Semantic Memory for Food and Brain Correlates

Semantic memory stores knowledge about different types of objects: plants, animals, vehicles, utensils, conspecifics and food, among the others. Our ability to quickly recognize and categorize an object when we encounter it depends upon having experienced that object before and on semantic knowledge integrity. Semantic memory is one the most resilient cognitive abilities, it is less prone to interference than episodic memory and more declines slowly. The interest in how semantic memory is organized traces way back, however a great impulse was provided by the first systematic neuropsychological observations of patients with category specific recognition deficits. However, this debate is far from being resolved. In my dissertation, I will show how the study of food as a semantic category is extremely suitable to shed light on the organization of semantic knowledge. The thesis is organized as follow. In Chapter 1, I will first define semantic memory, focusing on its characteristics, such as its relationship with experience, its resilience to cognitive decline and its neural correlates, and on how it has been studied by neuropsychologists. In addition, I will review the studies on the food category, focusing on some intrinsic dimensions such as the level of transformation. Chapter 2 includes Study 1, in which I have investigated the organization of semantic memory by using food (natural and transformed) and non-food (living and on-living things) in a group of patients suffering from temporal lobe atrophy (Alzheimer\u2019s disease, PPA and FTD) and healthy controls, using Voxel Based Morphometry and DTI. Results have shown that food breaks down in natural and transformed, and that this parsing mirrors that of living and non-living things, thus strongly supporting the Sensory-functional model of semantic knowledge. Chapter 3 contains Study 2, in which I have explored the relationship between semantic memory and experience. I collected information about life-long eating habits as a proxy of long-term experience with specific foods as well as information about semantic memory of food in participants of different ages (36 \u2013 108 years old). Results support the hypothesis that semantic memory is modulated by experience. In Chapter 4, the focus of Study 3 is on episodic memory. Here I investigated whether the difference between semantic memory for natural and transformed food highlighted in Study 2 extends also to episodic memory, and whether the animacy effect - a facilitation to remember living exemplars - holds for food as well. Specifically, I administered a recognition memory task to the same participants of Study 2, to a group of young participants and to patients with Alzheimer\u2019s disease, PPA and FTD. I found that young adults had better recognition memory for transformed foods compared to natural foods. This difference disappeared in centenarians, consistently with Study 2, and in patients. The natural/transformed distinction appears susceptible to decay only in the presence of a high degree of episodic memory impairment. Finally, with Study 4, described in Chapter 5, my aim was more translational, that is, to test whether a deficit in semantic memory for food could lead to specific eating disorders. This study empirically establishes the behavioural and neural correlates of abnormal changes in eating habits in dementia and their relationship with semantic memory. In this thesis, I have shown that natural and transformed food do have different neural correlates, and that they are differently represented in semantic memory. By drawing together evidence from my studies and from studies of others I was allowed to propose a comprehensive model of semantic knowledge. Additionally, in my thesis I showed how food can be employed to study the organization of semantic knowledge, the way in which semantic knowledge is shaped by learning and experience, and its effect on behaviour

Functional MRI-specific alterations in frontoparietal network in mild cognitive impairment: an ALE meta-analysis

BackgroundMild cognitive impairment (MCI) depicts a transitory phase between healthy elderly and the onset of Alzheimer's disease (AD) with worsening cognitive impairment. Some functional MRI (fMRI) research indicated that the frontoparietal network (FPN) could be an essential part of the pathophysiological mechanism of MCI. However, damaged FPN regions were not consistently reported, especially their interactions with other brain networks. We assessed the fMRI-specific anomalies of the FPN in MCI by analyzing brain regions with functional alterations.MethodsPubMed, Embase, and Web of Science were searched to screen neuroimaging studies exploring brain function alterations in the FPN in MCI using fMRI-related indexes, including the amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity. We integrated distinctive coordinates by activating likelihood estimation, visualizing abnormal functional regions, and concluding functional alterations of the FPN.ResultsWe selected 29 studies and found specific changes in some brain regions of the FPN. These included the bilateral dorsolateral prefrontal cortex, insula, precuneus cortex, anterior cingulate cortex, inferior parietal lobule, middle temporal gyrus, superior frontal gyrus, and parahippocampal gyrus. Any abnormal alterations in these regions depicted interactions between the FPN and other networks.ConclusionThe study demonstrates specific fMRI neuroimaging alterations in brain regions of the FPN in MCI patients. This could provide a new perspective on identifying early-stage patients with targeted treatment programs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432042, identifier: CRD42023432042

Strategies and cognitive reserve to preserve lexical production in aging.

In the absence of any neuropsychiatric condition, older adults may show declining performance in several cognitive processes and among them, in retrieving and producing words, reflected in slower responses and even reduced accuracy compared to younger adults. To overcome this difficulty, healthy older adults implement compensatory strategies, which are the focus of this paper. We provide a review of mainstream findings on deficient mechanisms and possible neurocognitive strategies used by older adults to overcome the deleterious effects of age on lexical production. Moreover, we present findings on genetic and lifestyle factors that might either be protective or risk factors of cognitive impairment in advanced age. We propose that "aging-modulating factors" (AMF) can be modified, offering prevention opportunities against aging effects. Based on our review and this proposition, we introduce an integrative neurocognitive model of mechanisms and compensatory strategies for lexical production in older adults (entitled Lexical Access and Retrieval in Aging, LARA). The main hypothesis defended in LARA is that cognitive aging evolves heterogeneously and involves complementary domain-general and domain-specific mechanisms, with substantial inter-individual variability, reflected at behavioral, cognitive, and brain levels. Furthermore, we argue that the ability to compensate for the effect of cognitive aging depends on the amount of reserve specific to each individual which is, in turn, modulated by the AMF. Our conclusion is that a variety of mechanisms and compensatory strategies coexist in the same individual to oppose the effect of age. The role of reserve is pivotal for a successful coping with age-related changes and future research should continue to explore the modulating role of AMF

Social cognition in older adults: Associations with ageing, general cognition, and genetic, neuroimaging, and socioenvironmental factors

Social cognition refers to the range of skills and abilities that enable humans to detect and process information from one’s social environment, formulate a mental understanding of one’s social situation, and behave in socially appropriate ways. These include abilities such as theory of mind (ToM; also referred to as cognitive empathy), affective empathy, and social perception, as well as social behaviour. A growing body of research has sought to gain an understanding of how these phenomena manifest in the ageing process, as opposed to younger adults. The general aim of this thesis was to study the changes in social cognition with ageing, examine its relationship with other cognitive functions, and determine its association with genetic, neuroanatomical, and socioenvironmental factors. The first study explored the effect of polymorphisms of the oxytocin receptor gene on empathy using meta-analysis of existing studies including novel data from the Sydney Memory and Ageing Study (Sydney MAS). The second study developed a short-form version of the Reading the Mind in the Eyes Test (RMET), an assessment for theory of mind, via machine learning algorithms using Sydney MAS data. The third study explored social cognitive performance in Sydney MAS participants with subjective cognitive decline, mild cognitive impairment, and dementia. The fourth study identified key neuroimaging regions associated with empathy using volumetric analysis. The fifth study comprehensively indexed social cognition in nondemented community-dwelling older adults, and identified which subdomains were related to the ageing process and to other factors. This thesis found that normal ageing saw mild changes in ToM and social perception, and executive function somewhat compensated for this performance. Neurocognitive disorders were associated with far-reaching changes in these subdomains and some changes in social behavior. Empathy was related to volumes of the insula, supramarginal gyrus, and frontal lobe small vessel disease, and was not related to genetic sensitivity to oxytocin. A short-form version of the RMET was also developed. These findings improve on the understanding of social cognitive abilities in older adults, and facilitate the adoption of social cognition measures in clinical settings involving older adults

Induction of Hebbian associative plasticity through paired non-invasive brain stimulation of premotor-motor areas to elucidate the network's functional role

The ventral premotor cortex (PMv) is believed to play a pivotal role in a multitude of visuomotor behaviors, such as sensory-guided goal-directed visuomotor transformations, arbitrary visuomotor mapping, and hyper-learnt visuomotor associations underlying automatic imitative tendencies. All these functions are likely carried out through the copious projections connecting PMv to the primary motor cortex (M1). Yet, causal evidence investigating the functional relevance of the PMv-M1 network remains elusive and scarce. In the studies reported in this thesis we addressed this issue using a transcranial magnetic stimulation (TMS) protocol called cortico-cortical paired associative stimulation (ccPAS), which relies on multisite stimulation to induce Hebbian spike-timing dependent plasticity (STDP) by repeatedly stimulating the pathway connecting two target areas to manipulate their connectivity. Firstly, we show that ccPAS protocols informed by both short- and long-latency PMv-M1 interactions effectively modulate connectivity between the two nodes. Then, by pre-activating the network to apply ccPAS in a state-dependent manner, we were able to selectively target specific functional visuo-motor pathways, demonstrating the relevance of PMv-M1 connectivity to arbitrary visuomotor mapping. Subsequently, we addressed the PMv-to-M1 role in automatic imitation, and demonstrated that its connectivity manipulation has a corresponding impact on automatic imitative tendencies. Finally, by combining dual-coil TMS connectivity assessments and ccPAS in young and elderly individuals, we traced effective connectivity of premotor-motor networks and tested their plasticity and relevance to manual dexterity and force in healthy ageing. Our findings provide unprecedent causal evidence of the functional role of the PMv-to-M1 network in young and elderly individuals. The studies presented in this thesis suggest that ccPAS can effectively modulate the strength of connectivity between targeted areas, and coherently manipulate a networks’ behavioral output. Results open new research prospects into the causal role of cortico-cortical connectivity, and provide necessary information to the development of clinical interventions based on connectivity manipulation

Brain Rhythms and Working Memory in Healthy Ageing

Working memory (WM), the ability to maintain and manipulate information to guide immediate cognitive processing, is vulnerable to age-related decline. Compared with younger adults, older adults demonstrate smaller WM capacities, a decrease in the ability to manipulate items held in WM, and a greater susceptibility to interference from distracting information. However, the neural underpinnings of WM decline in normal ageing are unclear. One technique that can be used to investigate the neurophysiological processes underlying cognition is electroencephalography (EEG), which non-invasively records activity from the awake human brain. The research described in this thesis uses EEG to investigate the neurophysiology of WM in healthy younger and older adults, with a particular focus on neural oscillatory activity in the alpha frequency range (8-12 Hz). As such, Chapter 1 consists of a review of the literature relevant to use of EEG to investigate the neurophysiology of WM performance in younger and older adults. WM performance deficits in older adults are particularly salient under increasing WM loads. Alpha oscillations have been shown to support verbal WM performance under high loads in younger adults, so the aim of Chapter 2 was to investigate the load-dependent modulation of alpha oscillatory power and frequency in younger and older adults during verbal WM. No age differences in verbal WM performance were found, and alpha power and alpha peak frequency were modulated in a similar task- and load-dependent manner in both younger and older adults. Another factor influencing WM performance in older adults is a decline in selective attention. Older adults perform worse on and are less able to modulate alpha power than younger adults in tasks involving cues about ‘where’ or ‘when’ a memory set will appear. The study described in Chapter 3 investigated whether providing cues towards memory set presentation time led to enhanced selective attention before the onset of the memory set, as indexed by alpha oscillatory activity. Predictive cues led to improved WM performance in both age groups, but alpha power in preparation of the memory set did not influence task performance. In Chapter 3, there were no age differences in WM performance when manipulating memory set presentation time. However, processing speed may not only limit the speed at which items are encoded into WM, but also the speed at which stimuli are transformed into a stable memory representation (i.e., WM consolidation). Therefore, the study contained in Chapter 4 investigated age differences in the ability to consolidate items into visual WM. In this study, older adults demonstrated poorer WM performance and slower consolidation at low WM loads, providing evidence for altered visual WM consolidation with age. Finally, visual WM is severely limited in capacity, highlighting the importance of encoding task-relevant information while ignoring distractors. The modulation of alpha oscillatory power has been implicated in the inhibition of distractors during WM in younger adults, but it is unclear if alpha power modulation also supports distractor inhibition in older adults. The study described in Chapter 5 investigated age differences in alpha oscillatory power before the onset of distractors during the visual WM retention period. Although there were no age differences in WM performance, younger adults demonstrated functionally relevant increases in alpha power before distractors, while older adults showed decreases in alpha power. Therefore, younger and older adults likely use different neural strategies to inhibit distractors during WM performance. Taken together, the results of the studies contained in this thesis provide further evidence for age-related changes to neural oscillatory activity, particularly in the alpha frequency band, even when age differences in WM performance are not present. These findings may have important implications for providing novel targets for detecting or preventing age-related cognitive decline.Thesis (Ph.D.) -- University of Adelaide, School of Biomedicine, 202

The Attentional Boost Effect: What limits and what causes it? A behavioural and functional study in older adults, euthymic bipolar patients and healthy subjects

La tesi rigurda un fenomeno controintuitivo chiamato “Attentional Boost Effect” (“Effetto dell’aumento attentivo”). Questo effetto è caratterizzato dal fatto che la detezione di un target (che richiede una risposta) durante la codifica di uno stimolo ad esso contemporaneo può migliorare la prestazione mnestica per quello stimolo in fase di test, rispetto a stimoli presentati contemporaneamente ad un distrattore (che non richiede una risposta). L’ “Attentional Boost Effect” è stato indagato con differenti tipi di materiali, in differenti condizioni attentive, con differenti paradigmi e in varie popolazioni. La tesi inizia con un’introduzione teorica dove sono esaminati la maggior parte degli studi effettuati sull’ “Attentional Boost Effect”. Sono inoltre presentati due capitoli in cui vengono riassunti i cambiamenti, principalmente cognitivi, che avvengono durante l’invecchiamento normale e nel disturbo bipolare. Infine, viene discusso un breve capitolo speculativo sul possibile ruolo di alcuni neurotrasmettitori nella genesi del fenomeno oggetto di interesse. In questo lavoro di tesi si è voluto estendere le conoscenze sull’ “Attentional Boost Effect”, iniziando con l’indagarne la presenza in anziani sani e pazienti bipolari eutimici, entrambe popolazioni che riportano disturbi cognitivi, principalmente attentivi e mnesici, rispetto a giovani controlli. Sono stati eseguiti 4 esperimenti sugli anziani, cambiando il materiale usato nel compito di memoria, il tipo di istruzioni date ai partecipanti e il tempo di presentazione dello stimolo in fase di codifica. In tutti gli esperimenti, l’effetto è robusto e significativo nel campione di controllo di giovani adulti mentre è abolito nel campione di anziani sani. È stato inoltre eseguito un ulteriore esperimento reclutando pazienti bipolari in una fase di remissione, che non hanno mostrato l’effetto. Interessante, i risultati in quest’ultimo studio sembrano indicare che l’ampiezza dell’effetto tende a diminuire all’aumentare dell’età (oltre i 35 anni) nel campione di controlli sani. Infine, è stato eseguito un esperimento di risonanza magnetica funzionale, volendo indagare l’attivazione cerebrale correlata al fenomeno in un campione di giovani adulti. I risultati indicano che una rete attentiva ventrale sembra essere alla base dell’effetto. Nel complesso, i dati sono in linea con la presenza di un deficit delle funzioni attentive negli anziani sani e nei pazienti bipolari eutimici che sarebbe alla base dell’assenza dell’effetto boost in queste popolazioni. Altre possibili ipotesi di spiegazione sono discusse nel capitolo conclusivo

Assessing Cognitive Function in Chronic Sport-Related Head Impacts and Aging

Healthy normal aging and cumulative head trauma (concussion and subconcussion), can influence cognition independently and concomitantly leading to substantial late-life cognitive impairments (e.g., as seen in increased rates of dementia). With this as motivation, this dissertation explores three aspects of aging, head injury and cognition using the Cambridge Brain Sciences (CBS) cognitive battery (www.cambridgebrainsciences.com). Study 1 (Chapter 2): Concussion-specific testing combines assessments from multiple domains to evaluate a variety of functions. While clinically relevant, their succinct nature limits the amount of cognitive information available. Eighteen male football athletes were examined at baseline using the Sport Concussion Assessment Tool (SCAT) 3, and CBS battery. SCAT3 cognition test (Standardized Assessment of Concussion) scores significantly correlated with just the verbal cognitive domain assessed by CBS. This suggests a narrow scope which may miss other aspects of cognition that could be equally vulnerable in concussion. Study 2 (Chapter 3): It is likely that both subconcussive and concussive impacts contribute to the cognitive changes seen in retired athletes. What remains unclear is when these changes first appear and how they can be detected. This study compared 81 male football athletes (high cumulative impact burden) and matched controls (low cumulative impact burden) on cognitive test performance and response time. Results demonstrated response time deficits (slowed and more variable) without score impairments in football athletes in comparison to controls, which may represent pre-clinical compensatory mechanisms mitigating an increased cognitive demand. To address limitations in repeating Study 2 in contact sport retirees, Study 3 (Chapter 4) employed discriminant function analysis (DFA) to reduce the CBS battery for better application in aging populations. 118 younger and 118 older participants were included. Five of the 12 CBS tests were necessary to retain 98% of the variance accounted for between groups in the full model. Additionally, CBS tests were divided into 3 categories based on significant differences in the full and reduced models: no significant differences (n = 2), ii significant differences only on full model (n = 5), and significant differences on both models (n = 5). Results support the use of a modified CBS battery in age-related studies