1,187 research outputs found

    A neuroimaging investigation of bipolar disorder and the neurocognitive effects of 5-HT7 antagonists

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    Bipolar disorder is a psychiatric disorder characterised by pathological mood states, but there is growing recognition of the role of cognitive impairment and dysfunction of emotional processes, which has a profound impact on quality of life. Many people with bipolar disorders exhibit brain volume impairment associated with cognitive dysfunction and an increased risk of dementia. In this thesis, I conducted a systematic review to understand the relationships between mood disorders and the 5-HT7 receptor. The 5-HT7 receptor is related to depression and anxiety, but the relationship between 5-HT7 and mania remains unclear; in addition, sleep and memory were also related to the 5-HT7 receptor. Followed by these findings, in the next two chapters, I examined the effects of 5-HT7 antagonists, using JNJ-18038683, on emotional and cognitive functioning, as well as their neural substrates. I then reported on neuroimaging investigations examining the effects of 5-HT7 antagonists on emotional processing and cognitive function in healthy volunteers to gain insight into their potential mode of action and utility for bipolar disorder. In fMRI analyses, the drug acted on 5-HT7 receptors potentially improving cognitive performance by modulating the function of the Cognitive Control Network in healthy controls. In the above-mentioned chapters, I gained a better understanding of the 5-HT7 antagonist, JNJ-18038683, and the putative promising effects for pharmacological treatments. However, the approach taken has some limitations, including a small sample size, potential participant bias, and a lack of systematic control of medication dose and duration of administration. In addition, in Chapter 5, I explored the brain basis of bipolar disorder and its links to cognitive and emotional dysfunction using a new ‘brain age’ approach. Individuals with bipolar disorder were found to have increased brain age compared to healthy controls. I hope that these findings can be applied to pharmacological treatment for individuals with bipolar disorder, ultimately allowing patients to benefit from the drug in the future

    Neuroimaging investigations of cortical specialisation for different types of semantic knowledge

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    Embodied theories proposed that semantic knowledge is grounded in motor and perceptual experiences. This leads to two questions: (1) whether the neural underpinnings of perception are also necessary for semantic cognition; (2) how do biases towards different sensorimotor experiences cause brain regions to specialise for particular types of semantic information. This thesis tackles these questions in a series of neuroimaging and behavioural investigations. Regarding question 1, strong embodiment theory holds that semantic representation is reenactment of corresponding experiences, and brain regions for perception are necessary for comprehending modality-specific concepts. However, the weak embodiment view argues that reenactment may not be necessary, and areas near to perceiving regions may be sufficient to support semantic representation. In the particular case of motion concepts, lateral occipital temporal cortex (LOTC) has been long identified as an important area, but the roles of its different subregions are still uncertain. Chapter 3 examined how different parts of LOTC reacted to written descriptions of motion and static events, using multiple analysis methods. A series of anterior to posterior sub-regions were analyzed through univariate, multivariate pattern analysis (MVPA), and psychophysical interaction (PPI) analyses. MVPA revealed strongest decoding effects for motion vs. static events in the posterior parts of LOTC, including both visual motion area (V5) and posterior middle temporal gyrus (pMTG). In contrast, only the middle portion of LOTC showed increased activation for motion sentences in univariate analyses. PPI analyses showed increased functional connectivity between posterior LOTC and the multiple demand network for motion events. These findings suggest that posterior LOTC, which overlapped with the motion perception V5 region, is selectively involved in comprehending motion events, while the anterior part of LOTC contributes to general semantic processing. Regarding question 2, the hub-and-spoke theory suggests that anterior temporal lobe (ATL) acts as a hub, using inputs from modality-specific regions to construct multimodal concepts. However, some researchers propose temporal parietal cortex (TPC) as an additional hub, specialised in processing and integrating interaction and contextual information (e.g., for actions and locations). These hypotheses are summarized as the "dual-hub theory" and different aspects of this theory were investigated in in Chapters 4 and 5. Chapter 4 focuses on taxonomic and thematic relations. Taxonomic relations (or categorical relations) occur when two concepts belong to the same category (e.g., ‘dog’ and ‘wolf’ are both canines). In contrast, thematic relations (or associative relations) refer to situations that two concepts co-occur in events or scenes (e.g., ‘dog’ and ‘bone’), focusing on the interaction or association between concepts. Some studies have indicated ATL specialization for taxonomic relations and TPC specialization for thematic relations, but others have reported inconsistent or even converse results. Thus Chapter 4 first conducted an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies contrasting taxonomic and thematic relations. This found that thematic relations reliably engage action and location processing regions (left pMTG and SMG), while taxonomic relations only showed consistent effects in the right occipital lobe. A primed semantic judgement task was then used to test the dual-hub theory’s prediction that taxonomic relations are heavily reliant on colour and shape knowledge, while thematic relations rely on action and location knowledge. This behavioural experiment revealed that action or location priming facilitated thematic relation processing, but colour and shape did not lead to priming effects for taxonomic relations. This indicates that thematic relations rely more on action and location knowledge, which may explain why the preferentially engage TPC, whereas taxonomic relations are not specifically linked to shape and colour features. This may explain why they did not preferentially engage left ATL. Chapter 5 concentrates on event and object concepts. Previous studies suggest ATL specialization for coding similarity of objects’ semantics, and angular gyrus (AG) specialization for sentence and event structure representation. In addition, in neuroimaging studies, event semantics are usually investigated using complex temporally extended stimuli, unlike than the single-concept stimuli used to investigate object semantics. Thus chapter 5 used representational similarity analysis (RSA), univariate analysis, and PPI analysis to explore neural activation patterns for event and object concepts presented as static images. Bilateral AGs encoded semantic similarity for event concepts, with the left AG also coding object similarity. Bilateral ATLs encoded semantic similarity for object concepts but also for events. Left ATL exhibited stronger coding for events than objects. PPI analysis revealed stronger connections between left ATL and right pMTG, and between right AG and bilateral inferior temporal gyrus (ITG) and middle occipital gyrus, for event concepts compared to object concepts. Consistent with the meta-analysis in chapter 4, the results in chapter 5 support the idea of partial specialization in AG for event semantics but do not support ATL specialization for object semantics. In fact, both the meta-analysis and chapter 5 findings suggest greater ATL involvement in coding objects' associations compared to their similarity. To conclude, the thesis provides support for the idea that perceptual brain regions are engaged in conceptual processing, in the case of motion concepts. It also provides evidence for a specialised role for TPC regions in processing thematic relations (pMTG) and event concepts (AG). There was mixed evidence for specialisation within the ATLs and this remains an important target for future research

    Impact of Head Injury on Cognitive Functioning and Social Cognition in UK-based Female Rugby Players

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    Introduction: Increasing attention is focused on the potential long-term impact of sports-related mild traumatic brain injuries (SRmTBI). Evidence suggests poorer cognitive and psychosocial outcomes in SRmTBI, including increased risk of developing certain neurodegenerative conditions. Research to date has focused on males neglecting female athletes, despite evidence suggesting sex-specific differences in frequency and recovery of SRmTBI. Aims: To explore the association between SRmTBI and cognitive functioning with a specific focus on social cognition in female rugby players. Method: A quantitative cross-sectional design was employed allowing for thirteen female rugby players with a history of SRmTBI to complete a neuropsychological battery of general cognitive functioning and social cognition. Results: Weaknesses relative to normative data, were found for domains of social cognition including theory of mind and cognitive empathy, despite typical scores on domains of general cognitive functioning relative to normative data. Group level analysis confirmed poorer performance for theory of mind and cognitive empathy measures in contrast to overall performance on domains of general cognitive functioning. Discussion: Findings from this preliminary study indicate that measures of social cognition should be incorporated into routine assessment and management of SRmTBI. Further research is needed to investigate the association between social cognition and SRmTBI

    Keep on track:Monitoring growth and development in children born preterm and full-term

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    Environmental factors in early life influence early development and growth, and influence long-term health. In this thesis we showed that in premature infants, the length and growth of the cerebral cortex (corpus callosum) is a good marker of brain growth and a predictor of later neurological development. An eye-tracking test (watching a video) at the age of 1 year also appeared to be a predictive factor for overall cognitive and motor development 1 year later. We also found that weight gain after preterm birth is associated with body composition in childhood. We also compared 2 methods of measuring body composition in children (DXA and ADP) and found that the results of fat mass (percentage) and fat-free mass at 3-5 years of age differ significantly between both methods, and that these differences are greater in very preterm children compared to full-term children. We present improvements to the algorithm to improve results with ADP. We also investigated sleep and found that parent-reported sleep characteristics and problems are similar between very preterm and full-term children at the age of 3 years. In the general population, we have shown that low birth weight (<2500 grams) and growth retardation during fetal life and childhood are associated with longer sleep duration and higher sleep efficiency at 10-15 years of age. Furthermore, at the same school age, greater intraday variability (fragmentation of the 24-hour activity rhythm) was associated with a higher fat mass index and higher visceral fat mass in boys

    Alzheimer’s And Parkinson’s Disease Classification Using Deep Learning Based On MRI: A Review

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    Neurodegenerative disorders present a current challenge for accurate diagnosis and for providing precise prognostic information. Alzheimer’s disease (AD) and Parkinson's disease (PD), may take several years to obtain a definitive diagnosis. Due to the increased aging population in developed countries, neurodegenerative diseases such as AD and PD have become more prevalent and thus new technologies and more accurate tests are needed to improve and accelerate the diagnostic procedure in the early stages of these diseases. Deep learning has shown significant promise in computer-assisted AD and PD diagnosis based on MRI with the widespread use of artificial intelligence in the medical domain. This article analyses and evaluates the effectiveness of existing Deep learning (DL)-based approaches to identify neurological illnesses using MRI data obtained using various modalities, including functional and structural MRI. Several current research issues are identified toward the conclusion, along with several potential future study directions

    Postmortem immunohistochemical diagnosis of diffuse axonal injury in cases of craniocerebral injury

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    Difuzna aksonska lezija (DAL) je veoma čest ali nedovoljno istražen tip kraniocerebralne traume, sa značajnim sudskome-dicinskim konsekvencama. Osnovni biomehanički princip njenog nastanka je akceleracijsko-deceleracijski mehanizam sa elemen-tima rotacije glave, što uzrokuje istezanje i smicanje pojedinih slojeva moždanog tkiva. Destrukcija aksonskog citoskeleta prekida aksoplazmatski transport i uzrokuje nakupljanje trans-portovanog materijala na mjestima aksonskih oštećenja. Odgovarajućim dijagnostičkim tehnikama (npr. imunohisto-hemijskim bojenjem na beta amiloid prekursor protein – βAPP) vizualizuje se kao nepravilna aksonska izvijuganost i zadebljanja oštećenih/prekinutih aksona. Najčešća distribucija ovih prom-jena je uz središnje cerebralne strukture: parasagitalna bijela masa cerebruma, kapsula interna, korpus kalozum, forniks, rostralni dijelovi moždanog stabla i dr. Ciljevi studije; Utvrditi prisustvo DAL-a u slučajevima nadživljavanja kraćeg od dva sata. Ispitati učestalost i topografsku distribuciju aksonske lezije, njenu povezanost s drugim vrstama tupe kraniocerebralne traume i udruženost sa traumatskim cerebralnim mikrokrvarenjima. Materijal i metode: Kao materijal za ovo prospektivno istraži-vanje poslužilo je moždano tkivo 36 smrtno stradalih osoba u akceleracijsko-deceleracijskim mehanizmima, podijljen u dvije grupe prema dužini nadživljavanja: 17 umrlih < 2 sata i 19 umrlih ≥ 2 sata. Uzimani su uzorci moždanog tkiva iz parasagi-talne bijele mase frontalnog režnja, genu i splenium korpus kalozuma, rostralnog dijela ponsa. Imunohistohemisjkim bojenjem registrovana je βAPP pozitivnost analiziranih isječaka i semikvantitativno procjenjena (skala po Gentleman-u) a za gradi-ranje težine DAL-a korištena je klasifikacija po Adamsu. Za testiranje razlika u raspodjeli atributivnih obilježja korišten je χ2 test a Kruskal-Wallis testom razlike u raspodjeli varijabli sa ordinalnom skalom mjerenja između nezavisnih varijabli. Za analizu povezanosti dva obilježja sa ordinalnom skalom posluži-la je Spirmanova neparametrijska korelacija. Rezultati: Akosnska lezija utvrđena je u 88,9% slučajeva ukupnog uzorka (82,3% u grupi nadživljavanja < 2 sata, 94,7% u grupi nadživljavanja ≥ 2 sata). Najkraće vrijeme nadživljavanja sa potvrđenom βAPP ekspresijom iznosilo je 20-25 minuta, u tri slučaja. Registrovana je prilično ravnomjerna zastupljenost aksonske lezije kroz posmatrane regije mozga uz pomjeranje incidence i jačine βAPP ekspresije ka zadnjim strukturama moždanog tkiva i najveća učestalost jako izražene imunopo-zitivnosti u ponsu. Spirmanov test neparametrijske korelacije potvrdio je značajnu povezanost između βAPP pozitivnosti u parasagitalnoj bijeloj masi frontalnog režnja i genu korpus kalozuma (ρ=0,395) i između splenium korpus kalozuma i ponsa (ρ=0,627). ustanovljena je povezanost ekspresije βAPP imunopo-zitivnosti u genu korpus kalozuma sa prisustvom petehijalnih krvarenja u bijeloj masi frontalnog režnja (p=0,023) te βAPP imunopozitivnosti u ponsu sa interhemisferično-paramezen-cefaličnom subarahnoidalnom hemoragijom (p=0,035). χ2 test potvrdio je povezanost traumatskih mikrokrvarenja u genu korpus kalozuma sa βAPP imunopozitivnošću u sve četiri posmatrane regije mozga, uz najizraženiju vezu upravo u genu korpus kalozuma (p=0,011). Kada se podaci grupišu (prisutna/nije prisutna aksonska lezija), χ2 test potvrdio je značajnu vezu između prisustva aksonske lezije i mikrokrvarenja u bijeloj masi frontalnog režnja (p=0,028), kao i genu korpus kalozuma (p=0,004). Nije potvrđena značajna razlika u težini aksonske lezije (po Adamsu) između grupa kao ni u βAPP ekspresivnosti po analiziranim lokalizaci-jama moždanog tkiva između grupa. Zaključci: Imunohistohemijsko bojenje na βAPP marker pokazalo se visoko efikasnim u dokazivanju traumatske aksonske lezije kod nadživljavanja kraćeg od 2 sata. Nema značajne razlike u distribu-ciji aksonske lezije kroz posmatrane središnje regije mozga, uz primjetnu jaču βAPP ekspresivnost u ponsu. Potvrđena je pozitivna korelacija između prisutva aksonske lezije u ponsu i interhemisferično-paramezencefalično lokalizovane subara-hnoidalne hemoragije. Nađena pozitivna korelacija između prisustva mikrohemoragija i βAPP pozitivnosti u genu korpus kalozuma u skladu je sa aktuelnim stavovima da postoji određena veza između traumatske cerebralne mikrohemoragije i aksonske lezije u mediosagitalnim regijama mozga.Introduction: Diffuse axonal lesion (DAL) is a very common but understudied type of craniocerebral trauma, with significant forensic consequences. The basic biomechanical principle of its origin is an acceleration-deceleration mechanism with elements of head rotation, which causes stretching and shearing of certain layers of brain tissue. Destruction of the axonal cytoskeleton interrupts axoplasmic transport and the accumulation of transported material at the sites of axonal damage. With appropriate diagnostic techniques (eg immunohistochemical staining for beta-amyloid precursor protein - ßAPP) it is visualized as irregular axonal tortuosity and thickening of damaged/broken axons. The most common distribution of these changes is along the central cerebral structures: parasagittal white mass of the cerebrum, internal capsule, corpus callosum, fornix, rostral parts of the brainstem, etc. Aims of the research: Determine the presence of DAL in cases of survival of less than two hours. To examine the frequency and topographical distribution of axonal lesions, its association with other types of blunt craniocerebral injury, and an association of DAL with traumatic cerebral microbleeds. Material and methods: The material for this prospective research was the brain tissue of 36 persons who died in acceleration-deceleration mechanisms, divided into two groups according to the length of survival: 17 died in a time period of less than 2 hours and 19 died in a time period of more than or equal to 2 hours. Brain tissue samples were taken from the parasagittal white matter of the frontal lobe, the genu and splenium of the corpus callosum, and the rostral part of the pons. Immunohistochemical staining registered ßAPP positivity of the analyzed sections and semiquantitatively assessed according to the Gentleman scale, while grading of the severity of DAL was done according to the Adams classification. The χ2 test was used to test differences in the distribution of attributive characteristics, and the Kruskal-Wallis test was used to test differences in the distribution of variables with an ordinal measurement scale between independent variables. The analysis of the association of two characteristics with an ordinal scale was performed using Spearman's non-parametric correlation. Results: The presence of an axonal lesion was determined in 88.9% of cases of the total sample (in the group of survival less than 2 hours in 82.3%, and in the group of survival more than or equal to 2 hours in 94.7% of cases). The shortest survival time with confirmed βAPP expression was 20 - 25 minutes, in three cases. A fairly even distribution of axonal lesions was registered throughout the observed brain regions with a shift in the incidence and intensity of βAPP immunoexpression towards the posterior structures of the brain tissue and the highest frequency of strong immunopositivity in the pons region. Spearman's non-parametric correlation test confirmed a statistically significant correlation between βAPP immunopositivity in the parasagittal white matter of the frontal lobe and the genu of the corpus callosum (ρ=0.395) and between the splenium of the corpus callosum and the pons (ρ=0.627). There was a correlation between the expression of βAPP immunopositivity in the anterior segment of the corpus callosum (genu) and the presence of petechial hemorrhages in the white matter of the cerebrum (p=0.023), and the expression of βAPP immunopositivity in the pons with interhemispheric-paramesencephalic subarachnoid hemorrhage (p=0.035). The χ2 test confirmed the association of traumatic microhemorrhages in the anterior part of the corpus callosum with βAPP immunopositivity in all four observed brain regions, with the most pronounced connection precisely in the corpus callosum genu (p=0.011). When data are grouped (axonal lesion present/absent), the χ2 test confirmed a significant association between the presence of an axonal lesion and microbleeds in the white matter of the frontal lobes (p=0.028), as well as the genu of the corpus callosum (p=0.004). No statistically significant difference was confirmed between the groups in the severity of the axonal lesion (according to Adams) nor in the βAPP expressivity by the analyzed brain tissue localizations. Conclusions: Immunohistochemical staining for the βAPP marker proved to be highly effective in proving the presence of traumatic axonal lesions in a survival period of less than two hours. There is no significant difference in the distribution of the axonal lesion through the observed central regions of the brain, with a noticeable stronger βAPP expressivity in the pons. A positive correlation was confirmed between the presence of an axonal lesion in the pons and interhemispheric-paramesencephalically localized subarachnoid hemorrhage. The positive correlation found between the presence of microhemorrhages and βAPP immunopositivity in the anterior aspects of the corpus callosum is consistent with the current views that there is most likely a certain connection between traumatic cerebral microhemorrhages and axonal lesions in the mediosagittal regions of the brain

    The cortical regions and white matter tracts underlying auditory comprehension in patients with primary brain tumor

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    The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi-modal neuroimaging analyses on a group of patients with low-grade gliomas to localize cortical regions and white matter tracts responsible for auditory language comprehension. Region-of-interests and voxel-level whole-brain analyses showed that cortical areas in the posterior temporal lobe are crucial for language comprehension. The fiber integrity assessed with diffusion tensor imaging of the arcuate fasciculus and the inferior longitudinal fasciculus was strongly correlated with both auditory comprehension and the grey matter volume of the inferior temporal and middle temporal gyri. Together, our findings provide direct evidence for an integrated network of auditory comprehension whereby the superior temporal gyrus and sulcus, the posterior parts of the middle and inferior temporal gyri serve as auditory comprehension cortex, and the arcuate fasciculus and the inferior longitudinal fasciculus subserve as crucial structural connectivity. These findings provide critical evidence on the neural underpinnings of language comprehension

    Morphometric reorganization induced by working memory training: perspective from vertex and network levels

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    Der sich beschleunigende globale Alterungsprozess und die Tatsache, dass sich die kog-nitiven Fähigkeiten mit dem Alter verschlechtern, was sich erheblich auf die Lebensquali-tät älterer Erwachsener auswirkt, insbesondere bei altersbedingten Störungen (z. B. kogni-tiver Beeinträchtigung, Demenz), weisen auf einen dringenden Bedarf an Ansätzen zum Schutz und zur Verbesserung der kognitiven Fähigkeiten sowie an Untersuchungen der neuronalen Substrate altersbedingter Veränderungen und der Neuroplastizität hin. Da man davon ausgeht, dass das Arbeitsgedächtnis (WM) die grundlegende Ursache für altersbe-dingte kognitive Beeinträchtigungen bei einer Vielzahl von kognitiven Fähigkeiten dar-stellt, ist das Arbeitsgedächtnistraining (WMT) zu einem aktuellen Thema und einem be-liebten Ansatz geworden. Frühere Studien haben gezeigt, dass das Arbeitsgedächtnistrai-ning (WMT) die kognitive Leistung verbessert. Die spezifischen Auswirkungen sowie die zugrunde liegenden neurobiologischen Mechanismen sind jedoch nach wie vor um-stritten. Ziel dieser Arbeit ist es, die durch das WMT induzierte neuronale strukturelle Plastizität auf mehreren Ebenen sowie die Verhaltenseffekte des WMT zu untersuchen. In der ers-ten Studie untersuchten wir die topographischen Veränderungen der Morphologie der grauen Substanz durch WMT, indem wir vier strukturelle Metriken (d.h. die kortikale Dicke, das kortikale Volumen, die kortikale Oberfläche und den lokalen Gyrifikationsin-dex, LGI) sowie die subkortikalen Volumina explorierten. Konkret wurden 59 gesunde Probanden mittleren Alters nach dem Zufallsprinzip entweder einem adaptiven WMT oder einer nicht-adaptiven Intervention zugewiesen. Alle Teilnehmer unterzogen sich vor und nach der 8-wöchigen WMT-Phase einer Neurobildgebung sowie kognitiven Tests. Vor und nach dem WMT wurden vier kortikale Metriken auf Scheitelpunktniveau und sieben subkortikale Volumina sowie die globale mittlere kortikale Dicke berechnet. Das wich-tigste Ergebnis war, dass die WMT-Gruppe im Vergleich zur aktiven Kontrollgruppe eine größere Zunahme der kortikalen Faltung in den bilateralen parietalen Regionen zeigte. Die Ergebnisse deuten darauf hin, dass strukturelle Veränderungen durch WMT in WM-bezogenen Regionen, insbesondere in parietalen Regionen, die Verarbeitung einer höhe-ren WM-Belastung erleichtern können. Darüber hinaus könnte die kortikale Faltung das relevanteste und plastischste Merkmal von WM und Lernen sein und WMT-Effekte stär-ker widerspiegeln als andere Metriken. Basierend auf den Ergebnissen der ersten Studie haben wir darüber hinaus untersucht, ob die trainingsinduzierten Effekte des WMT in der kortikalen Faltung auf Vertex-Ebene von topologischen Veränderungen begleitet werden. Zu diesem Zweck untersuchten wir in Studie zwei die durch WMT verursachte Plastizität auf Netzwerkebene mit Hilfe eines strukturellen Kovarianzansatzes (SC), der auf denselben Stichproben basiert. Es wurden gyrifikationsbasierte SC-Matrizen für jede Gruppe vor und nach dem Training sowie lon-gitudinale gyrifikationsbasierte SC-Matrizen erstellt. Innerhalb jeder Gruppe ergab die LGI-basierte SC-Analyse keine Hinweise auf WMT-induzierte Veränderungen der kor-tiko-kortikalen Verbindungen, weder in der WMT- noch in der aktiven Kontrollgruppe. Die Ergebnisse der longitudinalen SC-Analyse (unkorrigiert p < 0,005) zeigten, dass die trainingsinduzierten Veränderungen der kortikalen Faltungsintensität signifikante Unter-schiede zwischen Paaren von parietalen Regionen sowie Paaren von frontalen Regionen aufwiesen. Insgesamt deuten die kombinierten Ergebnisse dieser beiden Studien darauf hin, dass ers-tens WMT neuronale strukturelle Plastizität hervorrufen kann; zweitens die kortikale Fal-tung das relevanteste und plastischste Merkmal von WM und Lernen sein könnte, das die Auswirkungen von WMT besser widerspiegelt als andere Indikatoren auf Vertex-Ebene; und drittens die trainingsinduzierten lokalisierten Veränderungen der kortikalen Faltung von einem ähnlichen Muster vergleichbarer struktureller Veränderungen zwischen ROIs innerhalb der Regionen begleitet wurden. In Zukunft sind weitere Forschungen erforder-lich, um diese Ergebnisse zu wiederholen und zu validieren sowie um trainingsinduzierte topologische und topografische Veränderungen anhand einer breiteren Palette von Metri-ken und Eigenschaften zu untersuchen.The accelerating global aging process and the fact that cognitive abilities deteriorate with age, which has a significant impact on the quality of life of older adults, particularly those with age-related disorders (e.g., cognitive impairment, dementia), all point to an urgent need for approaches to protect and enhance cognitive abilities, as well as studies of the neural substrates of aging-related changes and neuroplasticity. Since working memory (WM) has been assumed to be the fundamental source of age-related cognitive impair-ments in a variety of cognitive abilities, working memory training (WMT) has become a hot topic as well as a popular approach. Previous studies have established that working memory training (WMT) improves cognitive performance. However, the specific effects, as well as the underlying neurobiological mechanisms, remain a matter of controversy. The purpose of this thesis is to investigate WMT-induced neural structural plasticity at multiple levels together with the behavioral effects of WMT. In study one, we investigated the topographic changes of grey matter morphology due to WMT by combining four structural metrics (i.e., cortical thickness (CT), cortical volume (CV), cortical surface area (CSA), and local gyrification index (LGI)) as well as subcortical volumes. Specifically, 59 healthy volunteers between the ages of 50 and 65 were randomly assigned to either an adaptive or a non-adaptive intervention. All participants underwent neuroimaging as well as cognitive testing before and after the 8-week intervention. Four cortical metrics at ver-tex level and seven subcortical volumes, as well as global mean cortical thickness, were calculated before and after the intervention. The most important finding was that the adap-tive WMT group showed greater increases in cortical folding in bilateral parietal regions in comparison to the active control group who performed the non-adaptive intervention. The results indicate that structural changes due to adaptive WMT in WM related regions, particularly parietal regions, may facilitate the processing of a higher WM load. In addi-tion, the cortical folding might be the most relevant and plastic feature of WM and learn-ing, reflecting WMT effects more than other metrics. Based on the findings of study one, we further asked whether the training-induced effects of WMT in cortical folding at vertex-level are accompanied by topological changes. To this end, study two investigated network-level plasticity due to WMT by using the struc-tural covariance (SC) approach based on the same samples. Gyrification based SC matri-ces for each group before and after training, together with longitudinal gyrification SC matrices, were constructed. Within each group, the LGI-based SC analysis revealed no evidence of WMT-induced changes in cortical-cortical connections, either in the WMT or the active control groups. The results of the longitudinal SC analysis (uncorrected p < 0.005) revealed that the training induced changes of cortical folding intensity showed sig-nificant difference between pairs of parietal regions as well as pairs of frontal regions. Overall, the combined findings of these two studies indicate that: firstly, WMT can pro-duce neural structural plasticity; secondly, cortical folding might be the most relevant and plastic feature of WM and learning, better reflecting the effects of WMT than other vertex-level indicators; and thirdly, the training induced localized changes in cortical folding were accompanied by the pattern of similar structural changes between ROIs within the regions. In the future, more research is required to replicate and validate these findings, as well as to investigate training-induced topological and topographic changes using a broader set of metrics and properties

    Biomarker presentation, amyloid status, and connectivity between the prefrontal cortex and hippocampus in studies of clinical Alzheimer’s disease/dementia

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    Through rigorous research over the past 100 years, great strides have been made in identifying the neuropathological basis of Alzheimer’s disease (AD), its’ prognosis, and the onset of cognitive symptoms. Proteins such as amyloid-beta (Aβ) plaques and tau are recognized as primary biomarkers that define AD and neuroimaging methods have been developed to measure these proteins in vivo allowing for changes to be monitored in life. These advances have led to the view that AD is a continuum rather than one inclusive state. However, there remains a great deal about AD that is still not understood. Such ambiguities range from an imprecise understanding of the neuropathological events that result in dementia to remaining uncertainty as to why some older adults exhibit symptoms of dementia whereas other retain sharp cognitive abilities in old age despite similar underlying pathology. In an effort to fill some of these gaps in our knowledge, the overarching goals of the work in this dissertation were to disambiguate some of these nuances by examining neurobiological features of AD in living older adults. Data for the first two studies was collected from older adults enrolled in the nationwide Alzheimer’s Disease Neuroimaging Initiative (ADNI) and data in the third study came from participants aged 50 years and older enrolled in a cohort study at the Boston University Alzheimer’s Disease Research Center (BU-ADRC). In the first study, our objective was to investigate links between brain structure, cognitive performance, and neuropathology in participants within the ADNI who identified as Black or African American (BoAA). Relatively little is known about dementia in this population so our goal was to assess if there would be an increase in AD biomarkers abnormalities between the three clinical syndrome groups: cognitively normal, mildly cognitively impaired (MCI), and dementia. Our findings supported this hypothesis as we found decreased cortical thickness in five of seven selected regions of interest (ROI), decreased hippocampal volume, increased white matter hyperintensities, worsened measures of cognition and function, decreased cerebrospinal fluid (CSF) measures of Aβ1-42 , and elevated measures of CSF tau between clinical syndrome groups. In the next study, we utilized a different subset of ADNI participants to examine how crossing the threshold in Aβ burden from being amyloid negative (A-) to amyloid positive (A+) as measured on positron emission tomography (PET) scans may relate to other neuropathological AD biomarkers and cognition. To make this assessment, we identified two groups of ADNI participants: one who converted in Aβ burden from A- to A+ as measured by amyloid retention on [18F]-labeled florbetapir PET and another who did not convert (e.g. remained A-) over the same follow-up period. We found increased prevalence of APOE ε4, greater annualized percent volume loss in selected brain regions, and lower CSF Aβ1-42 in the amyloid converter group compared to the non-converter group. Amyloid ligand binding on florbetapir PET was also significantly different between the two groups on PET scans taken at two timepoints. In the last study, we used diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) data from the BU-ADRC to assess the integrity of the cingulum bundle in participants cognitively ranging from normal to amnestic MCI to those with dementia. We found weakened integrity of the cingulum bundle in both dorsal and ventral circuits in participants with worsened cognitive function. Furthermore, we found relationships between diffusion metrics of the cingulum, volume of selected ROI, and measures of executive function and memory. The findings of this study show that age-related changes are likely present in a circuit that connects the prefrontal cortex to medial temporal regions of the brain and that weakening of structural connectivity is related to cognitive decline. This collection of studies reiterates the complicated nature of AD. Factors such as race, genetics, transitions in biomarker status and perhaps yet to be discovered forms of pathology, all have the potential to modify the clinical presentation of AD. The studies completed in this dissertation help to advance our knowledge but more work is needed to solidify our understanding of the basis of AD

    Hydrocephalus: A neuropsychological and theoretical primer.

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    Hydrocephalus is a common neurological condition, the hallmark feature of which is an excess in production, or accumulation, of cerebrospinal fluid in the ventricles. Although it is associated with diffuse damage to paraventricular brain areas, patients are broadly typified by a particular pattern of cognitive impairments that include deficits in working memory, attention, and spatial abilities. There have, however, been relatively few neuropsychological accounts of the condition. Moreover, theories of the relationship between aetiology and impairment appear to have emerged in isolation of each other, and proffer fundamentally different accounts. In this primer, we aim to provide a comprehensive and contemporary overview of hydrocephalus for the neuropsychologist, covering cognitive sequelae and theoretical interpretations of their origins. We review clinical and neuropsychological assays of cognitive profiles, along with the few studies that have addressed more integrative behaviours. In particular, we explore the distinction between congenital or early-onset hydrocephalus with a normal-pressure variant that can be acquired later in life. The relationship between these two populations is a singularly interesting one in neuropsychology since it can allow for the examination of typical and atypical developmental trajectories, and their interaction with chronic and acute impairment, within the same broad neurological condition. We reflect on the ramifications of this for our subject and suggest avenues for future research. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
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