Université de Caen Normandie
Psychology
A sensitive marker for monitoring progression of early Alzheimer's disease would help to develop and test new therapeutic strategies. The present study is aimed at investigating brain metabolism changes over time, as a potential... more
A sensitive marker for monitoring progression of early Alzheimer's disease would help to develop and test new therapeutic strategies. The present study is aimed at investigating brain metabolism changes over time, as a potential monitoring marker, in patients with amnestic mild cognitive impairment, according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen amnestic mild cognitive impairment patients underwent magnetic resonance imaging and 18 FDG-positron emission tomography scans both at inclusion and 18 months later. Baseline and follow-up positron emission tomography data were corrected for partial volume effects and spatially normalized using magnetic resonance imaging data, scaled to the vermis and compared using SPM2. 'PET-PAC' maps reflecting metabolic per cent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than non-converters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18 FDG-positron emission tomography for monitoring early Alzheimer's disease progression. Abbreviations: aMCI = amnestic mild cognitive impairment; BA = Brodmann areas; 18 FDG = 2-[ 18 F]-Fluoro-2-Deoxy-D-Glucose; PAC = per cent annual change; VOI = volume of interest
Background: Cerebral microbleeds (CMBs) can be detected with T2*weighted Gradient Echo sequence Magnetic Resonance Imaging (MRI) and are frequently seen in the general population. We previously reported that microbleeds in deep or... more
Background: Cerebral microbleeds (CMBs) can be detected with T2*weighted Gradient Echo sequence Magnetic Resonance Imaging (MRI) and are frequently seen in the general population. We previously reported that microbleeds in deep or infratentorial regions were associated with hypertension, whereas lobar microbleeds shared risk factors with cerebral amyloid angiopathy (CAA). We hypothesized that if lobar microbleeds in asymptomatic older persons indeed reflect amyloid angiopathy, their spatial distribution should follow the predilection sites of microbleeds in CAA. We investigated the spatial distribution of lobar microbleeds in the population based Rotterdam Scan Study. Methods: We used a three-dimensional T2* GRE sequence in 1062 participants of the population-based Rotterdam Scan Study to detect microbleeds which were defined as focal areas of very low signal intensity, smaller than 10 mm in size. Among those with lobar microbleeds (n ¼ 204), we assessed with Pearson's Chi Square test whether the CMBs were equally distributed throughout the brain and with a binomial test whether the number of microbleeds per lobe were proportionate to the mean volume of the lobe on the template scan. We repeated our analysis taking clustering effects into account by adding random effects for within subject variation to our model and by weighting each microbleed as a percentage of the total number of microbleeds in each subject. Finally, we excluded all persons with additional non-lobar microbleeds and reran our analyses in persons with strictly lobar microbleeds (n ¼ 146). Results: In total, we counted 1,010 lobar microbleeds. The median number of lobar microbleeds was 1 (range 1-114). Compared with the expected distribution of microbleeds based on the volume of the lobes, we found that lobar as well as strictly lobar cerebral microbleeds occurred significantly more often in the temporal lobe (p-value < 0.05). Analysis accounting for the possibility of clustering confirmed our findings. Conclusions: In the general population, lobar microbleeds show a predilection for the posterior brain regions, particularly the temporal lobes. This corroborates the presumed association of lobar microbleeds with CAA in the general population.
uptake ratios were calculated within a ROI including frontal, temporoparietal, and retrosplenial cortices (FLR-ROI), using the cerebellum as reference region. Based on a FLR-threshold of 1.15, subjects were divided into PIBpositive (+)... more
uptake ratios were calculated within a ROI including frontal, temporoparietal, and retrosplenial cortices (FLR-ROI), using the cerebellum as reference region. Based on a FLR-threshold of 1.15, subjects were divided into PIBpositive (+) and -negative (-). Three age-matched groups were studied: A) 12 PIB(-) cognitively normal elderly controls, B) 12 PIB(+) cognitively normal elderly controls and C) 13 PIB(+) MCI-patients. Voxel-based and ROI-based statistical analyses were performed. The overlap between hypometabolism and WBC-abnormalities in MCI was used to define a ROI to extract values for correlation analysis between different modalities. Results: Group comparison between MCI and PIB(-) controls revealed significant hypometabolism and regionally overlapping WBC-reductions in MCI in posterior cingulate cortex/precuneus (typical cortical hubs, see ). PIB-FLR values were negatively correlated with FDG-values (r ¼ -0.67) and WBC-values (r ¼ -0.42) and a linear positive correlation was found between FDG and WBC-values (r ¼ 0.51) across the entire population (groups A, B and C). These results survived correction for age and grey matter density. Conclusions: These results indicate that disruption of functional connectivity and hypometabolism may represent early functional consequences of emerging molecular Alzheimer-pathology, evolving prior to clinical onset of dementia. The spatial overlap between hypometabolism and disruption of connectivity in cortical hubs points to a particular susceptibility of these regions to early Alzheimer-type neurodegeneration and may reflect a link between synaptic dysfunction and functional disconnection.
Purpose: Absence epilepsy is characterized by 3-Hz generalized spike-and-wave discharges (GSWD) on the electroencephalogram, associated with behavioral arrest. It may be severe, and even in childhood benign absence epilepsy cognitive... more
Purpose: Absence epilepsy is characterized by 3-Hz generalized spike-and-wave discharges (GSWD) on the electroencephalogram, associated with behavioral arrest. It may be severe, and even in childhood benign absence epilepsy cognitive delay is frequent, yet the metabolic/hemodynamic aspects of this kind of epilepsy have not been established. We aimed to determine if the GSWD were related to hemodynamic changes by using a new technique with high temporal resolution: near infrared spectroscopy (NIRS).Methods: NIRS is gaining acceptance as a technique particularly suitable for routine follow-up in children, using the specific absorption properties of living tissues in the near infrared range to measure changes in the concentrations of oxy-, deoxy- and total hemoglobin (HbO2, HHb, and HbT, respectively). We performed simultaneous electroencephalography (EEG) and left frontal NIRS recordings in six children with GSWD. We also tested if the discharges were related to changes in cardiac or respiratory rates.Results: GSWD were associated in the frontal area with an oxygenation (beginning 10 s before the GSWD) followed by strong deoxygenation, then oxygenation again with [HbT] increase, and a return to baseline. We did not identify any relationship between the onset of the GSWD and heart or respiratory rates.Discussion: Our results partially differ from previous studies on GSWD hemodynamic aspects (many of which described a simple deactivation), probably due to differences in temporal resolution and data processing. Simultaneous acquisition of EEG and NIRS can optimize the use of both techniques and help shed light on the mechanisms underlying spike-and-wave discharges.
Electroencephalography of premature neonates shows a physiological discontinuity of electrical activity during quiet sleep. Near infrared spectroscopy (NIRS) shows spontaneous oscillations of hemoglobin oxygenation and volume. Similar... more
Electroencephalography of premature neonates shows a physiological discontinuity of electrical activity during quiet sleep. Near infrared spectroscopy (NIRS) shows spontaneous oscillations of hemoglobin oxygenation and volume. Similar oscillations are visible in term neonates and adults, with NIRS and other functional imaging techniques (fMRI, Doppler, etc.), but are generally thought to result from vasomotion and to be a physiological artifact of limited interest. The origin and possible relationship to neuronal activity of the baseline changes in the NIRS signal have not been established. We carried out simultaneous EEG-NIRS recordings on six healthy premature neonates and four premature neonates presenting neurological distress, to determine whether changes in the concentration of cerebral oxy- and deoxy- and total hemoglobin were related to the occurrence of spontaneous bursts of cerebral electric activity. Bursts of electroencephalographic activity in neonates during quiet sleep were found to be coupled to a transient stereotyped hemodynamic response involving a decrease in oxy-hemoglobin concentration, sometimes beginning a few seconds before the onset of electroencephalographic activity, followed by an increase, and then a return to baseline. This pattern could be either part of the baseline oscillations or superimposed changes to this baseline, influencing its shape and phase. The temporal patterns of NIRS parameters present an unique configuration, and tend to be different between our healthy and pathological subjects. Studies of physiological activities and of the effects of intrinsic regulation on the NIRS signal should increase our understanding of these patterns and EEG-NIRS studies should facilitate the integration of NIRS into the set of clinical tools used in neurology.
With the causes of perinatal brain injuries still unclear and the probable role of hemodynamic instability in their etiology, bedside monitoring of neonatal cerebral hemodynamics with standard values as a function of age are needed. In... more
With the causes of perinatal brain injuries still unclear and the probable role of hemodynamic instability in their etiology, bedside monitoring of neonatal cerebral hemodynamics with standard values as a function of age are needed. In this study, we combined quantitative frequency domain near infrared spectroscopy (FD-NIRS) measures of cerebral tissue oxygenation (StO 2 ) and cerebral blood volume (CBV) with diffusion correlation spectroscopy (DCS) measures of a cerebral blood flow index (CBF ix ) to test the validity of the CBV-CBF relationship in premature neonates and to estimate cerebral metabolic rate of oxygen (rCMRO 2 ) with or without the CBF ix measurement. We measured 11 premature neonates (28-34 weeks gestational age) without known neurological issues, once a week from one to six weeks of age. In nine patients, cerebral blood velocities from the middle cerebral artery were collected by transcranial Doppler (TCD) and compared with DCS values. Results show a steady decrease in StO 2 during the first six weeks of life while CBV remains stable, and a steady increase in CBF ix . rCMRO 2 estimated from FD-NIRS remains constant but shows wide interindividual variability. rCMRO 2 calculated from FD-NIRS and DCS combined increased by 40% during the first six weeks of life with reduced interindividual variability. TCD and DCS values are positively correlated. In conclusion, FD-NIRS combined with DCS offers a safe and quantitative bedside method to assess CBV, StO 2 , CBF, and rCMRO 2 in the premature brain, facilitating individual follow-up and comparison among patients. A stable CBV-CBF relationship may not be valid for premature neonates.
Purpose: Absence epilepsy may be severe and is frequently accompanied by cognitive delay, yet its metabolic/hemodynamic aspects have not been established. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an isomorphic,... more
Purpose: Absence epilepsy may be severe and is frequently accompanied by cognitive delay, yet its metabolic/hemodynamic aspects have not been established. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an isomorphic, predictive, and homologous model of human absence epilepsy. We studied hemodynamic changes related to generalized spike-and-wave discharges (GSWDs) in GAERS by using a technique with high temporal resolution: near-infrared spectroscopy (NIRS). We hypothesized that conflicting results from other techniques might be due to the averaging of a biphasic response such as the one we described in children.Methods: NIRS is particularly suitable for monitoring changes in the concentrations of oxy-, deoxy-, and total hemoglobin (HbO2, HHb, and HbT), using the specific absorption properties of living tissues in the near infrared range. We obtained concomitant high quality electroencephalography (EEG)–NIRS recordings in six GAERS (total of 444 seizures), and tested whether the discharges were related to changes in cardiac or respiration rates.Results: The onset of GSWDs was preceded by a deactivation, followed by an activation that was possibly due to seizure-suppression mechanisms. The end was marked by a deactivation. The onset of GSWDs was associated with a decrease and the end with a brief increase in respiratory rate.Discussion: Our results differ partially from those of previous studies on hemodynamic aspects of GSWDs (many of which describe a simple deactivation), probably due to differences in temporal resolution and data processing; however, they are consistent with metabolic studies, functional magnetic resonance imaging (fMRI) studies on WAG/Rij rats, and some results in children with absence epilepsy.
In preterm newborns, evoked hemoglobin responses often show inversed patterns when compared to patterns observed in adults. We suspect that changes in hematocrit during the transition from fetal to adult hemoglobin and the consequent... more
In preterm newborns, evoked hemoglobin responses often show inversed patterns when compared to patterns observed in adults. We suspect that changes in hematocrit during the transition from fetal to adult hemoglobin and the consequent period of low hematocrit cause such an inversion. To test this assumption, we performed a longitudinal auditory functional study in six premature neonates with a total of 18 recording sessions. Using near-infrared spectroscopy (NIRS), we measured both local (de)oxy-hemoglobin changes during auditory stimulation with a continuous-wave (CW-NIRS) system and baseline absolute (de)oxy-hemoglobin concentrations with a frequency domain (FD-NIRS) system. Our results show that the inversion in the functional hemodynamic responses in infants correlates with the total hemoglobin concentration. These results suggest that the available hemoglobin supply during the low hematocrit period is not sufficient to overcome oxygen demand during functional activation.
Understanding the evolution of regional and hemispheric asymmetries in the early stages of life is essential to the advancement of developmental neuroscience. By using 2 noninvasive optical methods, frequency-domain near-infrared... more
Understanding the evolution of regional and hemispheric asymmetries in the early stages of life is essential to the advancement of developmental neuroscience. By using 2 noninvasive optical methods, frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy, we measured cerebral hemoglobin oxygenation (SO 2 ), blood volume (CBV), an index of cerebral blood flow (CBF i ), and the metabolic rate of oxygen (CMRO 2i ) in the frontal, temporal, and parietal regions of 70 premature and term newborns. In concordance with results obtained using more invasive imaging modalities, we verified both hemodynamic (CBV, CBF i , and SO 2 ) and metabolic (CMRO 2i ) parameters were greater in the temporal and parietal regions than in the frontal region and that these differences increased with age. In addition, we found that most parameters were significantly greater in the right hemisphere than in the left. Finally, in comparing age-matched males and females, we found that males had higher CBF i in most cortical regions, higher CMRO 2i in the frontal region, and more prominent right--left CBF i asymmetry. These results reveal, for the first time, that we can detect regional and hemispheric asymmetries in newborns using noninvasive optical techniques. Such a bedside screening tool may facilitate early detection of abnormalities and delays in maturation of specific cortical areas.
Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The... more
Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO 2 ). Thus, measures of CMRO 2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO 2 an ideal target for bedside measurement of brain health.
Electroencephalography of premature neonates shows a physiological discontinuity of electrical activity during quiet sleep. Near infrared spectroscopy (NIRS) shows spontaneous oscillations of hemoglobin oxygenation and volume. Similar... more
Electroencephalography of premature neonates shows a physiological discontinuity of electrical activity during quiet sleep. Near infrared spectroscopy (NIRS) shows spontaneous oscillations of hemoglobin oxygenation and volume. Similar oscillations are visible in term neonates and adults, with NIRS and other functional imaging techniques (fMRI, Doppler, etc.), but are generally thought to result from vasomotion and to be a physiological artifact of limited interest. The origin and possible relationship to neuronal activity of the baseline changes in the NIRS signal have not been established. We carried out simultaneous EEG-NIRS recordings on six healthy premature neonates and four premature neonates presenting neurological distress, to determine whether changes in the concentration of cerebral oxy-and deoxy-and total hemoglobin were related to the occurrence of spontaneous bursts of cerebral electric activity. Bursts of electroencephalographic activity in neonates during quiet sleep were found to be coupled to a transient stereotyped hemodynamic response involving a decrease in oxy-hemoglobin concentration, sometimes beginning a few seconds before the onset of electroencephalographic activity, followed by an increase, and then a return to baseline. This pattern could be either part of the baseline oscillations or superimposed changes to this baseline, influencing its shape and phase. The temporal patterns of NIRS parameters present an unique configuration, and tend to be different between our healthy and pathological subjects. Studies of physiological activities and of the effects of intrinsic regulation on the NIRS signal should increase our understanding of these patterns and EEG-NIRS studies should facilitate the integration of NIRS into the set of clinical tools used in neurology.
The near infrared spectroscopy (NIRS) frequency-domain multi-distance (FD-MD) method allows for the estimation of optical properties in biological tissue using the phase and intensity of radiofrequency modulated light at different... more
The near infrared spectroscopy (NIRS) frequency-domain multi-distance (FD-MD) method allows for the estimation of optical properties in biological tissue using the phase and intensity of radiofrequency modulated light at different source-detector separations. In this study, we evaluated the accuracy of this method to retrieve the absorption coefficient of the brain at different ages. Synthetic measurements were generated with Monte Carlo simulations in magnetic resonance imaging (MRI)-based heterogeneous head models for four ages: newborn, 6 and 12 month old infants, and adult. For each age, we determined the optimal set of sourcedetector separations and estimated the corresponding errors. Errors arise from different origins: methodological (FD-MD) and anatomical (curvature, head size and contamination by extra-cerebral tissues). We found that the brain optical absorption could be retrieved with an error between 8-24% in neonates and infants, while the error increased to 19-44% in adults over all source-detector distances. The dominant contribution to the error was found to be the head curvature in neonates and infants, and the extra-cerebral tissues in adults.
Funding information Fondation de France; The Region Normandie council Preterm infants frequently develop atypical sensory profiles, the tactile modality being particularly affected. However, there is a lack of recent investigation of... more
Funding information Fondation de France; The Region Normandie council Preterm infants frequently develop atypical sensory profiles, the tactile modality being particularly affected. However, there is a lack of recent investigation of neonatal tactile perception in a passive context, especially in preterms who are particularly exposed to this tactile stimuli. Our aims were to provide evidence of orienting responses (behavioral modifications directing subject's attention towards stimuli) and habituation to passive tactile stimuli in preterm neonates, to explore their ability to perceive spatial and temporal aspects of the stimulus, and to evaluate the effect of clinical factors on these abilities. We included 61 preterm neonates, born between 32 and 34 weeks of gestational age. At 35 weeks of corrected gestational age, we measured orienting responses (forearm, hand, and fingers movements) during vibrotactile stimulation of their hand and forearm; during a habituation and dishabituation paradigm, the dishabituation being either a location change or a pause in the stimulation sequence. Preterm newborns displayed a manual orienting response to vibrotactile stimuli which significantly decreased when the stimulus was repeated, regardless of the stimulated location on the limb. Habituation was delayed in subjects born at a younger gestational age, smaller birth weight, and having experienced more painful care procedures. Preterm neonates perceived changes in stimulus location and interstimulus time interval. Our findings provide insights on several aspects of the perception of repeated tactile stimuli by preterm neonates, and the first evidence of the early development of temporal processing abilities in the tactile modality. Future work will investigate the links between this ability and neurodevelopmental disorders. K E Y W O R D S
In mammals, somatosensation and chemosensation are the first sensory systems by which the developing organism becomes acquainted with its environment (Segond, 2008). Somatosensory perception includes tactile, thermal and pain perception... more
In mammals, somatosensation and chemosensation are the first sensory systems by which the developing organism becomes acquainted with its environment (Segond, 2008). Somatosensory perception includes tactile, thermal and pain perception through cutaneous receptors, as well as postural and movement information through muscle and tendon receptors. Chemosensory perception includes the olfactory, gustatory and trigeminal systems, involved in nutrition, social interactions, and emotional reactivity and regulation. In humans, these two systems emerge in utero and prepare the foetus for neonatal life. Because of this developmental heterochrony, they are the foundation of cognitive and affective development (Humphrey, 1970; Lecanuet & Schaal, 1996; Schaal, 2000; Schaal, Hummel, & Soussignan, 2004). Although the importance of these ontogenetically and phylogenetically earlier systems for individual development has been acknowledged for a long time, they are the least studied in the human neo...