Antipsychotic treatment is the first-line treatment option for schizophrenia. Individual studies suggested they can significantly affect brain structure and account for progressive brain changes ...observed during the illness.
To quantitatively examine the effect of antipsychotics as compared to illness related factors on progressive brain changes in schizophrenia.
Electronic databases were searched until April 2012. All magnetic resonance imaging studies reporting progressive brain changes in schizophrenia subjects and antipsychotic exposure were retrieved.
30 longitudinal MRI studies with antipsychotic administration in schizophrenia patients met the inclusion criteria.
Brain volumes before and after antipsychotic exposure, duration of illness, severity of psychotic symptoms as well as demographic, clinical, and methodological variables were extracted from each publication, or obtained directly from its authors.
The overall sample was of 1046 schizophrenia patients and 780 controls for a median duration of follow-up of 72.4 weeks. At baseline, patients showed significant whole brain volume reductions and enlarged lateral ventricle (LV) volumes compared to controls. No baseline volumetric abnormalities were detected in the gray matter volumes (GMV), white matter volumes, cerebrospinal fluid and caudate nucleus. Longitudinally, there were progressive GMV decreases and LV enlargements in patients but not in controls. The GMV decreases were inversely correlated with cumulative exposure to antipsychotic treatments, while no effects were observed for duration of illness or illness severity.
Schizophrenia is characterized by progressive gray matter volume decreases and lateral ventricular volume increases. Some of these neuroanatomical alterations may be associated with antipsychotic treatment.
This study proposes a bioinspired exotendon routing configuration for a tendon-based mechanism to provide finger flexion and extension that utilizes a single motor to reduce the complexity of the ...system. The configuration was primarily inspired by the extrinsic muscle-tendon units of the human musculoskeletal system. The function of the intrinsic muscle-tendon units was partially compensated by adding a minor modification to the configuration of the extrinsic units. The finger kinematics produced by this solution during flexion and extension were experimentally evaluated on an artificial finger and compared to that obtained using the traditional mechanism, where one exotendon was inserted at the distal phalanx. The experiments were conducted on nine healthy subjects who wore a soft exoskeleton glove equipped with the novel tendon mechanism. Contrary to the traditional approach, the proposed mechanism successfully prevented the hyperextension of the distal interphalangeal (DIP) and the metacarpophalangeal (MCP) joints. During flexion, the DIP joint angles produced by the novel mechanism were smaller than the angles generated by the traditional approach for the same proximal interphalangeal (PIP) joint angles. This provided a flexion trajectory closer to the voluntary flexion motion and avoided straining the interphalangeal coupling between the DIP and PIP joints. Finally, the proposed solution generated similar trajectories when applied to a stiff artificial finger (simulating spasticity). The results, therefore, demonstrate that the proposed approach is indeed an effective solution for the envisioned soft hand exoskeleton system.
The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since ...then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30 years, considering the drugs, potential targets, late‐stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late‐stage Alzheimer's disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta‐analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild‐to‐moderate Alzheimer's disease criteria, recently extending to early or prodromal Alzheimer disease or ‘mild cognitive impairment due to Alzheimer's disease’, for drugs considered to be disease modifying. The duration of trials has remained at 6–12 months for drugs intended to improve symptoms; 18‐ to 24‐month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living, global change and severity ratings have persisted as the primary clinically relevant outcomes. Regulatory guidance and oversight have evolved to allow for enrichment of early‐stage Alzheimer's disease trial samples using biomarkers and phase‐specific outcomes. In conclusion, validated drug targets for Alzheimer's disease remain to be developed. Only drugs that affect an aspect of cholinergic function have shown consistent, but modest, clinical effects in late‐phase trials. There is opportunity for substantial improvements in drug discovery and clinical development methods.
This paper presents the EXOTIC- a novel assistive upper limb exoskeleton for individuals with complete functional tetraplegia that provides an unprecedented level of versatility and control. The ...current literature on exoskeletons mainly focuses on the basic technical aspects of exoskeleton design and control while the context in which these exoskeletons should function is less or not prioritized even though it poses important technical requirements. We considered all sources of design requirements, from the basic technical functions to the real-world practical application. The EXOTIC features: (1) a compact, safe, wheelchair-mountable, easy to don and doff exoskeleton capable of facilitating multiple highly desired activities of daily living for individuals with tetraplegia; (2) a semi-automated computer vision guidance system that can be enabled by the user when relevant; (3) a tongue control interface allowing for full, volitional, and continuous control over all possible motions of the exoskeleton. The EXOTIC was tested on ten able-bodied individuals and three users with tetraplegia caused by spinal cord injury. During the tests the EXOTIC succeeded in fully assisting tasks such as drinking and picking up snacks, even for users with complete functional tetraplegia and the need for a ventilator. The users confirmed the usability of the EXOTIC.
For an individual with tetraplegia assistive robotic arms provide a potentially invaluable opportunity for rehabilitation. However, there is a lack of available control methods to allow these ...individuals to fully control the assistive arms.
Here we show that it is possible for an individual with tetraplegia to use the tongue to fully control all 14 movements of an assistive robotic arm in a three dimensional space using a wireless intraoral control system, thus allowing for numerous activities of daily living. We developed a tongue-based robotic control method incorporating a multi-sensor inductive tongue interface. One abled-bodied individual and one individual with tetraplegia performed a proof of concept study by controlling the robot with their tongue using direct actuator control and endpoint control, respectively.
After 30 min of training, the able-bodied experimental participant tongue controlled the assistive robot to pick up a roll of tape in 80% of the attempts. Further, the individual with tetraplegia succeeded in fully tongue controlling the assistive robot to reach for and touch a roll of tape in 100% of the attempts and to pick up the roll in 50% of the attempts. Furthermore, she controlled the robot to grasp a bottle of water and pour its contents into a cup; her first functional action in 19 years.
To our knowledge, this is the first time that an individual with tetraplegia has been able to fully control an assistive robotic arm using a wireless intraoral tongue interface. The tongue interface used to control the robot is currently available for control of computers and of powered wheelchairs, and the robot employed in this study is also commercially available. Therefore, the presented results may translate into available solutions within reasonable time.
Individuals with tetraplegia have a challenging life due to a lack of independence and autonomy. Assistive robots have the potential to assist with the activities of daily living and thus improve the ...quality of life. However, an efficient and reliable control interface for severely disabled individuals is still missing. An intraoral tongue-computer interface (ITCI) for people with tetraplegia has previously been introduced and tested for controlling a robotic manipulator in a study deploying discrete tongue robot mapping. To improve the efficiency of the interface, the current study proposed the use of virtual buttons based on the ITCI and evaluated them in combination with a joystick-like control implementation, enabling continuous control commands. Twelve able-bodied volunteers participated in a three-day experiment. They controlled an assistive robotic manipulator through the tongue to perform two tasks: Pouring water in a cup (PW) and picking up a roll of tape (PUT). Four different tongue-robot mapping methods were compared. The results showed that using continuous commands reduced the task completion time by 16% and the number of commands of the PUT test by 20% compared with discrete commands. The highest success rate for completing the tasks was 77.8% for the PUT test and 100% for the PW test, both achieved by the control methods with continuous commands. Thus, the study demonstrated that incorporating continuous commands can improve the performance of the ITCI system for controlling robotic manipulators.
Pathways to Alzheimer's disease Hardy, J.; Bogdanovic, N.; Winblad, B. ...
Journal of internal medicine,
March 2014, Letnik:
275, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Recent trials of anti‐amyloid agents have not produced convincing improvements in clinical outcome in Alzheimer's disease; however, the reason for these poor or inconclusive results remains unclear. ...Recent genetic data continue to support the amyloid hypothesis of Alzheimer's disease with protective variants being found in the amyloid gene and both common low‐risk and rare high‐risk variants for disease being discovered in genes that are part of the amyloid response pathways. These data support the view that genetic variability in how the brain responds to amyloid deposition is a potential therapeutic target for the disease, and are consistent with the notion that anti‐amyloid therapies should be initiated early in the disease process.
Individuals with severe tetraplegia can benefit from brain-computer interfaces (BCIs). While most movement-related BCI systems focus on right/left hand and/or foot movements, very few studies have ...considered tongue movements to construct a multiclass BCI. The aim of this study was to decode four movement directions of the tongue (left, right, up, and down) from single-trial pre-movement EEG and provide a feature and classifier investigation. In offline analyses (from ten individuals without a disability) detection and classification were performed using temporal, spectral, entropy, and template features classified using either a linear discriminative analysis, support vector machine, random forest or multilayer perceptron classifiers. Besides the 4-class classification scenario, all possible 3-, and 2-class scenarios were tested to find the most discriminable movement type. The linear discriminant analysis achieved on average, higher classification accuracies for both movement detection and classification. The right- and down tongue movements provided the highest and lowest detection accuracy (95.3±4.3% and 91.7±4.8%), respectively. The 4-class classification achieved an accuracy of 62.6±7.2%, while the best 3-class classification (using left, right, and up movements) and 2-class classification (using left and right movements) achieved an accuracy of 75.6±8.4% and 87.7±8.0%, respectively. Using only a combination of the temporal and template feature groups provided further classification accuracy improvements. Presumably, this is because these feature groups utilize the movement-related cortical potentials, which are noticeably different on the left- versus right brain hemisphere for the different movements. This study shows that the cortical representation of the tongue is useful for extracting control signals for multi-class movement detection BCIs.
Schizophrenia involves abnormalities in the medial frontal cortex that lead to cognitive deficits. Here we investigate a novel strategy to normalize medial frontal brain activity by stimulating ...cerebellar projections. We used an interval timing task to study elementary cognitive processing that requires both frontal and cerebellar networks that are disrupted in patients with schizophrenia. We report three novel findings. First, patients with schizophrenia had dysfunctional delta rhythms between 1-4 Hz in the medial frontal cortex. We explored cerebellar-frontal interactions in animal models and found that both frontal and cerebellar neurons were modulated during interval timing and had delta-frequency interactions. Finally, delta-frequency optogenetic stimulation of thalamic synaptic terminals of lateral cerebellar projection neurons rescued timing performance as well as medial frontal activity in a rodent model of schizophrenia-related frontal dysfunction. These data provide insight into how the cerebellum influences medial frontal networks and the role of the cerebellum in cognitive processing.
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