Kelly S. Giovanello

Evidence on the emergence of the brain's default network from 2-week-old to 2-year-old healthy pediatric subjects

Several lines of evidence have implicated the existence of the brains default network during passive or undirected mental states. Nevertheless, results on the emergence of the default network in very young pediatric subjects are lacking. Using resting functional magnetic resonance imaging in healthy pediatric subjects between 2 weeks and 2 years of age, we describe the temporal evolution of the default network in a critical, previously unstudied, period of early human brain development. Our results demonstrate that a primitive and incomplete default network is present in 2-week-olds, followed by a marked increase in the number of brain regions exhibiting connectivity, and the percent of connection at 1 year of age. By 2 years of age, the default network becomes similar to that observed in adults, including medial prefrontal cortex (MPFC), posterior cingulate cortex/retrosplenial (PCC/Rsp), inferior parietal lobule, lateral temporal cortex, and hippocampus regions. While the anatomical representations of the default network highly depend on age, the PCC/Rsp is consistently observed at in both age groups and is central to the most and strongest connections of the default network, suggesting that PCC/Rsp may serve as the main “hub” of the default network as this region does in adults. In addition, although not as remarkable as the PCC/Rsp, the MPFC also emerges as a potential secondary hub starting from 1 year of age. These findings reveal the temporal development of the default network in the critical period of early brain development and offer new insights into the emergence of brain default network.

Temporal and spatial evolution of brain network topology during the first two years of life.

The mature brain features high wiring efficiency for information transfer. However, the emerging process of such an efficient topology remains elusive. With resting state functional MRI and a large cohort of normal pediatric subjects (n = 147) imaged during a critical time period of brain development, 3 wk- to 2 yr-old, the temporal and spatial evolution of brain network topology is revealed. The brain possesses the small world topology immediately after birth, followed by a remarkable improvement in whole brain wiring efficiency in 1 yr olds and becomes more stable in 2 yr olds. Regional developments of brain wiring efficiency and the evolution of functional hubs suggest differential development trend for primary and higher order cognitive functions during the first two years of life. Simulations of random errors and targeted attacks reveal an age-dependent improvement of resilience. The lower resilience to targeted attack observed in 3 wk old group is likely due to the fact that there are fewer well-established long-distance functional connections at this age whose elimination might have more profound implications in the overall efficiency of information transfer. Overall, our results offer new insights into the temporal and spatial evolution of brain topology during early brain development.

Disproportionate deficit in associative recognition relative to item recognition in global amnesia.

In two experiments, we tested the hypothesis that medial temporal lobe (MTL) amnesic patients and, likewise, diencephalic (DNC) amnesic patients evidence a disproportionate deficit in memory for associations in comparison with memory for single items. In Experiment 1, we equated item recognition in amnesic and control participants and found that, under these conditions, associative recognition remained impaired both for MTL patients and for DNC patients. To rule out an alternative interpretation of the results of Experiment 1, in Experiment 2 we compared the performance of amnesic and control participants on a one-item recognition task and a two-item recognition task that required no memory for the association between members of word pairs. In the MTL group, when single-item recognition was equated to that of the controls, two-item nonassociative pair memory was equivalent as well. In the DNC group, nonassociative pair memory was impaired, but this impairment did not fully account for the impairment in associative memory. These findings indicate that memory for novel associations between items is disproportionately impaired in comparison with memory for single items in amnesia.

The contribution of familiarity to associative memory in amnesia

In Experiment 1, using the remember/know paradigm with control participants, we compared the contribution of recollection and familiarity to associative recognition for compound stimuli and for unrelated word pairs. It was demonstrated that familiarity makes a greater contribution to associative recognition of compound stimuli than to associative recognition of unrelated word pairs. In Experiment 2, we examined associative recognition memory in medial temporal lobe amnesics, diencephalic amnesics, and control participants for the stimuli employed in Experiment 1. Whereas associative recognition for compounds and unrelated words was nearly identical in control participants, associative recognition was higher for compounds than for unrelated word pairs in amnesic patients. This pattern was observed in the medial temporal amnesic group as well as in the diencephalic amnesic group. These results suggest that associative recognition in amnesia is enhanced to the extent that performance can be supported by study-induced familiarity for the studied pair.

Distinct hippocampal regions make unique contributions to relational memory.

Neuroscientific research has shown that the hippocampus is important for binding or linking together the various components of a learning event into an integrated memory. In a prior study, we demonstrated that the anterior hippocampus is involved in memory for the relations among informational elements to a greater extent that it is involved in memory for individual elements (Giovanello et al., 2004. Hippocampus 14:5–8). In the current study, we extend those findings by further specifying the role of anterior hippocampus during relational memory retrieval. Specifically, anterior hippocampal activity was observed during flexible retrieval of learned associations, whereas posterior hippocampal activity was detected during reinstatement of study episodes. These findings suggest a functional dissociation across the long axis of human hippocampus based on the nature of the mnemonic process rather than the stage of memory processing or type of stimulus.

Differential neural activity during search of specific and general autobiographical memories elicited by musical cues

Previous neuroimaging studies that have examined autobiographical memory specificity have utilized retrieval cues associated with prior searches of the event, potentially changing the retrieval processes being investigated. In the current study, musical cues were used to naturally elicit memories from multiple levels of specificity (i.e., lifetime period, general event, and event-specific). Sixteen young adults participated in a neuroimaging study in which they retrieved autobiographical memories associated with musical cues. These musical cues led to the retrieval of highly emotional memories that had low levels of prior retrieval. Retrieval of all autobiographical memory levels was associated with activity in regions in the autobiographical memory network, specifically the ventromedial prefrontal cortex, posterior cingulate, and right medial temporal lobe. Owing to the use of music, memories from varying levels of specificity were retrieved, allowing for comparison of event memory and abstract personal knowledge, as well as comparison of specific and general event memory. Dorsolateral and dorsomedial prefrontal regions were engaged during event retrieval relative to personal knowledge retrieval, and retrieval of specific event memories was associated with increased activity in the bilateral medial temporal lobe and dorsomedial prefrontal cortex relative to retrieval of general event memories. These results suggest that the initial search processes for memories of different specificity levels preferentially engage different components of the autobiographical memory network. The potential underlying causes of these neural differences are discussed.

Remembering what could have happened: Neural correlates of episodic counterfactual thinking

Recent evidence suggests that our capacities to remember the past and to imagine what might happen in the future largely depend on the same core brain network that includes the middle temporal lobe, the posterior cingulate/retrosplenial cortex, the inferior parietal lobe, the medial prefrontal cortex, and the lateral temporal cortex. However, the extent to which regions of this core brain network are also responsible for our capacity to think about what could have happened in our past, yet did not occur (i.e., episodic counterfactual thinking), is still unknown. The present study examined this issue. Using a variation of the experimental recombination paradigm (Addis, Pan, Vu, Laiser, & Schacter, 2009. Neuropsychologia. 47: 2222-2238), participants were asked both to remember personal past events and to envision alternative outcomes to such events while undergoing functional magnetic resonance imaging. Three sets of analyses were performed on the imaging data in order to investigate two related issues. First, a mean-centered spatiotemporal partial least square (PLS) analysis identified a pattern of brain activity across regions of the core network that was common to episodic memory and episodic counterfactual thinking. Second, a non-rotated PLS analysis identified two different patterns of brain activity for likely and unlikely episodic counterfactual thoughts, with the former showing significant overlap with the set of regions engaged during episodic recollection. Finally, a parametric modulation was conducted to explore the differential engagement of brain regions during counterfactual thinking, revealing that areas such as the parahippocampal gyrus and the right hippocampus were modulated by the subjective likelihood of counterfactual simulations. These results suggest that episodic counterfactual thinking engages regions that form the core brain network, and also that the subjective likelihood of our counterfactual thoughts modulates the engagement of different areas within this set of regions.

Reduced specificity of hippocampal and posterior ventrolateral prefrontal activity during relational retrieval in normal aging

Neuroimaging studies of episodic memory in young adults demonstrate greater functional neural activity in ventrolateral pFC and hippocampus during retrieval of relational information as compared with item information. We tested the hypothesis that healthy older adults—individuals who exhibit behavioral declines in relational memory—would show reduced specificity of ventrolateral prefrontal and hippocampal regions during relational retrieval. At study, participants viewed two nouns and were instructed to covertly generate a sentence that related the words. At retrieval, fMRIs were acquired during item and relational memory tasks. In the relational task, participants indicated whether the two words were previously seen together. In the item task, participants indicated whether both items of a pair were previously seen. In young adults, left posterior ventrolateral pFC and bilateral hippocampal activity was modulated by the extent to which the retrieval task elicited relational processing. In older adults, activity in these regions was equivalent for item and relational memory conditions, suggesting a reduction in ventrolateral pFC and hippocampal specificity with normal aging.

Age-related neural changes during memory conjunction errors

Human behavioral studies demonstrate that healthy aging is often accompanied by increases in memory distortions or errors. Here we used event-related fMRI to examine the neural basis of age-related memory distortions. We used the memory conjunction error paradigm, a laboratory procedure known to elicit high levels of memory errors. For older adults, right parahippocampal gyrus showed significantly greater activity during false than during accurate retrieval. We observed no regions in which activity was greater during false than during accurate retrieval for young adults. Young adults, however, showed significantly greater activity than old adults during accurate retrieval in right hippocampus. By contrast, older adults demonstrated greater activity than young adults during accurate retrieval in right inferior and middle prefrontal cortex. These data are consistent with the notion that age-related memory conjunction errors arise from dysfunction of hippocampal system mechanisms, rather than impairments in frontally mediated monitoring processes.

Sex differences in grey matter atrophy patterns among AD and aMCI patients: Results from ADNI

We used longitudinal magnetic resonance imaging (MRI) data to determine whether there are any gender differences in grey matter atrophy patterns over time in 197 individuals with probable Alzheimers disease (AD) and 266 with amnestic mild cognitive impairment (aMCI), compared with 224 healthy controls participating in the Alzheimers Disease Neuroimaging Initiative (ADNI). While previous research has differentiated probable AD and aMCI groups from controls in brain atrophy, it is unclear whether and how sex plays a role in patterns of change over time. Using regional volumetric maps, we fit longitudinal models to the grey matter data collected at repeated occasions, seeking differences in patterns of volume change over time by sex and diagnostic group in a voxel-wise analysis. Additionally, using a region-of-interest approach, we fit longitudinal models to the global volumetric data of predetermined brain regions to determine whether this more conventional approach is sufficient for determining sex and group differences in atrophy. Our longitudinal analyses revealed that, of the various grey matter regions investigated, males and females in the AD group and the aMCI group showed different patterns of decline over time compared to controls in the bilateral precuneus, bilateral caudate nucleus, right entorhinal gyrus, bilateral thalamus, bilateral middle temporal gyrus, left insula, and right amygdala. As one of the first investigation to model more than two time points of structural MRI data over time, our findings add insight into how AD and aMCI males and females differ from controls and from each other over time.