Altered Brain Functional Connectivity in Small-Cell Lung Cancer Patients after Chemotherapy Treatment: A Resting-State fMRI Study

Previous studies in small-cell lung cancer (SCLC) patients have mainly focused on exploring neurocognitive deficits associated with prophylactic cranial irradiation (PCI). Little is known about functional brain alterations that might occur due to chemotherapy treatment in this population before PCI is administered. For this reason, we used resting-state functional Magnetic Resonance Imaging (fMRI) to examine potential functional connectivity disruptions in brain networks, including the Default Mode Network (DMN), the Sensorimotor Network, and the Task-Positive Network (TPN). Nineteen SCLC patients after platinum-based chemotherapy treatment and thirteen controls were recruited in the current study. ROI-to-ROI and Seed-to-Voxel analyses were carried out and revealed functional connectivity deficits in patients within all the networks investigated demonstrating the possible negative effect of chemotherapy in cognitive functions in SCLC populations

Neurocognitive function in patients undergoing stereotactic radiosurgery for brain metastases

National Institute of Clinical Excellence (NICE) recommends Stereotactic radiosurgery (SRS) as the treatment of choice for patients with limited brain metastases, which is defined as volume <20 cc, with performance status 0-2, controlled or controllable extracranial disease and expected prognosis of greater than 6 months. Despite its precision, studies have reported 24-60% of patients can develop neurocognitive impairment following SRS alone. Dose to the hippocampus is thought to be related to development of neurocognitive impairment following fractionated radiotherapy for primary brain tumours and whole brain radiotherapy for brain metastases. However, this has not been studied in patients undergoing SRS. This thesis investigates the importance of hippocampus delineation and dose delivered to this organ in patients undergoing SRS and its impact on neurocognitive decline following treatment. Multi-parametric MRI imaging identifies changes in the hippocampus structure, blood flow, metabolites, and diffusion tensor imaging of the tracts involved in the limbic system. We utilised this opportunity to perform novel microstructure MRI imaging of the metastases to understand the tumour microenvironment and oxygenation

Crosstalk between Depression, Anxiety, and Dementia: Comorbidity in Behavioral Neurology and Neuropsychiatry

This Special Issue highlights the most recent research on depression, anxiety and dementia, with attention to comorbidity in a range of diseases. The symptoms of depression, anxiety and dementia are the most common comorbid manifestations present in patients suffering from neurodegenerative and psychiatric diseases. Together, these illnesses constitute an extremely complex and challenging research field due to their inherent multifactorial causative factors, heterogeneous pathogenesis, and mental and behavioral manifestations. This Special Issue covers laboratory, clinical and statistical studies on the crosstalk between depression, anxiety, dementia, Alzheimer’s disease, multiple sclerosis, schizophrenia, diabetes mellitus, Down’s syndrome, and/or compulsive disorders. It contains contributions from 71 authors, has been reviewed by 25 referees, and edited by three academic editors and one managing editor

Augmentation of Brain Function: Facts, Fiction and Controversy. Volume III: From Clinical Applications to Ethical Issues and Futuristic Ideas

The final volume in this tripartite series on Brain Augmentation is entitled “From Clinical Applications to Ethical Issues and Futuristic Ideas”. Many of the articles within this volume deal with translational efforts taking the results of experiments on laboratory animals and applying them to humans. In many cases, these interventions are intended to help people with disabilities in such a way so as to either restore or extend brain function. Traditionally, therapies in brain augmentation have included electrical and pharmacological techniques. In contrast, some of the techniques discussed in this volume add specificity by targeting select neural populations. This approach opens the door to where and how to promote the best interventions. Along the way, results have empowered the medical profession by expanding their understanding of brain function. Articles in this volume relate novel clinical solutions for a host of neurological and psychiatric conditions such as stroke, Parkinson’s disease, Huntington’s disease, epilepsy, dementia, Alzheimer’s disease, autism spectrum disorders (ASD), traumatic brain injury, and disorders of consciousness. In disease, symptoms and signs denote a departure from normal function. Brain augmentation has now been used to target both the core symptoms that provide specificity in the diagnosis of a disease, as well as other constitutional symptoms that may greatly handicap the individual. The volume provides a report on the use of repetitive transcranial magnetic stimulation (rTMS) in ASD with reported improvements of core deficits (i.e., executive functions). TMS in this regard departs from the present-day trend towards symptomatic treatment that leaves unaltered the root cause of the condition. In diseases, such as schizophrenia, brain augmentation approaches hold promise to avoid lengthy pharmacological interventions that are usually riddled with side effects or those with limiting returns as in the case of Parkinson’s disease. Brain stimulation can also be used to treat auditory verbal hallucination, visuospatial (hemispatial) neglect, and pain in patients suffering from multiple sclerosis. The brain acts as a telecommunication transceiver wherein different bandwidth of frequencies (brainwave oscillations) transmit information. Their baseline levels correlate with certain behavioral states. The proper integration of brain oscillations provides for the phenomenon of binding and central coherence. Brain augmentation may foster the normalization of brain oscillations in nervous system disorders. These techniques hold the promise of being applied remotely (under the supervision of medical personnel), thus overcoming the obstacle of travel in order to obtain healthcare. At present, traditional thinking would argue the possibility of synergism among different modalities of brain augmentation as a way of increasing their overall effectiveness and improving therapeutic selectivity. Thinking outside of the box would also provide for the implementation of brain-to-brain interfaces where techniques, proper to artificial intelligence, could allow us to surpass the limits of natural selection or enable communications between several individual brains sharing memories, or even a global brain capable of self-organization. Not all brains are created equal. Brain stimulation studies suggest large individual variability in response that may affect overall recovery/treatment, or modify desired effects of a given intervention. The subject’s age, gender, hormonal levels may affect an individual’s cortical excitability. In addition, this volume discusses the role of social interactions in the operations of augmenting technologies. Finally, augmenting methods could be applied to modulate consciousness, even though its neural mechanisms are poorly understood. Finally, this volume should be taken as a debate on social, moral and ethical issues on neurotechnologies. Brain enhancement may transform the individual into someone or something else. These techniques bypass the usual routes of accommodation to environmental exigencies that exalted our personal fortitude: learning, exercising, and diet. This will allow humans to preselect desired characteristics and realize consequent rewards without having to overcome adversity through more laborious means. The concern is that humans may be playing God, and the possibility of an expanding gap in social equity where brain enhancements may be selectively available to the wealthier individuals. These issues are discussed by a number of articles in this volume. Also discussed are the relationship between the diminishment and enhancement following the application of brain-augmenting technologies, the problem of “mind control” with BMI technologies, free will the duty to use cognitive enhancers in high-responsibility professions, determining the population of people in need of brain enhancement, informed public policy, cognitive biases, and the hype caused by the development of brain- augmenting approaches

Evidence-based Positron Emission Tomography

This open access book summarizes the findings of recent evidence-based articles (meta-analyses) on the use of positron emission tomography (PET) for various clinical indications. It is divided into five main sections, starting with an introduction to PET and meta-analysis. In turn, the second part addresses evidence-based PET in oncology, providing a broad overview of its use for different types of tumours. The remaining sections are focused on the use of PET in cardiology, in infectious and inflammatory diseases, and in neurology, respectively. Given its scope and the wealth of information it provides, the book will be an invaluable tool for clinicians with various specialties, as well as international scientific societies interested to the recent evidence-based data about PET

Autophagy in health and disease

In our lab in Sabanci University, Istanbul, we focus on signaling events regulating mammalian autophagy in health and disease. To discover new autophagy regulators and coordinators, we performed several unbiased functional screens. Our microRNA (miRNA) screens led to the discovery of several miRNAs targeting autophagy at various steps of the pathway. miRNAs are able to affect the expression of a number of proteins at once. Therefore, miRNA networks seem to integrate cellular stress response pathways including autophagy and apoptosis, and coordinate them to shape cell faith. Our published and unpublished results allowed us to have a better picture of the miRNA networks modulating autophagic responses in human health and disease. Protein interaction screens performed in our lab led us to discover novel proteins involved in autophagy regulation. In fact, some of these proteins were directly interacting with the core autophagy machinery components. Unexpected direct links between autophagy and other important cellular pathways were found, allowing us to reveal novel entry points for autophagy regulation and coordination in cells. Interestingly, some of this interactions seemed to be autophagy signal specific, and our work revealed novel dynamics in autophagy regulation. Results from our recently published and unpublished studies will be presented and physiological and pathological implications of our results will be discussed.*This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) 1001 Grant number: 114Z982 and Sabanci University