Elizabeth Kehoe

ABSTRACT Background Dementia is a worldwide concern, where the primary risk factor is age. Prior literature reports age-related changes to regional brain volume, cognitive decline and changes to neurometabolites. In particular the posterior cingulate cortex (PCC) experiences decreased metabolism associated with brain atrophy and amyloid deposition in Alzheimer’s disease. Chiu et al. (2013) reported a significant positive correlation of choline, creatine, and N-acetyl-aspartate (NAA) with age, while Reyngoudt et al. (2012) only found increases of total creatine and myo-inositol in the PCC in aging. The purpose of this study was to investigate glutamate (Glu) changes in the posterior cingulate cortex across age. Methods Single voxel spectroscopy was performed using point resolved spectroscopy (PRESS) with an echo time of 105 ms and repetition time of 2000 ms on a 3T scanner. We measured neurometabolites concentration changes during resting state by placing a voxel in the posterior cingulate gyrus in healthy young and healthy elderly participants in Wales (7 young, 8 elderly) and Ireland (26 young, 27 elderly). Results In the Welsh cohort a significant decrease was observed in NAA/H2O (t (13) = 2.94, p = .011) and Glu/H2O (t (13) = 5.13, p < .001) with age, showing a strong, negative correlation for NAA (r = -.67, p < .01) and Glu (r = -.74, p < .01) (fig. 1). The same result was found in the Irish cohort: a decrease in NAA/H2O (t (51) = 7.00, p < .001) and Glu/H2O (t (40) = 2.56, p = .014) in healthy elderly compared to healthy young participants. Additionally a negative correlation was established between NAA (r = -.72, p < .001) and Glu (r = -.35, p = .01) with age. Conclusion Age-related decline in NAA levels may suggest a decrease in the number of neurons, while a decline in Glu may imply an early marker of cognitive decline. Examining changes in neurometabolites across age may supplement neuropsychological tests in evaluating the progression of dementia.

This fMRI study explored the neural substrates of cognitive dissonance during dissonance ‘induction’. A novel task was developed based on the results of a separate item selection study (n=125). Items were designed to generate dissonance by prompting participants to reflect on everyday personal experiences that were inconsistent with values they had expressed support for. Three control conditions (justification, consonance, non-self related inconsistency) were used for comparison. Items of all four types were presented to each participant (n=14) in a randomized design. The fMRI analysis used a whole brain approach focusing on the moments dissonance was induced. Results showed that in comparison with the control conditions the dissonance experience led to higher levels of activation in several brain regions. Specifically dissonance was associated with increased neural activation in key brain regions including the anterior cingulate cortex, anterior insula, inferior frontal gyrus, and precuneus. This supports current perspectives which emphasize the role of anterior cingulate and insula in dissonance processing. Less extensive activation in the prefrontal cortex than in some previous studies is consistent with this study’s emphasis on dissonance induction, rather than reduction. This paper also contains a short review and comparison with other fMRI studies of cognitive dissonance.

It is known that the default mode network (DMN) may be modulated by a cognitive task and by performance level. Changes in the DMN have been examined by investigating resting state activation levels, but there have been very few studies examining the modulation of effective connectivity of the DMN during a task in healthy older subjects. In this study we examined how effective connectivity changed in the DMN between rest and during a memory task. We also investigated whether there was any relationship between effective connectivity modulation in the DMN and memory performance, in order to establish whether variations in cognitive performance are related to neural network effective connectivity, either at rest or during task performance. Twenty-eight healthy older participants underwent a resting-state functional MRI (rfMRI) scan and an emotional face-name encoding task. Effective connectivity analyses were performed on the DMN in order to examine the effective connectivity modulation in these two different conditions. During the resting state there was strong self-influence in the regions of the DMN, whille the main regions with statistically significant cross-regional effective connectivity were the posterior cingulate cortex (PCC) and the hippocampus (HP). During the memory task the self-influence effective connectivites remained statistically significant across the DMN and there were statistically significant effective connectivites from the PCC, HP, amygdala (AM) and parahippocampal region to other DMN regions. We found that effective connectivities from PCC, HP and AM (in both resting state and during task) were linearly correlated to memory performance. The results suggest that superior memory ability in this older cohort was associated with effective connectity both at rest and during the memory task of three DMN regions which are also known to be important for memory fuction. Keywords: Effective connectivity modulation, ageing, emotional face processing, default mode network, fMRI.

With the prevalence of Alzheimer's disease (AD) predicted to increase substantially over the coming decades, the development of effective biomarkers for the early detection of the disease is paramount. In this short review, the main neuroimaging techniques which have shown potential as biomarkers for AD are introduced, with a focus on MRI. Structural MRI measures of the hippocampus and medial temporal lobe are still the most clinically validated biomarkers for AD, but newer techniques such as functional MRI and diffusion tensor imaging offer great scope in tracking changes in the brain, particularly in functional and structural connectivity, which may precede gray matter atrophy. These new advances in neuroimaging methods require further development and crucially, standardization; however, before they are used as biomarkers to aid in the diagnosis of AD.

Arousal and valence play key roles in emotional perception, with normal aging leading to changes in the neural substrates supporting valence processing. The objective of this study was to investigate normal age-related changes in the neural substrates of emotional arousal processing. Twenty-three young and 23 older, healthy women underwent functional magnetic resonance imaging as they viewed images which were neutral or positive in valence and which varied in arousal level from low to high. Using a parametric modulation approach, we examined how the blood oxygen-level dependent signal varied with single trial subjective ratings of valence and arousal, and whether this differed with age. In accordance with previous studies we found that the older group showed greater activation in response to positive valence, in the left amygdala, left middle temporal gyrus and right lingual gyrus. In contrast however, they showed reduced reactivity to emotional arousal, in occipital and temporal visual cortices bilaterally, the left inferior parietal cortex, and the supplementary motor area bilaterally. This study represents the first of its kind to clearly dissociate how aging affects the neural correlates of emotional arousal and valence. The changes in arousal processing may in part be mediated by the functional reorganization evident in the aging brain, such as reduced activation of the posterior cortices as described by the posterior-anterior shift in ageing (PASA) effect.

Animals can use both allocentric and egocentric strategies to learn a spatial task. Our results suggest that allocentric cues are more dominant than idiothetic cues in guiding navigation. Animals do not necessarily learn an egocentric strategy automatically, instead they probably hold just one solution to any particular task at a time until forced to learn an alternative strategy. Further, with overtraining animals do not always switch from allocentric to an egocentric learning strategy perhaps challenging suggestions of a stored hierarchy of strategies.

The influence of personality on the neural correlates of emotional processing is still not well characterized. We investigated the relationship between extraversion and neuroticism and emotional perception using functional magnetic resonance imaging (fMRI) in a group of 23 young, healthy women. Using a parametric modulation approach, we examined how the blood oxygenation level dependent (BOLD) signal varied with the participants’ ratings of arousal and valence, and whether levels of extraversion and neuroticism were related to these modulations. In particular, we wished to test Eysenck's biological theory of personality, which links high extraversion to lower levels of reticulothalamic–cortical arousal, and neuroticism to increased reactivity of the limbic system and stronger reactions to emotional arousal. Individuals high in neuroticism demonstrated reduced sustained activation in the orbitofrontal cortex (OFC) and attenuated valence processing in the right temporal lobe while viewing emotional images, but an increased BOLD response to emotional arousal in the right medial prefrontal cortex (mPFC). These results support Eysenck's theory, as well as our hypothesis that high levels of neuroticism are associated with attenuated reward processing. Extraversion was inversely related to arousal processing in the right cerebellum, but positively associated with arousal processing in the right insula, indicating that the relationship between extraversion and arousal is not as simple as that proposed by Eysenck.