Mónica Giménez

Cerebral atrophy in Parkinson's disease patients with visual hallucinations

Although visual hallucinations (VH) are relatively frequent in Parkinsons disease (PD) patients, their neural substrates are only known from neuropathological and functional magnetic resonance studies. The aim of this study was to investigate possible structural brain changes on MRI in non‐demented PD patients with VH using voxel‐based morphometry. Eighteen PD patients with VH were compared to 20 patients with PD without VH and 21 healthy controls. Compared with both controls and the non‐hallucinating PD group, PD patients with VH had grey matter volume reductions in the lingual gyrus and superior parietal lobe. Structural changes in these areas involved in higher visual processing may be important in understanding the VH and visual deficits in PD patients.

Patterns of cerebral white matter damage and cognitive impairment in adolescents born very preterm.

There is increasing evidence about the presence of white matter damage in subjects with a history of premature birth, even in those classified as good outcome because of an apparently normal development. Although intellectual performance is within normal limits in premature children it is significantly decreased compared to paired controls. The purpose of this study was to investigate the relationship between a lower performance intelligence quotient and white matter damage in preterm adolescents. The sample comprised 44 adolescents (mean age ± S.D.: 14.4 ± 1.6 years) born before 32 weeks of gestational age and 43 term‐born adolescents (14.5 ± 2.1 years). Individual voxel‐based morphometry analyses demonstrated that 35/44 (80%) preterm subjects had white matter abnormalities. The centrum semiovale and the posterior periventricular regions were the most frequently affected areas. Correlation analysis showed that in preterms the performance intelligence quotient correlated with the whole‐brain white matter volume (r = 0.32; P = 0.036) but not with grey matter volume. Complementary analysis showed that low scores in the Digit Symbol subtest, a measure of processing speed, in the preterm group correlated with reductions in white matter concentration. These results suggest that white matter damage is highly common and that it persists until adolescence. Hence, diffuse white matter loss may be responsible for performance intelligence quotient and processing speed decrements in subjects with very preterm birth.

Hippocampal gray matter reduction associates with memory deficits in adolescents with history of prematurity

Using optimized voxel-based morphometry (VBM), we compared the relationship between hippocampal and thalamic gray matter loss and memory impairment in 22 adolescents with history of prematurity (HP) and 22 normal controls. We observed significant differences between groups in verbal learning and verbal recognition, but not in visual memory. VBM analysis showed significant left hippocampal and bilateral thalamic reductions in HP subjects. Using stereological methods, we also observed a reduction in hippocampal volume, with left posterior predominance. We found correlations between left hippocampal gray matter reductions (assessed by VBM) and verbal memory (learning and percentage of memory loss) in the premature group. The stereological analysis showed a correlation between verbal learning and the left posterior hippocampus. Our results suggest that left hippocampal tissue loss may be responsible for memory impairment and is probably related to the learning disabilities that HP subjects present during schooling.

Accelerated cerebral white matter development in preterm infants: A voxel-based morphometry study with diffusion tensor MR imaging

Twenty-seven preterm infants were compared to 10 full-term infants at term equivalent age using a voxel-based analysis of diffusion tensor imaging of the brain. Preterm infants exhibited higher fractional anisotropy values, which may suggest accelerated maturation, in the location of the sagittal stratum. While some earlier findings in preterm infants have suggested developmental delays, the results of this study are more consistent with accelerated white matter development, possibly as a result of increased sensorimotor stimulation in the extrauterine environment. These results are the first to suggest that the increased intensity of stimulation associated with preterm birth may advance the process of white matter maturation in the human brain. Questions remain about whether these findings reflect acceleration of the process of white matter maturation generally, or localized alterations induced specifically by activity in affected pathways.

White matter volume and concentration reductions in adolescents with history of very preterm birth: a voxel-based morphometry study.

Very preterm birth (VPTB) is an important risk factor for white matter (WM) damage. We used voxel-based morphometry (VBM) to examine regional WM brain abnormalities in 50 adolescents with antecedents of very preterm birth (VPTB) without evidence of WM damage on T2-weighted MRI. This group was compared with a group of 50 subjects born at term and matched for age, handedness and socio-cultural status. We also examined the relationship between WM changes and gestational age (GA) and weight (GW) at birth in VPTB subjects. Both modulated and unmodulated VBM analyses showed significant abnormalities in several WM brain regions in the VPTB group, involving all the cerebral lobes. However, density analyses (unmodulated data) mainly identified periventricular damage and the involvement of the longitudinal fascicles while volume analyses (modulated data) detected WM decreases in regions distant from the ventricular system, located at the origin and end of the long fascicles. A significant correlation was found between WM decreases and both GA and GW in various brain regions: the lower the GA and GW, the lower the WM integrity. This study supports the current view that widespread white matter impairment is associated with immature birth.

Corpus Callosum and Prefrontal Functions in Adolescents with History of Very Preterm Birth.

Very preterm (VPT) birth can account for thinning of the corpus callosum and poorer cognitive performance. Research findings about preterm and VPT adolescents usually describe a small posterior corpus callosum, although our research group has also found reductions of the anterior part, specifically the genu. The aim of the present study was to investigate the functional implications of this concrete reduction. Fifty-two VPT adolescents were compared with 52 adolescents born at term; there were no significant differences in age and gender, and socioeconomic status was similar between the groups. All participants underwent a magnetic resonance imaging (MRI) study and assessment of prefrontal functioning and vocabulary. The VPT group showed significant reductions of the genu, isthmus and splenium, as well as a significantly worse performance on category verbal fluency, executive functions, everyday memory and vocabulary. Although several parts of the corpus callosum correlated with some prefrontal functions, the genu was the part which principally explained these correlations. The subtest Vocabulary only correlated with the splenium. The relationship between genu and prefrontal functions and between splenium and vocabulary may be due to the fact that these parts of the corpus callosum connect prefrontal and posterior parietal cortex, respectively. The work presented here provides evidence of specific associations between reductions in the anterior corpus callosum (genu) and lower prefrontal functioning in VPT adolescents.

Gestational Age at Preterm Birth in Relation to Corpus Callosum and General Cognitive Outcome in Adolescents

Prematurity is associated with corpus callosum abnormalities and low general cognitive functioning. The present study explores the specific relationship between gestational age, corpus callosum, and intelligence quotient (IQ) in a sample of preterm-born adolescents. Sixty-four adolescents born at a gestational age of 36 weeks or less were divided into 4 groups attending to their gestational age (GA) (group 1, ≤ 27; group 2, 28-30; group 3, 31-33; group 4, 34-36). These individuals were compared with 53 adolescents born at term and of similar age, gender, and sociocultural status. Individuals born at a gestational age of 27 or less (group 1) presented a generalized corpus callosum reduction in the posterior part (posterior midbody, isthmus, and splenium) as well as in the anterior part (anterior midbody and genu), a reduced total white-matter volume, and a low Full-Scale IQ. Group 2 (GA between 28 and 30) also showed a low IQ, but corpus callosum reduction was only found in the splenium, without total white-matter volume reductions. Group 3 (GA between 31 and 33) did not present differences in corpus callosum size or a reduced total white- matter volume, but they showed a low Full-Scale IQ. Group 4 (GA between 34 and 36) did not show a smaller corpus callosum or a lower general cognitive performance. Specific significant correlations were found between corpus callosum subregions and gestational age. These results suggest the importance of gestational age in prematurity in relation to brain structural and functional outcome. Premature babies born at a gestational age of 27 weeks or less are the target group for long-term corpus callosum and white-matter anomalies and for a low IQ.

Sex differences in the human olfactory system.

The olfactory system (accessory) implicated in reproductive physiology and behavior in mammals is sexually dimorphic. These brain sex differences present two main characteristics: they are seen in neural circuits related to sexual behavior and sexual physiology and they take one of two opposite morphological patterns (male>female or female>male). The present work reports sex differences in the olfactory system in a large homogeneous sample of men (40) and women (51) using of voxel-based morphology. Gray matter concentration showed sexual dimorphism in several olfactory regions. Women have a higher concentration in the orbitofrontal cortex involving Brodmanns areas 10, 11 and 25 and temporomedial cortex (bilateral hippocampus and right amygdala), as well as their left basal insular cortex. In contrast, men show a higher gray matter concentration in the left entorhinal cortex (Brodmanns area 28), right ventral pallidum, dorsal left insular cortex and a region of the orbitofrontal cortex (Brodmanns area 25). This study supports the hypothesis that the mammalian olfactory system is a sexually dimorphic network and provides a theoretical framework for the morphofunctional approach to sex differences in the human brain.

Hippocampal functional magnetic resonance imaging during a face-name learning task in adolescents with antecedents of prematurity.

Functional magnetic resonance imaging (fMRI) was used to map hippocampal activation during a declarative memory task in a sample of 14 adolescents with antecedents of prematurity (AP). The sample with AP was matched by age, sex and handedness with 14 full-term controls with no history of neurological or psychiatric illness. The target task consisted in learning 16 novel face-name pairs, and the control task involved the examination of two repeated face-name pairs. Stereological methods were also used to quantify hippocampal volumes. In both groups, we observed increased activation in the learning condition compared to the control task in the right fusiform gyrus and the left inferior occipital gyrus, but only premature subjects activated the hippocampus. Group comparison of the activation versus control conditions showed that prematures had greater activity in the right hippocampus than controls during the encoding of the word-face association. Volumetric analyses showed a significant left hippocampal volume loss in adolescents with AP. In addition, we found a significant positive correlation in the premature group between right hippocampal activation and face-name recognition. Functional MRI data also correlated with structural MRI data: right hippocampal activation correlated positively with right hippocampal volume. Our findings are consistent with previous studies of brain plasticity after focal lesions. Left hippocampal tissue loss may be related to an increase in contralateral brain activity, probably reflecting a compensatory mechanism. Our data also suggest that this plasticity is not enough to achieve normal performance.

Basal ganglia N-acetylaspartate correlates with the performance in the procedural task ‘Tower of Hanoi’ of neuroleptic-naive schizophrenic patients

We tested the hypothesis that basal ganglia dysfunction may be related to procedural learning impairment in schizophrenia. We determined the N-acetylaspartate/choline (NAA/Cho) ratio in the left striatal area in 11 young first-episode antipsychotic-naive patients and matched controls. Procedural learning was assessed by the four-disk version of the Tower of Hanoi. Analysis of variance showed that the number of moves and the execution time had a significant group effect (P=0.02, P<0.0001, respectively). Correlation analysis between procedural learning and the NAA/Cho ratio showed a negative significant correlation only in patients, measured by both time (P=0.006) and by moves (P=0.001). In summary, we found that schizophrenic patients have impaired procedural learning, and that this impairment is related to basal ganglia metabolism.