BACKGROUND: Sleep deprivation is one of the first symptoms to manifest in schizophrenia patients. An important proponent for both sleep and cognition, sleep spindles have been investigated to understand the connection between sleep and schizophrenia. This thesis aims to conduct a meta-analysis on this topic to conglomerate previous research and come to a definitive conclusion on how sleep and schizophrenia interact. Multiple studies have reported associations between sleep, schizophrenia, and the thalamus. Novel methods have allowed researchers to segment the thalamus into 25 different nuclei. Therefore, this thesis will also attempt to validate these findings and use new segmentation software to investigate which specific nuclei affect schizophrenia. This thesis also extends this thalamic investigation to explore white matter tracts related to the thalamus. Using both arms of this study, we aim to further understand the complex relationship between brain structure, sleep, and schizophrenia. METHODS: The meta-analysis portion of this thesis pooled fifteen studies for a total of 321 patients and 323 healthy controls. The patient population was made up of first-episode psychosis (FEP), family high-risk (FHR), and schizophrenia (SZ) populations. R Studio was utilized to run a meta-analysis on sleep spindle density (SSD) values pulled from each study. This dataset was also used for meta-regressions and funnel plots. The imaging aspect of this thesis pulled subjects from two separate Boston studies for a total of 54 early course patients (EC) and 27 healthy controls (HC). A brain editing software, FreeSurfer, was used to quality control and segment the thalamus. This segmentation provided volumes for each nuclei. A free-water imaging pipeline was used to process diffusion weighted images so that free-water (FW) and corrected fractional anisotropy (FAt) could be collected. These values were run through Tract-Based Spatial Statistics (TBSS) to standardize scans and identify white matter regions of interest. RESULTS: This thesis reports an effect size of -1.24 between HC and the collective subject groups with a confidence interval of -1.63 to -.84. Via meta-regression, we report that illness duration, publication year, and spindle frequency gap (SFG) all are associated with sleep spindles. The thalamic volumetric analysis showed that four nuclei differed between EC and HC and two nuclei differed between EC and FH. The imaging aspect of this thesis discovered no significant FAt findings comparing volume to population, though heat maps revealed a trend where FHR and EC had lower FAt than HC. For FW analysis, we found a similar trend where FHR and EC had higher FW than HC. CONCLUSION: Using both analyses, this thesis connected sleep spindles, schizophrenia, and brain structure. We illuminated consistent reports of schizophrenia populations having lower sleep spindle density compared to healthy controls. This thesis reports a difference in thalamic nuclei volumes between both HC and FHR versus EC as well as FAt and FW differences between both FHR and EC and HC. / 2021-06-07T00:00:00Z

Οι διάφορες δραστηριότητες του εγκεφάλου συχνά χαρακτηρίζονται από ειδικούς ρυθμούς στο ηλεκτροεγκεφαλογράφημα (ΗΕΓ). Το 2ο στάδιο του ύπνου χωρίς ταχείες οφθαλμικές κινήσεις (στάδιο NREM) χαρακτηρίζεται από τις ατράκτους που σηματοδοτούν την ουσιαστική έναρξη του ύπνου. Αποτελούν 0.5-1 δευτερόλεπτα ρυθμικής διαδοχής κύρια αρνητικών κυμάτων γενικευμένα στο ΗΕΓ τα οποία παρουσιάζουν προϊούσα αύξηση και μετά μείωση του πλάτους τους. Οι άτρακτοι συμμετέχουν σε διάφορες σημαντικές λειτουργίες του εγκεφάλου. Η κατανόηση του πολύπλευρου και πολύ σημαντικού ρόλου των ατράκτων έχει αποτελέσει αφορμή ώστε να γίνουν προσπάθειες εντοπισμού των υπεύθυνων για τη γένεσή τους εγκεφαλικών κυκλωμάτων. Σκοπός της προτεινόμενης μεθόδου είναι η εφαρμογή της μεθόδου εντοπισμού σημάτων σε πολυκαναλικές καταγραφές χρησιμοποιώντας περιορισμούς που στηρίζονται στο πεδίο του χώρου (spatial constraints) και το πεδίο της συχνότητας (frequency constraints) χρησιμοποιώντας την τεχνική ανάλυσης σε ανεξάρτητες συνιστώσες (ICA). Η μέθοδος εφαρμόστηκε για την ανάλυση βραδέων και ταχέων ατράκτων σε εγκεφαλογραφήματα ύπνου. Στο εργαστήριο Φυσιολογίας έχουν γίνει ΗΕΓ καταγραφές ολονύκτιου ύπνου με καταμέτρηση πολλών εκατοντάδων ατράκτων οι οποίες χρησιμοποιήθηκαν για την ανάπτυξη της παραπάνω μεθόδου αυτομάτου ανίχνευσης και εντοπισμού των ατράκτων. / Several brain activities are characterized by specific rhythms in electroencephalogram (EEG). The non rapid eye movement (NREM) stage of sleep is characterized by sleep spindles signaling the beginning of sleep. Spindles are rhythmic generalized negative waves in EEG with progressively increasing and gradually decreasing amplitude lasting 0.5-1 sec. Spindles are involved in several brain functions. The comprehension of the significance and multilateral role of spindles has driven efforts to detect the brain circuits involved in their generation. The purpose of this study is the introduction of a signal detection method in multichannel records, using Independent Component Analysis with spatial and frequency constraints. This automatic detection method was applied to the analysis of fast and slow spindles in sleep EEG, obtained from whole-night sleep recording in the laboratory of Physiology Department at University of Patras.

Orientador: Ney Lemke / Resumo: O sono (do latim, somnus) é um período que apresenta uma atividade fisiológica característica, que pode ser registrada com o EEG. Algumas ondas em um sinal de EEG são vistas apenas durante o sono, como os fusos do sono e complexos K. O fuso é um dos elementos mais bem conhecidos no estudo do sono. No presente estudo serão estudados fusos globais e potenciais complexos K, os quais são observados simultaneamente em todos os canais de EEG. Para isto, um novo método de investigação foi proposto, que estuda tanto o envelope do sinal quanto a fase/frequência de cada fuso. Através da análise da fase do fuso global, foi mostrado que 90% dos fusos de indivíduos saudáveis sincronizam com um tempo de latência de 0,11s. O método também avalia a frequência de modulação (chirp) de fusos globais, e foi averiguado que não há correlação entre o chirp destes fusos e sua sincronização. Através do estudo do envelope do sinal juntamente com a implementação de um modelo de propagação isotrópico, foi possível estimar a origem do fuso e sua velocidade de propagação. Os resultados obtidos indicam que através desta abordagem simples e não invasiva é possível determinar, com uma precisão razoável, o local de origem dos fusos do sono, e sua velocidade estimada de propagação de 0,12m/s. Os potenciais complexos K detectados foram usados para avaliar a robustez do método desenvolvido, e apresentaram frequências, durações e amplitudes dentro das faixas esperadas para complexos K. A velocidade do propagação ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Sleep (derived from the Latim, somnus) is a brain state with distinct physiological activity that can be investigated by EEG evaluation. Some waves are unique in sleep EEG such as sleep spindles and K complexes. Spindles are one of the best known elements in sleep studies. In this work we considered global spindles and K complexes, which are spindles that are observed simultaneously in all EEG channels. We propose a method that investigates both the signal envelope and phase/frequency of each global spindle. By analysing the spindle phase we showed that 90% of spindles in healthy subjects synchronize with a median latency time of 0.11 s. The method also measured the frequency slope (chirp) of global spindles and found that global spindle chirp and synchronization are not correlated. By investigating the signal envelopes and implementing a homogeneous and isotropic propagation model, we could estimate both the signal origin and velocity in global spindles. Our results indicate that this simple and non-invasive approach could determine with reasonable precision the spindle origin, and allowed us to estimate a signal speed of 0.12 m/s.Potential K complexes are used to assess the robustness of developed method and shows that frequencies, durations and amplitudes within the K complex expected range. Propagation velocity in potential K complexes are around 0.05 m/s which is lower than spindles velocity. Partial synchronization tendencies were detected in potential K complex, a... (Complete abstract click electronic access below) / Doutor

Submitted by Rafael Toledo Fernandes de Souza (rafael@ibb.unesp.br) on 2016-04-27T21:08:41Z No. of bitstreams: 1 TeseRafaelTFS.pdf: 24959368 bytes, checksum: f8cc766a544e297b446817f14d467e4e (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-04-29T22:14:03Z (GMT) No. of bitstreams: 1 souza_rtf_dr_bot.pdf: 24959368 bytes, checksum: f8cc766a544e297b446817f14d467e4e (MD5) / Made available in DSpace on 2016-04-29T22:14:03Z (GMT). No. of bitstreams: 1 souza_rtf_dr_bot.pdf: 24959368 bytes, checksum: f8cc766a544e297b446817f14d467e4e (MD5) Previous issue date: 2016-03-10 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O sono (do latim, somnus) é um período que apresenta uma atividade fisiológica característica, que pode ser registrada com o EEG. Algumas ondas em um sinal de EEG são vistas apenas durante o sono, como os fusos do sono e complexos K. O fuso é um dos elementos mais bem conhecidos no estudo do sono. No presente estudo serão estudados fusos globais e potenciais complexos K, os quais são observados simultaneamente em todos os canais de EEG. Para isto, um novo método de investigação foi proposto, que estuda tanto o envelope do sinal quanto a fase/frequência de cada fuso. Através da análise da fase do fuso global, foi mostrado que 90% dos fusos de indivíduos saudáveis sincronizam com um tempo de latência de 0,11s. O método também avalia a frequência de modulação (chirp) de fusos globais, e foi averiguado que não há correlação entre o chirp destes fusos e sua sincronização. Através do estudo do envelope do sinal juntamente com a implementação de um modelo de propagação isotrópico, foi possível estimar a origem do fuso e sua velocidade de propagação. Os resultados obtidos indicam que através desta abordagem simples e não invasiva é possível determinar, com uma precisão razoável, o local de origem dos fusos do sono, e sua velocidade estimada de propagação de 0,12m/s. Os potenciais complexos K detectados foram usados para avaliar a robustez do método desenvolvido, e apresentaram frequências, durações e amplitudes dentro das faixas esperadas para complexos K. A velocidade do propagação encontrada para os potenciais complexos K foi de 0,05m/s, menor do que a dos fusos do sono. Os potenciais complexos K mostraram ter uma tendência de sincronização parcial, propriedade esta descrita para os complexos K na literatura. O método desenvolvido também foi aplicado em indivíduos com Apneia Obstrutiva do Sono (AOS). A maioria dos parâmetros analisados não apresentaram diferenças significativas entre indivíduos saudáveis e com AOS; exceto que, em indivíduos com AOS, a duração da sincronização apresentou um valor 34,18% menor, e a posição de origem dos fusos apresentou dois focos diferentes. Desta maneira, conclui-se que o método desenvolvido foi aplicado com sucesso nos grafoelementos avaliados, pois consegue recuperar as informações esperadas, e pode ser útil como uma ferramenta diagnóstica não invasiva. / Sleep (derived from the Latim, somnus) is a brain state with distinct physiological activity that can be investigated by EEG evaluation. Some waves are unique in sleep EEG such as sleep spindles and K complexes. Spindles are one of the best known elements in sleep studies. In this work we considered global spindles and K complexes, which are spindles that are observed simultaneously in all EEG channels. We propose a method that investigates both the signal envelope and phase/frequency of each global spindle. By analysing the spindle phase we showed that 90% of spindles in healthy subjects synchronize with a median latency time of 0.11 s. The method also measured the frequency slope (chirp) of global spindles and found that global spindle chirp and synchronization are not correlated. By investigating the signal envelopes and implementing a homogeneous and isotropic propagation model, we could estimate both the signal origin and velocity in global spindles. Our results indicate that this simple and non-invasive approach could determine with reasonable precision the spindle origin, and allowed us to estimate a signal speed of 0.12 m/s. Potential K complexes are used to assess the robustness of developed method and shows that frequencies, durations and amplitudes within the K complex expected range. Propagation velocity in potential K complexes are around 0.05 m/s which is lower than spindles velocity. Partial synchronization tendencies were detected in potential K complex, a propriety described for K complex in the literature. Obstructive Sleep Apnea (OSA) subjects were also assessed by our method. The majority of analysed parameters do not present significant difference between healthy and OSA subjects except by synchronization duration (34.18% lower in OSA) and two distinct focal points in OSA spindle origin. The proposed methodology retrieved the expected results, obtained by EEG analysis and other more complex techniques and our results indicate that it can be used as a diagnosis tool and to explore other sleep phenomena, such as K complexes. / FAPESP: 2012/22413-2

Les fuseaux de sommeil sont des ondes électroencéphalographiques reflétant les mécanismes électrophysiologiques de protection du sommeil. Les adultes autistes ont un sommeil léger et moins de fuseaux de sommeil que des adultes neurotypiques. L’étude vérifie si les enfants autistes montrent également moins de fuseaux de sommeil que les enfants neurotypiques et documente leur évolution avec l’âge. Nous avons enregistré le sommeil de 34 adultes (16 autistes) et 26 enfants (13 autistes) et comparé la quantité de fuseaux de sommeil enregistrés aux électrodes préfrontales (Fp1, Fp2) et centrales (C3, C4). Les deux groupes montrent une diminution similaire des fuseaux en vieillissant. Le groupe d’enfants autistes montre moins de fuseaux que le groupe témoin aux électrodes Fp2 et C4; les adultes autistes montrent significativement moins de fuseaux que les adultes contrôles aux deux électrodes centrales. Le mauvais sommeil des autistes pourrait être causé par une faible protection du sommeil déjà présente en bas âge. / Autism is characterized by poor sleep maintenance. Sleep spindles are electroencephalographic markers representing a sleep protective mechanism. Autistic adults display less spindles than matched controls. This study investigates sleep spindle activity in children and adults with and without autism. The sleep of 34 adults (16 autistics) and 26 children (13 autistics) was recorded. Sleep spindles were counted and compared between groups at prefrontal (Fp1, Fp2) and central (C3, C4) electrodes. Both diagnostic groups showed a similar decrease in sleep spindle with age. Autistic children had significantly less spindles than controls at Fp2 and C4; adults with autism had significantly less spindles than controls at the two central electrodes. Poor sleep in children and adults with autism may be due to impaired protective mechanisms. The developmental pattern of sleep spindle topography suggests an atypical maturational course of the thalamo-cortical loop in autism.

Les fuseaux de sommeil sont des ondes électroencéphalographiques reflétant les mécanismes électrophysiologiques de protection du sommeil. Les adultes autistes ont un sommeil léger et moins de fuseaux de sommeil que des adultes neurotypiques. L’étude vérifie si les enfants autistes montrent également moins de fuseaux de sommeil que les enfants neurotypiques et documente leur évolution avec l’âge. Nous avons enregistré le sommeil de 34 adultes (16 autistes) et 26 enfants (13 autistes) et comparé la quantité de fuseaux de sommeil enregistrés aux électrodes préfrontales (Fp1, Fp2) et centrales (C3, C4). Les deux groupes montrent une diminution similaire des fuseaux en vieillissant. Le groupe d’enfants autistes montre moins de fuseaux que le groupe témoin aux électrodes Fp2 et C4; les adultes autistes montrent significativement moins de fuseaux que les adultes contrôles aux deux électrodes centrales. Le mauvais sommeil des autistes pourrait être causé par une faible protection du sommeil déjà présente en bas âge. / Autism is characterized by poor sleep maintenance. Sleep spindles are electroencephalographic markers representing a sleep protective mechanism. Autistic adults display less spindles than matched controls. This study investigates sleep spindle activity in children and adults with and without autism. The sleep of 34 adults (16 autistics) and 26 children (13 autistics) was recorded. Sleep spindles were counted and compared between groups at prefrontal (Fp1, Fp2) and central (C3, C4) electrodes. Both diagnostic groups showed a similar decrease in sleep spindle with age. Autistic children had significantly less spindles than controls at Fp2 and C4; adults with autism had significantly less spindles than controls at the two central electrodes. Poor sleep in children and adults with autism may be due to impaired protective mechanisms. The developmental pattern of sleep spindle topography suggests an atypical maturational course of the thalamo-cortical loop in autism.

Le trouble du déficit de l’attention/hyperactivité (TDA/H) est le désordre du comportement le plus commun chez les enfants. Les études suggèrent qu'un pourcentage élevé d'enfants atteints de TDA/H souffre de problèmes de sommeil et de somnolence diurne. Le mécanisme sous-jacent à ces difficultés demeure inconnu. Plusieurs études ont suggéré que les fuseaux de sommeil jouent un rôle dans les mécanismes de protection du sommeil. L'objectif de cette étude est de comparer les fuseaux lents (11-13 Hz) et rapides (14-15 Hz) chez des enfants atteints du TDA/H et des sujets contrôles. Nous prévoyons que comparativement aux enfants contrôles, les enfants atteints du TDA/H montreront une plus faible densité des fuseaux lents et rapides, et auront des fuseaux plus courts (sec), moins amples (uV) et plus rapides (cycle/sec). Enfin, nous prévoyons que ces effets seront plus prononcés dans les dérivations cérébrales antérieures que dans les dérivations plus postérieures du cerveau. Les enregistrements polysomnographiques (PSG) du sommeil de nuit ont été menés chez 18 enfants diagnostiqués avec le TDA/H et chez 26 sujets témoins âgés entre 7 et 11 ans. Un algorithme automatique a permis de détecter les fuseaux lents et rapides sur les dérivations frontales, centrales, pariétales et occipitales. Les résultats ont montré que, les caractéristiques PSG du sommeil ne différaient pas significativement entre les deux groupes. On ne note aucune différence significative entre les groupes sur nombre/densité des fuseaux lents et rapides ainsi que sur leurs caractéristiques respectives. Cette étude suggère que les mécanismes de synchronisation du l'EEG en sommeil lent, tel que mesuré par la densité et les caractéristiques des fuseaux lents et rapides en sommeil lent ne différent pas chez les enfants atteints du TDA/H. / Attention Deficit Hyperactivity Disorder (ADHD) is a commonly diagnosed behavioural disorder in children. Evidence suggests that a high proportion of children with ADHD suffer from sleep difficulties and daytime sleepiness. However, the mechanism underlying this deficit in alertness is unknown. Various studies suggest that sleep spindles inhibit arousing sensory input and help preserve sleep. The objective of this study was to compare slow (11-13 Hz) and fast (14-15 Hz) spindle activity between children with ADHD and controls. We expected that compared to controls, children with ADHD would show a lower density (number of spindles per minute of NREM sleep) of slow and fast spindles. We also predicted that children with ADHD will have shorter (sec) fast and slow spindles, lower amplitude (uV) and faster frequency (Hz) than controls. Finally, we expected these effects would be more pronounced in the frontal rather than more posterior derivations of the brain. Overnight sleep recordings were conducted in 18 children diagnosed with ADHD without comorbid psychiatric problems and in 26 healthy controls. The subjects’ ages ranged from 7 to 11 years. An automatic algorithm detected the slow and fast spindles on the frontal, central, parietal and occipital derivations. The results showed that children with ADHD had similar PSG sleep architecture (sleep efficiency, stages of sleep) compared to controls. Sleep spindle activity did not significantly differ between the two groups in terms of number, density, amplitude and length. This study suggests that mechanisms of sleep EEG synchronization, as expressed by the number and density of sleep spindles presently identified in the ongoing EEG, do not differ between children with ADHD and controls.

No description available.

Patients diagnosed with schizophrenia (SZ) show major deficits in cognitive functioning andsleep spindle activity. As much indicates that sleep spindle activity is related to cognitive performance, this literature review intended to investigate the degree of their relationship inpatients with SZ. The eligible criteria for the studies were that they measured sleep spindle activity and cognitive functioning in patients with SZ and included a non-clinical controlgroup. Studies with comorbid diagnoses were excluded. Searches were conducted between the 5th and 6th of March 2023 on PsycINFO, PubMed, Web of Science, and Medline databases. Seven studies met the eligibility criteria. The studies were written in English and published between 2007 and 2022. The quality of the studies was assessed using the JBICritical Appraisal Checklist for Analytical Cross-Sectional Studies. The results were synthesized by following a structured narrative and tables. The total number of participants with SZ was 141 and 149 in the non-clinical control group. The age of the participants ranged between 18 and 65 and were mainly men. Patients with SZ showed significantly reduced sleep spindle activity and cognitive performance compared to the control group. Several studies found positive correlations between cognitive performance and spindle density inboth groups. Some correlations were only significant for patients with SZ, indicating thatsleep spindle activity affects cognitive performance up to one point. A suggestion for further studies is to investigate the possibility to assess cognitive impairments in patients with SZ by inducing sleep spindle density. / Patienter diagnostiserade med schizofreni (SZ) uppvisar nedsättning i både kognitiv förmåga och aktiviteten av sömnspindlar. Då mycket tyder på att sömnspindlar är relaterade till kognitiv prestation, så ämnade denna systematiska litteraturstudie att undersöka denna relation hos patienter med SZ. Kriterierna för kvalificering var att studierna utförde mätningar av sömnspindel aktivitet och kognitiv förmåga hos patienter med SZ, samt inkluderade en frisk kontrollgrupp. Studier med komorbida diagnoser exkluderades. Litteratursökningar utfördes mellan den 5e och 6e mars 2023 på databaserna PsycINFO,PubMed, Web of Science, och Medline. Det var 7 studier som uppfyllde kriterierna. Studierna var skrivna på engelska och var publicerade mellan år 2007 och 2022. Kvaliteten av de inkluderade studierna bedömdes med JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Resultaten syntetiserades med ett strukturerat narrativ och tabeller. Det totala antalet deltagare med SZ var 141 och 149 i kontrollgruppen. Deltagarna var främst män mellan 18 och 65 år. Deltagarna med SZ visade signifikant lägre sömnspindel aktivitet samt kognitiv prestation jämfört med kontrollgruppen. De flesta studierna fann signifikanta positiva korrelationer mellan spindeldensitet och kognitiv förmåga för både SZ och kontrollgruppen. Vissa resultat var endast signifikanta för patienter med SZ vilket tyder på att sömnspindel aktivitet endast påverkar kognitiv prestation upp till en viss nivå. Förslag för framtida studier är att undersöka möjligheten att inducera spindeldensiteten hos patienter medSZ för att förhöja den kognitiva förmågan.

This study employed multiple assessments, including sleep/resting waking EEG (visual scoring and power spectral analysis) and psychomotor vigilance task, to access effects of varying pulse-modulated microwaves (such as: 'talk', 'listen' and 'standby' mode signals) emitted from a standard mobile phone. The idea was prompted by a finding that the pulse modulation frequencies of mobile phone signals correspond to the frequencies of brain delta and alpha waves. Thereby it is possible the brain is able to recognize and respond to the low-frequency components of the mobile phone signals. Supporting evidence comes from repetitively reported EEG alpha and spindle effects of the 2, 8 and 217-Hz pulsed microwave exposure. Furthermore, brain imaging (EEG and PET) studies reveal 'low-frequency pulse-modulated waves' rather than the 'microwave frequency carrier waves' is the sine qua non for inducing these brain physiological effects [Huber et al., 2002, 2005; Regel et al., 2007a]. On the other hand, recent converging evidence, from molecular, behavioural and electrophysiological level, have shown that brain plasticity is a continuous process from waking to sleep and, sleep, a well-defined physiological condition, is 'shaped' by the waking experiences. The latter findings suggest certain sleep EEG features may characterize levels of cortical plasticity during wakefulness. The work presented in this thesis was inspired by these studies and aimed to understand how the real mobile phone signals with different low-frequency pulsing components [such as 'talk' (8, 217 Hz pulsed), 'listen' (2, 8, 217 Hz pulsed) and 'stand by' mode < 2 Hz pulsed)] change human brain electrical activities from waking to sleep. We approached this question based on EEG analysis in two domains: (1) EEG visual scoring; (2) EEG spectral analysis from relaxed waking to the deeper stages of non-NREM sleep. We also looked at the effects on the psychomotor vigilance performance. Results suggest 'talk' and 'Iisten/standby' modes have inverse effects on the distinctive thalamo-cortical oscillation modes and may thus impart inverse effects on their sleep structures. The implications of this study are of practical importance as it suggests the thalamo-cortical oscillations can be modulated by synchronizing rTMS/tDCS/DBS and sleeplwaking EEG. This concept may be applied to modulate the brain oscillation modes for enhancing sleep-dependent brain plastiCity or information processing.