Assessing neural tuning for object perception in schizophrenia and bipolar disorder with multivariate pattern analysis of fMRI data.

IntroductionDeficits in visual perception are well-established in schizophrenia and are linked to abnormal activity in the lateral occipital complex (LOC). Related deficits may exist in bipolar disorder. LOC contains neurons tuned to object features. It is unknown whether neural tuning in LOC or other visual areas is abnormal in patients, contributing to abnormal perception during visual tasks. This study used multivariate pattern analysis (MVPA) to investigate perceptual tuning for objects in schizophrenia and bipolar disorder.MethodsFifty schizophrenia participants, 51 bipolar disorder participants, and 47 matched healthy controls completed five functional magnetic resonance imaging (fMRI) runs of a perceptual task in which they viewed pictures of four different objects and an outdoor scene. We performed classification analyses designed to assess the distinctiveness of activity corresponding to perception of each stimulus in LOC (a functionally localized region of interest). We also performed similar classification analyses throughout the brain using a searchlight technique. We compared classification accuracy and patterns of classification errors across groups.ResultsStimulus classification accuracy was significantly above chance in all groups in LOC and throughout visual cortex. Classification errors were mostly within-category confusions (e.g., misclassifying one chair as another chair). There were no group differences in classification accuracy or patterns of confusion.ConclusionsThe results show for the first time MVPA can be used successfully to classify individual perceptual stimuli in schizophrenia and bipolar disorder. However, the results do not provide evidence of abnormal neural tuning in schizophrenia and bipolar disorder

Exploration of digital biomarkers in chronic low back pain and Parkinson’s disease

Chronic pain and Parkinson’s disease are illnesses with personal disease progression, symptoms, and the experience of these. The ability to measure and monitor the symptoms by digitally and remotely is still limited. The aim was to study the usability and feasibility of real-world data from wearables, mobile devices, and patients in exploring digital biomarkers in these diseases. The key hypothesis was that this allows us to measure, analyse and detect clinically valid digital signals in movement, heart rate and skin conductance data. The laboratory grade data in chronic pain were collected in an open feasibility study by using a program and built-in sensors in virtual reality devices. The real-world data were collected with a randomized clinical study by clinical assessments, built-in sensors, and two wearables. The laboratory grade dataset in Parkinson’s disease was obtained from Michael J. Fox Foundation. It contained sensor data from three wearables with clinical assessments. The real-world data were collected with a clinical study by clinical assessments, a wearable, and a mobile application. With both diseases the laboratory grade data were first explored, before the real-world data were analyzed. The classification of chronic pain patients with the laboratory grade movement data was possible with a high accuracy. A novel real-world digital signal that correlates with clinical outcomes was found in chronic low back pain patients. A model that was able to detect different movement states was developed with laboratory grade Parkinson’s disease data. A detection of these states followed by the quantification of symptoms was found to be a potential method for the future. The usability of data collection methods in both diseases were found promising. In the future the analyses of movement data in these diseases could be further researched and validated as a movement based digital biomarkers to be used as a surrogate or additional endpoint. Combining the data science with the optimal usability enables the exploitation of digital biomarkers in clinical trials and treatment.Digitaalisten biomarkkereiden tunnistaminen kroonisessä alaselkäkivussa ja Parkinsonin taudissa Krooninen kipu ja Parkinsonin tauti ovat oireiden, oirekokemuksen sekä taudin kehittymisen osalta yksilöllisiä sairauksia. Kyky mitata ja seurata oireita etänä on vielä alkeellista. Väitöskirjassa tutkittiin kaupallisten mobiili- ja älylaitteiden hyödyntämistä digitaalisten biomarkkereiden löytämisessä näissä taudeissa. Pääolettamus oli, että kaupallisten älylaitteiden avulla kyetään tunnistamaan kliinisesti hyödyllisiä digitaalisia signaaleja. Kroonisen kivun laboratorio-tasoinen data kerättiin tätä varten kehitettyä ohjelmistoa sekä kaupallisia antureita käyttäen. Reaaliaikainen kipudata kerättiin erillisen hoito-ohjelmiston tehoa ja turvallisuutta mitanneessa kliinisessä tutkimuksessa sekä kliinisiä arviointeja että anturidataa hyödyntäen. Laboratorio-tasoinena datana Parkinsonin taudissa käytettiin Michael J. Fox Foundationin kolmella eri älylaitteella ja kliinisin arvioinnein kerättyä dataa. Reaaliaikainen data kerättiin käyttäen kliinisia arviointeja, älyranneketta ja mobiilisovellusta. Molempien indikaatioiden kohdalla laboratoriodatalle tehtyä eksploratiivista analyysia hyödynnettiin itse reaaliaikaisen datan analysoinnissa. Kipupotilaiden tunnistaminen laboratorio-tasoisesta liikedatasta oli mahdollista korkealla tarkkuudella. Reaaliaikaisesta liikedatasta löytyi uusi kliinisten arviointien kanssa korreloiva digitaalinen signaali. Parkinsonin taudin datasta kehitettiin uusi liiketyyppien tunnistamiseen tarkoitettu koneoppimis-malli. Sen hyödyntäminen liikedatan liiketyyppien tunnistamisessa ennen varsinaista oireiden mittausta on lupaava menetelmä. Käytettävyys molempien tautien reaaliaikaisissa mittausmenetelmissä havaittiin toimivaksi. Reaaliaikaiseen, kaupallisin laittein kerättävään liikedataan pohjautuvat digitaaliset biomarkkerit ovat lupaava kohde jatkotutkimukselle. Uusien analyysimenetelmien yhdistäminen optimaaliseen käytettävyyteen mahdollistaa tulevaisuudessa digitaalisten biomarkkereiden hyödyntämisen sekä kroonisten tautien kliinisessä tutkimuksessa että itse hoidossa

Are cocaine-seeking “habits” necessary for the development of addiction-like behavior in rats?

Drug self-administration models of addiction typically require animals to make the same response (e.g., a lever-press or nose-poke) over and over to procure and take drugs. By their design, such procedures often produce behavior controlled by stimulus-response (S-R) habits. This has supported the notion of addiction as a “drug habit”, and has led to considerable advances in our understanding of the neurobiological basis of such behavior. However, for addicts to procure drugs, like cocaine, often requires considerable ingenuity and flexibility in seeking behavior, which, by definition, precludes the development of habits. To better model drug-seeking behavior in addicts we first developed a novel cocaine self-administration procedure (the Puzzle Self-Administration Procedure; PSAP) that required rats to solve a new puzzle every day to gain access to cocaine, which they then self-administered on an Intermittent Access (IntA) schedule. Such daily problem-solving precluded the development of S-R seeking habits. We then asked whether prolonged PSAP/IntA experience would nevertheless produce ‘symptoms of addiction’. It did, including escalation of intake, sensitized motivation for drug, continued drug use in the face of adverse consequences and very robust cue-induced reinstatement of drug-seeking, especially in a subset of ‘addiction-prone’ rats. Furthermore, drug-seeking behavior continued to require dopamine neurotransmission in the core of the nucleus accumbens (but not the dorsolateral striatum). We conclude that the development of S-R seeking habits is not necessary for the development of cocaine addiction-like behavior in rats

Epilepsy attacks recognition based on 1D octal pattern, wavelet transform and EEG signals

Electroencephalogram (EEG) signals have been generally utilized for diagnostic systems. Nowadays artificial intelligence-based systems have been proposed to classify EEG signals to ease diagnosis process. However, machine learning models have generally been used deep learning based classification model to reach high classification accuracies. This work focuses classification epilepsy attacks using EEG signals with a lightweight and simple classification model. Hence, an automated EEG classification model is presented. The used phases of the presented automated EEG classification model are (i) multileveled feature generation using one-dimensional (1D) octal-pattern (OP) and discrete wavelet transform (DWT). Here, main feature generation function is the presented octal-pattern. DWT is employed for level creation. By employing DWT frequency coefficients of the EEG signal is obtained and octal-pattern generates texture features from raw EEG signal and wavelet coefficients. This DWT and octal-pattern based feature generator extracts 128 × 8 = 1024 (Octal-pattern generates 128 features from a signal, 8 signal are used in the feature generation 1 raw EEG and 7 wavelet low-pass filter coefficients). (ii) To select the most useful features, neighborhood component analysis (NCA) is deployed and 128 features are selected. (iii) The selected features are feed to k nearest neighborhood classifier. To test this model, an epilepsy seizure dataset is used and 96.0% accuracy is attained for five categories. The results clearly denoted the success of the presented octal-pattern based epilepsy classification model

Use of Image Processing Techniques to Automatically Diagnose Sickle-Cell Anemia Present in Red Blood Cells Smear

Sickle Cell Anemia is a blood disorder which results from the abnormalities of red blood cells and shortens the life expectancy to 42 and 48 years for males and females respectively. It also causes pain, jaundice, shortness of breath, etc. Sickle Cell Anemia is characterized by the presence of abnormal cells like sickle cell, ovalocyte, anisopoikilocyte. Sickle cell disease usually presenting in childhood, occurs more commonly in people from parts of tropical and subtropical regions where malaria is or was very common. A healthy RBC is usually round in shape. But sometimes it changes its shape to form a sickle cell structure; this is called as sickling of RBC. Majority of the sickle cells (whose shape is like crescent moon) found are due to low haemoglobin content. An image processing algorithm to automate the diagnosis of sickle-cells present in thin blood smears is developed. Images are acquired using a charge-coupled device camera connected to a light microscope. Clustering based segmentation techniques are used to identify erythrocytes (red blood cells) and Sickle-cells present on microscopic slides. Image features based on colour, texture and the geometry of the cells are generated, as well as features that make use of a priori knowledge of the classification problem and mimic features used by human technicians. The red blood cell smears were obtained from IG Hospital, Rourkela. The proposed image processing based identification of sickle-cells in anemic patient will be very helpful for automatic, sleek and effective diagnosis of the disease

Multimodal imaging of the self-regulating developing brain

Self-regulation refers to the ability to control behavior, cognition, and emotions, and self-regulation failure is related to a range of neuropsychiatric problems. It is poorly understood how structural maturation of the brain brings about the gradual improvement in self-regulation during childhood. In a large-scale multicenter effort, 735 children (4-21 y) underwent structural MRI for quantification of cortical thickness and surface area and diffusion tensor imaging for quantification of the quality of major fiber connections. Brain development was related to a standardized measure of cognitive control (the flanker task from the National Institutes of Health Toolbox), a critical component of self-regulation. Ability to inhibit responses and impose cognitive control increased rapidly during preteen years. Surface area of the anterior cingulate cortex accounted for a significant proportion of the variance in cognitive performance. This finding is intriguing, because characteristics of the anterior cingulum are shown to be related to impulse, attention, and executive problems in neurodevelopmental disorders, indicating a neural foundation for self-regulation abilities along a continuum from normality to pathology. The relationship was strongest in the younger children. Properties of large-fiber connections added to the picture by explaining additional variance in cognitive control. Although cognitive control was related to surface area of the anterior cingulate independently of basic processes of mental speed, the relationship between white matter quality and cognitive control could be fully accounted for by speed. The results underscore the need for integration of different aspects of brain maturation to understand the foundations of cognitive development

Pharmacological Comparative Characterization of REL-1017 (Esmethadone-HCl) and Other NMDAR Channel Blockers in Human Heterodimeric N-Methyl-D-Aspartate Receptors

Excessive Ca2+ currents via N-methyl-D-aspartate receptors (NMDARs) have been implicated in many disorders. Uncompetitive NMDAR channel blockers are an emerging class of drugs in clinical use for major depressive disorder (MDD) and other neuropsychiatric diseases. The pharmacological characterization of uncompetitive NMDAR blockers in clinical use may improve our understanding of NMDAR function in physiology and pathology. REL-1017 (esmethadone-HCl), a novel uncompetitive NMDAR channel blocker in Phase 3 trials for the treatment of MDD, was characterized together with dextromethorphan, memantine, (±)-ketamine, and MK-801 in cell lines over-expressing NMDAR subtypes using fluorometric imaging plate reader (FLIPR), automated patch-clamp, and manual patch-clamp electrophysiology. In the absence of Mg2+, NMDAR subtypes NR1-2D were most sensitive to low, sub-μM glutamate concentrations in FLIPR experiments. FLIPR Ca2+ determination demonstrated low μM affinity of REL-1017 at NMDARs with minimal subtype preference. In automated and manual patch-clamp electrophysiological experiments, REL-1017 exhibited preference for the NR1-2D NMDAR subtype in the presence of 1 mM Mg2+ and 1 μM L-glutamate. Tau off and trapping characteristics were similar for (±)-ketamine and REL-1017. Results of radioligand binding assays in rat cortical neurons correlated with the estimated affinities obtained in FLIPR assays and in automated and manual patch-clamp assays. In silico studies of NMDARs in closed and open conformation indicate that REL-1017 has a higher preference for docking and undocking the open-channel conformation compared to ketamine. In conclusion, the pharmacological characteristics of REL-1017 at NMDARs, including relatively low affinity at the NMDAR, NR1-2D subtype preference in the presence of 1 mM Mg2+, tau off and degree of trapping similar to (±)-ketamine, and preferential docking and undocking of the open NMDAR, could all be important variables for understanding the rapid-onset antidepressant effects of REL-1017 without psychotomimetic side effects