Josep Maria Mercader

Decreased Regional Brain Volume and Cognitive Impairment in Preterm Children at Low Risk

OBJECTIVE: To investigate whether preterm children with low risk for neurodevelopmental deficits show long-term changes in gray matter (GM) and white matter (WM) volumes compared with term children and to relate these changes to cognitive outcome. METHODS: MRI was used to evaluate 20 preterm children who were determined to be at low risk for neurodevelopmental deficits and were born between 30 and 34 weeks’ gestational age without major neonatal morbidity or cerebral pathology in the neonatal period and 22 matched, term control subjects. Volumetric images were analyzed by means of voxel-based morphometry to identify regional cerebral alterations. Children also underwent cognitive and behavioral/emotional assessments. RESULTS: Preterm children showed global and regional GM volume reductions in several brain areas, including temporal and parietal lobes and concomitant WM volume reductions in the same areas, although only the left temporal regions achieved statistical significance. Global intellectual performance in the preterm group was significantly decreased compared with control subjects. Neither behavioral nor emotional problems were found in the preterm group. In the whole sample, we found a positive correlation between GM volume bilaterally in the middle temporal and in the postcentral gyri with IQ. Positive correlations were observed between GM and gestational age at birth in parietal and temporal cerebral regions and with WM in parietal regions. CONCLUSION: Preterm birth has an important impact on the neurodevelopmental and cognitive outcome of children at 9 years of age, being a risk factor for decreased regional cortical GM and WM even in preterm children with low risk for neurodevelopmental deficits.

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.

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.

MRI and genetic correlates of cognitive function in elders with memory impairment

The present study investigated the relationship between genetic variation, MRI measurements and neuropsychological function in a sample of 58 elders exhibiting memory decline. In agreement with previous reports, we found that the epsilon4 allele of the apolipoprotein E (APOE) and the D allele of the angiotensin converting enzyme (ACE) polymorphisms negatively modulated the cognitive performance. Further, we found an association between the A allele of the apolipoprotein C1 (APOC1) polymorphism and poorer memory and frontal lobe function. No clear associations emerged between MRI measures of white matter lesions (WML) or hippocampal sulcal cavities (HSC) and the cognitive performance after controlling for age effects. Further, the degree of WML or HSC lesions was in general not predisposed genetically except for the presence of the A allele of the APOC1 polymorphism that was related to a higher severity of HSC scores. Our results suggest that WML or HSC do not represent important brain correlates of genetic influences on cognitive performance in memory impaired subjects.

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.

Cognitive and behavioral changes after unilateral posteroventral pallidotomy: relationship with lesional data from MRI.

We investigated cognitive and behavioral changes after unilateral posteroventral pallidotomy, and their relationship with lesion size and location as identified in magnetic resonance image quantitative analysis. Fifteen consecutive patients with Parkinsons disease were assessed neuropsychologically before and after unilateral posteroventral pallidotomy (five right and 10 left). Immediate postsurgery evaluation (1 week) demonstrated significant worsening of memory, motor learning, motor speed, and verbal fluency. In the 3‐month follow up, learning, memory, and speed returned to the presurgical level, but verbal fluency remained below the baseline. Significant improvements were observed in visuospatial functions and obsessive‐compulsive behavior. Lesional volume did not correlate with neuropsychologic changes. Left lesions produced more impairment in verbal fluency than right‐sided lesions. Regression analysis identified two lesional areas in the pallidum mediale internum. These regions accounted for 68% of the variance in the visuospatial changes.

Functional connectivity of the hippocampus in elderly with mild memory dysfunction carrying the APOE ɛ4 allele

The purpose of the present study was to evaluate functional connectivity of the hippocampus during a fMRI face-name learning task in a group of elders with mild memory impairment on the basis of the presence or absence of the APOE epsilon4 allele. Twelve epsilon4 carriers and 20 non-carriers with mild memory dysfunction and exhibiting equivalent performance in clinical evaluations of global cognitive function and memory were studied. Subjects underwent a fMRI session consisting of a face-name encoding memory task. Following scanning, subjects were asked to pair faces with their corresponding proper name. Functional connectivity of the hippocampus was measured by using coherence analysis to evaluate the activity of brain circuits related to memory encoding processes. In contrast to non-APOE epsilon4 allele bearers, APOE epsilon4 carriers showed enhanced connectivity with the anterior cingulate, inferior parietal/postcentral gyrus region and the caudate nucleus. Enhanced hippocampal connectivity with additional brain regions in APOE epsilon4 allele carriers during the performance of an associative memory task may reveal the existence of additional activity in the cortico-subcortical network engaged during memory encoding in subjects carrying this genetic variant.

Proton Magnetic Resonance Spectroscopy Reveals Medial Temporal Metabolic Abnormalities in Adolescents With History of Preterm Birth

Prematurity is associated with volumetric reductions in specific brain areas such as the hippocampus and with metabolic changes that can be detected by spectroscopy. Short echo time (35 ms) Proton magnetic resonance spectroscopy (1H MRS) was performed to assess possible medial temporal lobe metabolic abnormalities in 21 adolescents with preterm birth (mean age: 14.8, SD: 1.3) compared with an age-matched control sample (mean age: 14.8, SD: 1.6). 1H MRS spectra were analyzed with linear combination model fitting, obtaining the absolute metabolite concentrations for Creatine (Cr), and myo-inositol (Ins). In addition, the following metabolite sums were measured: total Cho (glycerophospho-choline + phosphocholine), total N-acetyl-aspartate + N-acetyl-aspartylglutamate (NA), and total Glx (glutamate + glutamine). A stereological analysis was performed to calculate hippocampal volume. Absolute Cr, and total NA values were decreased in the preterm group (p = 0.016; p = 0.002, respectively). The preterm also showed a hippocampal reduction (p < 0.0001). Significant relationships were found between gestational age and different metabolites and the hippocampal volume. Moreover, hippocampal volume correlated with brain metabolites in the whole sample. Results demonstrate that prematurity affects medial temporal lobe metabolites, and that the alteration is related to structural changes, suggesting that the cerebral changes persist until adolescence.

Medial temporal MR spectroscopy is related to memory performance in normal adolescent subjects

In addition to the study of pathological conditions, magnetic resonance spectroscopy can provide useful information about brain–behavior relationships in normal subjects. Recently, there have been reports of correlations between N-acetylaspartate (NAA) values and cognitive functions in normal adults. We tested the possible specific relationship between the NAA/choline (Cho) ratio in the medial temporal lobe and memory performance in normal adolescents. The medial temporal NAA/Cho ratio was unrelated to age, gender and general intelligence but presented a clear correlation with several memory measures. In the regression analysis two memory variables (RAVLT learning and a face–name recognition task) explained 55.6% of NAA/Cho variance. We conclude that NAA values in the medial temporal lobe are related to memory abilities but not to global intelligence in normal adolescent subjects.