Corpus callosum and prefrontal functions in adolescents with history of very preterm birth
Introduction
Very preterm (VPT) individuals have an increased risk of brain abnormalities, especially prominent in white matter, which are evident in both childhood (Hüppi et al., 1998, Inder et al., 1999, Nagy et al., 2003) and adolescence (Giménez, Junqué, Narberhaus, Bargalló et al., 2006; Stewart et al., 1999). The corpus callosum is the main interhemispheric commissure of the brain (Tomasch, 1954). In humans it begins to develop 9 weeks after conception and continues to grow post-natally, showing morphological changes related to the ongoing myelination of interhemispheric fibers (Volpe, 2001).
Magnetic resonance imaging (MRI) studies have demonstrated thinning of the corpus callosum in VPT or preterm children and adolescents (Caldú et al., 2006, Narberhaus et al., 2007bNosarti et al., 2004, Peterson et al., 2000, Stewart et al., 1999). Such injury may be partly explained by the vulnerability of the developing corpus callosum to hypoxic-ischemic damage, possibly due to intrinsic vulnerability of immature oligodendrocytes (Back et al., 2001).
Peterson et al. (2000) reported that 8-year-old VPT subjects showed a generalized corpus callosum reduction, including the anterior and posterior regions. In a qualitative MRI study of 14–15-year-old VPT individuals, Stewart et al. (1999) reported a reduction predominantly in the posterior corpus callosum. In the same sample, Nosarti et al. (2004) confirmed this result through a quantitative MRI technique able to detect even subtle cerebral abnormalities. More recently, and also using this technique, our research group has consistently found reductions of both the posterior and anterior corpus callosum, specifically the genu, in preterm and VPT adolescents (Caldú et al., 2006, Narberhaus et al., 2007b).
In the corpus callosum, the region which extends from the rostrum to the posterior part of the midbody is predominantly made up of fibers interconnecting the prefrontal cortex (Park et al., in press). This fact enhances the importance of studying cognitive functions that are highly dependent on the prefrontal cortex, namely prefrontal functions.
Preterm adolescents seem to perform significantly worse than term born subjects in phonetic verbal fluency (Giménez, Junqué, Narberhaus, Botet et al., 2006; Taylor, Minich, Bangert, Filipek, & Hack, 2004) and category verbal fluency (Allin et al., 2001; Giménez, Junqué, Narberhaus, Botet et al., 2006). For other prefrontal functions, studies report contradictory results. For instance, while Tideman (2000) and Rushe et al. (2001) described no significant differences in attention/concentration, Taylor, Klein, Minich, and Hack (2000) found specific difficulties on this cognitive function. As regards executive functioning, Taylor et al., 2000, Taylor et al., 2004 reported significant differences between preterms and controls on several different measures. Tideman (2000) also showed a significantly worse performance, but only on one specific task the Trail Making Test (TMT) B, mainly measuring planning and cognitive flexibility (Baron, 2004). In contrast, Rushe et al. (2001) and, recently, Saavalainen et al. (2006) observed no differences in executive functions between groups assessed through the TMT B and the Stroop test, respectively. Related to the above mentioned studies, it is noteworthy that Taylor et al., 2000, Taylor et al., 2004 differ from the others in that they explore specifically extremely and very low birth weight subjects.
Additionally some studies report a significantly worse performance in preterm adolescents compared to term controls in everyday memory, as assessed by the Rivermead Behavioural Memory Test (RBMT) (Caldú et al., 2006, Isaacs et al., 2000, Narberhaus et al., 2007a). This test mainly evaluates episodic memory, prospective memory and orientation, so the medial temporal lobe and finally the prefrontal cortex are involved (Kahn et al., 2005; Lezak, Howieson, & Loring, 2004; Rami et al., 2003; Umeda, Nagumo, & Kato, 2006).
Corpus callosum reduction has been related to a worse general cognitive performance in VPT children (Peterson et al., 2000) and adolescents (Caldú et al., 2006). Only two studies have analyzed the relationship between prefrontal functions and corpus callosum in VPT adolescents. Results showed an association between phonetic verbal fluency and the mid-posterior surface area (Nosarti et al., 2004), and between everyday memory and total corpus callosum area (Caldú et al., 2006). However, in this study the authors did not analyze the possible correlations between prefrontal functions and each part of the corpus callosum, while Nosarti et al. (2004) only found this relationship for VPT boys (n = 33). To our knowledge there is no study addressing the issue about the relationship between the different parts of the corpus callosum and prefrontal functioning in VPT adolescents.
The specific aim of the present study was to examine the functional implications of the reductions in the anterior corpus callosum, specifically the genu. We hypothesised that a smaller genu would be associated with worse prefrontal functioning in VPT adolescents compared to the term control group.
Section snippets
Participants
Subjects with a history of prematurity were selected from the population born between 1982 and 1994 at the Hospital Clínic i Provincial, and between 1988 and 1989 at the Hospital Vall d’Hebron, both in Barcelona (Spain). In the archives of these hospitals 488 cases of prematurity were currently available at their databases. Inclusion criteria for the present study were: gestational age <33 weeks (VPT) and age at assessment between 11 and 18 years; remaining 278 cases, from which the clinical
Brain measurements
Regarding the corpus callosum sub-regions, Student's t-test yielded a significant difference in the genu, isthmus and splenium, being more pronounced in this last mentioned part. All these areas were smaller in the VPT subjects. This group also showed a significant reduction in whole cerebral white matter volume (Table 2).
Neuropsychological results
In all the analyzed prefrontal functions, the VPT group obtained worse scores than did controls. Significant differences were found for category verbal fluency, executive
Discussion
Our findings about a more pronounced reduction in the posterior part of the corpus callosum agree with previous studies about VPT adolescents (Nosarti et al., 2004, Stewart et al., 1999). This result could be related to the fact that in normal development, in the range 11–15 years, the posterior corpus callosum shows a more rapid growth pattern (Thompson et al., 2000). This data may reflect a more pronounced development of interhemispheric connections in posterior regions during this period (
Acknowledgments
This study was supported by grants 2005FIR 00095 (Generalitat de Catalunya) to A. Narberhaus, AP2002-0737 (Ministerio de Educación, Cultura y Deporte) to M. Giménez, 2003FI 00191 (Generalitat de Catalunya) to X. Caldú, and by the grant SAF2005-07340 (Ministerio de Educación y Ciencia); with the support of the “Departament d’Educació i Universitats de la Generalitat de Catalunya i Fons Social Europeu”.
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