The Pros and Cons of Using Machine Learning and Interpretable Machine Learning Methods in psychiatry detection applications, specifically depression disorder: A Brief Review

The COVID-19 pandemic has forced many people to limit their social activities, which has resulted in a rise in mental illnesses, particularly depression. To diagnose these illnesses with accuracy and speed, and prevent severe outcomes such as suicide, the use of machine learning has become increasingly important. Additionally, to provide precise and understandable diagnoses for better treatment, AI scientists and researchers must develop interpretable AI-based solutions. This article provides an overview of relevant articles in the field of machine learning and interpretable AI, which helps to understand the advantages and disadvantages of using AI in psychiatry disorder detection applications.Comment: 12 page

Diagnosis and Treatment of Parkinson's Disease

Parkinson's disease is diagnosed by history and physical examination and there are no laboratory investigations available to aid the diagnosis of Parkinson's disease. Confirmation of diagnosis of Parkinson's disease thus remains a difficulty. This book brings forth an update of most recent developments made in terms of biomarkers and various imaging techniques with potential use for diagnosing Parkinson's disease. A detailed discussion about the differential diagnosis of Parkinson's disease also follows as Parkinson's disease may be difficult to differentiate from other mimicking conditions at times. As Parkinson's disease affects many systems of human body, a multimodality treatment of this condition is necessary to improve the quality of life of patients. This book provides detailed information on the currently available variety of treatments for Parkinson's disease including pharmacotherapy, physical therapy and surgical treatments of Parkinson's disease. Postoperative care of patients of Parkinson's disease has also been discussed in an organized manner in this text. Clinicians dealing with day to day problems caused by Parkinson's disease as well as other healthcare workers can use beneficial treatment outlines provided in this book

Dementia in Parkinson’s Disease

An estimated 50% to 80% of individuals with Parkinson’s disease experience Parkinson’s disease dementia (PDD). Based on the prevalence and clinical complexity of PDD, this book provides an in-depth update on topics including epidemiology, diagnosis, and treatment. Chapters discuss non-medical therapies and examine views on end-of-life issues as well. This book is a must-read for anyone interested in PDD whether they are a patient, caregiver, or doctor

Aberrant NF-kappaB expression in autism spectrum condition: a mechanism for neuroinflammation.

Autism spectrum condition (ASC) is recognized as having an inflammatory component. Post-mortem brain samples from patients with ASC display neuroglial activation and inflammatory markers in cerebrospinal fluid, although little is known about the underlying molecular mechanisms. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein found in almost all cell types and mediates regulation of immune response by inducing the expression of inflammatory cytokines and chemokines, establishing a feedback mechanism that can produce chronic or excessive inflammation. This article describes immunodetection and immunofluorescence measurements of NF-κB in human post-mortem samples of orbitofrontal cortex tissue donated to two independent centers: London Brain Bank, Kings College London, UK (ASC: n = 3, controls: n = 4) and Autism Tissue Program, Harvard Brain Bank, USA (ASC: n = 6, controls: n = 5). The hypothesis was that concentrations of NF-κB would be elevated, especially in activated microglia in ASC, and pH would be concomitantly reduced (i.e., acidification). Neurons, astrocytes, and microglia all demonstrated increased extranuclear and nuclear translocated NF-κB p65 expression in brain tissue from ASC donors relative to samples from matched controls. These between-groups differences were increased in astrocytes and microglia relative to neurons, but particularly pronounced for highly mature microglia. Measurement of pH in homogenized samples demonstrated a 0.98-unit difference in means and a strong (F = 98.3; p = 0.00018) linear relationship to the expression of nuclear translocated NF-κB in mature microglia. Acridine orange staining localized pH reductions to lysosomal compartments. In summary, NF-κB is aberrantly expressed in orbitofrontal cortex in patients with ASC, as part of a putative molecular cascade leading to inflammation, especially of resident immune cells in brain regions associated with the behavioral and clinical symptoms of ASC.This work was supported by grants to Adam Young from Archimedes Pharmaceuticals, the University of St Andrews, and the Pathological Society of Great Britain and Irelan

DicerHET primäärinen hermosoluviljemämalli miRNA-biogeneesireitin roolin tutkimiseksi Parkinsonin taudissa

Tiettyjen hermosoluryhmien vajaatoiminta ja rappeutuminen on ikään liittyville hermoston rappeumasairauksille yhteinen ilmentymä. Parkinsonin tauti (PD) on yleinen etenevä hermoston rappeumasairaus, jonka oireet pahenevat taudin edetessä. Tautia luonnehtii dopamiinia (DA) tuottavien hermosolujen asteittainen rappeutuminen sekä merkittävät proteiinikertymälöydökset, ns. Lewyn kappaleet (Lewy body; LB), jotka koostuvat lähinnä presynaptisesta proteiinista nimeltä α-synukleiini (αSyn). PD:n hoitoratkaisut painottuvat edelleen oireiden lievitykseen, sillä hermorappeumaa käynnistäviä tautimekanismeja ei vielä täysin ymmärretä. Kahden edellisen vuosikymmenen aikana mikroRNA (miRNA)-molekyylit ovat herättäneet suurta kiinnostusta eri biolääketieteen aloilla ja saaneet erityistä huomiota hermorappeumasairauksien tutkimuksessa. Viimeisimmät kehitykset viittaavat siihen, että miRNA-tasot muuttuvat sekä ikääntymiskudoksessa että monien ikään liittyvien sairauksien yhteydessä, kuten PD:ssä. Tuoreissa tutkimuksissa on myös havaittu, että Dicer:in, miRNA-molekyylien synteesireitin tärkeimmän entsyymin, ilmentyminen alentuu ikääntymisen myötä. Tätä mekanismia on pyritty jäljittelemään DicerHET hiirimallilla, joka perustuu Dicer-geenin heterotsygoottiseen mutageneesiin. Alustavissa tutkimuksissa DicerHET-malli osoittautui lupaavaksi tutkimusmalliksi häiriintyneen miRNA-synteesireitin ja PD:hen liittyvän hermorappeuman välisen yhteyden tutkimiseen. Täten, tulevien tutkimustöiden helpottamiseksi ja lääkeaineseulontojen nopeuttamiseksi, tässä työssä olemme pyrkineet tuottamaan vastaavaa DicerHET in vitro mallia soveltamalla kätevää perimänmuokkauksen menetelmää. Tavoitteena oli kelpuuttaa malli ja luoda yhdenmukainen ja toistettava menetelmä tuleviin töihin, joissa tutkitaan miRNA-biosynteesin roolia PD:n tautimekanismissa. DicerHET-genotyyppi tuotettiin soluviljelmissä, yhdistämällä perinteistä Cre/loxP-systeemiä viruksen välittämään Cre-synteesiin. Tarkemmin ottaen, aivokuoren primääriviljelmät, jotka olivat peräisin Dicer flox/+ -hiirien alkioista, transdusoitiin Cre:tä ilmentävillä lentivirusvektoreilla (lenti-hSYN-T2A-Cre) "loxp-rajatun" Dicer-alleelin poistamiseksi. Määrittääksemme menetelmälle optimaaliset parametrit, arvioimme rekombinaatiotehokkuutta eri transduktio-olosuhteissa. Optimaalisissa olosuhteissa pystyimme saavuttamaan tehokkaan rekombinaation 5 päivän induktion jälkeen viljelmissä. Immunohistokemialliset värjäykset osoittivat kuitenkin, että DicerHET -genotyyppi ei heikentänyt solujen eloonjäämistä. Havainnollistaaksemme tutkimusmallin konseptia, altistimme DicerHET-viljelmät vielä ns. ennalta muodostetuille fibrilleille (pre-formed fibrils; PFF) – tämä on PD:een liittyvä stressitekijä, joka saa αSyn-proteiinit kertymään rykelmiin. pSer129-αSyn-positiivisia LB:n kaltaisia rykelmiä havaittiin kaikissa PFF-käsitellyissä viljelmissä. Rykelmiä kertyi kuitenkin enemmän DicerHET-viljelmiin. Tämä ei kuitenkaan aiheuttanut lisääntynyttä solukuolemaa, mikä viittaa siihen, että DicerHET -genotyyppi ei lisää aivokuoren neuronien haavoittuvuutta pSer129-αSyn-kertymiä kohtaan. Aikaisempien tutkimuksiemme perusteella oletamme, että DA-hermosolut ovat erityisen herkkiä ikääntymiseen liittyvää Dicer-entsyymitason alentumista kohtaan. Tästä kiehtovasta yhteydestä olisi mahdollista saada lisänäyttöä tulevissa tutkimuksissa soveltamalla DicerHET- mallia yhtä helposti primäärisiin DA-neuroneihin.Selective degeneration and dysregulation of specific neuronal populations is a common hallmark shared by neurodegenerative diseases affecting the aging population. Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases with debilitating clinical manifestations that follow a chronic and progressive course. Pathological hallmarks of PD involve gradual and specific loss of DA (DA) neurons and widespread presence of Lewy body (LB) inclusions that consist of aggregated presynaptic protein, α-Synuclein (αSyn). Treatment of PD remains to be at symptomatic management as the underlying mechanisms that trigger neurodegeneration are still not fully elucidated. Over the past two decades, microRNAs (miRNAs) have become a major area of interest within biomedical fields and gained increasing momentum in the context of neurodegenerative diseases. In recent developments, changes in mature miRNA profiles have been reported in aging tissue and many age-related diseases, including PD. More recently, a number of studies have found that the most essential enzyme in the miRNA biogenesis pathway, Dicer, exhibits reduced expression with aging. To these ends, a genetic mouse model based on heterozygous knockout of Dicer (DicerHET) was introduced to simulate Dicer downregulation. Initial investigations identified the DicerHET model as a promising tool for studying the relationship between disrupted miRNA biogenesis and neurodegeneration associated with PD. To facilitate future investigations and speed up screening of potential therapeutic compounds using this genetic model, in the current work, we aimed to produce a DicerHET in vitro model with a practical and convenient genetic engineering approach. The main focus of this work was to validate the model and establish a standardized reproducible approach suitable for research that addresses the role of miRNA biogenesis in PD. The desired DicerHET genotype was generated in vitro by employing traditional Cre/loxP system in conjunction with a virally mediated Cre expression. More specifically, primary cortical cultures, derived from Dicer flox/+ mice embryos, were transduced with Cre expressing lentiviral vectors (lenti-hSYN-T2A-Cre) to delete the “floxed” Dicer allele. To establish optimal parameters for the procedure, we analysed recombination efficiency under different transduction conditions. The most efficient recombination was achieved after 5 days of induction in cultures. However, we observed that DicerHET genotype did not attenuate survival of the cells, as assessed by immunohistochemistry. Further, as a proof of concept, we exposed the DicerHET cultures to pre-formed fibrils (PFFs) - a PD related stressor that causes αSyn aggregation. pSer129-αSyn-positive LB-like aggregates were detected in all the PFF-treated cultures, however, with a greater accumulation in the DicerHET cultures. Interestingly, increased aggregation was not accompanied by increased cell death, suggesting that DicerHET genotype does not increase vulnerability of cortical neurons to pSer129-αSyn aggregation. Based on our earlier studies we presume that DA neurons may bear a specific vulnerability towards the age-related Dicer depletion. More conclusive evidence on this intriguing relationship could be provided in future research using the DicerHET model that can be readily applied to primary DA cultures

Nonpharmacological Interventions for Mild Cognitive Impairment in Parkinson’s Disease

This research examined mild cognitive impairment in Parkinson’s Disease (PD-MCI) and the therapeutic potential of nonpharmacological interventions (e.g., cognitive training and transcranial direct current stimulation) for improving cognition, activities of daily living, and quality of life for people with PD-MCI. The results from this research suggest that cognitive training, tDCS, and cognitive training combined with tDCS may involve stimulation and compensation-focussed strategies that improve cognition, activities of daily living, and quality of life in PD-MCI

Use of functional neuroimaging and optogenetics to explore deep brain stimulation targets for the treatment of Parkinson's disease and epilepsy

Deep brain stimulation (DBS) is a neurosurgical therapy for Parkinson’s disease and epilepsy. In DBS, an electrode is stereotactically implanted in a specific region of the brain and electrical pulses are delivered using a subcutaneous pacemaker-like stimulator. DBS-therapy has proven to effectively suppress tremor or seizures in pharmaco-resistant Parkinson’s disease and epilepsy patients respectively. It is most commonly applied in the subthalamic nucleus for Parkinson’s disease, or in the anterior thalamic nucleus for epilepsy. Despite the rapidly growing use of DBS at these classic brain structures, there are still non-responders to the treatment. This creates a need to explore other brain structures as potential DBS-targets. However, research in patients is restricted mainly because of ethical reasons. Therefore, in order to search for potential new DBS targets, animal research is indispensable. Previous animal studies of DBS-relevant circuitry largely relied on electrophysiological recordings at predefined brain areas with assumed relevance to DBS therapy. Due to their inherent regional biases, such experimental techniques prevent the identification of less recognized brain structures that might be suitable DBS targets. Therefore, functional neuroimaging techniques, such as functional Magnetic Resonance Imaging and Positron Emission Tomography, were used in this thesis because they allow to visualize and to analyze the whole brain during DBS. Additionally, optogenetics, a new technique that uses light instead of electricity, was employed to manipulate brain cells with unprecedented selectivity

Do informal caregivers of people with dementia mirror the cognitive deficits of their demented patients?:A pilot study

Recent research suggests that informal caregivers of people with dementia (ICs) experience more cognitive deficits than noncaregivers. The reason for this is not yet clear. Objective: to test the hypothesis that ICs ‘mirror' the cognitive deficits of the demented people they care for. Participants and methods: 105 adult ICs were asked to complete three neuropsychological tests: letter fluency, category fluency, and the logical memory test from the WMS-III. The ICs were grouped according to the diagnosis of their demented patients. One-sample ttests were conducted to investigate if the standardized mean scores (t-scores) of the ICs were different from normative data. A Bonferroni correction was used to correct for multiple comparisons. Results: 82 ICs cared for people with Alzheimer's dementia and 23 ICs cared for people with vascular dementia. Mean letter fluency score of the ICs of people with Alzheimer's dementia was significantly lower than the normative mean letter fluency score, p = .002. The other tests yielded no significant results. Conclusion: our data shows that ICs of Alzheimer patients have cognitive deficits on the letter fluency test. This test primarily measures executive functioning and it has been found to be sensitive to mild cognitive impairment in recent research. Our data tentatively suggests that ICs who care for Alzheimer patients also show signs of cognitive impairment but that it is too early to tell if this is cause for concern or not