Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

Age-Related Functional Recruitment for Famous Name Recognition: An Event-Related fMRI Study

Recent neuroimaging research shows that older adults exhibit recruitment, or increased activation on various cognitive tasks. The current study evaluated whether a similar pattern also occurs in semantic memory by evaluating age-related differences during recognition of Recent (since the 1990s) and Enduring (1950s to present) famous names. Fifteen healthy older and 15 healthy younger adults performed the name recognition task with a high and comparable degree of accuracy, although older adults had slower reaction time in response to Recent famous names. Event-related functional MRI showed extensive networks of activation in the two groups including posterior cingulate, right hippocampus, temporal lobe and left prefrontal regions. The Recent condition produced more extensive activation than the Enduring condition. Older adults had more extensive and greater magnitude of activation in 15 of 20 regions, particularly for the Recent condition (15 of 15; 7 of 15 also differed for Enduring); young adults did not show greater activation magnitude in any region. There were no group differences for non-famous names, indicating that age differences are task-specific. The results support and extend the existing literature to semantic memory tasks, indicating that older adult brains use functional recruitment to support task performance, even when task performance accuracy is high

Cerebral tissue pO2 response to stimulation is preserved with age in awake mice

Published in final edited form as: Neurosci Lett. 2019 April 23; 699: 160–166. doi:10.1016/j.neulet.2019.02.007.Compromised oxygen supply to cerebral tissue could be an important mechanism contributing to age-related cognition decline. We recently showed in awake mice that resting cerebral tissue pO2 decreases with age, a phenomenon that manifests mainly after middle-age. To extend these findings, here we aimed to study how tissue pO2 response to neuronal stimulation is affected by aging. We used two-photon phosphorescence lifetime microscopy to directly measure the brain tissue pO2 response to whisker stimulation in healthy awake young, middle-aged and old mice. We show that despite a decrease in baseline tissue pO2, the amplitude of the tissue pO2 response to stimulation is well preserved with age. However, the response dynamics are altered towards a slower response with reduced post-stimulus undershoot in older ages, possibly due to stiffer vessel wall among other factors. An estimation of the net oxygen consumption rate using a modified Krogh model suggests that the O2 overshoot during stimulation may be necessary to secure a higher capillary O2 delivery to the tissue proportional to increased CMRO2 to maintain the capillary tissue pO2. It was observed that the coupling between the CMRO2 and capillary O2 delivery is preserved with age.Accepted manuscrip

Reduced haemodynamic response in the ageing visual cortex measured by absolute fNIRS

The effect of healthy ageing on visual cortical activation is still to be fully explored. This study aimed to elucidate whether the haemodynamic response (HDR) of the visual cortex altered as a result of ageing. Visually normal (healthy) participants were presented with a simple visual stimulus (reversing checkerboard). Full optometric screening was implemented to identify two age groups: younger adults (n = 12, mean age 21) and older adults (n = 13, mean age 71). Frequency-domain Multi-distance (FD-MD) functional Near-Infrared Spectroscopy (fNIRS) was used to measure absolute changes in oxygenated [HbO] and deoxygenated [HbR] haemoglobin concentrations in the occipital cortices. Utilising a slow event-related design, subjects viewed a full field reversing checkerboard with contrast and check size manipulations (15 and 30 minutes of arc, 50% and 100% contrast). Both groups showed the characteristic response of increased [HbO] and decreased [HbR] during stimulus presentation. However, older adults produced a more varied HDR and often had comparable levels of [HbO] and [HbR] during both stimulus presentation and baseline resting state. Younger adults had significantly greater concentrations of both [HbO] and [HbR] in every investigation regardless of the type of stimulus displayed (p<0.05). The average variance associated with this age-related effect for [HbO] was 88% and [HbR] 91%. Passive viewing of a visual stimulus, without any cognitive input, showed a marked age-related decline in the cortical HDR. Moreover, regardless of stimulus parameters such as check size, the HDR was characterised by age. In concurrence with present neuroimaging literature, we conclude that the visual HDR decreases as healthy ageing proceeds

Comparability of Functional MRI Response in Young and Old During Inhibition

When using fMRI to study age-related cognitive changes, it is important to establish the integrity of the hemodynamic response because, potentially, it can be affected by age and disease. However, there have been few attempts to document such integrity and no attempts using higher cognitive rather than perceptual or motor tasks. We used fMRI with 28 healthy young and older adults on an inhibitory control task. Although older and young adults differed in task performance and activation patterns, they had comparable hemodynamic responses. We conclude that activation during cognitive inhibition, which was predominantly increased in elders, was not due to vascular confounds or specific changes in hemodynamic coupling

BOLD Neurovascular Coupling Does Not Change Significantly with Normal Aging

Studies of cognitive function that compare the blood oxygenation level dependent (BOLD) signal across age groups often require the assumption that neurovascular coupling does not change with age. Tests of this assumption have produced mixed results regarding the strength of the coupling and its relative time course. Using deconvolution, we found that age does not have a significant effect on the time course of the hemodynamic impulse response function or on the slope of the BOLD versus stimulus duration relationship. These results suggest that in cognitive studies of healthy aging, group differences in BOLD activation are likely due to age-related changes in cognitive-neural interactions and information processing rather than to impairments in neurovascular coupling

Early changes in alpha band power and DMN BOLD activity in Alzheimer's disease: a simultaneous resting state EEG-fMRI study

Simultaneous resting state functional magnetic resonance imaging (rsfMRI)-resting state electroencephalography (rsEEG) studies in healthy adults showed robust positive associations of signal power in the alpha band with BOLD signal in the thalamus, and more heterogeneous associations in cortical default mode network (DMN) regions. Negative associations were found in occipital regions. In Alzheimer's disease (AD), rsfMRI studies revealed a disruption of the DMN, while rsEEG studies consistently reported a reduced power within the alpha band. The present study is the first to employ simultaneous rsfMRI-rsEEG in an AD sample, investigating the association of alpha band power and BOLD signal, compared to healthy controls (HC). We hypothesized to find reduced positive associations in DMN regions and reduced negative associations in occipital regions in the AD group. Simultaneous resting state fMRI-EEG was recorded in 14 patients with mild AD and 14 HC, matched for age and gender. Power within the EEG alpha band (8-12 Hz, 8-10 Hz, and 10-12 Hz) was computed from occipital electrodes and served as regressor in voxel-wise linear regression analyses, to assess the association with the BOLD signal. Compared to HC, the AD group showed significantly decreased positive associations between BOLD signal and occipital alpha band power in clusters in the superior, middle and inferior frontal cortex, inferior temporal lobe and thalamus (p < 0.01, uncorr., cluster size ≥ 50 voxels). This group effect was more pronounced in the upper alpha sub-band, compared to the lower alpha sub-band. Notably, we observed a high inter-individual heterogeneity. Negative associations were only reduced in the lower alpha range in the hippocampus, putamen and cerebellum. The present study gives first insights into the relationship of resting-state EEG and fMRI characteristics in an AD sample. The results suggest that positive associations between alpha band power and BOLD signal in numerous regions, including DMN regions, are diminished in AD

Neural differentiation is moderated by age in scene- but not face-selective cortical regions

The aging brain is characterized by neural dedifferentiation, an apparent decrease in the functional selectivity of category-selective cortical regions. Age-related reductions in neural differentiation have been proposed to play a causal role in cognitive aging. Recent findings suggest, however, that age-related dedifferentiation is not equally evident for all stimulus categories and, additionally, that the relationship between neural differentiation and cognitive performance is not moderated by age. In light of these findings, in the present experiment, younger and older human adults (males and females) underwent fMRI as they studied words paired with images of scenes or faces before a subsequent memory task. Neural selectivity was measured in two scene-selective (parahippocampal place area (PPA) and retrosplenial cortex (RSC)] and two face-selective [fusiform face area (FFA) and occipital face area (OFA)] regions using both a univariate differentiation index and multivoxel pattern similarity analysis. Both methods provided highly convergent results, which revealed evidence of age-related reductions in neural dedifferentiation in scene-selective but not face-selective cortical regions. Additionally, neural differentiation in the PPA demonstrated a positive, age-invariant relationship with subsequent source memory performance (recall of the image category paired with each recognized test word). These findings extend prior findings suggesting that age-related neural dedifferentiation is not a ubiquitous phenomenon, and that the specificity of neural responses to scenes is predictive of subsequent memory performance independently of age

Caffeine-Induced Global Reductions in Resting-State BOLD Connectivity Reflect Widespread Decreases in MEG Connectivity.

In resting-state functional magnetic resonance imaging (fMRI), the temporal correlation between spontaneous fluctuations of the blood oxygenation level dependent (BOLD) signal from different brain regions is used to assess functional connectivity. However, because the BOLD signal is an indirect measure of neuronal activity, its complex hemodynamic nature can complicate the interpretation of differences in connectivity that are observed across conditions or subjects. For example, prior studies have shown that caffeine leads to widespread reductions in BOLD connectivity but were not able to determine if neural or vascular factors were primarily responsible for the observed decrease. In this study, we used source-localized magnetoencephalography (MEG) in conjunction with fMRI to further examine the origins of the caffeine-induced changes in BOLD connectivity. We observed widespread and significant (p &lt; 0.01) reductions in both MEG and fMRI connectivity measures, suggesting that decreases in the connectivity of resting-state neuro-electric power fluctuations were primarily responsible for the observed BOLD connectivity changes. The MEG connectivity decreases were most pronounced in the beta band. By demonstrating the similarity in MEG and fMRI based connectivity changes, these results provide evidence for the neural basis of resting-state fMRI networks and further support the potential of MEG as a tool to characterize resting-state connectivity

Age-differential relationships among dopamine D1 binding potential, fusiform BOLD signal, and face-recognition performance

Facial recognition ability declines in adult aging, but the neural basis for this decline remains unknown. Cortical areas involved in face recognition exhibit lower dopamine (DA) receptor availability and lower blood-oxygen-level-dependent (BOLD) signal during task performance with advancing adult age. We hypothesized that changes in the relationship between these two neural systems are related to age differences in face-recognition ability. To test this hypothesis, we leveraged positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to measure D1 receptor binding potential (BPND) and BOLD signal during facerecognition performance. Twenty younger and 20 older participants performed a face-recognition task during fMRI scanning. Face recognition accuracy was lower in older than in younger adults, as were D1 BPND and BOLD signal across the brain. Using linear regression, significant relationships between DA and BOLD were found in both age-groups in face-processing regions. Interestingly, although the relationship was positive in younger adults, it was negative in older adults (i.e., as D1 BPND decreased, BOLD signal increased). Ratios of BOLD:D1 BPND were calculated and relationships to face-recognition performance were tested. Multiple linear regression revealed a significant Group BOLD:D1 BPND Ratio interaction. These results suggest that, in the healthy system, synchrony between neurotransmitter (DA) and hemodynamic (BOLD) systems optimizes the level of BOLD activation evoked for a given DA input (i.e., the gain parameter of the DA input-neural activation function), facilitating task performance. In the aged system, however, desynchronization between these brain systems would reduce the gain parameter of this function, adversely impacting task performance and contributing to reduced face recognition in older adults