially followed by a 12-second delay. A target stimulus then appeared and subjects made a judgement by pressing a button box that recorded responses. During the matching task, subjects judged whether the target stimulus matched one of the previous numbers. During the multiplication task, subjects judged whether the target stimulus was the product of the previous numbers. For the control task, the numbers were always zeros, and the subjects responded to a target stimulus that was always four zeros. Composite statistical parametric maps of the time course of activation comparing the control task with the matching and multiplication tasks, respectively, were generated and the significance of signal changes was estimated by randomization of statistical parametric maps. RESULTS: The matching and multiplication tasks resulted in activation (P < .005) in the medial superior frontal gyrus; the anterior cingulate gyrus; the intraparietal sulci, bilaterally; the right superior frontal sulcus bilaterally; the middle, inferior and precentral frontal gyri (left greater than right); the left basal ganglia; and the right lateral and inferior occipital gyri. There was a larger area of early activation in the right middle frontal gyrus during the matching task compared with the multiplication task, and there was a longer interval of activation in the left middle frontal gyrus during the multiplication task (10 seconds) than in the matching task (6 seconds). CONCLUSION: Multiplication and memory of numbers share an integrated network of brain regions. The left frontal lobe, an area also involved in memory and language processes, appears to play an important role in multiplication.

Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome.

BACKGROUND: Recognition of individual faces is an integral part of both interpersonal interactions and successful functioning within a social group. Therefore, it is of considerable interest that individuals with autism and related conditions have selective deficits in face recognition (sparing nonface object recognition). METHOD: We used functional magnetic resonance imaging (fMRI) to study face and subordinate-level object perception in 14 high-functioning individuals with autism or Asperger syndrome (the autism group), in comparison with 2 groups of matched normal controls (normal control group ] [NC1] and normal control group 2 [NC2]) (n = 14 for each). Regions of interest (ROIs) were defined in NC1 and then applied in comparisons between NC2 and the autism group. Regions of interest were also defined in NC2 and then applied to comparisons between NC1 and the autism group as a replication study. RESULTS: In the first set of comparisons, we found significant task x group interactions for the size of activation in the right fusiform gyrus (FG) and right inferior temporal gyri (ITG). Post hoc analyses showed that during face (but not object) discrimination, the autism group had significantly greater activation than controls in the right ITG and less activation of the right FG. The replication study showed again that the autism group used the ITG significantly more for processing faces than the control groups, but for these analyses, the effect was now on the left side. Greater ITG activation was the pattern found in both control groups during object processing. CONCLUSIONS: Individuals with autism spectrum disorders demonstrate a pattern of brain activity during face discrimination that is consistent with feature-based strategies that are more typical of nonface object perception.

An event-related neuroimaging study distinguishing form and content in sentence processing.

Two coordinated experiments using functional Magnetic Resonance Imaging (fMRI) investigated whether the brain represents language form (grammatical structure) separately from its meaning content (semantics). While in the scanner, 14 young, unimpaired adults listened to simple sentences that were either nonanomalous or contained a grammatical error (for example, *Trees can grew.), or a semantic anomaly (for example, *Trees can eat.). A same⁄different tone pitch judgment task provided a baseline that isolated brain activity associated with linguistic processing from background activity generated by attention to the task and analysis of the auditory input. Sites selectively activated by sentence processing were found in both hemispheres in inferior frontal, middle, and superior frontal, superior temporal, and temporo-parietal regions. Effects of syntactic and semantic anomalies were differentiated by some nonoverlapping areas of activation: Syntactic anomaly triggered significantly increased activity in and around Broca's area, whereas semantic anomaly activated several other sites anteriorly and posteriorly, among them Wernicke's area. These dissociations occurred when listeners were not required to attend to the anomaly. The results confirm that linguistic operations in sentence processing can be isolated from nonlinguistic operations and support the hypothesis of a specialization for syntactic processing.

Cerebrospinal fluid cleft with cortical dimple: MR imaging marker for focal cortical dysgenesis.

PURPOSE: To determine whether the magnetic resonance (MR) imaging feature of a cerebrospinal fluid (CSF) cleft and cortical dimple can be used as a marker for cortical dysgenesis. MATERIALS AND METHODS: MR images in 875 patients with epilepsy were evaluated for the following features of focal cortical dysgenesis: cortical thickening, indistinct junction between gray and white matter, macrogyria, and abnormal sulcal pattern. Images with these features were reevaluated to determine the relationship between the CSF cleft-cortical dimple complex and focal cortical dysgenesis and its contribution to diagnosis. The cleft-dimple complex was defined as a prominent CSF space associated with a region of cortical volume loss adjacent to the dysgenesis. RESULTS: Seventy-one patients had cortical dysgenesis, including 27 with cellular proliferation abnormalities, 18 with migration abnormalities, 25 with cortical organization abnormalities, and one with miscellaneous anomalies. Histologic correlation was available in 20 patients. There was an associated cortical dimple in 29 (41%) patients. This association was strongest in patients with cortical organization abnormalities: It was present in 22 of the 25 (88%) patients. In 12 (48%) patients with abnormalities of cortical organization, the CSF cleft was easier to detect than other features of cortical dysgenesis or contributed directly to the MR imaging diagnosis. CONCLUSION: The cleft-dimple complex is a marker for subtle cases of focal cortical dysgenesis and may be due to maldevelopment. In patients with seizures, the presence of a cleft-dimple complex should alert the physician to scrutinize adjacent regions for developmental anomalies.

The angular gyrus in developmental dyslexia: task-specific differences in functional connectivity within posterior cortex.

Converging evidence from neuroimaging studies of developmental dyslexia reveals dysfunction at posterior brain regions centered in and around the angular gyrus in the left hemisphere. We examined functional connectivity (covariance) between the angular gyrus and related occipital and temporal lobe sites, across a series of print tasks that systematically varied demands on phonological assembly. Results indicate that for dyslexic readers a disruption in functional connectivity in the language-dominant left hemisphere is confined to those tasks that make explicit demands on assembly. In contrast, on print tasks that do not require phonological assembly, functional connectivity is strong for both dyslexic and nonimpaired readers. The findings support the view that neurobiological anomalies in developmental dyslexia are largely confined to the phonological-processing domain. In addition, the findings suggest that right-hemisphere posterior regions serve a compensatory role in mediating phonological performance in dyslexic readers.

The cerebellum's role in reading: a functional MR imaging study.

BACKGROUND AND PURPOSE: Long considered to have a role limited largely to motor-related functions, the cerebellum has recently been implicated as being involved in both perceptual and cognitive processes. Our purpose was to determine whether cerebellar activation occurs during cognitive tasks that differentially engage the component processes of word identification in reading. METHODS: Forty-two neurologically normal adults underwent functional MR imaging of the cerebellum with a gradient-echo echo-planar technique while performing tasks designed to study the cognitive processing used in reading. A standard levels-of-processing paradigm was used. Participants were asked to determine whether pairs of words were written in the same case (orthographic processing), whether pairs of words and non-words rhymed with each other, respectively (phonologic assembly), and whether pairs of words belonged to the same category (semantic processing). Composite maps were generated from a general linear model based on a randomization of statistical parametric maps. RESULTS: During phonologic assembly, cerebellar activation was observed in the middle and posterior aspects of the posterior superior fissure and adjacent simple lobule and semilunar lobule bilaterally and in posterior aspects of the simple lobule, superior semilunar lobule, and inferior semilunar lobule bilaterally. Semantic processing, however, resulted in activation in the deep nuclear region on the right and in the inferior vermis, in addition to posterior areas active in phonologic assembly, including the simple, superior semilunar, and inferior semilunar lobules. CONCLUSION: The cerebellum is engaged during reading and differentially activates in response to phonologic and semantic tasks. These results indicate that the cerebellum contributes to the cognitive processes integral to reading.

Predicting midsagittal pharynx shape from tongue position during vowel production.

The shape of the pharynx has a large effect on the acoustics of vowels, but direct measurement of this part of the vocal tract is difficult. The present study examines the efficacy of inferring midsagittal pharynx shape from the position of the tongue, which is much more amenable to measurement. Midsagittal magnetic resonance (MR) images were obtained for multiple repetitions of 11 static English vowels spoken by two subjects (one male and one female). From these, midsagittal widths were measured at approximately 3-mm intervals along the entire vocal tract. A regression analysis was then used to assess whether the pharyngeal widths could be predicted from the locations and width measurements for four positions on the tongue, namely, those likely to be the locations of a receiver coil for an electromagnetometer system. Predictability was quite high throughout the vocal tract (multiple r> 0.9), except for the extreme ends (i.e., larynx and lips) and small decreases for the male subject in the uvula region. The residuals from this analysis showed that the accuracy of predictions was generally quite high, with 89.2% of errors being less than 2 mm. The extremes of the vocal tract, where the resolution of the MRI was poorer, accounted for much of the error. For languages like English, which do not use advanced tongue root (ATR) distinctively, the midsagittal pharynx shape of static vowels can be predicted with high accuracy.

Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.

CONTEXT: Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women. OBJECTIVE: To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998. SETTING: Community volunteers tested in a hospital setting. PATIENTS: Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years). INTERVENTION: Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments. MAIN OUTCOME MEASURES: Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. RESULTS: Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks. CONCLUSIONS: Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.