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Presurgical motor and somatosensory cortex mapping with functional magnetic resonance imaging and positron emission tomography.

OBJECT: Accurate identification of eloquent cortex is important to ensure that resective surgery in the region surrounding the central sulcus is performed with minimum risk of permanent neurological deficit. Functional localization has traditionally been accomplished using intraoperative cortical stimulation (ICS). However, this technique suffers from several disadvantages that make the development and validation of noninvasive methods desirable. Functional localization accomplished by activation studies in which positron emission tomography (PET) scanning and the tracer [15O]H2O have been used has been shown to correlate well with the results of ICS. Another noninvasive method for functional localization is functional magnetic resonance (fMR) imaging. We compared the locations of activation peaks obtained in individual patients using fMR and [15O]H2O PET imaging. METHODS: Twenty-six combined PET activation-fMR imaging studies were performed in 11 patients who were admitted for evaluation before undergoing surgery in the region surrounding the central sulcus. The PET scans were obtained using bolus injections of the cerebral blood flow tracer [15O]H2O (10 mCi). Multislice T2*-weighted gradient-echo echoplanar images were acquired using a 1.5-tesla MR imaging system. Activation maps were aligned with anatomical MR images and transformed into stereotactic space, after which the locations of activation peaks obtained using both modalities were compared. The average distance between activation peaks obtained using fMR imaging and those obtained using PET imaging was 7.9+/-4.8 mm (p>0.05), with 96% of the peaks being located on either the same or adjacent sulci and gyri. Overlapping of voxels activated by each modality occurred in 92% of the studies. Functional MR imaging failed to activate the primary sensorimotor cortex in one study and produced results that were ambiguous in the clinical setting in three cases. CONCLUSIONS: Overall, fMR imaging produced activation that correlated well with that obtained using PET scanning. Discrepancies between the sites of activation identified using these two techniques may reflect differences in their physiological bases.

Brain Diseases↗

Burst generation in neocortical neurons after GABA withdrawal in the rat.

1. gamma-Aminobutyric acid (GABA) withdrawal syndrome (GWS) represents a particular model of focal epilepsy consecutive to the interruption of a chronic intracortical GABA infusion and is characterized by the appearance of focal epileptic electroencephalographic (EEG) discharges and localized clinical signs on withdrawal of GABA. Effects of Ca2+ channel blockers and N-methyl-D-aspartate (NMDA) antagonists were evaluated in living rats presenting a GWS after interruption of a 5-day GABA infusion into the somatomotor cortex and in neocortical slices obtained from such rats. Bursting properties and morphology of neurons were also analyzed in slices. 2. In living rats, the noncompetitive NMDA antagonist phencyclidine [1-(1-phenylcyclohexyl)piperidine] and the Ca2+ antagonist flunarizine [E-1 (bis(4fluorophenyl)methyl)-4(3phenyl2-propenyl)-piperazine] were administered systemically to two groups of rats. Rats in the first group (n = 12) were injected with the drug 30-60 min before discontinuation of the GABA infusion. In this case, phencyclidine (10 mg/kg ip) prevented the development of GWS (n = 5), whereas flunarizine (40 mg/kg ip) had no consistent effect on the GWS appearance and characteristics (n = 7). Rats in the second group (n = 12) were injected 60-90 min after GABA discontinuation, i.e., during a fully developed GWS. In that case, neither drug suppressed GWS. 3. Neuronal activities in the epileptic focus were studied in slices with conventional intracellular recording and stimulation techniques. From the 65 neurons recorded, 29 responded with EPSPs and paroxysmal depolarization shifts (PDSs) to white matter stimulation (synaptic bursting or SB cells). Nineteen other neurons presented, in addition to synaptically induced PDSs, bursts of action potentials (APs) induced by intracellular depolarizing current injection (intrinsic bursting or IB cells). The remaining 17 neurons presented no bursting properties to either synaptic stimulation or depolarizing current injection (nonbursting or NB cells). 4. The recorded neurons were located 0.7-1.2 mm distant from the lesion because of the penetration of the GABA infusion cannula. Intracellular injection of neurons (n = 4) with biocytin or Lucifer yellow revealed that both SB and IB neurons were large, spiny pyramidal neurons localized in layer V of the sensorimotor cortex. 5. Bath application of the selective antagonist of NMDA receptors DL-2amino-5phosphonovalerate or DL-2amino-7phosphonoheptanoate (10-50 microM) reversibly reduced the amplitude (by 25-50%) and the duration (by 20-25%) of PDSs in all cases (n = 17).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Cerebellothalamocortical and pallidothalamocortical projections to the primary and supplementary motor cortical areas: a multiple tracing study in macaque monkeys.

The goal of the present study was to clarify whether the primary motor cortex (M1) and the supplementary motor cortex (SMA) both receive, via the motor thalamus, input from cerebellar and basal ganglia output nuclei. This is the first investigation that explores the problem by direct comparison, in the same animal, of thalamic zones that 1) project to M1 and SMA and 2) receive cerebellar-nuclear (CN) and pallidal (GP) afferents. These four zones were mapped in two monkeys by means of two retrograde tracers for M1 and SMA injections and of two anterograde tracers for CN and GP injections. All injections were performed under electrophysiological control (microstimulation and multiunit recordings). Injections in cortical areas were restricted to the hand/arm representation; in the SMA, the tracer deposit was within the "SMA-proper" (or "area F3") and did not include its rostral extension ("pre-SMA" or "area F6"). It was found that zones of all four types formed a number of highly complex patches of labeling that were usually not confined to one cytoarchitectonically defined thalamic nucleus. The overlap of clusters of labeled terminals and perikarya was evaluated morphometrically (area measurements) on a number of coronal sections along the anteroposterior extent of the motor thalamus. In line with previous studies, the thalamic territories innervated by CN and GP afferents rarely overlapped. However, zones projecting to M1 and/or to SMA included thalamic regions receiving CN as well as GP projections, providing the first evidence of such overlap from individual animals. The present observations support the previous conclusion from this laboratory (based on transsynaptic labeling) that the SMA receives, apart from its strong pallidal transthalamic input, a CN transthalamic input. These present findings that both M1 and SMA are recipients of transthalamic inputs from GP and CN thus support the concept that a mixed subcortical input consisting of weighted contributions from cerebellum, basal ganglia, substantia nigra, and spinothalamic tract is directed to each functional component of the sensorimotor cortex.

Animals↗

Isolated, chronic, epilepsia partialis continua in an HIV-infected patient.

BACKGROUND: The characteristic clinical feature of epilepsia partialis continua (EPC) is chronic focal myoclonus, usually involving the distal part of one extremity. A variety of pathogenetic factors have been implicated in EPC. In children, the most common cause is Rasmussen encephalitis; in adults, it is vascular disease or tumor involving the sensorimotor cortex. Epileptic seizures are a relatively common manifestation of central nervous system involvement in patients infected with human immunodeficiency virus (HIV), but, to our knowledge, isolated, chronic EPC has not been previously reported. OBJECTIVE: To describe a case of typical EPC in a patient infected with HIV. DESIGN AND SETTING: Case report from an epilepsy center. PATIENT: A 58-year-old man infected with HIV had continuous myoclonus that involved the right arm and was associated with intermittent motor seizures. The electroencephalographic findings were normal at the onset of the symptoms, but left central theta rhythm appeared later. Serial magnetic resonance imaging scans obtained over a 3-month period showed a progressively increasing left rolandic T2-weighted hypersignal. Histologic study of a stereotactic biopsy specimen demonstrated inflammation characterized by perivascular mononuclear cell infiltration. The only detectable cause was HIV infection. Immunocytochemical tests ruled out JC virus. Neuropsychological testing showed no evidence of cognitive impairment. An electroencephalographic-electromyographic "back-averaging" study showed a reproducible transient left biphasic complex preceding the bursts by about 30 milliseconds on the C3 and F3 electrodes, thus demonstrating that the myoclonus was of cortical origin. High-dose corticosteroid (prednisone, 100 mg/d) and anti-HIV- 1 therapy led to marked radiological and clinical improvement. Infection with HIV enhances the risk of seizures, but, to our knowledge, this is the first reported case of "inflammatory" EPC. CONCLUSIONS: The present case suggests that the possibility of central nervous system involvement by HIV-1 should be taken into account in the diagnostic workup of patients with EPC. This case also indicates that treatment can be effective.

Chronic Disease↗

Improving hand function in chronic stroke.

BACKGROUND: Recovery of function following stroke plateaus in about 1 year, typically leaving upper arm function better than that in the hand. Since there is competition among body parts for territory in the sensorimotor cortex, even limited activity of the upper arm might prevent the hand from gaining more control, particularly when the territory is reduced in size because of the stroke. Deafferentation of a body part in a healthy brain enhances cortical representations of adjacent body parts, and this effect is markedly increased by voluntary activity of the adjacent part. OBJECTIVE: To explore whether deafferentation of the upper arm, produced by a new technique of regional anesthesia during hand motor practice, helps recovery of hand function in patients with long-term stable weakness of their hand following stroke. METHODS AND RESULTS: Deafferentation, produced by a new technique of regional anesthesia of the upper arm during hand motor practice, dramatically improved hand motor function including some activities of daily living. The improvement was associated with an increase in transcranial magnetic stimulation-evoked motor output to the practice hand muscles. CONCLUSION: This is a novel therapeutic strategy that may help improve hand function in patients with long-term weakness after stroke.

Afferent Pathways↗

Brain gamma-aminobutyric acid changes in stiff-person syndrome.

BACKGROUND: Patients with stiff-person syndrome (SPS) have circulating antibodies against glutamic acid decarboxylase, the rate-limiting enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA). Although the patients' symptoms of stiffness and unexpected spasms can be explained on the basis of reduced or impaired inhibitory neurotransmitters, such as GABA, it is unclear whether the level of GABA in the brains of these patients is reduced and, if so, whether the reduction is due to anti-glutamic acid decarboxylase antibodies. OBJECTIVE: To measure GABA levels in the brains of patients with SPS. DESIGN: Prospective case-control study. SETTING: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md. PATIENTS: Eight patients with SPS with high titers of circulating anti-glutamic acid decarboxylase antibodies and typical clinical symptoms of SPS and 16 control subjects. MAIN OUTCOME MEASURES: Results of brain magnetic resonance imaging and magnetic resonance spectroscopy, which measures GABA levels in specific brain regions. RESULTS: No abnormalities were noted on brain magnetic resonance images. A prominent and significant decrease in GABA level was, however, observed in the sensorimotor cortex and a smaller decrease in the posterior occipital cortex but not in the cingulate cortex or pons. CONCLUSIONS: The reduction of brain GABA in patients with SPS supports the clinical symptoms and indicates that the inhibitory GABAergic pathways are involved in the disease. Regardless of the responsible autoantigens, in SPS autoantibodies block the function of GABAergic neurons and interfere with the synthesis of GABA but do not cause structural changes in the brain.

Adult↗

Ultrastructural study of external cuneothalamic neurons and their synaptic relationships with primary afferents in the gerbil.

The present study examined the synaptic organization of external cuneothalamic neurons and their relationships with primary afferents in the gerbil external cuneate nucleus (ECN) following an injection of horseradish peroxidase (HRP) into the anterodorsal cap of the ventrobasal thalamus in conjunction with a simultaneous injection of HRP into the contralateral brachial and cervical nerve plexuses. The thalamus-projecting neurons have been shown to be confined to the intermediate portion of the caudal half of the ECN at the light microscopic level (Lan et al., 1994c). In this study, HRP-labelled external cuneothalamic neurons were ultrastructurally characterized by their relatively small-sized soma bearing a variable number of somal spines. Their nucleus had a slightly indented contour with an eccentric nucleolus. The HRP-labelled somata were postsynaptic to many axon terminals, which were classified into round (Rs type; 53.0%), pleomorphic (Ps type; 32.7%), and flattened (Fs type; 14.3%) vesicle-containing boutons. The HRP-labelled dendritic elements were postsynaptic to a greater number of axon terminals, which were also classified into the round (Rd; 64.7%), pleomorphic (Pd; 25.2%), and flattened (Fd; 10.1%) type boutons. These presynaptic axonal boutons tended to synapse on distal and secondary dendrites of external cuneothalamic neurons. In the present simultaneous HRP labelling study, some of the primary afferent terminals made direct synaptic contacts with the dendrites of the external cuneothalamic neurons. In view of the multiple inputs onto the external cuneothalamic neurons, impinging particularly on their somata and secondary dendrites, it is suggested that the proprioceptive information reaching these neurons is intensively modulated and integrated before transmission ultimately to the cerebral sensorimotor cortex.

Animals↗

Microglial response to N-methyl-D-aspartate-mediated excitotoxicity in the immature rat brain.

The intracerebral injection of N-methyl-D-aspartate (NMDA) has been proposed as a model for hypoxic-ischemic insult in the immature brain. In this light, the aim of this study was to describe the time course of the microglial reaction in the areas undergoing primary degeneration at the site of intracortical NMDA injection as well as in areas undergoing secondary anterograde and/or retrograde degeneration. Fifty nanomoles of NMDA were injected in the sensorimotor cortex of 6-day-old rats. After survival times ranging from 10 hours to 28 days, cryostat sections were stained for routine histology and for the demonstration of microglial cells by means of tomato lectin histochemistry. The areas affected by primary degeneration caused by the intracortical injection of NMDA were the neocortex, the hippocampus, and the rostral thalamus. Secondary degeneration (retrograde and anterograde) was observed in the ventrobasal complex of the thalamus. The cortical lesion also caused Wallerian degeneration of the cortical descending efferents as observed in the basilar pons. Microglial reactivity in all these areas was present at 10 hours postinjection and was restricted to the areas undergoing neuronal or axonal degeneration. Reactive microglial cells were stained intensely and showed a round or pseudopodic morphology. At 3 days, an apparent increase in the number of tomato lectin-positive cells was observed in the areas undergoing neuronal death. By 7 days after the injection, the lesion became nonprogressive, and by 14 and 28 days, microglial cells showed moderate lectin binding and a more ramified morphology.

Animals↗

Cortical lesions induce an increase in cell number and PSA-NCAM expression in the subventricular zone of adult rats.

The subventricular zone (SVZ) bordering the lateral ventricle is one of the few regions of adult brain that contains dividing cells. These cells can differentiate into neurons in vivo after migration into the olfactory bulb and in vitro in the presence of appropriate growth factors. Little is known, however, about the fate of these cells in vivo after brain injury in adults. We examined cell number and expression of differentiation markers in the SVZ of adult rats after cortical lesions. Aspiration lesions of the sensorimotor cortex in adult rats induced a transient doubling of the number of cells in the SVZ at the level of the striatum without consistent increases in bromodeoxyuridine-labeled cells. Immunoreactivity to the polysialylated neural cell adhesion molecule, expressed by the majority of cells of the SVZ during development, increased dramatically after lesion. In contrast, immunolabeling for molecules found in mature neurons and glia did not increase in the SVZ after lesion, and immunoreactivity for growth factors that induce differentiation of SVZ cells in vitro decreased or remained undetectable, suggesting that lack of appropriate growth factor expression may contribute to the lack of differentiation of the newly accumulated cells in vivo. The data reveal that cells of the SVZ are capable of plasticity in the adult rat after brain injury in vivo and that the newly accumulated cells retain characteristics seen during development.

Animals↗

Arborisation and termination of single motor thalamocortical axons in the rat.

The aim of this study was to examine the arborisations and terminations of individual thalamocortical axons in the motor system of the rat. Small, extracellular injections of an anterograde tracer (dextran-biotin) were made into the ventrolateral (VL) or ventral posterolateral (VPL) thalamic nuclei to label thalamocortical projections. Eleven motor axons and one somatosensory axon were reconstructed through serial sections just rostral from the injection site to their terminations in sensorimotor cortex. The smallest arbor arising from a single motor axon extended approximately 0.9 mm rostrocaudal and 0.9 mm mediolateral, the largest extended 3.9 mm rostrocaudal and 1.0 mm mediolateral. In some cases, two distinct plexuses of terminals were formed by an axon. In addition, motor axons formed terminals in cortical layer V only or in layers I, III, and V. By contrast (and in keeping with previous reports), the somatosensory axon formed a single plexus of terminals in layer IV of the cortex that extended approximately 0.3 mm rostrocaudal and 0.4 mm mediolateral. It is concluded that individual motor thalamocortical neurones are in a position to influence much more widespread cortical regions than somatosensory thalamocortical neurones.

Animals↗

Immunocytochemical localization of the insulin-responsive glucose transporter 4 (Glut4) in the rat central nervous system.

We have previously reported that the insulin-responsive glucose transporter GLUT4 is strongly expressed by discrete areas of the rat brain (Leloup et al. [1996] Molec. Brain Res. 38:45-53). In the present study, a sensitive immunocytochemical technique has been used to analyze extensively the anatomical and ultrastructural localizations of GLUT4 in the rat central nervous system in order to gain insight into the physiological role of this transporter. We confirm that GLUT4 is expressed by numerous neurons of the brain and spinal cord, whereas glial cells are more scarcely labeled. In both light and electron microscopy, we observe that the immunoreactivity for GLUT4 is localized mainly in the somatodendritic portion of neurons, where some cisterns of rough endoplasmic reticulum, ribosomal rosettes, certain Golgi saccules, and some intracytoplasmic vesicles are labeled. In contrast, axons and nerve terminals are only occasionally immunostained in certain brain regions such as the neocortex and the ventricular surfaces for example. The GLUT4-immunoreactive structures appear concentrated and most prominently immunostained in motor areas, such as the sensorimotor cortex, most basal ganglia and related nuclei, the cerebellum and deep cerebellar nuclei, a number of reticular fields, motor nuclei of cranial nerves, and motor neurons of the ventral horn of the spinal cord. The labeled regions, which also include some sensory nuclei, are often those in which Vissing et al. ([1996] J. Cerebral Blood Flow Metab. 16:729-736) have shown that exercise stimulates local cerebral glucose utilization, so that GLUT4 might be involved in this effect. On the other hand, the fact that the anatomical localizations of GLUT4 reported here generally agree with the distribution of insulin- or insulin-receptor- related receptors is important since it indicates that the translocation of GLUT4 might also be regulated by insulin in the central nervous system.

Amygdala↗

Reproducibility of BOLD-based functional MRI obtained at 4 T.

The reproducibility of activation patterns in the whole brain obtained by functional magnetic resonance imaging (fMRI) experiments at 4 Tesla was studied with a simple finger-opposition task. Six subjects performed three runs in one session, and each run was analyzed separately with the t-test as a univariate method and Fisher's linear discriminant analysis as a multivariate method. Detrending with a first- and third-order polynomial as well as logarithmic transformation as preprocessing steps for the t-test were tested for their impact on reproducibility. Reproducibility across the whole brain was studied by using scatter plots of statistical values and calculating the correlation coefficient between pairs of activation maps. In order to compare reproducibility of "activated" voxels across runs, subjects and models, 2% of all voxels in the brain with the highest statistical values were classified as activated. The analysis of reproducible activated voxels was performed for the whole brain and within regions of interest. We found considerable variability in reproducibility across subjects, regions of interest, and analysis methods. The t-test on the linear detrended data yielded better reproducibility than Fisher's linear discriminant analysis, and therefore seems to be a robust although conservative method. Preliminary data indicate that these modeling results may be reversed by preprocessing to reduce respiratory and cardiac physiological noise effects. The reproducibility of both the position and number of activated voxels in the sensorimotor cortex was highest, while that of the supplementary motor area was much lower, with reproducibility of the cerebellum falling in between the other two areas.

Adult↗

Frequency dependence of the functional MRI response after electrical median nerve stimulation.

Localizing sensorimotor areas with high resolution functional MRI is of considerable interest for a wide range of medical applications from the preoperative planning of neurosurgical interventions to determining the course of neuroplastic reorganisation after brain lesions. We examined the effect of the stimulation frequency on the blood oxygen level dependent (BOLD) fMRI response and on perfusion weighted fMRI using electrical median nerve stimulation at 5, 15, 40, and 100 Hz. BOLD fMRI was performed using a single shot gradient echo EPI sequence to acquire 15 contiguous slices. For the qualitative flow sensitive studies, a single slice inversion recovery prepared spin echo echoplanar sequence (IR-SE EPI) was used. In the primary sensorimotor cortex, a linear increase of the fMRI-BOLD response, affecting both the number of activated pixels and the amplitude of the signal changes, was seen with increasing stimulation frequencies. The qualitative in-flow sensitive studies, using the IR-SE EPI sequence, indicate that the tissue perfusion also increases over the same range of frequencies. This implicates that larger fMRI responses can be obtained if electrical median nerve stimulation is performed at higher frequencies. The results are compared with electrophysiological data, which show a decrease of the early somatosensory evoked potentials at higher frequencies.

Adult↗

Cortical neurite outgrowth and growth cone behaviors reveal developmentally regulated cues in spinal cord membranes.

Corticospinal axon outgrowth in vivo and the ability to sprout or regenerate after injury decline with age. This developmental decline in growth potential has been correlated with an increase in inhibitory myelin-associated proteins in older spinal cord. However, previous results have shown that sprouting of corticospinal fibers after contralateral lesions begins to diminish prior to myelination, suggesting that a decrease in growth promoting and/or an increase in inhibitory molecules in spinal gray matter may also regulate corticospinal axon outgrowth. To address this possibility, we carried out in vitro experiments to measure neurite outgrowth from explants of 1-day-old hamster forelimb sensorimotor cortex that were plated onto membrane carpets or membrane stripe assays prepared from white or gray matter of 1-to 22-day-old cervical spinal cord. On uniform carpets and in the stripe assays cortical neurites grew robustly on young but not older membranes from both white and gray matter. Mixtures of membranes from 1- and 15-day spinal cord inhibited neurite outgrowth, suggesting that the presence of inhibitory molecules in the 15-day cord overwhelmed permissive or growth promoting molecules in membranes from 1-day cord. Video microscopic observations of growth cone behaviors on membrane stripe assays transferred to glass coverslips supported this view. Cortical growth cones repeatedly collapsed at borders between permissive substrates (laminin or young membrane stripes) and nonpermissive substrates (older membrane stripes). Growth cones either turned away from the older membranes or reduced their growth rates. These results suggest that molecules in both the gray and white matter of the developing spinal cord can inhibit cortical neurite outgrowth.

Aging↗

Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps.

We have recently demonstrated using functional magnetic resonance imaging the presence of synchronous low-frequency fluctuations of signal intensities from the resting human brain that have a high degree of temporal correlation (p < 0.0001) both within and across the sensorimotor cortex. A statistically significant overlap between the resting-state functional connectivity map and the task-activation map due to bilateral finger tapping was obtained. Similar results have been obtained in the auditory and visual cortex. Because the pulse sequence used for collecting data was sensitive to blood flow and blood oxygenation, these low-frequency fluctuations of signal intensity may have arisen from variations of both. The objective of this study was simultaneously to determine the contribution of the blood oxygenation level signal and the flow signal to physiological fluctuations in the resting brain using the flow-sensitive alternating inversion recovery pulse sequence. In all subjects, the functional connectivity maps obtained from BOLD had a greater coincidence with task-activation maps than the corresponding functional connectivity maps obtained from blood-flow signals at the same level of statistical significance. Results of this study suggest that while variations in blood flow might contribute to functional connectivity maps, BOLD signals play a dominant role in the mechanism that gives rise to functional connectivity in the resting human brain.

Adolescent↗

Recurrent seizures induced by cortical iron injection: a model of posttraumatic epilepsy.

A single injection of 5 or 10 microliters of ferrous or ferric chloride into rat or cat sensorimotor cortex resulted in chronic recurrent focal paroxysmal electroencephalographic discharges as well as behavioral convulsions and electrical seizures. Iron-filled macrophages, ferruginated neurons, and astroglical cells surrounded the focus of seizure discharge. Recurrent focal epileptiform discharges caused by cortical injection of iron salts suggests that the development of human posttraumatic epilepsy may depend, in part, on neurochemical alterations induced by the principal metallic ions found in whole blood.

Animals↗

Positron emission tomography study of human brain functional development.

From over 100 children studied with 2-deoxy-2[18F]fluoro-D-glucose and positron emission tomography we selected 29 children (aged 5 days to 15.1 years) who had suffered transient neurological events not significantly affecting normal neurodevelopment. These 29 children were reasonably representative of normal children and provided an otherwise unobtainable population in which to study developmental changes in local cerebral metabolic rates for glucose (lCMRGlc). In infants less than 5 weeks old lCMRGlc was highest in sensorimotor cortex, thalamus, brainstem, and cerebellar vermis. By 3 months, lCMRGlc had increased in parietal, temporal, and occipital cortices; basal ganglia; and cerebellar cortex. Frontal and dorsolateral occipital cortical regions displayed a maturational rise in lCMRGlc by approximately 6 to 8 months. Absolute values of lCMRGlc for various grey matter regions were low at birth (13 to 25 mumol/min/100 gm), and rapidly rose to reach adult values (19 to 33 mumol/min/100 gm) by 2 years. lCMRGlc continued to rise until, by 3 to 4 years, it reached values of 49 to 65 mumol/min/100 gm in most regions. These high rates were maintained until approximately 9 years, when they began to decline, and reached adult rates again by the latter part of the second decade. The highest increases of lCMRGlc over adult values occurred in cerebral cortical structures; lesser increases were seen in subcortical structures and in the cerebellum. This time course of lCMRGlc changes matches that describing the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. The determination of changing metabolic patterns accompanying normal brain development is a necessary prelude to the study of abnormal brain development with positron emission tomography.

Adolescent↗

A positron emission tomography study of essential tremor: evidence for overactivity of cerebellar connections.

The origin of essential tremor is unknown. Animal models have suggested that the inferior olivary nucleus may act as a tremor generator. We used positron emission tomography to study changes in regional cerebral blood flow associated with involuntary postural tremor and passive wrist oscillation in patients with essential tremor. Activation due to voluntary wrist oscillation and arm extension without tremor was studied in normal control subjects. The essential tremor group had bilaterally increased cerebellar blood flow at rest (without tremor) compared with the control group. Involuntary postural tremor was associated with further bilateral cerebellar activation, and also contralateral striatal, thalamic, and sensorimotor cortex activation. Voluntary wrist oscillation, maintained arm extension without tremor, and passive wrist oscillation were all associated with significant ipsilateral rather than bilateral cerebellar activation. We conclude that essential tremor is associated with increased bilateral cerebellar activity both at rest and during tremor.

Adult↗