Testing the domain-general nature of monitoring in the spatial and verbal cognitive domains

While it is well-established that monitoring the environment for the occurrence of relevant events represents a key executive function, it is still unclear whether such a function is mediated by domain-general or domain-specific mechanisms. We investigated this issue by combining event-related potentials (ERPs) with a behavioral paradigm in which monitoring processes (non-monitoring vs. monitoring) and cognitive domains (spatial vs. verbal) were orthogonally manipulated in the same group of participants. They had to categorize 3-dimensional visually presented words on the basis of either spatial or verbal rules. In monitoring blocks, they additionally had to check whether the word displayed a specific spatial configuration or whether it contained a certain consonant. The behavioral results showed slower responses for both spatial and verbal monitoring trials compared to non-monitoring trials. The ERP results revealed that monitoring did not interact with domain, thus suggesting the involvement of common underlying mechanisms. Specifically, monitoring acted on lower-level perceptual processes (as expressed by an enhanced visual N1 wave and a sustained posterior negativity for monitoring trials) and on higher-level cognitive processes (involving larger positive modulations by monitoring trials over frontal and parietal scalp regions). The source reconstruction analysis of the ERP data confirmed that monitoring was associated with increased activity in visual areas and in right prefrontal and parietal regions (i.e., superior and inferior frontal gyri and posterior parietal cortex), which previous studies have linked to spatial and temporal monitoring. Our findings extend this research by supporting the domain-general nature of monitoring in the spatial and verbal domains

The neural bases of event monitoring across domains: a simultaneous ERP-fMRI study.

The ability to check and evaluate the environment over time with the aim to detect the occurrence of target stimuli is supported by sustained/tonic as well as transient/phasic control processes, which overall might be referred to as event monitoring. The neural underpinning of sustained control processes involves a fronto-parietal network. However, it has not been well-defined yet whether this cortical circuit acts irrespective of the specific material to be monitored and whether this mediates sustained as well as transient monitoring processes. In the current study, the functional activity of brain during an event monitoring task was investigated and compared between two cognitive domains, whose processing is mediated by differently lateralized areas. Namely, participants were asked to monitor sequences of either faces (supported by right-hemisphere regions) or tools (left-hemisphere). In order to disentangle sustained from transient components of monitoring, a simultaneous EEG-fMRI technique was adopted within a block design. When contrasting monitoring versus control blocks, the conventional fMRI analysis revealed the sustained involvement of bilateral fronto-parietal regions, in both task domains. Event-related potentials (ERPs) showed a more positive amplitude over frontal sites in monitoring compared to control blocks, providing evidence of a transient monitoring component. The joint ERP-fMRI analysis showed that, in the case of face monitoring, these transient processes rely on right-lateralized areas, including the inferior parietal lobule and the middle frontal gyrus. In the case of tools, no fronto-parietal areas correlated with the transient ERP activity, suggesting that in this domain phasic monitoring processes were masked by tonic ones. Overall, the present findings highlight the role of bilateral fronto-parietal regions in sustained monitoring, independently of the specific task requirements, and suggest that right-lateralized areas subtend transient monitoring processes, at least in some task contexts

Interregional synchrony of visuomotor tracking: perturbation effects and individual differences

The present study evaluated the neural and behavioural correlates associated with a visuomotor tracking task during which a sensory perturbation was introduced that created a directional bias between moving hand and cursor position. The results revealed that trajectory error increased as a result of the perturbation in conjunction with a dynamic neural reorganization of cluster patterns that reflected distinct processing. In particular, a negatively activated cluster, characterizing the degraded information processing due to the perturbation, involved both hemispheres as well as midline area. Conversely, a positively activated cluster, indicative of compensatory processing was strongly confined to the left (dominant) hemisphere. In addition, a brain-behavioural association of good vs. poor performing participants enabled to localize a neural circuit within the left hemisphere and midline area that linked with successful performance. Overall, these data reinforce the functional significance of interregional synchrony in defining response output and behavioural success

A 4-Year Longitudinal Neuroimaging Study of Cognitive Control Using Latent Growth Modeling: Developmental Changes and Brain-Behavior Associations

Despite theoretical models suggesting developmental changes in neural substrates of cognitive control in adolescence, empirical research has rarely examined intraindividual changes in cognitive control-related brain activation using multi-wave multivariate longitudinal data. We used longitudinal repeated measures of brain activation and behavioral performance during the multi-source interference task (MSIT) from 167 adolescents (53% male) who were assessed annually over four years from ages 13 to 17 years. We applied latent growth modeling to delineate the pattern of brain activation changes over time and to examine longitudinal associations between brain activation and behavioral performance. We identified brain regions that showed differential change patterns: (1) the fronto-parietal regions that involved bilateral insula, bilateral middle frontal gyrus, left pre-supplementary motor area, left inferior parietal lobule, and right precuneus; and (2) the rostral anterior cingulate cortex (rACC) region. Longitudinal confirmatory factor analyses of the fronto-parietal regions revealed strong measurement invariance across time implying that multivariate functional magnetic resonance imaging data during cognitive control can be measured reliably over time. Latent basis growth models indicated that fronto-parietal activation decreased over time, whereas rACC activation increased over time. In addition, behavioral performance data, age-related improvement was indicated by a decreasing trajectory of intraindividual variability in response time across four years. Testing longitudinal brain-behavior associations using multivariate growth models revealed that better behavioral cognitive control was associated with lower fronto-parietal activation, but the change in behavioral performance was not related to the change in brain activation. The current findings suggest that reduced effects of cognitive interference indicated by fronto-parietal recruitment may be a marker of a maturing brain that underlies better cognitive control performance during adolescence

Resting state connectivity between medial temporal lobe regions and intrinsic cortical networks predicts performance in a path integration task

Humans differ in their individual navigational performance, in part because successful navigation relies on several diverse abilities. One such navigational capability is path integration, the updating of position and orientation during movement, typically in a sparse, landmark-free environment. This study examined the relationship between path integration abilities and functional connectivity to several canonical intrinsic brain networks. Intrinsic networks within the brain reflect past inputs and communication as well as structural architecture. Individual differences in intrinsic connectivity have been observed for common networks, suggesting that these networks can inform our understanding of individual spatial abilities. Here, we examined individual differences in intrinsic connectivity using resting state magnetic resonance imaging (rsMRI). We tested path integration ability using a loop closure task, in which participants viewed a single video of movement in a circle trajectory in a sparse environment, and then indicated whether the video ended in the same location in which it started. To examine intrinsic brain networks, participants underwent a resting state scan. We found that better performance in the loop task was associated with increased connectivity during rest between the central executive network (CEN) and posterior hippocampus, parahippocampal cortex (PHC) and entorhinal cortex. We also found that connectivity between PHC and the default mode network (DMN) during rest was associated with better loop closure performance. The results indicate that interactions between medial temporal lobe (MTL) regions and intrinsic networks that involve prefrontal cortex (PFC) are important for path integration and navigation.This work was supported by the Office of Naval Research (ONR MURI N00014-10-1-0936 and MURI N00014-16-1-2832). fMRI scanning was completed at the Athinoula A. Martinos Center for Biomedical Imaging (Charlestown, MA, USA), which receives support from the National Center for Research Resources (NCRR P41RR14075). (ONR MURI N00014-10-1-0936 - Office of Naval Research; MURI N00014-16-1-2832 - Office of Naval Research; NCRR P41RR14075 - National Center for Research Resources)Published versio

Memory precision across space and time in Alzheimer's disease

This thesis aimed to deepen current understanding of the mechanisms underlying visual short-term memory (VSTM) impairments in Alzheimer’s Disease (AD). The mixture model of working memory (WM) was deployed to dissect the differential contributions of distinct VSTM processes: ability to detect a target, swapping an item with another item in memory (misbinding), random guessing and precision of item representation (memory precision). Proficiency in filtering an unwanted item out (filtering ability), whether presented simultaneously with the to-be-remembered stimuli (encoding) or during the retention phase (maintenance) was also studied. In addition, measures of overall task performance, spatial localisation errors and reaction times were analysed. Chapter 2 showed that healthy ageing was associated with a decline in VSTM memory precision, while in AD patients higher guessing and lower target detection were the main sources of memory errors. AD patients were also particularly affected when a distractor was presented during maintenance (filtering at maintenance), but not at encoding. As a comparator, patients with Parkinson’s Disease (PD) showed higher guessing rates, but preserved filtering abilities. In Chapter 3 the “What was where” Oxford Memory Task (OMT), was used to assess VSTM performance in people at risk of developing AD dementia, i.e., patients with subjective cognitive impairment (SCI) and mild cognitive impairment (MCI), compared to patients with established AD dementia. Apart from reaction time measures, most metrics derived from the OMT task were able to discriminate between healthy controls and patients with MCI, and between MCI and AD dementia. Mixture model metrics and spatial localization error also differed significantly between people with SCI and MCI. All metrics were correlated with hippocampal atrophy. Chapter 4 showed that OMT metrics clustered into four specific spatial patterns of atrophy in the grey matter across a cohort of healthy controls and AD patients, with the Precuneus being associated only with metrics that carried spatial information. In Chapter 5 a key white matter region encompassing three tracts (Optic radiation, Forceps Major and Middle Longitudinal Fasciculus) was identified to be associated with VSTM performance on OMT in the left hemisphere in AD patients, but in the right hemisphere in healthy controls. Finally, In Chapter 6 OMT metrics and several other cognitive measures derived from an online battery testing VSTM, executive functions, processing speed, long-term memory and visuospatial abilities, were related to plasma biomarkers of AD; phospotau (pTau)181, Glial fibrillary acidic protein (GFAP), Neurofilament Light Chain (NfL), and amyloid β 42/40 ratio (Aβ42/40 ratio). The results showed that of these biomarkers, pTau181 was most closely correlated to cognitive performance. However, cognitive measures and plasma biomarkers had different degrees of test-retest reliability, with pTau181 showing the highest degree of variability among plasma biomarkers in this sample