Transient global amnesia: implicit/explicit memory dissociation and PET assessment of brain perfusion and oxygen metabolism in the acute stage

OBJECTIVES: To assess explicit memory and two components of implicit memory--that is, perceptual-verbal skill learning and lexical-semantic priming effects--as well as resting cerebral blood flow (CBF) and oxygen metabolism (CMRO2) during the acute phase of transient global amnesia. METHODS: In a 59 year old woman, whose amnestic episode fulfilled all current criteria for transient global amnesia, a neuropsychological protocol was administered, including word learning, story recall, categorical fluency, mirror reading, and word stem completion tasks. PET was performed using the (15)O steady state inhalation method, while the patient still exhibited severe anterograde amnesia and was interleaved with the cognitive tests. RESULTS: There was a clear cut dissociation between impaired long term episodic memory and preserved implicit memory for its two components. Categorical fluency was significantly altered, suggesting word retrieval strategy--rather than semantic memory--impairment. The PET study disclosed a reduced CMRO2 with relatively or fully preserved CBF in the left prefrontotemporal cortex and lentiform nucleus, and the reverse pattern over the left occipital cortex. CONCLUSIONS: The PET alterations with patchy CBF-CMRO2 uncoupling would be compatible with a migraine-like phenomenon and indicate that the isolated assessment of perfusion in transient global amnesia may be misleading. The pattern of metabolic depression, with sparing of the hippocampal area, is one among the distinct patterns of brain dysfunction that underlie the (apparently) uniform clinical presentation of transient global amnesia. The finding of a left prefrontal hypometabolism in the face of impaired episodic memory and altered verbal fluency would fit present day concepts from PET activation studies about the role of this area in episodic and semantic memory encoding/retrieval. Likewise, the changes affecting the lenticular nucleus but sparing the caudate would be consistent with the normal performance in perceptual-verbal skill learning. Finally, unaltered lexical-semantic priming effects, despite left temporal cortex hypometabolism, suggest that these processes are subserved by a more distributed neocortical network.     

The interaction between mood and cognitive function studied with PET

BACKGROUND: Experimentally induced depressed mood is a suggested model for retarded depression. We describe the neural response associated with induced mood and the locus of the interaction between systems mediating mood and cognitive function. METHODS: Normal subjects performed a verbal fluency task during induced elated and depressed mood states. Regional cerebral blood flow (rCBF) was measured as an index of neural activity using Positron Emission Tomography (PET). RESULTS: In both elated and depressed mood state rCBF was increased in lateral orbitofrontal cortex, rCBF was also increased in the midbrain in elated mood. In the depressed condition rCBF was decreased in rostral medial prefrontal cortex. Verbal fluency produced an expected increase of rCBF in left dorsolateral prefrontal, inferior frontal and premotor cortex, anterior cingulate and insula cortex bilaterally, the left supramarginal gyrus posteriorly and the thalamus. Activation in the verbal fluency task was attenuated throughout the left prefrontal, premotor and cingulate cortex and thalamus in both elated and depressed mood conditions. An attenuation of anterior cingulate activation was specific to depressed mood. CONCLUSIONS: Alteration of mood is associated with activation of orbitofrontal cortex which may be critical to the experience of emotion. The mood induced modulation of verbal fluency induced activations is consistent with resting state findings of decreased function in these regions in depressed patients. The present data suggest that resting state rCBF profile may represent the modulation of spontaneous activity in this network by a core system that is dysfunctional in depression.     

Morphological investigation of the neuroprotective effects of graded hypothermia after diverse periods of global cerebral ischemia in gerbils

Cerebral dysgenesis is a subject of interest because of its relationship to cerebral development and dysfunction and to epilepsy. The authors present a detailed study of a 16-year-old boy who underwent surgery for a severe seizure disorder. This patient had dysgenesis of the right hemisphere, which was composed of a giant central frontoparietal nodular gray matter heterotopia with overlying large islands of cortical dysplasia around a displaced central fissure. Exceptional insight into the function, biochemistry, electrophysiology, and histological structure of this lesion was obtained from neurological studies that revealed complementary information: magnetic resonance (MR) imaging, [18]fluoro-2-deoxy-D-glucose positron emission tomography (PET), functional PET scanning, proton MR spectroscopic (1H-MRS) imaging, intraoperative cortical mapping and electrocorticography, in vitro electrophysiology, and immunocytochemistry. These studies demonstrated compensatory cortical reorganization and showed that large areas of heterotopia and cortical dysplasia in the central area may retain normal motor and sensory function despite strikingly altered cytoarchitectonic organization and neuronal metabolism. Such lesions necessitate appropriate functional imaging studies prior to surgery and cortical mapping to avoid creating neurological deficits. Integrated studies, such as PET, 1H-MRS imaging, cortical mapping, immunocytochemistry, and electrophysiology may provide information on the function of developmental disorders of cerebral organization.     

Frontal dysfunction in neurologically normal chronic alcoholic subjects: metabolic and neuropsychological findings

BACKGROUND: Neuropsychological and imaging studies suggest that frontal dysfunction may occur in apparently normal chronic alcoholic subjects. METHODS: To investigate this issue further, we performed neuropsychological and fluorodeoxy-glucose-PET studies in 17 chronic alcoholics without patent neurological and psychiatric complications. RESULTS: Metabolic abnormalities were found in the mediofrontal and in the left dorsolateral prefrontal cortex, but not in the orbitofrontal cortex. Neuropsychological testing revealed significantly reduced verbal fluency and impaired performance on the Stroop test. The mediofrontal hypometabolism correlated with the reduction in verbal fluency and the time necessary to perform the interference condition of the Stroop test. The left dorsolateral prefrontal hypometabolism correlated with the number of errors on the Stroop test. CONCLUSION: These data indicate that circumscribed frontal dysfunctions may occur in chronic alcoholic subjects before clinically obvious neurological complications, and may account for some of the alcohol-related neuropsychological and behavioural impairments.     

Magnetic resonance imaging and positron emission tomography of band heterotopia

A case of band heterotopia was reported with findings of positron emission tomography (PET). The patient was an 8-year-old girl who had mild mental retardation and intractable partial epilepsy. Her MRI showed another diffuse layer of gray matter underlying the normal-looking cortex and separated from it by an apparently normal layer of white matter. PET scan with [18F]fluorodeoxyglucose revealed that band heterotopia had the same degree of glucose metabolism as that of the overlying cortex.     

Characterization of two rice MADS box genes that control flowering time

This study utilised positron emission tomography (PET) to identify the cortical areas involved in verbal initiation and suppression in normal subjects whilst performing a sentence completion test (the Hayling Test). In the first condition (response initiation) subjects were required to complete a sentence from which the last word was omitted, whereas in the second condition (response suppression) subjects were asked to complete a sentence with a word which made no sense in the context of the sentence. Subjects were also required to perform a control task in which they had to read out the last word of given sentences. Compared to the control task, response initiation was associated with left-sided activation of the frontal operculum, inferior frontal gyrus, middle temporal gyrus and the right anterior cingulate gyrus, whereas response suppression was associated with left frontal operculum, inferior frontal gyrus and right anterior cingulate gyrus activation. The difference in activation between the two conditions of the Hayling Test lay in the increased activation of the left middle temporal gyrus and the left inferior frontal gyrus during response initiation.     

Task-related activations in heterotopic brain malformations: a PET study

Positron emission tomography (PET) studies have shown normal or elevated levels of glucose metabolism in neuronal heterotopia, raising the issue of potential participation of heterotopic neurons in cognitive processing. We studied three patients with heterotopic malformations, using [(15)O]water PET and experimental conditions selected according to the location of the malformations. Task performance was associated with blood flow increases of > 17% within the heterotopia in each patient. In two, these occurred in left frontal heterotopia during sentence generation. In the third patient, activations for facial and visuospatial discrimination and picture naming were found in a right posterior heterotopion. Our findings may reflect participation of heterotopia in cognitive function and suggest that heterotopic neurons synapse with neurons in other brain regions.     

Activation patterns of covert word generation detected by fMRI: comparison with 3D PET

PURPOSE: The aim of our study was to compare the activation patterns of higher cognitive function detected by functional MRI (fMRI) with those by H2(15)O positron emission tomography (PET). METHOD: Activation studies with both modalities were performed in six normal volunteers with identical covert word generation tasks and statistical analysis. For PET, each subject had five rest scans and five task scans at 10 min intervals. fMRI was performed with a 1.5 T magnet using T2*-weighted echo planar sequences. Each scanning session consisted of two rest and two task periods of 30 s each, alternating rest and task. RESULTS: In group analysis, the activation patterns on both PET and fMRI were similar, whereas the deactivation patterns differed, presumably due to the noise of fMRI. In single-subject analysis, PET showed fewer activated areas and fMRI showed more areas of activation than in group analysis. CONCLUSION: fMRI has an advantage over 3D PET in its better signal-to-noise ratio for detecting change in neuronal activity for higher brain function.     

Cerebral interregional correlations of associative language processing: a positron emission tomography activation study using fluorine-18 fluorodeoxyglucose

Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose (18F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca's area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional decoupling of the strict intercorrelation pattern.     

Assessment of T2- and T1-weighted MRI brain lesion load in patients with subcortical vascular encephalopathy

Previous cross-sectional studies in patients with subcortical vascular encephalopathy (SVE) have shown little or no correlation between brain lesion load and clinical disability, which could be due to the low specificity of T2-weighted MRI. Recent studies have indicated that T1-weighted MRI may be more specific than T2-weighted MRI for severe tissue destruction. We studied 37 patients with a diagnosis of SVE and 11 normal controls with standardised T1- and T2-weighted MRI. All patients underwent detailed clinical assessment including a neuropsychological test battery and computerised gait analysis. Both the T2- and T1-weighted total MRI lesion loads different between patients and controls different, particularly T1. The ratio of T2-/T1-weighted lesion load was lower in controls than in patients. There was no overall correlation of T1- or T2-weighted lesion load with clinical disability, but group comparison of patients with severe and mild clinical deficits showed different lesion loads. We suggest that T1- and T2-weighted MRI lesion loads demonstrate relevant structural abnormality in patients with SVE.     

Correlations of Regional Cerebral Metabolism With Memory Performance and Executive Function in Patients With Herpes Encephalitis or Frontal Lobe Lesions.

Cerebral [1?F]fluorodeoxyglucose positron emission tomography (1?FDG-PET) data from patients suffering amnesia following herpes encephalitis (n = 7) or frontal lobe pathology (n = 14) were compared with data from age-matched nonamnesic subjects (n = 10). All subjects received structural MRI, resting 1?FDG-PET scans, and neuropsychological evaluation. PET data were analyzed using complementary statistical parametric mapping and region-of-interest methods. Differential patterns of hypometabolism were found in patients relative to healthy controls. Factor analysis of the neuropsychological data revealed that memory performance was associated with retrosplenial and medial temporal metabolism, and executive function was associated with dorsolateral frontal metabolism. The association between memory performance and retrosplenial metabolism remained statistically significant after accounting for measures of cerebral atrophy using MRI. The significance of the retrosplenium as a major relay station between the thalamus and the medial temporal and frontal lobes--sensitive to changes in either--is discussed in the light of the findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance

Reports that estrogen may protect against age-associated memory decline and Alzheimer's Disease have kindled interest in the effects of estrogen replacement therapy (ERT) on cognition and brain function. As part of a 9-year study in the Baltimore Longitudinal Study of Aging, we are performing annual magnetic resonance imaging, positron emission tomography (PET), and neuropsychological assessments to examine brain structure and function in individuals aged 55 and older. PET measurements of regional cerebral blood flow (rCBF) are obtained under 3 conditions: rest and verbal and figural delayed recognition memory tasks. Fifteen women receiving ERT (with or without the addition of progesterone) were compared with a matched sample of 17 untreated women. There were no significant differences between groups in regional brain volumes or ventricular size. However, ERT users and nonusers showed significant differences in PET-rCBF relative activation patterns during the memory tasks. During verbal memory processing, there were significant interactions in rCBF activations for the right parahippocampal gyrus, right precuneus, right frontal regions, and left hypothalamus. During figural memory processing, significant interactions were observed for right parahippocampal and inferior parietal regions and for left visual association and anterior thalamic regions. ERT users also showed better performance on neuropsychological tests of figural and verbal memory and on some aspects of the PET activation tests, although the two groups did not differ in education, overall verbal ability, or performance on other neuropsychological tests. These findings confirm our previous observation of the beneficial effects of ERT on figural memory. Moreover, differences in rCBF activation patterns between ERT users and nonusers suggest an area for future research to examine mechanisms through which ERT may influence memory and other cognitive abilities.     

Radiographic osteoarthritis in the hands of rock climbers

We reviewed the MRI of 17 patients with hemimegalencephaly to investigate abnormal myelination in this condition. On images of seven patients aged 18 months or less, the white matter on the affected side suggested advanced myelination for the age. On T1-weighted images of three patients aged 1 month, the anterior limb of the internal capsule in the affected hemisphere was myelinated, and T1 shortening was not clearly seen in the pre- and postcentral gyri. The cortical grey matter and subcortical white matter was isointense in two patients. Images of two patients aged 4 to 5 months and of five patients aged 8-18 months showed myelination that extended more peripherally in the white matter of the affected hemisphere.     

Myosin light chains (MLCs) heterogeneity in mammalian smooth and cardiac muscle

Tuberous sclerosis (TS) is well known to be occasionally associated with subependymal giant cell astrocytoma (SGCA). SGCA is considered to be a benign tumor in its clinical course and morphology. However, this tumor is grown sometimes so rapid and caused hydrocephalus. To our knowledge, little is known about hemocirculation and metabolism, particularly in relation with proliferating activity of TS and SGCA. We measured hemocirculation and metabolism of SGCA developed in a case of TS using positron emission tomography (PET). A 13-year-old-boy who had frequently developed convulsions four months after birth. He was diagnosed as TS and had been medically treated with anticonvulsants, since multiple intraventricular calcifications were detected by CT, at the age of five months. The convulsions had been well controlled. In March 1993, he presented with syncopal attack and admitted to our hospital. CT showed multiple subependymal nodules. Among the nodules, one of the left anterior horn exceeded 2cm in size obliterated Monro's foramen. The tumor was homogeneously enhanced with contrast medium. The lesion detected by postcontrast T1-weighted MR imaging had almost the same status as that by CT. T2-weighted image revealed cortical tubers as high intensity area at the left frontal and parietooccipital regions. PET was performed with the Headtome IV. Hemocirculation of the tumor was lower than that of contralateral gray matter, which suggested poor blood supply. The oxygen and glucose metabolism of the tumor were decreased compared with contralateral gray matter, indicative of a low activity of proliferation and a clinically benign tumor in the present case.(ABSTRACT TRUNCATED AT 250 WORDS)     

"Willed action": a functional MRI study of the human prefrontal cortex during a sensorimotor task

Functional MRI (fMRI) was used to examine human brain activity within the dorsolateral prefrontal cortex during a sensorimotor task that had been proposed to require selection between several responses, a cognitive concept termed "willed action" in a positron emission tomography (PET) study by Frith et al. [Frith, C. D., Friston, K., Liddle, P. F. & Frackowiak, R. S. J. (1991) Proc. R. Soc. London Ser. B 244, 241-246]. We repeated their sensorimotor task, in which the subject chooses to move either of two fingers after a stimulus, by fMRI experiments in a 2.1-T imaging spectrometer. Echo-planar images were acquired from four coronal slices in the prefrontal cortex from nine healthy subjects. Slices were 5 mm thick, centers separated by 7 mm, with nominal in-plane spatial resolution of 9.6 x 5.0 mm2 for mean data. Our mean results are in agreement with the PET results in that we saw similar bilateral activations. The present results are compared with our previously published fMRI study of a verbal fluency task, which had also been proposed by Frith et al. to elicit a "willed action" response. We find a clear separation of activation foci in the left dorsolateral prefrontal cortex for the sensorimotor (Brodmann area 46) and verbal fluency (Brodmann area 45) tasks. Hence, assigning a particular activated region to "willed action" is not supported by the fMRI data when examined closely because identical regions are not activated with different modalities. Similar modality linked activations can be observed in the original PET study but the greater resolution of the fMRI data makes the modality linkages more definite.     

Ophthalmoplegia, hemiparesis and cheiro-oral syndrome in basilar artery migraine

A patient with migraine developed ophthalmoplegia, hemiparesis and cheiro-oral syndrome on the left side. T2-weighted MRI showed infarcts in the tegmentum of bilateral midbrains and right pons but no lesion in the cerebral or cerebellar hemisphere. Infarction in the tegmentum of brainstem secondary to the involvement of perforating arteries has not been reported in basilar artery migraine until now.     

A rabbit model of human familial, nonsyndromic unicoronal suture synostosis. II. Intracranial contents, intracranial volume, and intracranial pressure

This two-part study reviews data from a recently developed colony of New Zealand white rabbits with familial, nonsyndromic unilateral coronal suture synostosis, and this second part presents neuropathological findings and age-related changes in intracranial volume (ICV) and intracranial pressure (ICP) in 106 normal rabbits and 56 craniosynostotic rabbits from this colony. Brain morphology and anteroposterior length were described in 44 rabbit fetuses and perinates (27 normal; 17 synostosed). Middle meningeal artery patterns were qualitatively assessed from 2-D PCC MRI VENC scans and endocranial tracings from 15, 126-day-old rabbits (8 normal, 7 rabbits with unicoronal synostosis). Brain metabolism was evaluated by assessing 18F-FDG uptake with high-resolution PET scanning in 7, 25-day-old rabbits (3 normal, 4 with unicoronal or bicoronal synostosis). Intracranial contents and ICV were assessed using 3-D CT scanning of the skulls of 30 rabbits (20 normal,10 with unicoronal synostosis) at 42 and 126 days of age. Serial ICP data were collected from 66 rabbits (49 normal; 17 with unicoronal synostosis) at 25 and 42 days of age. ICP was assessed in the epidural space using a Codman NeuroMonitor microsensor transducer. Results revealed that cerebral cortex morphology was similar between normal and synostosed fetuses around the time of synostosis. Significantly (P<0.05) decreased A-P cerebral hemisphere growth rates and asymmetrical cortical remodeling were noted with increasing age in synostotic rabbits. In addition, rabbits with unicoronal suture synostosis exhibited asymmetrical middle meningeal artery patterns, decreased and asymmetrical brain metabolism, a "beaten-copper" intracranial appearance, significantly (P<0.05) decreased ICV, and significantly (P<0.01) elevated ICP compared with normal control rabbits. The advantages and disadvantages of these rabbits as a model for human familial, nonsyndromic unicoronal suture synostosis are discussed, especially in light of recent clinical neuropathological, ICV, and ICP findings recorded in human craniosynostotic studies.     

Positron emission tomography metabolic data corrected for cortical atrophy using magnetic resonance imaging

The correct interpretation of clinical positron emission tomography (PET) data depends largely on the physical limits of the PET scanner. The partial volume effect (PVE) is related to the size of the studied object compared to the spatial resolution. It represents one of the most important limiting factors in quantitative data analysis. This effect is increased in the case of atrophy, as in patients with Alzheimer disease (AD), and it influences measurement of the metabolic reduction generally seen in cerebral degeneration. In this case, interpretation can be biased, because cortical activity will be underestimated due to the atrophy. In general, anatomical images of AD patients have shown diffuse atrophy, while PET studies have found widespread hypometabolism affecting the parietal and temporal lobes. Although hypometabolic areas usually correspond to atrophic regions, they also occur without such changes. Thus, the aim is to differentiate authentic hypometabolism (decrease of glucose consumption per unit volume of gray matter) from that due to PVE from atrophy (cell loss). Consequently, we are using a method for three-dimensional (3D) correction of human PET data with 3D magnetic resonance imaging (MRI). We measured atrophy and metabolism by using both T1-weighted MR images and high and medium resolution PET scans. We injected 12 patients and controls with [18F]fluorodeoxyglucose for glucose consumption measurements. Atrophy was estimated in the following way. We isolated the cerebral structures, using a segmentation technique on the MRI scans, into gray matter (GM), white matter, and cerebrospinal fluid. We superimposed the PET images onto the MR images to obtain anatomo-functional correlations. We degraded the segmented MR images to the resolution of the PET images by a convolution process to create a PET image correction map. We corrected the metabolic PET data for the PVE. We studied the cerebral metabolic rate of glucose in the GM where metabolic variation is the most relevant to AD. By dealing with problems relating to the sensitivity to the segmentation and to the PET-MRI coregistration, computation of MRI convolution processes provided the degree of PVE on a pixel-by-pixel basis, allowing correction of hypometabolisms contained in GM PET values. Global cortical metabolism increased after correction for PVE by, on average, 29 and 24% for tomographs acquired with medium (TTV03 LETI) and high (ECAT 953B CTI/Siemens) resolution, respectively, whereas the cortical metabolism increased by 75 and 65% for the respective tomographs in AD patients. The difference of metabolism between scans after correction for PVE was less than before correction, decreasing from 31 to 17%. This difference was most marked in the frontal and temporal lobes. Fusion imaging allowed correction for PVE in metabolic data using 3D MRI and determination of whether a change in the apparent radiotracer concentration in PET data reflected an alteration in GM volume, a change in radiotracer concentration per unit volume of GM, or both.     

Radiation myelopathy: a clinicopathological study with special reference to correlation between MRI findings and neuropathology

We describe magnetic resonance imaging (MRI) and neuropathological findings in a patient with chronic progressive radiation myelopathy (CPRM). An 81-year-old man with esophageal cancer underwent radiotherapy. Four years later he developed a progressive neurological deficit below the irradiated level of the spinal cord. Neurological examination revealed spastic paraplegia. MRI findings showed an area of high signal intensity on T2-weighted images of the thoracic spinal cord. On the basis of clinical and MRI findings, we diagnosed his condition as CPRM. MRI performed thirteen months after onset of neurological signs revealed mild atrophy of the spinal cord detected on T1-weighted images and an area of high signal intensity within the spinal cord detected on T2-weighted images. Neuropathological examination revealed findings consistent with radiation myelopathy. We speculate that the area of high signal intensity within the spinal cord detected on T2-weighted images might be a result of proliferation of small vessels, which was discovered upon autopsy.     

Fluency and memory differences between ischemic vascular dementia and Alzheimer's disease.

This study compared 32 patients with ischemic vascular dementia (IVD) to 32 patients with probable Alzheimer's disease (AD) on select language and verbal memory tests. The IVD and AD patients were individually matched on the basis of age, dementia severity, years of education, and gender. The IVD patients had poorer verbal fluency, but better free recall, fewer recall intrusions, and better recognition memory than the AD patients. Relationships between the neuropsychological measures and radiological indexes of cortical and subcortical pathology were also examined. Number of infarcts, white-matter lucency, and ventricular enlargement correlated with some of the neuropsychological measures; cortical atrophy correlated with most of the measures. The findings suggest that neuropsychological deficits in IVD may be related to dysfunction of frontal-subcortical circuits, although an associated degenerative cortical process may also be involved. (PsycINFO Database Record (c) 2010 APA, all rights reserved)