Chemosensory event-related potentials in early blind humans.

While the effects of early visual deprivation on auditory and tactile functions have been widely studied, little is known about olfactory function in early blind subjects. The present study investigated the potential effect of early blindness on the electrophysiological correlates of passive odour perception. Event-related potentials (ERPs) were recorded in eight early blind humans and eight sighted controls matched for age, sex and handedness during olfactory stimulation with 2-phenyl ethyl alcohol and trigeminal stimulation with CO2 Latencies, amplitudes and topographical distributions were analysed. As expected, the olfactory and trigeminal ERP components showed normal latencies, amplitudes and topography in both groups. Olfactory stimuli generated responses of smaller amplitude than those observed in response to trigeminal stimulation. In addition, ERP analyses did not reveal any major difference in electrocortical responses in occipital areas in early blind and sighted subjects. These results suggest that passive olfactory and trigeminal stimulation elicit the same electrophysiological responses in both groups, confirming that the neurophysiological correlates of the cross-modal compensatory mechanisms in early blind subjects do not appear during passive olfactory and trigeminal perception.

Reorganisation of the right occipito-parietal stream for auditory spatial processing in early blind humans. A transcranial magnetic stimulation study.

It is well known that, following an early visual deprivation, the neural network involved in processing auditory spatial information undergoes a profound reorganization. In particular, several studies have demonstrated an extensive activation of occipital brain areas, usually regarded as essentially "visual", when early blind subjects (EB) performed a task that requires spatial processing of sounds. However, little is known about the possible consequences of the activation of occipitals area on the function of the large cortical network known, in sighted subjects, to be involved in the processing of auditory spatial information. To address this issue, we used event-related transcranial magnetic stimulation (TMS) to induce virtual lesions of either the right intra-parietal sulcus (rIPS) or the right dorsal extrastriate occipital cortex (rOC) at different delays in EB subjects performing a sound lateralization task. Surprisingly, TMS applied over rIPS, a region critically involved in the spatial processing of sound in sighted subjects, had no influence on the task performance in EB. In contrast, TMS applied over rOC 50 ms after sound onset, disrupted the spatial processing of sounds originating from the contralateral hemifield. The present study shed new lights on the reorganisation of the cortical network dedicated to the spatial processing of sounds in EB by showing an early contribution of rOC and a lesser involvement of rIPS.

Auditory motion perception activates visual motion areas in early blind subjects.

We have previously shown that some visual motion areas can be specifically recruited by auditory motion processing in blindfolded sighted subjects [Poirier, C., Collignon, O., De Volder, A.G., Renier, L., Vanlierde, A., Tranduy, D., Scheiber, C., 2005. Specific activation of V5 brain area by auditory motion processing: an fMRI study. Brain Res. Cogn. Brain Res. 25, 650-658]. The present fMRI study investigated whether auditory motion processing may recruit the same brain areas in early blind subjects. The task consisted of simultaneously determining both the nature of a sound stimulus (pure tone or complex sound) and the presence or absence of its movement. When a movement was present, blind subjects had to identify its direction. Auditory motion processing, as compared to static sound processing, activated the brain network of auditory and visual motion processing classically observed in sighted subjects. Accordingly, brain areas previously considered as specific to visual motion processing could be specifically recruited in blind people by motion stimuli presented through the auditory modality. This indicates that the occipital cortex of blind people could be organized in a modular way, as in sighted people. The similarity of these results with those we previously observed in sighted subjects suggests that occipital recruitment in blind people could be mediated by the same anatomical connections as in sighted subjects.

The Ponzo illusion with auditory substitution of vision in sighted and early-blind subjects.

We tested the effects of using a prosthesis for substitution of vision with audition (PSVA) on sensitivity to the Ponzo illusion. The effects of visual experience on the susceptibility to this illusion were also assessed. In one experiment, both early-blind and blindfolded sighted volunteers used the PSVA to explore several variants of the Ponzo illusion as well as control stimuli. No effects of the illusion were observed. The results indicate that subjects focused their attention on the two central horizontal bars of the stimuli, without processing the contextual cues that convey perspective in the Ponzo figure. In a second experiment, we required subjects to use the PSVA to consider the two converging oblique lines of the stimuli before comparing the length of the two horizontal bars. Here we were able to observe susceptibility to the Ponzo illusion in the sighted group, but to a lesser extent than in a sighted non-PSVA control group. No clear effect of the ilusion was obtained in early-blind subjects. These results suggest that, at least in sighted subjects, perception obtained with the PSVA shares perceptual processes with vision. Visual experience appears mandatory for a Ponzo illusion to occur with the PSVA.

Auditory triggered mental imagery of shape involves visual association areas in early blind humans.

Previous neuroimaging studies identified a large network of cortical areas involved in visual imagery in the human brain, which includes occipitotemporal and visual associative areas. Here we test whether the same processes can be elicited by tactile and auditory experiences in subjects who became blind early in life. Using positron emission tomography, regional cerebral blood flow was assessed in six right-handed early blind and six age-matched control volunteers during three conditions: resting state, passive listening to noise sounds, and mental imagery task (imagery of object shape) triggered by the sound of familiar objects. Activation foci were found in occipitotemporal and visual association areas, particularly in the left fusiform gyrus (Brodmann areas 19-37), during mental imagery of shape by both groups. Since shape imagery by early blind subjects does involve similar visual structures as controls at an adult age, it indicates their developmental crossmodal reorganization to allow perceptual representation in the absence of vision.

Cerebral blood flow and glucose metabolism in hypothyroidism: a positron emission tomography study.

Hypothyroidism is often associated with defective memory, psychomotor slowing, and depression. However, the relationship between thyroid status and cognitive or psychiatric disturbances remains unclear. Using psychometric scales, 10 patients who had undergone total thyroidectomy for thyroid carcinoma were evaluated for depression, anxiety, and psychomotor slowing; they were examined both when euthyroid and hypothyroid after thyroid hormone withdrawal. Positron emission tomography was used, with oxygen-15-labeled water and fluorine-18F-labeled 2-deoxy-2fluoro-D-glucose as the tracers, to correlate the regional cerebral blood flow and cerebral glucose metabolism with the mental state in patients. Two different image analysis techniques (regions of interest and statistical parametric maps) were applied. In hypothyroidism, there was a generalized decrease in regional cerebral blood flow (23.4%, P < 0.001) and in cerebral glucose metabolism (12.1%, P < 0.001) and there were no specific local defects. Patients were also significantly more depressed (P < 0.001), anxious (P < 0.001) and psychomotor slowed (P < 0.005) in hypo than in euthyroid status. These results indicate that the brain activity was globally reduced in severe hypothyroidism of short duration without the regional modifications usually observed in primary depression.

Occipital activation by pattern recognition in the early blind using auditory substitution for vision.

This PET study aimed at investigating the neural structures involved in pattern recognition in early blind subjects using sensory substitution equipment (SSE). Six early blind and six blindfolded sighted subjects were studied during three auditory processing tasks: a detection task with noise stimuli, a detection task with familiar sounds, and a pattern recognition task using the SSE. The results showed a differential activation pattern with the SSE as a function of the visual experience: in addition to the regions involved in the recognition process in sighted control subjects, occipital areas of early blind subjects were also activated. The occipital activation was more important when the early blind subjects used SSE than during the other auditory tasks. These results suggest that activity of the extrastriate visual cortex of early blind subjects can be modulated and bring additional evidence that early visual deprivation leads to cross-modal cerebral reorganization.

Comparison of regional cerebral blood flow and glucose metabolism in the normal brain: effect of aging.

The regional cerebral blood flow (rCBF) and metabolic rate for glucose (rCMRGlc) are associated with functional activity of the neural cells. The present work reports a comparison study between rCBF and rCMRGlc in a normal population as a function of age. 10 young (25.9+/-5.6 years) and 10 old (65.4+/-6.1 years) volunteers were similarly studied at rest. In each subject, rCBF and rCMRGlc were measured in sequence, during the same session. Both rCBF and rCMRGlc values were found to decrease from young (mean rCBF=43.7 ml/100 g per min; mean rCMRGlc=40.6 micromol/100 g per min) to old age (mean rCBF=37.3 ml/100 g per min; mean rCMRGlc=35.2 micromol/100 g per min), resulting in a drop over 40 years of 14.8% (0.37%/year) and 13.3% (0.34%/year), respectively. On a regional basis, the frontal and the visual cortices were observed to have, respectively, the highest and the lowest reduction in rCBF, while, for rCMRGlc, these extremes were observed in striatum and cerebellum. Despite these differences, the ratio of rCBF to rCMRGlc was found to have a similar behavior in all brain regions for young and old subjects as shown by a correlation coefficient of 88%. This comparative study indicates a decline in rCBF and rCMRGlc values and a coupling between CBF and CMRGlc as a function of age.

[11C]flumazenil metabolite measurement in plasma is not necessary for accurate brain benzodiazepine receptor quantification.

In this work, a mathematical correction for metabolites has been validated which estimates the relative amount of [11C]flumazenil ([11C]FMZ) in the total plasma curve from the tissue kinetic data without the need for direct metabolite measurement in blood plasma samples. Kinetic data were obtained using a 90-min three-injection protocol on five normal volunteers. First, the relative amount of [11C]FMZ in plasma was modelled by a two-parameter exponential function. The parameters were estimated either directly by fitting this model to the blood plasma metabolite measurements, or indirectly from the simultaneous fitting of tissue time activity curves from several brain regions with a non-linear FMZ kinetic model. Second, the direct and indirect metabolite corrections were fixed and the FMZ compartmental parameters were determined on a regional basis in the brain. The validation was performed by comparing the regional values of benzodiazepine receptor density Bmax and equilibrium dissociation constant Kd obtained with the direct metabolite correction with those values obtained with the indirect correction. For Bmax, the correlation coefficient r2 was above 0.97 for all subjects and the slope values of the linear regression were within the interval [0.97, 1.2]. For Kd, r2 was above 0.96, and the slope values of the linear regression were within the interval [0.99, 1.1]. Simulation studies were performed in order to evaluate whether this metabolite correction method could be used in a clinical protocol where only a single [11C]FMZ injection and a linear compartmental model are used. The resulting [11C]FMZ distribution volume estimates were found to be linearly correlated with the true values, with r2=1.0 and a slope value of 1.1. The mathematical metabolite correction proved to be a feasible and reliable method to estimate the relative amount of [11C]FMZ in plasma and the compartmental model parameters for three-injection protocols. Although validation with real data is necessary, simulation results suggest that our analysis method may also be applied to single-injection protocols.

A standardized blood sampling scheme in quantitative FDG-PET studies.

Quantitative estimation of brain glucose metabolism (rCMRGlc) with positron emission tomography and fluorodeoxyglucose involves arterial blood sampling to estimate the delivery of radioactivity to the brain. Usually, for an intravenous injection of 30 s duration, an accurate input curve requires a frequency of one sample every 5 s or less to determine the peak activity in arterial plasma during the first 2 min after injection. In this work, 13 standardized sampling times were shown to be sufficient to accurately define the input curve. This standardized input curve was subsequently fitted by a polynomial function for its rising part and by spectral analysis for its decreasing part. Using the measured, the standardized, and the fitted input curves, rCMRGlc was estimated in 32 cerebral regions of interest in 20 normal volunteers. Comparison of rCMRGlc values obtained with the measured and the fitted input curves showed that both procedures gave consistent results, with a maximal relative error in mean rCMRGlc of 1% when using the autoradiographic method and 2% using kinetic analysis of dynamic data. This input-curve-fitting technique, which is not dependent on the peak time occurrence, allows an accurate determination of the input-curve shape from reduced sampling schemes.

Changes in occipital cortex activity in early blind humans using a sensory substitution device.

The purpose of this study was to investigate the neural networks involved when using an ultrasonic echolocation device, which is a substitution prosthesis for blindness through audition. Using positron emission tomography with fluorodeoxyglucose, regional brain glucose metabolism was measured in the occipital cortex of early blind subjects and blindfolded controls who were trained to use this prosthesis. All subjects were studied under two different activation conditions: (i) during an auditory control task, (ii) using the ultrasonic echolocation device in a spatial distance and direction evaluation task. Results showed that the abnormally high metabolism already observed in early blind occipital cortex at rest [C. Veraart, A.G. De Volder, M.C. Wanet-Defalque, A. Bol, C. Michel, A.M. Goffinet, Glucose utilization in human visual cortex is, respectively elevated and decreased in early versus late blindness, Brain Res. 510 (1990) 115-121.] was also present during the control task and showed a trend to further increase during the use of the ultrasonic echolocation device. This specific difference in occipital cortex activity between the two tasks was not observed in control subjects. The metabolic recruitment of the occipital cortex in early blind subjects using a substitution prosthesis could reflect a concurrent stimulation of functional cross-modal sensory connections. Given the unfamiliarity of the task, it could be interpreted as a prolonged plasticity in the occipital cortex early deprived of visual afferences.

Evolution of brain glucose metabolism with age in epileptic infants, children and adolescents.

During the first years of life, the human brain undergoes repetitive modifications in its anatomical, functional, and synaptic construction to reach the complex functional organization of the adult central nervous system. As an attempt to gain further insight in those maturation processes, the evolution of cerebral metabolic activity was investigated as a function of age in epileptic infants, children and adolescents. The regional cerebral metabolic rates for glucose (rCMRGlc) were measured with positron emission tomography (PET) in 60 patients aged from 6 weeks to 19 years, who were affected by complex partial epilepsy. They were scanned at rest, without premedication, in similar conditions to 20 epileptic adults and in 49 adult controls. The distribution of brain metabolic activity successively extended from sensorimotor areas and thalamus in epileptic newborns to temporo-parietal and frontal cortices and reached the adult pattern after 1 year of age. The measured rCMRGlc in the cerebral cortex, excluding the epileptic lesions, increased from low values in infants to a maximum between 4 and 12 years, before it declined to stabilize at the end of the second decade of life. Similar age-related changes in glucose metabolic rates were not observed in the adult groups. Despite the use of medications, the observed variations of rCMRGlc with age in young epileptic humans confirm those previously described in pediatric subjects. These metabolic changes are in full agreement with the current knowledge of the synaptic density evolution in the human brain.

Brain energy metabolism in early blind subjects: neural activity in the visual cortex.

As an attempt to better understand the metabolic basis for the previously reported increases in glucose metabolism in the visual cortex of congenitally blind subjects, cerebral blood flow, oxygen consumption and glucose utilization were investigated with multitracer positron emission tomography. Measurements were carried out in three subjects who became blind early in life and in three age-matched blindfolded controls. Regional analysis of cerebral blood flow, metabolic rates for oxygen and glucose utilization revealed that these parameters were relatively higher in the visual cortex in case of early blindness (109.7 +/- 2.4%; 114.3 +/- 1.5%; 118.0 +/- 5.5%, respectively) than in controls (98.1 +/- 3.9%; 108.6 +/- 3.6%; 105.2 +/- 4.8%). There were slight differences, albeit statistically not significant, between early blind and control subjects in terms of oxygen-to-glucose metabolic ratios. The relatively preserved stoichiometry in the visual areas of blind subjects points to the lack of variation in the yield of glucose oxidation in this cortex. Those observations suggest that the high level of energy metabolism disclosed in early blind visual cortex is related to neural activity.

Brain glucose utilization in band heterotopia: synaptic activity of "double cortex".

Regional brain glucose utilization was investigated with positron emission tomography and fluorodeoxyglucose in 2 patients with a seizure disorder associated with diffuse band heterotopia, a condition known as "double cortex." Although 1 patient was examined shortly after the onset of the first seizures, the other had a long history of intractable epilepsy before examination. Magnetic resonance imaging revealed a symmetric and generalized band of ectopic gray matter and an overlying normal-looking cortex, without focal abnormality. Metabolic studies yielded comparable results in both patients, with similar and even higher glucose uptake in the layer of gray matter heterotopia compared to the normal cortex. These data suggest the persistence of some synaptic activity in the heterotopic neurons, which seems unaffected by age or by the time-course of epilepsy.

Brain glucose utilisation in acquired childhood aphasia associated with a sylvian arachnoid cyst: recovery after shunting as demonstrated by PET.

Regional brain glucose utilisation was investigated with PET and fluorodeoxyglucose (FDG) in a case of epileptic aphasia (Landau-Kleffner syndrome) associated with a left sylvian arachnoid cyst. CT and MRI had failed to disclose any mass effect of the cyst on surrounding brain structures. Sequential metabolic measurements showed a comparable pronounced hypometabolism in cortical regions around the cyst, involving speech areas, and suggested mild but chronic compression of the developing brain. After placement of a cyst-peritoneal shunt system, significant metabolic improvement occurred in all cortical regions, especially the inferior frontal gyrus and the perisylvian area, with predominant residual deficit in the left superior temporal gyrus. These findings were correlated with a pronounced increase in word fluency and slower progress in verbal auditory comprehension. This report suggests that PET is able to evaluate the functional disturbances associated with expanding arachnoid cysts, and to follow the neurological improvement after drainage.

Brain glucose metabolism in postanoxic syndrome due to cardiac arrest.

Using positron emission tomography (PET), thirteen studies of regional brain glucose utilization were performed in 12 patients with postanoxic syndrome due to cardiac arrest. Investigations were carried out at least one month after brain anoxia. Seven subjects were in a persistent vegetative state. The others had regained normal consciousness with various residual neurological signs. When compared with normal values obtained in 16 normal, age-matched subjects, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative cases, and to a lesser degree (+/- 25%) in conscious subjects. The most consistent regional alterations were observed in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories. Other selective anomalies were found in the frontomesial junction (5 cases), the striatum (3 cases with dystonia), and the visual cortex (2 cases with cortical blindness). This study suggests that cerebral anoxia results in a global brain hypometabolism, which appears related to the vigilance state, as well as in regional disturbances preferentially located in arterial border zones. Although our findings remain to be confirmed in larger series, they suggest that PET provides a useful index of residual brain tissue function after anoxia and may assist in the monitoring of postanoxic encephalopathies.

Neuronal ceroid-lipofuscinosis: preferential metabolic alterations in thalamus and posterior association cortex demonstrated by PET.

Regional brain glucose utilisation was investigated with positron emission tomography (PET) and fluorodeoxyglucose (FDG) in four siblings with neuronal ceroid-lipofuscinosis. A consistent pattern was found, namely a decrease of glucose utilisation in all grey structures but more marked at the level of the thalamus and posterior association cortex. The severity of metabolic anomalies was correlated with the degree of clinical impairment and with disease duration; they were the most severe in the oldest patient, who was also the most affected clinically, intermediate in two others, and minimal in the subject with the shortest period of development of the disease. These observations suggest that PET is useful for the definition of anatomical targets of metabolic diseases and for the investigation of their pathophysiology.

Brain glucose utilization under high sensory activation: hypoactivation of prefrontal cortex.

Brain glucose metabolism was studied, using positron emission tomography and [F-18]-2-deoxy-2-fluoro-D-glucose, in 13 healthy young adult men, at rest and under conditions of high visual and auditory stimulation with minor motor involvement. Despite high individual variations, the mean cerebral metabolic rate for glucose was highly increased during stimulation. Furthermore, the regional pattern of cerebral glucose utilization showed consistent differences between resting and activated states. Several brain areas, including temporal, motor-premotor and parieto-occipital cortices, and striatum, thalamus, and cerebellum showed a level of activation statistically comparable to that of mean gray. Significant preferential activation was found only in the visual cortex. By contrast, prefrontal and mesial cortical areas were relatively hypoactivated by the task. Inasmuch as prefrontal cortex is known to receive visual associative afferents, these observations are tentatively interpreted in terms of the "parallel" mode of information processing, along specific routes according to the environmental state.

Glucose utilization in human visual cortex is abnormally elevated in blindness of early onset but decreased in blindness of late onset.

Glucose utilization has been studied in the visual cortex of blind human subjects, by comparison with normal volunteers, using positron emission tomography. In 6 subjects who became blind early in life ('early blindness'), metabolism in visual cortex was elevated, comparable to that of normal subjects studied with the eyes open. By contrast, glucose utilization in visual areas of 6 human subjects who became blind after completion of visual development ('late blindness') was decreased, slightly lower than in normal volunteers studied with the eyes closed. This unexpected difference between early and late blind subjects might reflect the persistence, in early blindness, of supranumerary synapses which would escape the normal developmental decrease in synaptic density during infancy.

Decreased glucose utilization in the striatum and frontal lobe in probable striatonigral degeneration.

Nine positron emission tomography studies of regional cerebral glucose metabolism were performed in 7 patients with probable striatonigral degeneration, a disorder characterized by parkinsonian features and absent or poor response to L-dopa. When compared with values obtained in normal volunteers, mean cerebral glucose metabolism was slightly reduced in subjects with striatonigral degeneration who, in addition, had a marked (20.5%, +/- 3 SD) relative hypometabolism in putaminal and caudate nuclei. Significant hypometabolism was also found in motor/premotor as well as in prefrontal cortex. In 2 subjects who were studied twice a deterioration of relative striatal metabolism paralleled clinical evolution. Magnetic resonance imaging disclosed the presence of abnormal iron deposits in the putamen in all cases but showed no cortical anomalies. These results suggest that positron emission tomography with [18F]fluorodeoxyglucose may provide an index of cell and processes degeneration in the striatum in striatonigral degeneration and is able to detect functional deficits in frontal cortex. The presence of striatal hypometabolism might be a predictor of a poor response to L-dopa.