We found significant sex differences in aging of brain areas that are essential to higher cognitive functioning. Thus, our findings may explain some of the age-sex differences in human cognition and response to brain injury and disease.

Brain metabolic mapping techniques, such as positron emission tomography (PET), can provide information about the functional interactions within entire neural systems. With the large quantity of data that can accumulate from a mapping study, a network analysis, which makes sense of the complex interactions among neural elements, is necessary. A network analysis was performed on data obtained from a PET study that examined both the changes in regional cerebral blood flow (rCBF) and interregional correlations among human cortical areas during performance of an object vision (face matching) and spatial vision (dot-location matching) task. Brain areas for the network were selected based on regions showing significant rCBF or interregional correlations between tasks. Anterior temporal and frontal lobe regions were added to the network using a principal components analysis. Interactions among selected regions were quantified with structural equation modeling. In the structural equation models, connections between brain areas were based on known neuroanatomy and the interregional correlations were used to calculate path coefficients representing the magnitude of the influence of each directional path. The combination of the anatomical network and interregional correlations created a functional network for each task. The functional network for the right hemisphere showed that in the object vision task, dominant path influences were among occipitotemporal areas, while in the spatial vision task, occipitoparietal interactions were stronger. The network for the spatial vision task also had a strong feedback path from area 46 to occipital cortex, an effect that was absent in the object vision task. There were strong interactions between dorsal and ventral pathways in both networks. Functional networks for the left hemisphere did not differ between tasks. Networks for the interhemispheric interactions showed that the dominant pathway in the right hemisphere also had stronger effects on homologous left hemisphere areas and are consistent with a hypothesis that intrahemispheric interactions were greater in the right hemisphere in both tasks, and that these influences were transmitted callosally to the left hemisphere.

1. The objective was to examine how opposite learned behavioral responses to the same physical tone were differentiated by the pattern of interactions between extraauditory neural regions. This was pursued using a new approach combining behavior, neuroimaging, and network analysis to integrate information about differences in regional activity with differences in the covariance relationships between brain areas. 2. A tone was used as either a Pavlovian conditioned excitor or inhibitor. Rats were conditioned with reinforced trials of a conditioned excitor (A+) intermixed with nonreinforced trials of a tone-light compound (AX-). The tone was the excitor (A+) for the tone-excitor group and was the inhibitor (X-) for the tone-inhibitor group. After conditioning, all rats were injected with [14C(U)]2-fluoro-2-deoxyglucose (FDG) and presented with the same tone. 3. FDG autoradiography was used to measure regional activity and to generate interregional correlations of activity resulting from the presentation of the tone. A stepwise discriminant analysis was used to select brain regions that differentiated the excitor from the inhibitor effects. 4. Network analysis consisted of constructing an anatomic model of the brain regions, selected by the discriminant analysis, linking the regions with their known anatomical connections. Then, functional models for the tone-excitor and -inhibitor groups were constructed using structural equation modeling. Correlations of activity between regions were decomposed to calculate numerical weights, or path coefficients, for each anatomic path. These path coefficients were used to compare the interactions for the tone-excitor and -inhibitor models. 5. Regional differences in FDG uptake were found in the sulcal frontal cortex (SFC), lateral septum (LS), medial septum/diagonal band (MS/DB), retrosplenial cortex (RS), and dentate-interpositus nuclei of the cerebellum (DEN). Discriminant analysis selected three other regions that significantly discriminated the tone-excitor and -inhibitor groups: perirhinal cortex (PRh), nucleus accumbens (ACB), and the anteroventral nucleus of the thalamus (AVN). 6. Structural equation modeling identified two functional circuits that differentiated the groups. One involved the basal forebrain regions (LS, MS/DB, ACB) and the other limbic thalamocortical structures (SFC, RS, PRh, AVN). Differences in the interactions within these circuits were mainly in sign of the covariance relationships between regions, from positive for the tone-excitor model to negative path coefficients for the tone-inhibitor model. The path coefficient between the basal forebrain circuit and the limbic thalamocortical circuit showed the largest magnitude difference. This quantitative difference was mediated by a path from the MS/DB to PRh.(ABSTRACT TRUNCATED AT 400 WORDS)

No abstract