Clinical Neuroscience Research Research Articles

Emerging Subspecialties in Neurology: Neuroethics: An Emerging Career Path in Neurology.

Essential to responsible practice and progress in neurology and neuroscience research is robust engagement with associated ethical dimensions and challenges. By virtue of the privileged relationship between personhood and the brain, and the importance of properties of the nervous system to what for most makes life worth living, conditions that affect neurologic function introduce a growing host of novel ethical and philosophical issues. Rather than serving a reactionary role, it is important for neurologists to anticipate such issues and develop familiarity with ethical analysis to inform quality medical practice and to safeguard neuroscience research. The field of neuroethics is an emerging career path devoted to identifying and evaluating such issues with the aim of informing optimal clinical practice and responsible neuroscience research. This article describes the past, present, and future of neuroethics, informed by an interview with one of the field's key founders and luminaries, Dr. James Bernat, with specific focus on training and career opportunities for neurologists in training.

Rhythm and Music-Based Interventions in Motor Rehabilitation: Current Evidence and Future Perspectives.

Research in basic and clinical neuroscience of music conducted over the past decades has begun to uncover music’s high potential as a tool for rehabilitation. Advances in our understanding of how music engages parallel brain networks underpinning sensory and motor processes, arousal, reward, and affective regulation, have laid a sound neuroscientific foundation for the development of theory-driven music interventions that have been systematically tested in clinical settings. Of particular significance in the context of motor rehabilitation is the notion that musical rhythms can entrain movement patterns in patients with movement-related disorders, serving as a continuous time reference that can help regulate movement timing and pace. To date, a significant number of clinical and experimental studies have tested the application of rhythm- and music-based interventions to improve motor functions following central nervous injury and/or degeneration. The goal of this review is to appraise the current state of knowledge on the effectiveness of music and rhythm to modulate movement spatiotemporal patterns and restore motor function. By organizing and providing a critical appraisal of a large body of research, we hope to provide a revised framework for future research on the effectiveness of rhythm- and music-based interventions to restore and (re)train motor function.

Laboratoř neuropsychologie Neurologické kliniky 1. LF UK

The Laboratory of Neuropsychology (LN)—Jiří Diamant Neuropsychological Laboratory—is a generic base for research and teaching of clinical and experimental neuropsychology in close connection with clinical neuroscience research and postgraduate studies in neuroscience and medical psychology and psychopathology at the Department of Neurology. The LN provides medical services and participates in teaching and research as required by the Head of the Dept. of Neurology. The LN is a base for collaboration with external departments, especially in the areas of clinical and medical psychology, health psychology, brain imaging, neurosurgery, and psychopharmacology. The research program of the LN is mainly devoted to the neuropsychology of neurodegenerative diseases and the development of neuropsychological tools for the assessment of neuropsychiatric disorders.

Age- and Sex-Related Topological Organization of Human Brain Functional Networks and Their Relationship to Cognition.

Age and sex associated with changes in the functional brain network topology and cognition in large population of older adults have been poorly understood. We explored this question further by examining differences in 11 resting-state graph theory measures with respect to age, sex, and their relationships with cognitive performance in 17,127 United Kingdom Biobank participants (mean = 62.83 ± 7.41 years). Age was associated with an overall decrease in the effectiveness of network communication (i.e., integration) and loss of functional specialization (i.e., segregation) of specific brain regions. Sex differences were also observed, with women showing more efficient networks, which were less segregated than in men (FDR adjusted p < 0.05). The age-related changes were also more apparent in men than in women, which suggests that men may be more vulnerable to cognitive decline with age. Interestingly, while network segregation and strength of limbic network were only nominally associated with cognitive performance, the network measures collectively were significantly associated with cognition (FDR adjusted p ≤ 0.002). This may imply that individual measures may be inadequate to capture much of the variance in the neural activity or its output and need further refinement. The complexity of the organization of the functional brain may be shaped by the age and sex of an individual, which ultimately may influence the cognitive performance of older adults. Age and sex stratification may be used to inform clinical neuroscience research to identify older adults at risk of cognitive dysfunction.

Cause of Subharmonics in Local Field Potentials Recorded by Sensing-Enabled Neurostimulator.

Sensing-enabled neurostimulators have become an essential technology for recording local field potentials (LFPs) during neurostimulation. However, subharmonics from indeterminate sources make interpreting LFP recordings a challenge. In this study, we investigated the characteristics and the cause of the subharmonics recorded by sensing-enabled neurostimulators. We found that the amplitudes and frequencies of the subharmonics in clinical LFPs varied with stimulation parameters. Using simulated solutions, we demonstrated that these subharmonics were device-generated noise. The cause of the subharmonics was the ripples in the stimulation pulses residual in the final LFP recordings. Our results provided a method to discriminate the subharmonic artifacts and suggested that interpretation of the subharmonics at a fractional frequency of stimulations in LFP recordings should be performed carefully.Clinical Relevance- This study reveals the cause of subharmonics in LFP recordings for clinical neuroscience research.

Buyang Huanwu decoction improves neural recovery after spinal cord injury in rats through the mTOR signaling pathway and autophagy

Background: Spinal cord injury (SCI) refers to the interruption of the tracts inside the spinal cord caused by various factors. The repair of damaged axons has always been a difficult point in clinical treatment and neuroscience research. The treatment of SCI with Buyang huanwu decoction (BYHWD), a well-known recipe for invigorating Qi (a vital force forming part of any living entity in traditional Chinese culture) and promoting blood circulation, shows a good effect. Methods: The rubrospinal tract (RST) transection model in rats was established in this study and rats were administrated with low (BL), medium (BM), or high (BH) doses of BYHWD. Results: Compared with the SCI group, BL, BM moderately, and BH significantly improved the motor function of forelimbs and increased the number of red nucleus neurons in SCI rats. As for the possible molecular mechanism, BL, BM moderately, and BH significantly increased mTOR whereas decreased Beclin-1 and LC3 in the red nucleus. Conclusion: In conclusion, low, medium, and high doses of BYHWD could promote neural recovery in SCI rats through improving motor function and neuron survival in the red nucleus. The neuroprotective effects of BYHWD might be associated with affecting the mTOR signaling pathway and autophagy.

"Incidental Discovery of Dedifferentiated Liposarcoma of the Anterior Mediastinum: A Case Report"

Knauss HM1, Glosser LD1, Shi SX2* and Taleb M3 Author Affiliations 1Department of Medical Education, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA 2Clinical Neuroscience Research Center, Department of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA, USA 3Department of Pulmonary/Critical Care Medicine, University of Toledo Medical Center, Toledo, OH, USA Received: August 30, 2021 | Published: September 07, 2021 Corresponding author: Shi SX, Clinical Neuroscience Research Center, Department of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA, USA DOI: 10.26717/BJSTR.2021.38.006178

Sensitivity and resolution improvement for in vivo magnetic resonance current‐density imaging of the human brain

Magnetic resonance current-density imaging (MRCDI) combines MRI with low-intensity transcranial electrical stimulation (TES; 1-2 mA) to map current flow in the brain. However, usage of MRCDI is still hampered by low measurement sensitivity and image quality. Recently, a multigradient-echo-based MRCDI approach has been introduced that presently has the best-documented efficiency. This MRCDI approach has now been advanced in three directions and has been validated by phantom and in vivo experiments. First, the importance of optimum spoiling for brain imaging was verified. Second, the sensitivity and spatial resolution were improved by using acquisition weighting. Third, navigators were added as a quality control measure for tracking physiological noise. Combining these advancements, the optimized MRCDI method was tested by using 1 mA TES for two different injection profiles. For a session duration of 4:20 min, the new MRCDI method was able to detect TES-induced magnetic fields at a sensitivity level of 84 picotesla, representing a twofold efficiency increase against our original method. A comparison between measurements and simulations based on personalized head models showed a consistent increase in the coefficient of determination of ΔR2 = 0.12 for the current-induced magnetic fields and ΔR2 = 0.22 for the current flow reconstructions. Interestingly, some of the simulations still clearly deviated from the measurements despite the strongly improved measurement quality. This highlights the utility of MRCDI to improve head models for TES simulations. The achieved sensitivity improvement is an important step from proof-of-concept studies toward a broader application of MRCDI in clinical and basic neuroscience research.

Decision-making as transdiagnostic construct for mental health research

Transdiagnostic research and linking behavioral, neural, and symptom measures are important endeavors in clinical neuroscience and biological psychiatry. In this issue of Neuron, Moutoussis etal. (2021) describe a new cognitive construct-decision acuity-that is related to mental health symptoms and distinct resting-state networks.

Test-retest reliability of emotion regulation networks using fMRI at ultra-high magnetic field

Given the importance of emotion regulation in affective disorders, emotion regulation is at the focus of attempts to identify brain biomarkers of disease risk, treatment response, and brain development. However, to be useful as an indicator for individual characteristics of brain functions – particularly as a biomarker in a clinical context – ensuring reliability is a key challenge. Here, we systematically evaluated test-retest reliability of task-based functional magnetic resonance imaging (fMRI) activity within neural networks associated with emotion generation and regulation across three sessions. Acquiring fMRI data at ultra-high field (7T), we examined region- and voxel-wise test-retest reliability of brain activity in response to a well-established emotion regulation task for predefined region-of-interests (ROIs) implicated in four neural networks. Test-retest reliability varied considerably across the emotion regulation networks and respective ROIs. However, core emotion regulation regions, including the ventrolateral and dorsolateral prefrontal cortex (vlPFC and dlPFC) as well as the middle temporal gyrus (MTG) showed high reliability. Our findings thus support the role of these prefrontal and temporal regions as promising candidates for the study of individual differences in emotion regulation as well as for neurobiological biomarkers in clinical neuroscience research.

An Obituary to Jacques Glowinski (1936–2020)

This is an obituary of Dr. Jacques Glowinski (1936-2020), one of the last «giants» of Neuropharmacology trained in the sixties in the laboratory of Julius Axelrod (Nobel Prize in 1970). He was a founding father of this discipline in France and his famous laboratory (INSERM Unit 114) at the Collège de France in Paris has trained for 40 years (1966-2006) generations of fellows who became leader neuroscientists in France and abroad. His most important scientific contributions completely revisited the regulatory mechanisms of central dopaminergic neurotransmission and its implications in neuropsychiatric disorders.

Deep Brain Stimulation Initiative: Toward Innovative Technology, New Disease Indications, and Approaches to Current and Future Clinical Challenges in Neuromodulation Therapy.

Deep brain stimulation (DBS) is one of the most important clinical therapies for neurological disorders. DBS also has great potential to become a great tool for clinical neuroscience research. Recently, the National Engineering Laboratory for Neuromodulation at Tsinghua University held an international Deep Brain Stimulation Initiative workshop to discuss the cutting-edge technological achievements and clinical applications of DBS. We specifically addressed new clinical approaches and challenges in DBS for movement disorders (Parkinson's disease and dystonia), clinical application toward neurorehabilitation for stroke, and the progress and challenges toward DBS for neuropsychiatric disorders. This review highlighted key developments in (1) neuroimaging, with advancements in 3-Tesla magnetic resonance imaging DBS compatibility for exploration of brain network mechanisms; (2) novel DBS recording capabilities for uncovering disease pathophysiology; and (3) overcoming global healthcare burdens with online-based DBS programming technology for connecting patient communities. The successful event marks a milestone for global collaborative opportunities in clinical development of neuromodulation to treat major neurological disorders.

The Contribution of Physical Exercise to Brain Resilience

Increasing attention has been given to understanding resilience to brain diseases, often described as brain or cognitive reserve. Among the protective factors for the development of resilience, physical activity/exercise has been considered to play an important role. Exercise is known to induce many positive effects on the brain. As such, exercise represents an important tool to influence neurodevelopment and shape the adult brain to react to life's challenges. Among many beneficial effects, exercise intervention has been associated with cognitive improvement and stress resilience in humans and animal models. Thus, a growing number of studies have demonstrated that exercise not only recovers or minimizes cognitive deficits by inducing better neuroplasticity and cognitive reserve but also counteracts brain pathology. This is evidenced before disease onset or after it has been established. In this review, we aimed to present encouraging data from current clinical and pre-clinical neuroscience research and discuss the possible biological mechanisms underlying the beneficial effects of physical exercise on resilience. We consider the implication of physical exercise for resilience from brain development to aging and for some neurological diseases. Overall, the literature indicates that brain/cognitive reserve built up by regular exercise in several stages of life, prepares the brain to be more resilient to cognitive impairment and consequently to brain pathology.

Research data management in clinical neuroscience: the national research data infrastructure initiative

Abstract In clinical neuroscience, there are considerable difficulties in translating basic research into clinical applications such as diagnostic tools or therapeutic interventions. This gap, known as the “valley of death,” was mainly attributed to the problem of “small numbers” in clinical neuroscience research, i.e. sample sizes that are too small (Hutson et al., 2017). As a possible solution, it has been repeatedly suggested to systematically manage research data to provide long-term storage, accessibility, and federate data. This goal is supported by a current call of the DFG for a national research data infrastructure (NFDI). This article will review current challenges and possible solutions specific to clinical neuroscience and discuss them in the context of other national and international health data initiatives. A successful NFDI consortium will help to overcome not only the “valley of death” but also promises a path to individualized medicine by enabling big data to produce generalizable results based on artificial intelligence and other methods.

Chapter 10 - Spatial topography of the basal forebrain cholinergic projections: Organization and vulnerability to degeneration

The basal forebrain (BF) cholinergic system constitutes a heterogeneous cluster of large projection neurons that innervate the entire cortical mantle and amygdala. Cholinergic neuromodulation plays a critical role in regulating cognition and behavior, as well as maintenance of cellular homeostasis. Decades of postmortem histology research have demonstrated that the BF cholinergic neurons are selectively vulnerable to aging and age-related neuropathology in degenerative diseases such as Alzheimer's and Parkinson's diseases. Emerging evidence from in vivo neuroimaging research, which permits longitudinal tracking of at-risk individuals, indicates that cholinergic neurodegeneration might play an earlier and more pivotal role in these diseases than was previously appreciated. Despite these advances, our understanding of the organization and functions of the BF cholinergic system mostly derives from nonhuman animal research. In this chapter, we begin with a review of the topographical organization of the BF cholinergic system in rodent and nonhuman primate models. We then discuss basic and clinical neuroscience research in humans, which has started to translate and extend the nonhuman animal research using novel noninvasive neuroimaging techniques. We focus on converging evidence indicating that the selective vulnerability of cholinergic neurons in Alzheimer's and Parkinson's diseases is expressed along a rostral-caudal topography in the BF. We close with a discussion of why this topography of vulnerability in the BF may occur and why it is relevant to the clinician.

Altered reward responsiveness and depressive symptoms: An examination of social and monetary reward domains and interactions with rejection sensitivity

BackgroundAlterations in positive valence systems and social processes, including low reward responsiveness and high rejection sensitivity, have been observed in depression. Most reward research focuses on the monetary domain, but social reward responsiveness may be particularly relevant to understanding the etiology of depression, especially in combination with other social processes. Pathways to depression are complex, and research testing interactions between multiple factors is needed. The present study examined the interactive effects of reward responsiveness and rejection sensitivity on depressive symptoms using both social and monetary reward electroencephalogram (EEG) tasks. MethodsEmerging adults (N = 120) completed peer interaction and monetary incentive delay tasks while EEG data were recorded, as well as self-report measures of rejection sensitivity and depressive symptoms. ResultsThe interaction between social reward responsiveness and self-reported rejection sensitivity was significantly associated with depressive symptoms, such that rejection sensitivity was associated with greater depressive symptoms for those with a relatively reduced response to social reward. The interaction between monetary reward responsiveness and rejection sensitivity was not significant. LimitationsThe study was cross-sectional and used a non-clinical sample. ConclusionsResults suggest a possible pathway for depressive symptoms characterized by the combination of high rejection sensitivity and low social reward responsiveness. Findings highlight the need for consideration of multiple domains of reward responsiveness in clinical neuroscience research. With extension to longitudinal studies and clinical samples, the present findings may inform understanding of targets for intervention.

Editorial introductions

Editorial introductions

Recent advances in the application of predictive coding and active inference models within clinical neuroscience.

Research in clinical neuroscience is founded on the idea that a better understanding of brain (dys)function will improve our ability to diagnose and treat neurological and psychiatric disorders. In recent years, neuroscience has converged on the notion that the brain is a 'prediction machine,' in that it actively predicts the sensory input that it will receive if one or another course of action is chosen. These predictions are used to select actions that will (most often, and in the long run) maintain the body within the narrow range of physiological states consistent with survival. This insight has given rise to an area of clinical computational neuroscience research that focuses on characterizing neural circuit architectures that can accomplish these predictive functions, and on how the associated processes may break down or become aberrant within clinical conditions. Here, we provide a brief review of examples of recent work on the application of predictive processing models of brain function to study clinical (psychiatric) disorders, with the aim of highlighting current directions and their potential clinical utility. We offer examples of recent conceptual models, formal mathematical models, and applications of such models in empirical research in clinical populations, with a focus on making this material accessible to clinicians without expertise in computational neuroscience. In doing so, we aim to highlight the potential insights and opportunities that understanding the brain as a prediction machine may offer to clinical research and practice.

Programmable Transcranial Magnetic Stimulation: A Modulation Approach for the Generation of Controllable Magnetic Stimuli.

A transcranial magnetic stimulation system with programmable stimulus pulses and patterns is presented. The stimulus pulses of the implemented system expand beyond conventional damped cosine or near-rectangular pulses and approach an arbitrary waveform. The desired stimulus waveform shape is defined as a reference signal. This signal controls the semiconductor switches of an H-bridge inverter to generate a high-power imitation of the reference. The design uses a new paradigm for TMS, applying pulse-width modulation with a non-resonant, high-frequency switching architecture to synthesize waveforms that leverages the low-pass filtering properties of neuronal cells. The modulation technique enables control of the waveform, frequency, pattern, and intensity of the stimulus. A system prototype was developed to demonstrate the technique. The experimental measurements demonstrate that the system is capable of generating stimuli up to 4 kHz with peak voltage and current values of ±1000 V and ±3600 A, respectively. The maximum transferred energy measured in the experimental validation was 100.4 Joules. To characterize repetitive TMS modalities, the efficiency of generating consecutive pulse triplets and quadruplets with interstimulus intervals of 1 ms was tested and verified. The implemented TMS device can generate consecutive rectangular pulses with a predetermined time interval, widths and polarities, enables the synthesis of a wide range of magnetic stimuli. New waveforms promise functional advantages over the waveforms generated by current-generation TMS systems for clinical neuroscience research.

Advances in multimodal data fusion in neuroimaging: Overview, challenges, and novel orientation

Multimodal fusion in neuroimaging combines data from multiple imaging modalities to overcome the fundamental limitations of individual modalities. Neuroimaging fusion can achieve higher temporal and spatial resolution, enhance contrast, correct imaging distortions, and bridge physiological and cognitive information. In this study, we analyzed over 450 references from PubMed, Google Scholar, IEEE, ScienceDirect, Web of Science, and various sources published from 1978 to 2020. We provide a review that encompasses (1) an overview of current challenges in multimodal fusion (2) the current medical applications of fusion for specific neurological diseases, (3) strengths and limitations of available imaging modalities, (4) fundamental fusion rules, (5) fusion quality assessment methods, and (6) the applications of fusion for atlas-based segmentation and quantification. Overall, multimodal fusion shows significant benefits in clinical diagnosis and neuroscience research. Widespread education and further research amongst engineers, researchers and clinicians will benefit the field of multimodal neuroimaging.