Hadi Hosseini, Postdoctoral Faculty Sponsor
When functional blurring becomes deleterious: Reduced system segregation is associated with less white matter integrity and cognitive decline in aging.
Healthy aging is accompanied by progressive decline in cognitive performance and concomitant changes in brain structure and functional architecture. Age-accompanied alterations in brain function have been characterized on a network level as weaker functional connections within brain networks along with stronger interactions between networks. This phenomenon has been described as age-related differences in functional network segregation. It has been suggested that functional networks related to associative processes are particularly sensitive to age-related deterioration in segregation, possibly related to cognitive decline in aging. However, there have been only a few longitudinal studies with inconclusive results. Here, we used a large longitudinal sample of 284 participants between 25 to 80 years of age at baseline, with cognitive and neuroimaging data collected at up to three time points over a 10-year period. We investigated age-related changes in functional segregation among two large-scale systems comprising associative and sensorimotor-related resting-state networks. We found that functional segregation of associative systems declines in aging with exacerbated deterioration from the late fifties. Changes in associative segregation were positively associated with changes in global cognitive ability, suggesting that decreased segregation has negative consequences for domain-general cognitive functions. Age-related changes in system segregation were partly accounted for by changes in white matter integrity, but white matter integrity only weakly influenced the association between segregation and cognition. Together, these novel findings suggest a cascade where reduced white-matter integrity leads to less distinctive functional systems which in turn contributes to cognitive decline in aging.
View details for DOI 10.1016/j.neuroimage.2021.118449
View details for PubMedID 34358662
The effect of body posture on resting-state functional connectivity.
INTRODUCTION: An important but under-investigated confound of functional MRI (fMRI) is body posture. Although it is well-established that body position changes cerebral blood flow, the amount of cerebrospinal fluid in the brain, intracranial pressure, and even the firing rate of certain cell types, there is currently no study that directly examines its effect on fMRI measurements. Moreover, fMRI is typically done in a supine position, which often does not correspond to how these processes are performed in everyday settings.METHODS: In this study, 20 healthy adults underwent resting-state fMRI under three body positions: supine, right lateral decubitus (RLD), and left lateral decubitus (LLD). We first investigated whether there were differences in overall organization of whole-brain connectivity between conditions using graph theory. Second, we examined whether functional connectivity of two most studied default mode network (DMN) seeds to the rest of the brain was altered as a function of body position.RESULTS: Nonparametric statistical analyses revealed that global network measures differed among conditions, with the supine and LLD showing identical results compared to the RLD. There was decreased connectivity for DMN seeds in the RLD condition compared to the supine and LLD, but there were no significant differences between the latter two conditions.DISCUSSION: Potential mechanisms underlying these alterations include gravity, changes in physiology, and body anatomy. Our results suggest that, compared to supine and LLD, the RLD position leads to changes in whole-brain and DMN connectivity. Finally, depending on the research question, combining imaging modalities that allow for more naturalistic settings can provide a better understanding of certain phenomena.
View details for DOI 10.1089/brain.2021.0013
View details for PubMedID 34114506
Increased functional homotopy of the prefrontal cortex is associated with corpus callosum degeneration and working memory decline
NEUROBIOLOGY OF AGING
2020; 96: 68-78
Functional homotopy reflects the link between spontaneous activity in a voxel and its counterpart in the opposite hemisphere. Alterations in homotopic functional connectivity (FC) are seen in normal aging, with highest and lowest homotopy being present in sensory-motor and higher-order regions, respectively. Homotopic FC relates to underlying structural connections, but its neurobiological underpinnings remain unclear. The genu of the corpus callosum joins symmetrical parts of the prefrontal cortex (PFC) and is susceptible to age-related degeneration, suggesting that PFC homotopic connectivity is linked to changes in white-matter integrity. We investigated homotopic connectivity changes and whether these were associated with white-matter integrity in 338 individuals. In addition, we examined whether PFC homotopic FC was related to changes in the genu over 10 years and working memory over 5 years. There were increases and decreases in functional homotopy, with the former being prevalent in subcortical and frontal regions. Increased PFC homotopic FC was partially driven by structural degeneration and negatively associated with working memory, suggesting that it reflects detrimental age-related changes.
View details for DOI 10.1016/j.neurobiolaging.2020.08.008
View details for Web of Science ID 000596273000006
View details for PubMedID 32949903
Functional coherence of striatal resting-state networks is modulated by striatal iron content
2018; 183: 495-503
Resting-state spontaneous fluctuations have revealed individual differences in the functional architecture of brain networks. Previous research indicates that the striatal network shows alterations in neurological conditions but also in normal aging. However, the neurobiological mechanisms underlying individual differences in striatal resting-state networks (RSNs) have been less explored. One candidate that may account for individual differences in striatal spontaneous activity is the level of local iron accumulation. Excessive iron in the striatum has been linked to a loss of structural integrity and reduced brain activity during task performance in aging. Using independent component analysis in a sample of 42 younger and older adults, we examined whether higher striatal iron content, quantified using relaxometry, underlies individual differences in spontaneous fluctuations of RSNs in general, and of the striatum in particular. Higher striatal iron content was linked to lower spontaneous coherence within both caudate and putamen RSNs regardless of age. No such links were observed for other RSNs. Moreover, the number of connections between the putamen and other RSNs was negatively associated with iron content, suggesting that iron modulated the degree of cross-talk between the striatum and cerebral cortex. Importantly, these associations were primarily driven by the older group. Finally, a positive association was found between coherence in the putamen and motor performance, suggesting that this spontaneous activity is behaviorally meaningful. A follow-up mediation analysis also indicated that functional connectivity may mediate the link between striatal iron and motor performance. Our preliminary findings suggest that striatal iron potentially accounts for individual differences in spontaneous striatal fluctuations, and might be used as a locus of intervention.
View details for DOI 10.1016/j.neuroimage.2018.08.036
View details for Web of Science ID 000447750200043
View details for PubMedID 30125714
Neurocognitive Profiles of Older Adults with Working-Memory Dysfunction
2018; 28 (7): 2525-2539
Individuals differ in how they perceive, remember, and think. There is evidence for the existence of distinct subgroups that differ in cognitive performance within the older population. However, it is less clear how individual differences in cognition in old age are linked to differences in brain-based measures. We used latent-profile analysis on n-back working-memory (WM) performance to identify subgroups in a large sample of older adults (n = 181; age = 64-68 years). Our analysis identified one larger normal subgroup with higher performance (n = 113; 63%), and a second smaller subgroup (n = 55; 31%) with lower performance. The low-performing subgroup showed weaker load-dependent BOLD modulation and lower connectivity within the fronto-parietal network (FPN) as well as between FPN and striatum during n-back, along with lower FPN connectivity at rest. This group also exhibited lower FPN structural integrity, lower frontal dopamine D2 binding potential, inferior performance on offline WM tests, and a trend-level genetic predisposition for lower dopamine-system efficiency. By contrast, this group exhibited relatively intact episodic memory and associated brain measures (i.e., hippocampal volume, structural, and functional connectivity within the default-mode network). Collectively, these data provide converging evidence for the existence of a group of older adults with impaired WM functioning characterized by reduced cortico-striatal coupling and aberrant cortico-cortical integrity within FPN.
View details for DOI 10.1093/cercor/bhy062
View details for Web of Science ID 000437165800025
View details for PubMedID 29901790
View details for PubMedCentralID PMC5998950
Age-Related Differences in Dynamic Interactions Among Default Mode, Frontoparietal Control, and Dorsal Attention Networks during Resting-State and Interference Resolution
FRONTIERS IN AGING NEUROSCIENCE
2017; 9: 152
Resting-state fMRI (rs-fMRI) can identify large-scale brain networks, including the default mode (DMN), frontoparietal control (FPN) and dorsal attention (DAN) networks. Interactions among these networks are critical for supporting complex cognitive functions, yet the way in which they are modulated across states is not well understood. Moreover, it remains unclear whether these interactions are similarly affected in aging regardless of cognitive state. In this study, we investigated age-related differences in functional interactions among the DMN, FPN and DAN during rest and the Multi-Source Interference task (MSIT). Networks were identified using independent component analysis (ICA), and functional connectivity was measured during rest and task. We found that the FPN was more coupled with the DMN during rest and with the DAN during the MSIT. The degree of FPN-DMN connectivity was lower in older compared to younger adults, whereas no age-related differences were observed in FPN-DAN connectivity in either state. This suggests that dynamic interactions of the FPN are stable across cognitive states. The DMN and DAN were anti correlated and age-sensitive during the MSIT only, indicating variation in a task-dependent manner. Increased levels of anticorrelation from rest to task also predicted successful interference resolution. Additional analyses revealed that the degree of DMN-DAN anticorrelation during the MSIT was associated to resting cerebral blood flow (CBF) within the DMN. This suggests that reduced DMN neural activity during rest underlies an impaired ability to achieve higher levels of anticorrelation during a task. Taken together, our results suggest that only parts of age-related differences in connectivity are uncovered at rest and thus, should be studied in the functional connectome across multiple states for a more comprehensive picture.
View details for DOI 10.3389/fnagi.2017.00152
View details for Web of Science ID 000504246000001
View details for PubMedID 28588476
View details for PubMedCentralID PMC5438979