Persistent posterior and transient anterior medial temporal lobe activity during navigation.

A functional segregation along the posterior-anterior axis of the medial temporal lobe (MTL) has been suggested. In brief, it is thought that the posterior hippocampus represents environmental detail and/or encodes space, whereas the anterior part represents the environment more as a whole and/or subserves behavior. Different phases of navigation should thus recruit different structures within the MTL. Based on animal studies and neuroimaging data from humans, the initial phase of navigation, i.e., self-localization, target localization and path planning, should depend on the anterior MTL independent of upcoming navigational demands, whereas posterior MTL should be active throughout navigation. We tested this prediction using fMRI with navigation in a learned large-scale virtual office landscape with numerous complex landmarks under different navigational conditions. The initial navigational phase specifically engaged the anterior MTL. Increased activity was found bilaterally in the rostral and caudal entorhinal cortex. This is, to our knowledge, the first report of entorhinal activity in virtual navigation detected in a direct comparison. Also bilateral anterior hippocampus and anterior parahippocampal cortex were significantly more active during the initial phase. Activity lasting throughout the navigational period was found in the right posterior hippocampus and parahippocampal cortex. Hippocampal activity for the entire navigation period was only detected when the virtual environment remained unaltered. Navigational success was positively correlated with activity in the anterior right hippocampus for the initial phase, and more posteriorly in the hippocampus for the whole navigation period. Plots of the BOLD signal time course demonstrated that activity in the anterior hippocampus was transient whereas activity in the posterior hippocampus peaked regularly throughout the entire navigation period. These results support a functional segregation within the MTL with regard to navigational phases. The anterior MTL appears to complete associations related to the environment at large and provide a behavioral plan for navigation, whereas the posterior part keeps track of current location.

Associations of Changes in Cardiorespiratory Fitness and Symptoms of Anxiety and Depression With Brain Volumes: The HUNT Study.

Objective: We investigated the independent and joint associations of changes in estimated cardiorespiratory fitness (eCRF) and symptoms of anxiety and depression with brain volumes in individuals from the general population. Method: 751 participants (52% women, aged 50-67 years) from the Nord-Trøndelag Health Study (HUNT) MRI cohort were included. eCRF obtained from a non-exercise algorithm and symptoms of anxiety and depression were assessed twice; at HUNT2 (1995-97) and HUNT3 (2006-08). Brain MRI was performed shortly after HUNT3. Brain parenchymal fraction (BPF), bilateral hippocampal and total cortical volume were extracted from brain MRI obtained at 1.5T, using FreeSurfer and Statistical Parametric Mapping. Results: Multiple regression revealed that participants whose eCRF increased had larger BPF (ß = 0.09, 95% CI 0.02, 0.16) and larger hippocampal volume (ß = 0.09, 95% CI 0.03, 0.16) compared to participants whose eCRF remained low. Participants whose eCRF remained high had larger BPF (ß = 0.15, 95% CI 0.07, 0.22) and larger cortical volume (ß = 0.05, 95% CI 0.01, 0.09). Participants whose anxiety symptoms worsened had smaller BPF (ß = -0.09, 95% CI -0.15, -0.02) and cortical volume (ß = -0.05, -0.08, -0.01) than participants whose anxiety symptoms remained low. Each ml/kg/min increase in eCRF was associated with larger cortical volume among individuals with worsening of anxiety symptoms (ß = 0.13, 95% CI 0.001, 0.27), and larger BPF among individuals whose depressive symptoms improved (ß = 0.28, 95% CI 0.02, 0.53). Conclusion: Promoting exercise intended to improve eCRF may be an important public health initiative aimed at maintaining brain health among middle-aged individuals with and without changing psychological symptoms.

Changes in spatial cognition and brain activity after a single dose of testosterone in healthy women.

Studies have consistently shown that males perform better than females on several spatial tasks. Animal and human literature suggests that sex hormones have an important role in both establishing and maintaining this difference. The aim of the present study was to examine the effects of exogenous testosterone on spatial cognition and brain activity in healthy women. A cross-sectional, double-blind, randomized, placebo-controlled study was performed in 42 healthy young women who either received one dose of 0.5mg sublingual testosterone or placebo. They then learned a virtual environment and performed navigation tasks during functional magnetic resonance imaging (fMRI). Subsequently, their knowledge of the virtual environment, self-reported navigation strategy, and mental rotation abilities were measured. The testosterone group had improved representations of the directions within the environment and performed significantly better on the mental rotation task compared to the placebo group, but navigation success and navigation strategy were similar in the two groups. Nevertheless, the testosterone group had significantly increased activity within the medial temporal lobe during successful navigation compared to the placebo group, and a positive correlation between testosterone load and medial temporal lobe activity was found. Fetal testosterone levels, measured as second-to-fourth digit length ratio, interacted significantly with parahippocampal activity and tended towards giving higher mental rotation task scores. These results demonstrated that testosterone had a limited effect pertaining specifically to spatial cognition involving 3D-visualization in healthy women, while complex behaviors such as navigation, relying more on learned strategies, were not altered despite increased neuronal activity in relevant brain regions.

Perimenopausal hormone therapy is associated with regional sparing of the CA1 subfield: a HUNT MRI study.

Observational studies support a neuroprotective role of hormone therapy (HT) in the perimenopause, with hippocampal size being a widely used biomarker. We investigated the effect of HT started before the onset of menopause and lasting for at least 3 years on hippocampal volume and shape in 80 postmenopausal women and 80 controls matched on age and intracranial volume taken from a large community-based sample (Nord-Trøndelag Health Study-magnetic resonance imaging). The main effect of hormone group showed a statistically significant difference in hippocampal volumes (p = 0.028). Both the right (3.2%) and left (2.8%) hippocampal volumes were larger in the HT group but only significant for the right hippocampus (p = 0.023). Shape analysis revealed significant regional sparing of the medial aspect of the right hippocampal head and lateral aspect of the body extending to the tail, corresponding to the cornu ammonis, including part of the subiculum, in the HT group. A similar nonsignificant pattern was observed in the left hippocampus. The present study provides support for the critical window theory demonstrating that HT initiated in the perimenopause has neuroprotective properties.

Marked effects of intracranial volume correction methods on sex differences in neuroanatomical structures: a HUNT MRI study.

To date, there is no consensus whether sexual dimorphism in the size of neuroanatomical structures exists, or if such differences are caused by choice of intracranial volume (ICV) correction method. When investigating volume differences in neuroanatomical structures, corrections for variation in ICV are used. Commonly applied methods are the ICV-proportions, ICV-residuals and ICV as a covariate of no interest, ANCOVA. However, these different methods give contradictory results with regard to presence of sex differences. Our aims were to investigate presence of sexual dimorphism in 18 neuroanatomical volumes unrelated to ICV-differences by using a large ICV-matched subsample of 304 men and women from the HUNT-MRI general population study, and further to demonstrate in the entire sample of 966 healthy subjects, which of the ICV-correction methods gave results similar to the ICV-matched subsample. In addition, sex-specific subsamples were created to investigate whether differences were an effect of head size or sex. Most sex differences were related to volume scaling with ICV, independent of sex. Sex differences were detected in a few structures; amygdala, cerebellar cortex, and 3rd ventricle were larger in men, but the effect sizes were small. The residuals and ANCOVA methods were most effective at removing the effects of ICV. The proportions method suffered from systematic errors due to lack of proportionality between ICV and neuroanatomical volumes, leading to systematic mis-assignment of structures as either larger or smaller than their actual size. Adding additional sexual dimorphic covariates to the ANCOVA gave opposite results of those obtained in the ICV-matched subsample or with the residuals method. The findings in the current study explain some of the considerable variation in the literature on sexual dimorphisms in neuroanatomical volumes. In conclusion, sex plays a minor role for neuroanatomical volume differences; most differences are related to ICV.