Characterization of Neuroimage Coupling Between EEG and FMRI Using Within-Subject Joint Independent Component Analysis

The purpose of this dissertation was to apply joint independent component analysis (jICA) to electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to characterize the neuroimage coupling between the two modalities. EEG and fMRI are complimentary imaging techniques which have been used in conjunction to investigate neural activity. Understanding how these two imaging modalities relate to each other not only enables better multimodal analysis, but also has clinical implications as well. In particular, Alzheimer’s, Parkinson’s, hypertension, and ischemic stroke are all known to impact the cerebral blood flow, and by extension alter the relationship between EEG and fMRI. By characterizing the relationship between EEG and fMRI within healthy subjects, it allows for comparison with a diseased population, and may offer ways to detect some of these conditions earlier. The correspondence between fMRI and EEG was first examined, and a methodological approach which was capable of informing to what degree the fMRI and EEG sources corresponded to each other was developed. Once it was certain that the EEG activity observed corresponded to the fMRI activity collected a methodological approach was developed to characterize the coupling between fMRI and EEG. Finally, this dissertation addresses the question of whether the use of jICA to perform this analysis increases the sensitivity to subcortical sources to determine to what degree subcortical sources should be taken into consideration for future studies. This dissertation was the first to propose a way to characterize the relationship between fMRI and EEG signals using blind source separation. Additionally, it was the first to show that jICA significantly improves the detection of subcortical activity, particularly in the case when both physiological noise and a cortical source are present. This new knowledge can be used to design studies to investigate subcortical signals, as well as to begin characterizing the relationship between fMRI and EEG across various task conditions

Veränderung der Kontrollfähigkeit bei adulten Patienten mit einer ADHS im Verlauf einer Neurofeedbacktherapie durch Messung und Visualisierung der Hirnoxygenierung mittels Nahinfrarotspektroskopie

Hintergrund: Die Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) ist eine Erkrankung, welche in der Kindheit beginnt und häufig bis in das Erwachsenenalter fortbesteht. Die Erkrankung kann insbesondere auch durch die Ausbildung zahlreicher Komorbiditäten zu einer schweren Beeinträchtigung der Gesundheit und des sozialen Lebens von Betroffenen führen. Eine noch junge Behandlungsoption der ADHS ist die Anwendung eines Neurofeedbacktrainings. Diese Methode wird im Kinder- und Jugendbereich bereits erfolgreich mittels EEG angewandt. Bisher noch wenig erforscht ist die Anwendung eines Neurofeedbacks mittels Nahinfrarotspektroskopie. Ziele: In der vorliegenden Arbeit wurde untersucht, ob eine Behandlung mittels Neurofeedback mit Nahinfrarotspektroskopie bei erwachsenen ADHS-Patienten zu messbaren Veränderungen der Hirnoxygenierung führt und mit einem Rückgang der ADHS-Symptomatik bei den Betroffenen einhergeht. Methoden: Die Patienten erhielten insgesamt 30 Anwendungen einer Neurofeedbacktherapie mittels Nahinfrarotspektroskopie. Im Rahmen der Therapie sollten die Patienten lernen, die Oxygenierung des präfrontalen Cortex willentlich zu beeinflussen. Ergebnisse: Die Patienten konnten die Oxygenierung des präfrontalen Cortex numerisch in die gewünschte Richtung beeinflussen. Dabei blieben die Ergebnisse jedoch unterhalb des Signifikanzniveaus von 5%. Signifikant verbesserten sich hingegen die Gesamt-Symptomatik der ADHS sowie alle Kernsymptome (Unaufmerksamkeit, Hyperaktivität und Impulsivität). Fazit: Die Durchführung eines Neurofeedbacks mittels Nahinfrarotspektroskopie bei erwachsenen ADHS-Patienten geht mit einer Verbesserung der Symptomatik einher und führt möglicherweise zu einer Veränderung der Hirnoxygenierung im präfrontalen Cortex. Sie könnte damit in der Zukunft zu einer Behandlungsalternative zur medikamentösen Behandlung und zu einer Alternative zum Neurofeedback mittels EEG entwickelt werden.Background: Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric/psychiatric disorder beginning in childhood. The disease often persists into adulthood and massively affects the health and social life of patients particularly due to the formation of numerous comorbidities. An emergent treatment option of ADHD is neurofeedbacktraining. This method is already being successfully applied in the child- and youth sector employing EEG. An underexplored treatment option is the application of neurofeedback based on near infrared spectroscopy (NIRS). Objectives: The present study examined whether a treatment using neurofeedback with NIRS in adult ADHD patients leads to measurable changes of brain oxygenation and whether it is associated with a decline of the patients ADHD symptoms. Methods: The patients received a total of 30 applications of neurofeedback therapy employing NIRS. Over the course of the therapy it was attempted to affect the oxygenation of the prefrontal cortex intentionally. Results: The patients showed a tendency to be able to intentionally influence numerically the oxygenation of the prefrontal cortex in the desired direction. Yet, the result remained below the significance level of 5%. However, ADHD symptoms changed significantly. We also detected a significant improvement regarding the main symptoms inattention, hyperactivity and impulsivity. Conclusion: The implementation of neurofeedback employing near infrared spectroscopy in adult ADHD patients is associated with an improvement of symptoms and potentially leads to a change of brain oxygenation in the prefrontal cortex. Therefore the method offers an alternative way of treatment to the pharmacological treatment and EEG neurofeedback

Effects of cholinesterase inhibition on brain function

Pharmacological-functional imaging provides a non-invasive method by which the actions of neurotropic drugs on the human brain can be explored. Simply put, it assesses how neural activity patterns associated with cognitive functions of interest are modified by a drug challenge. Since one of the most widely-used cognitive-enhancing drugs in clinical practice are cholinesterase inhibitors, this thesis applies pharmacological functional imaging to the question of understanding how such drugs work - both in healthy people and dementia. The experiments in this thesis describe how brain activations – as revealed by functional magnetic resonance imaging (fMRI) – are modulated by the cholinesterase inhibitor physostigmine, during tasks designed to isolate sensory, attentional, and memory processes. While non-human and human psychophysical studies suggest that all three of these cognitive functions are under the control of the endogenous cortical cholinergic system, understanding how neurobiological models of cholinergic function translate into human brain activation modulations is unclear. One main question that is particularly relevant in this regard, that recurs through all the experiments, is how physostigmine-induced neuromodulations differ between sensory-driven ‘bottom-up’, and task-driven ‘top-down’, brain activations. The results are discussed with reference both to non-human physiological data and to existing human cholinergic-functional imaging studies (fifty studies published to date), which are themselves reviewed at the outset. Furthermore, assumptions based upon the physical and physiological principles of pharmacological functional imaging, being critical to interpretation, are discussed in detail within a general methods section