Clinical Neuroscience Research Articles

How patients become pilots of their disease

‚Patients need to know what the data is for, what the data means for them personally and, of course, for other patients,‘ explained Prof. Tjalf Ziemssen, MD, Director of the Centre for Clinical Neurosciences and Deputy Clinic Director of the Clinic and Polyclinic for Neurology at the Centre for Clinical Neurosciences at the Neurological University Hospital Dresden at the Roche Pharma DKVF Symposium entitled ‚Data use as an end in itself or for the benefit of the patient?‘. According to Ziemssen, it has often been the case in the past that although attempts have been made to obtain more and more data from patients in order to conduct research and introduce innovations, this is usually done without the patient benefiting directly or being able to understand what the data means for them personally. As a negative example, Mr Ziemssen cited the electronic patient file, which would have no structure that the patient would not be able to deal with operationally. The concept of the ‚digital twin‘, which he propagates, is different (see interview page 22 ff).

„Der ,Digitale Zwilling‘ kann die MS-Versorgung wirklich verbessern“

Prof. Dr Tjalf Ziemssen sees himself as a digital pioneer with a lot of passion. Alongside and parallel to his day-to-day work at the Centre for Clinical Neurosciences at the Neurological University Hospital Dresden, treating patients with multiple sclerosis, he and his team are developing the concept of the ‚digital MS twin‘. This can be thought of as a virtual copy, a digital dashboard or, in modern parlance, an avatar of a patient that is able to quantitatively describe the individual disease. The beauty of this is that a combination of artificial intelligence, machine learning and data analysis enables digital twins to uncover problems before they occur and optimise processes.

The effect of oral galactose on oxidative stress in the brain of a transgenic mice model of Alzheimer’s disease

AbstractBackgroundChanges in the brain energy metabolism and oxidative stress can be found before development of Aβ plaques in Alzheimer’s disease (AD) and galactose showed potential therapeutic effect in Tg2576 mice AD model. We aimed to investigate changes in the hippocampal (HPC) energy status and oxidative stress before and after galactose treatment in this model.MethodAdult male B6; SJL‐Tg(APPSWE)2576Kha transgenic (TG) mice (Tg2576) and wild types (WT) aged 5 (5M) and 10 (10M) months were used. Oral galactose therapy was given to half of WT (WT+G) and half of TG (TG+G) group for 2 months (200mg/kg/day), while another half of each group received water ad libitum. Protein expression of insulin receptor substrate (total and phosphorylated; IRS, pIRS), AMP‐activated protein kinase (AMPK, p‐AMPK) was measured by western blot. Corticosterone levels were measured by ELISA, and spectrophotometry were used to measure the parameters of oxidative stress (MnSOD; TBARS). Data were analyzed by Kruskal‐Wallis and Mann‐Whitney U‐test (p<0.05).ResultThe levels of corticosterone were decreased in 5M TG mice (p = 0.0055; n = 8) and galactose (5M TG+G) increased it to the levels of control. Galactose decreased MnSOD (p = 0.0329;n = 5) in 10M TG mice. The decrement in p/t IRS ratio (p = 0.043; n = 5) was seen only in 10M TG mice, and galactose (10M TG+G) reversed it to the levels of control. Increased AMPAK levels were found in 5M TG+G (p = 6,5e‐04; n = 5) and 5M WT+G (p = 8,6e‐05; n = 5) groups, while pAMPK was increased only in 5M TG (p = 0.013; n = 5), and decreased in 5M TG+G group after galactose treatment (p = 0.034: n = 5).ConclusionGalactose increased the corticosterone and AMPK levels in young TG mice, while in older TG mice oral galactose had the effect on the level of MnSOD and p/t IRS ratio. The potential therapeutic impact of oral galactose in Tg2576 mice seems to be connected to maintaining of oxidative stress and energy balance and depends on the animal age and AD stage at which the treatment was initiated. Supported by HRZZ IP‐2018‐01‐8938 and the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience (project “Experimental and clinical research of hypoxic‐ischemic damage in perinatal and adult brain”, GA KK01.1.1.01.0007 funded by the European Union)

The involvement of GLP1 signaling with the effect of oral galactose in the hypothalamus of sporadic Alzheimer’s disease rat model

AbstractBackgroundIntracerebroventricular (icv) application of streptozotocin (STZ) causes mytochondrial dysfunction, oxidative stress and other metabolic effects, which leads to accumulation of τ‐protein and Aß plaques that makes it suitable for animal model of sporadic Alzheimer’s disease (sAD). We aimed to explore whether acute effect of single oral galactose dose is mediated by glucagon‐like peptide‐1 (GLP‐1) in sAD rat model.MethodWistar rats were injected icv with STZ (3 mg/kg) or vehicle only (CTR). One month after the injection, animals were divided into three experiments. First experiment: 200 mg/kg galactose was given orally and CTR animals were sacrificed 30, 60 and 120 min after administration. Second experiment: GLP‐1R antagonist (Exendin 9‐39, 85 µg/kg; GLP1Ra) was administered icv in both groups and animals were sacrificed 30 min after the injection. Third experiment: 30 min prior to oral galactose, rats were injected icv with GLP‐1Ra, and animals were sacrificed 120 min after galactose load. PDH, COXIV, CytC and Casp‐3 levels were measured by Western blot method and lactate, ATP and SOD were measured by ELISA in HPT. Glucose, galactose and GLP‐1 levels were measured in plasma and CSF. Data were analyzed by principal component analysis and Spearman rank correlation.ResultMetabolic changes were found more pronounced 120 min after single galactose load: reduced levels of Casp‐3 and PDH and increased SOD levels in HPT; increased CSF glucose. GLP1Ra decreased the levels of lactate, COXIV and CytC and increased PDH and Casp‐3 levels in HPT, only in STZ treated animals. CytC was found negatively correlated with ATP and PDH levels in HPT. GLP1Ra decreased the levels of CytC and SOD and increased PDH levels in CTR only after oral galactose.ConclusionGLP1Ra might inhibit decreased PDH levels caused by single galactose load. GLP1R central inhibition has more pronounced effect in STZ‐icv treated rats suggesting the involvement of GLP1 signaling in model pathogenesis. Supported by Croatian Science Foundation and co‐financed by the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience (project “Experimental and clinical research of hypoxic‐ischemic damage in perinatal and adult brain”; GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund).

Toward a Unified Classification System for Brain-Mind Disorders: Putting Calls for Integrated Clinical Neuroscience Into Action.

Dividing the brain-mind into the specialized fields of neurology and psychiatry has produced many granular advantages, but these silos have imposed barriers to comprehensively understanding and contextualizing the fundamentals governing mental life and its maladies. Scientific inquiry into these fundamentals cannot reach its full potential without interdigitating the boundaries of two specialties of the same organ for both scholarship and clinical practice. We propose that to truly integrate disorders of the brain and the mind for research and clinical care, we must carefully reexamine the classification of its disorders (nosology) as an instrument to develop a coherent pathological and psychological framework. We call on professional organizations from neurology, psychiatry, behavioral neurology, neuropsychiatry, neuropsychology, and other relevant subspecialties (eg, geriatric psychiatry) to convene a multidisciplinary task force to define the current classification principles of their subspecialties and work toward developing an integrated nosology. The effect of a shared classification system, which we acknowledge is a difficult proposition philosophically and politically, would have transformative potential across educational, clinical, scientific, programmatic, and sociocultural realms. If accomplished, this initiative would provide a definitive step toward reducing stigma (and promoting reimbursement parity) for the full spectrum of complex brain disorders (regardless of traditional neurologic vs psychiatric conceptualizations).

The Problem of the Commemorative Function of Eponymous Terms in Clinical Neurosciences

Eponymous terminology plays an important role in medicine: it is impossible to imagine an area of study in which there would not be used compound terms with an onomastic component or common nouns derived from onyms. Nevertheless, there is an ambiguous attitude towards eponymous terms in the scientific community. From the point of view of displaying linguistic and cultural-historical information, the most important function which is realized in the eponymous terms with an anthroponomic core is the commemorative function. The aim of this study is to analyze the commemorative function of the eponymous terms of clinical neurosciences (neurology and psychiatry). Practical material is taken from MedicineNet.com. During the study, using the method of continuous sampling, 155 eponymous terms were selected. The study made it possible to identify the following problems of the current state of the terminological system of neurology and psychiatry: the use of patients’ surnames as an eponymous component of the term along with the surnames of doctors; inaccuracy of information about the history of the study of diseases associated with the perpetuation in terms of the names of doctors who are not pioneers; the presence in the terminology of negatively colored onyms associated with the ideologists and accomplices of Nazism.

Advances in Ultrafast Fiber Lasers for Multiphoton Microscopy in Neuroscience

Multiphoton microscopy (MPM) has emerged as a vital tool in neuroscience, enabling deeper imaging with a broader field of view, as well as faster and sub-cellular resolution. Recent innovations in ultrafast fiber laser technology have revolutionized MPM applications in living brains, offering advantages like cost-effectiveness and user-friendliness. In this review, we explore the progress in ultrafast fiber laser technology, focusing on its integration into MPM for neuroscience research. We also examine the utility of femtosecond fiber lasers in fluorescence and label-free two- and three-photon microscopy applications within the field. Furthermore, we delve into future possibilities, including next-generation fiber laser designs, novel laser characteristics, and their potential for achieving high spatial and temporal resolution imaging. We also discuss the integration of fiber lasers with implanted microscopes, opening doors for clinical and fundamental neuroscience investigations.

Diffuse Correlation Spectroscopy: A Review of Recent Advances in Parallelisation and Depth Discrimination Techniques

Diffuse correlation spectroscopy is a non-invasive optical modality used to measure cerebral blood flow in real time, and it has important potential applications in clinical monitoring and neuroscience. As such, many research groups have recently been investigating methods to improve the signal-to-noise ratio, imaging depth, and spatial resolution of diffuse correlation spectroscopy. Such methods have included multispeckle, long wavelength, interferometric, depth discrimination, time-of-flight resolution, and acousto-optic detection strategies. In this review, we exhaustively appraise this plethora of recent advances, which can be used to assess limitations and guide innovation for future implementations of diffuse correlation spectroscopy that will harness technological improvements in the years to come.

The Major Hypotheses of Alzheimer's Disease: Related Nanotechnology-Based Approaches for Its Diagnosis and Treatment.

Alzheimer's disease (AD) is a well-known chronic neurodegenerative disorder that leads to the progressive death of brain cells, resulting in memory loss and the loss of other critical body functions. In March 2019, one of the major pharmaceutical companies and its partners announced that currently, there is no drug to cure AD, and all clinical trials of the new ones have been cancelled, leaving many people without hope. However, despite the clear message and startling reality, the research continued. Finally, in the last two years, the Food and Drug Administration (FDA) approved the first-ever medications to treat Alzheimer's, aducanumab and lecanemab. Despite researchers' support of this decision, there are serious concerns about their effectiveness and safety. The validation of aducanumab by the Centers for Medicare and Medicaid Services is still pending, and lecanemab was authorized without considering data from the phase III trials. Furthermore, numerous reports suggest that patients have died when undergoing extended treatment. While there is evidence that aducanumab and lecanemab may provide some relief to those suffering from AD, their impact remains a topic of ongoing research and debate within the medical community. The fact is that even though there are considerable efforts regarding pharmacological treatment, no definitive cure for AD has been found yet. Nevertheless, it is strongly believed that modern nanotechnology holds promising solutions and effective clinical strategies for the development of diagnostic tools and treatments for AD. This review summarizes the major hallmarks of AD, its etiological mechanisms, and challenges. It explores existing diagnostic and therapeutic methods and the potential of nanotechnology-based approaches for recognizing and monitoring patients at risk of irreversible neuronal degeneration. Overall, it provides a broad overview for those interested in the evolving areas of clinical neuroscience, AD, and related nanotechnology. With further research and development, nanotechnology-based approaches may offer new solutions and hope for millions of people affected by this devastating disease.

Providing Buffers, Solving Barriers: Value-Driven Policies and Actions that Protect Clients Today and Increase the Chances of Thriving Tomorrow

AbstractBetween 1990 and 2018, regions spent between 2.67% (Europe) and 3.6% (North America) of their GDP to treat harmful behavioral, medical, and other effects of significant adverse experience (Bellis et al., 2019 The Lancet Public Health, 4(10), e517–e528). Although dose-dependent exposure to adverse childhood experiences harms long-term medical health (e.g., Anda et al., 2006; European Archives of Psychiatry & Clinical Neuroscience, 256, 174–186, Anda et al., 2008; American Journal of Preventive Medicine, 34(5), 396–403, Dong et al., 2004; Circulation, 110(13), 1761–1766, Felitti and Anda, 2009), six specific buffers (nurturing relationships; nutrition; physical activity; sleep; mental health support; and reducing stress) protect against these harmful health impacts (Purewal et al., 2016, Zero to Three, 37(1), 10–17). However, barriers related to access, information, resources, or behavioral needs prevent many from experiencing the benefits. This article describes an approach in which each buffer area is addressed in the context of its overlap with behavior analytic practice, and supported by related policy suggestions. Providers are invited to adopt an informative buffer policy as an antecedent to client services; establish a collaborative network of providers and resources; and expand buffer promotion beyond clients to other stakeholders including caregivers and staff. The aim of this article is to inspire and empower individuals to use several specific actions: (1) learn about buffers and consider barriers to them; (2) educate others about buffers and barriers to them; (3) scan a client’s environment for buffers and barriers; and (4) consider ways to install buffers and resolve barriers for clients or others as appropriate.

Predictive Clinical Neuroscience Portal (PCNportal): instant online access to research-grade normative models for clinical neuroscientists.

Background The neurobiology of mental disorders remains poorly understood despite substantial scientific efforts, due to large clinical heterogeneity and to a lack of tools suitable to map individual variability. Normative modeling is one recently successful framework that can address these problems by comparing individuals to a reference population. The methodological underpinnings of normative modelling are, however, relatively complex and computationally expensive. Our research group has developed the python-based normative modelling package Predictive Clinical Neuroscience toolkit (PCNtoolkit) which provides access to many validated algorithms for normative modelling. PCNtoolkit has since proven to be a strong foundation for large scale normative modelling, but still requires significant computation power, time and technical expertise to develop. Methods To address these problems, we introduce PCNportal. PCNportal is an online platform integrated with PCNtoolkit that offers access to pre-trained research-grade normative models estimated on tens of thousands of participants, without the need for computation power or programming abilities. PCNportal is an easy-to-use web interface that is highly scalable to large user bases as necessary. Finally, we demonstrate how the resulting normalized deviation scores can be used in a clinical application through a schizophrenia classification task applied to cortical thickness and volumetric data from the longitudinal Northwestern University Schizophrenia Data and Software Tool (NUSDAST) dataset. Results At each longitudinal timepoint, the transferred normative models achieved a mean[std. dev.] explained variance of 9.4[8.8]%, 9.2[9.2]%, 5.6[7.4]% respectively in the control group and 4.7[5.5]%, 6.0[6.2]%, 4.2[6.9]% in the schizophrenia group. Diagnostic classifiers achieved AUC of 0.78, 0.76 and 0.71 respectively. Conclusions This replicates the utility of normative models for diagnostic classification of schizophrenia and showcases the use of PCNportal for clinical neuroimaging. By facilitating and speeding up research with high-quality normative models, this work contributes to research in inter-individual variability, clinical heterogeneity and precision medicine.

GLIOMA-06 THE GLIOMA CONNECTOME PROJECT – UPDATE

Abstract The ability to define specific fiber tracts in individual patients before, during and following surgery represents a major advance in neurosurgical oncology. The Human Connectome Project (Glasser, 2016) generated insights into the organization of critically important “hubs” and pathways (edges) defining 7 major networks. There is a paradigm shift in our view of neurological functions from an outdated “modular” concept to a network perspective (Fox, 2018). Connectomics affects all branches of clinical neuroscience, including neuropsychiatry, stroke, trauma, neurodegenerative diseases, and especially glioblastoma. We first developed individualized maps of white matter (WM) pathways for a connectivity-based paradigm for neurosurgical planning (Tunç, 2016). We reviewed the principles and the potential applications of connectomics in the neurosurgical treatment of gliomas (Henderson, 2020). Working with key thought leaders, experienced neurosurgeons, and scientific partners (Omniscient Neurotechnology; Michael Sughrue), we developed the Glioma Connectome Project protocol, accruing the first patients at the University of Pennsylvania (UPCC#22321), funded by the StacheStrong, and now accruing patients nationwide: U. Miami (PI, Michael Ivan), Northwestern (PI, Matthew Tate), U. of Nebraska (Michele Aizenberg), Henry Ford Hospital (Ian Lee), University of Texas (Yoshua Esquenazi), and U. Pittsburgh (Costas Hadjipanayis). The specific aims of the GCP include 1) validation of connectomic metrics (global efficiency, FWHM, betweenness centrality, etc.); 2) cognitive correlates using the NIH Toolbox; 3) mapping the trajectory of recovery; 4) the effects of treatment at the level of WM fiber tracts; 5) re-imagining surgical approaches and 6) developing biomarkers for “virtual trials” to assess response to therapy. In the past 2.5 years since the inception of the GCP, we have overcome numerous technical and organizational challenges to develop a federated system to harmonize “big data”. The scientific and practical lessons learned will be highlighted.

Decoding the brain’s role in preventing and recovering from knee injuries

Decoding the brain’s role in preventing and recovering from knee injuries Dustin Grooms, Professor of Clinical Neuroscience at Ohio University, tells us about his research on the brain’s role in shaping injury-risk movement patterns and how this knowledge could aid rehabilitation practices and the development of new therapies to mitigate the risk of knee injuries. In sports, where split-second decisions and fast movements are crucial, knee injuries like torn ACLs pose a challenge. Experts focus on biomechanics and lower body strength, but a new frontier explores the brain’s impact on prevention and recovery. With nearly 200,000 annual ACL injuries in the US, especially among young athletes, research delves into the connection between neural adaptation and physical performance. Recent studies from our lab highlight the brain’s role in shaping injury-risk movement patterns and provide a roadmap for reducing injury risk by understanding how the brain processes sensory inputs.

11.P. Workshop: Inequities in physical and mental health, and health care utilization for LGBTQ groups across Europe

Abstract Compared to heterosexual cisgender-identified individuals, lesbian, gay, bisexual, and transgender and queer (LGBTQ) individuals evidence pronounced poor mental and physical health outcomes, as well as sub-optimal healthcare access and utilization. Yet, most of the evidence documenting these disparities comes from a small group of Western countries. This limited knowledge across health conditions and geographical regions leaves multiple important questions unanswered. In particular, it remains unknown to what degree these disparities may be generalizable to contexts that have not yet been studied. This workshop includes novel reports on disparities in health, wellbeing, and healthcare access between LGBTQ groups and their heterosexual cisgender counterparts across several European countries where such data were not previously available. Through these four presentations, we explore health inequalities across Europe in physical and mental health, as well as healthcare utilization. Findings emphasize a continued need for attention to systems that can be modified (e.g., trainings of healthcare cadre, resource allocation) to reduce health disparities that uniquely burden LGBTQ groups. Andreas Pfister (Zurich University of Applied Sciences, Switzerland) will present the first national systematically documented psychosocial burden and healthcare access disparities for LGBTQ individuals compared to their heterosexual cisgender counterparts in Switzerland. Sladjana Baros (Centre for Disease Prevention and Control, Department for HIV, Hepatitis, Sexually Transmitted Infections and Tuberculosis, Institute of Public Health of Serbia ‘Dr Milan Jovanovic Batut’, Republic of Serbia) will present findings from the HIV testing cascade among men who have sex with men at high risk for HIV. Michal Pitonak (Center for Epidemiological and Clinical Research of Drug Abuse and Dependence, National Institute of Mental Health, Klecany, Czech Republic) will present data on disproportionate rates of psychological distress reported by lesbian, gay and bisexual individuals compared to heterosexual individuals in the Czech Republic. Lastly, Luis Roxo (Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Sweden) will present population-based data on differences in mental health services and unmet mental health needs based on sexual orientation among Swedish young adults. Key messages • Despite being the first of such evidence, findings from these four European countries are consistent with reports from other global regions, signalling that these disparities are universal. • A clear need emerges for structural changes to increase access to and expertise in affirmative LGBTQ healthcare to reduce disproportionate morbidity rates for LGBTQ people in Europe.

Brain Health Registry Study Partner Portal: Novel infrastructure for digital, dyadic data collection.

In Alzheimer's disease (AD) research, subjective reports of cognitive and functional decline from participant-study partner dyads is an efficient method of assessing cognitive impairment and clinical progression. Demographics and subjective cognitive/functional decline (Everyday Cognition Scale [ECog]) scores from dyads enrolled in the Brain Health Registry (BHR) Study Partner Portal were analyzed. Associations between dyad characteristics and both ECog scores and study engagement were investigated. A total of 10,494 BHR participants (mean age=66.9±12.16 standard deviations, 67.4% female) have enrolled study partners (mean age=64.3±14.3 standard deviations, 49.3% female), including 8987 dyads with a participant 55 years of age or older. Older and more educated study partners were more likely to complete tasks and return for follow-up. Twenty-five percent to 27% of older adult participants had self and study partner-report ECog scores indicating a possible cognitive impairment. The BHR Study Partner Portal is a unique digital tool for capturing dyadic data, with high impact applications in the clinical neuroscience and AD fields. Highlights The Brain Health Registry (BHR) Study Partner Portal is a novel, digital platform of>10,000 dyads. Collection of dyadic online subjective cognitive and functional data is feasible. The portal has good usability as evidenced by positive study partner feedback. The portal is a potential scalable strategy for cognitive impairment screening in older adults.

Introducing some BANN members

Julie Derbyshire introduces Annette Hand and Emily Ashcroft, detailing their clinical experience and neuroscience background. Both exceptional individuals and advocates for neuroscience nursing, it is fantastic to see the breadth of clinical and academic expertise represented both on the British Association of Neuroscience Nurses (BANN) committee and within its membership.

Medical Metaverse, Part 2: Artificial Intelligence Algorithms and Large Language Models in Psychiatry and Clinical Neurosciences.

Medical Metaverse, Part 2: Artificial Intelligence Algorithms and Large Language Models in Psychiatry and Clinical Neurosciences.

Accelerated transcranial magnetic stimulation for major depressive disorder: A quick path to relief?

Transcranial magnetic stimulation (TMS) is a safe, tolerable, and evidence-based intervention for major depressive disorder (MDD). However, even after decades of research, nearly half of the patients with MDD fail to respond to conventional TMS, with responding slowly and requiring daily attendance at the treatment site for 4-6 weeks. To intensify antidepressant efficacy and shorten treatment duration, accelerated TMS protocols, which involve multiple sessions per day over a few days, have been proposed and evaluated for safety and viability. We reviewed and summarized the current knowledge in accelerated TMS, including stimulation parameters, antidepressant efficacy, anti-suicidal efficacy, safety, and adverse effects. Limitations and suggestions for future directions are also addressed, along with a brief discussion on the application of accelerated TMS during the COVID-19 pandemic. This article is categorized under: Neuroscience > Clinical Neuroscience.

Integrating basic, clinical, and health system science in a medical neuroscience course of an integrated pre-clerkship curriculum.

Basic science, clinical science, and health system science (HSS) have become three pillars of integration upon which modern, post-Flexner, medical education is now based. Because of this new approach to curricular integration in a clinical presentation curruculum, medical training is now placed in the context of healthcare delivery. This study described the design, implementation, and assessment of an integrated teaching strategy, including the effect on students' performance in a medical neuroscience course's summative and formative examinations of an integrated clinical presentation curriculum. The integrated teaching of basic science content, clinical case discussion, and HSS was performed in the first year of an allopathic integrated pre-clerkship curriculum. The two cohorts were from two different years, spring 2018 and 2019. The acceptance of the integrated teaching strategy by medical students was above 80% in all categories that were assessed, including enhancing the integrated experience in learning basic and clinical science materials in the context of HSS; understanding of the learning lessons; facilitation of self-directed learning; provision of a better learning environment; and a holistic understanding of materials including the relevance of HSS issues in the discussion of neurological cases in the medical career of the students. More than 90% of the students scored ≥70% in summative questions mapped to the four learning objectives of the integrated teaching session. The objectives are the correlation of structure to specific functions (94.0 ± 0.21), clinical anatomical features of the nervous system (95.0 ± 0.27), cross-sectional features of the nervous system (96.0 ± 0.31), and the effect of lesions on the structure and functional pathways of the nervous system (97.0 ± 0.34). This result was significantly higher when compared to students' performance in the non-integrated teaching cohort (p < 0.05). Formative assessments (F(7,159) = 92.52, p < 0.001) were significantly different between the two groups. When medical students were evaluated using the same questions for formative assessment, they performed better in the integrated teaching cohort (*p < 0.05) compared to the non-integrated teaching cohort (**p < 0.05).

Chronic subdural electrocorticography in nonhuman primates by an implantable wireless device for brain-machine interfaces.

Subdural electrocorticography (ECoG) signals have been proposed as a stable, good-quality source for brain-machine interfaces (BMIs), with a higher spatial and temporal resolution than electroencephalography (EEG). However, long-term implantation may lead to chronic inflammatory reactions and connective tissue encapsulation, resulting in a decline in signal recording quality. However, no study has reported the effects of the surrounding tissue on signal recording and device functionality thus far. In this study, we implanted a wireless recording device with a customized 32-electrode-ECoG array subdurally in two nonhuman primates for 15 months. We evaluated the neural activities recorded from and wirelessly transmitted to the devices and the chronic tissue reactions around the electrodes. In addition, we measured the gain factor of the newly formed ventral fibrous tissue in vivo. Time-frequency analyses of the acute and chronic phases showed similar signal features. The average root mean square voltage and power spectral density showed relatively stable signal quality after chronic implantation. Histological examination revealed thickening of the reactive tissue around the electrode array; however, no evident inflammation in the cortex. From gain factor analysis, we found that tissue proliferation under electrodes reduced the amplitude power of signals. This study suggests that subdural ECoG may provide chronic signal recordings for future clinical applications and neuroscience research. This study also highlights the need to reduce proliferation of reactive tissue ventral to the electrodes to enhance long-term stability.