Adaptive optics, microscopy, and beyond: an interview with Professor Na Ji.

Prof. Na Ji (UC Berkeley) discusses her pioneering work and motivation in adaptive optics, microscopy, and beyond, in an interview with former trainee Anderson Chen (Prisma Therapeutics, Inc.).

Screening, Assessment, and Pharmacologic Treatment of Mild Cognitive Impairment and Early Alzheimer's Disease: The Role for Monoclonal Antibodies.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord. 2023;25(6):23f03544. Author affiliations are listed at the end of this article.

Optical coherence tomography-based design for a real-time motion corrected scanning microscope.

While two-photon fluorescence microscopy is a powerful platform for the study of functional dynamics in living cells and tissues, the bulk motion inherent to these applications causes distortions. We have designed a motion tracking module based on spectral domain optical coherence tomography which compliments a laser scanning two-photon microscope with real-time corrective feedback. The module can be added to fluorescent imaging microscopes using a single dichroic and without additional contrast agents. We demonstrate that the system can track lateral displacements as large as 10 µm at 5 Hz with latency under 14 ms and propose a scheme to extend the system to 3D correction with the addition of a remote focusing module. We also propose several ways to improve the module's performance by reducing the feedback latency. We anticipate that this design can be adapted to other imaging modalities, enabling the study of samples subject to motion artifacts at higher resolution.

Neurophotonic tools for microscopic measurements and manipulation: status report.

Neurophotonics was launched in 2014 coinciding with the launch of the BRAIN Initiative focused on development of technologies for advancement of neuroscience. For the last seven years, Neurophotonics' agenda has been well aligned with this focus on neurotechnologies featuring new optical methods and tools applicable to brain studies. While the BRAIN Initiative 2.0 is pivoting towards applications of these novel tools in the quest to understand the brain, this status report reviews an extensive and diverse toolkit of novel methods to explore brain function that have emerged from the BRAIN Initiative and related large-scale efforts for measurement and manipulation of brain structure and function. Here, we focus on neurophotonic tools mostly applicable to animal studies. A companion report, scheduled to appear later this year, will cover diffuse optical imaging methods applicable to noninvasive human studies. For each domain, we outline the current state-of-the-art of the respective technologies, identify the areas where innovation is needed, and provide an outlook for the future directions.

Model of dynamic speckle evolution for evaluating laser speckle contrast measurements of tissue dynamics.

We introduce a dynamic speckle model (DSM) to simulate the temporal evolution of fully developed speckle patterns arising from the interference of scattered light reemitted from dynamic tissue. Using this numerical tool, the performance of laser speckle contrast imaging (LSCI) or speckle contrast optical spectroscopy (SCOS) systems which quantify tissue dynamics using the spatial contrast of the speckle patterns with a certain camera exposure time is evaluated. We have investigated noise sources arising from the fundamental speckle statistics due to the finite sampling of the speckle patterns as well as those induced by experimental measurement conditions including shot noise, camera dark and read noise, and calibrated the parameters of an analytical noise model initially developed in the fundamental or shot noise regime that quantifies the performance of SCOS systems using the number of independent observables (NIO). Our analysis is particularly focused on the low photon flux regime relevant for human brain measurements, where the impact of shot noise and camera read noise can become significant. Our numerical model is also validated experimentally using a novel fiber based SCOS (fb-SCOS) system for a dynamic sample. We have found that the signal-to-noise ratio (SNR) of fb-SCOS measurements plateaus at a camera exposure time, which marks the regime where shot and fundamental noise dominates over camera read noise. For a fixed total measurement time, there exists an optimized camera exposure time if temporal averaging is utilized to improve SNR. For a certain camera exposure time, photon flux value, and camera noise properties, there exists an optimized speckle-to-pixel size ratio (s/p) at which SNR is maximized. Our work provides the design principles for any LSCI or SCOS systems given the detected photon flux and properties of the instruments, which will guide the experimental development of a high-quality, low-cost fb-SCOS system that monitors human brain blood flow and functions.

Treatment of Electroconvulsive Therapy-Emergent Hypomania and Mania: A Systematic Review of the Literature.

Objective: Electroconvulsive therapy (ECT)-emergent hypomania/mania is a clinically significant problem that has lacked evidence-based guidelines for effective management. The aim of this systematic literature review is to compile the current published literature on treating ECT-emergent hypomania/mania to help guide treatment course in patients with unipolar and bipolar depression.Data Sources: MEDLINE/PubMed was searched for studies published from 1980 through August 2020 that evaluated the treatment of ECT-emergent hypomania/mania. Search terms included Boolean combinations of the following: mania, hypomania, ECT, ECT induced mania, and ECT induced hypomania.Study Selection: There were 1,662 articles reviewed, and all published studies detailing the treatment of ECT-emergent hypomania/mania written in English that met inclusion criteria were included. Due to the limited number of articles, there were no restrictions.Data Extraction: Two reviewers extracted relevant articles and assessed each study based on inclusion criteria.Results: The literature review identified 12 articles that described the treatment course of ECT-emergent hypomania/mania in 17 patients. There were 9 patients who had no known history of manic or hypomanic episodes and were diagnosed with unipolar depression and 8 patients diagnosed with bipolar disorder. There were 4 primary treatment courses identified: continuing ECT alone, continuing ECT in conjunction with lithium, discontinuing ECT with no medication treatment, or discontinuing ECT and starting a medication.Conclusions: The available data are insufficient to support definitive conclusions; however, potential treatment guidelines are suggested within the review to providers based on the limited data available.

An adaptive optics module for deep tissue multiphoton imaging in vivo.

Understanding complex biological systems requires visualizing structures and processes deep within living organisms. We developed a compact adaptive optics module and incorporated it into two- and three-photon fluorescence microscopes, to measure and correct tissue-induced aberrations. We resolved synaptic structures in deep cortical and subcortical areas of the mouse brain, and demonstrated high-resolution imaging of neuronal structures and somatosensory-evoked calcium responses in the mouse spinal cord at great depths in vivo.

The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An update on management of behavioral and psychological symptoms in dementia.

Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present an update of our previously published algorithms for the use of psychopharmacologic agents in these patients taking into account more recent studies and findings in meta-analyses, reviews, and other published algorithms. We propose three algorithms: BPSD in an emergent, urgent, and non-urgent setting. In the emergent setting when intramuscular (IM) administration is necessary, the first-line recommendation is for olanzapine (since IM aripiprazole, previously favored, is no longer available) and haloperidol injection is the second choice, followed by possible consideration of an IM benzodiazepine. In the urgent setting, the first line would be oral second-generation antipsychotics (SGAs) aripiprazole and risperidone. Perhaps next could be then prazosin, and lastly electroconvulsive therapy is a consideration. There are risks associated with these agents, and adverse effects can be severe. Dosing strategies, discontinuation considerations, and side effects are discussed. In the non-emergent setting, medications are proposed for use in the following order: trazodone, donepezil and memantine, antidepressants such as escitalopram and sertraline, SGAs, prazosin, and carbamazepine. Other options with less support but potential future promise are discussed.

Chronic Imaging of Mouse Brain: From Optical Systems to Functional Ultrasound.

Utilization of functional ultrasound (fUS) in cerebral vascular imaging is gaining popularity among neuroscientists. In this article, we describe a chronic surgical preparation method that allows longitudinal studies and therefore is applicable to a wide range of studies, especially on aging, stroke, and neurodegenerative diseases. This method can also be used with awake mice; hence, the deleterious effects of anesthesia on neurovascular responses can be avoided. In addition to fUS imaging, this surgical preparation allows researchers to take advantage of common optical imaging methods to acquire complementary datasets to help increase the technical rigor of studies. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Surgical preparation of mouse chronic cranial windows using polymethylpentene Basic Protocol 2: Imaging of mice with chronic cranial windows.

COVID-19 Pandemic: Impact on psychiatric care in the United States.

The World Health Organization declared the coronavirus outbreak a pandemic on March 11, 2020. Infection by the SARS-CoV2 virus leads to the COVID-19 disease which can be fatal, especially in older patients with medical co-morbidities. The impact to the US healthcare system has been disruptive, and the way healthcare services are provided has changed drastically. Here, we present a compilation of the impact of the COVID-19 pandemic on psychiatric care in the US, in the various settings: outpatient, emergency room, inpatient units, consultation services, and the community. We further present effects seen on psychiatric physicians in the setting of new and constantly evolving protocols where adjustment and flexibility have become the norm, training of residents, leading a team of professionals with different expertise, conducting clinical research, and ethical considerations. The purpose of this paper is to provide examples of "how to" processes based on our current front-line experiences and research to practicing psychiatrists and mental health clinicians, inform practitioners about national guidelines affecting psychiatric care during the pandemic, and inform health care policy makers and health care systems about the challenges and continued needs of financial and administrative support for psychiatric physicians and mental health systems.

What We Know About Massively Multiplayer Online Role-Playing Games.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders defines internet gaming disorder without differentiating games from their respective genres, such as first-person shooter versus real-time strategy versus online gaming. Our review of the literature on massively multiplayer online role-playing games (MMORPGs) suggests that MMORPGs are different from other games because they are the most addictive, and therefore deserve to be looked at separately. MMORPGs are internet platforms for online users to interact with each other in a virtual story line. The overview of the existing literature delineates the positive and negative aspects of MMORPGs and also the available evidence on neuroscientific and neuroanatomical correlates between internet gaming disorder and other addictions. Evidence shows that a player's characteristics and motivations can determine his or her risk of developing problematic play. Problematic MMORPG use may lead to mental disorders such as depression and addiction, and can negatively affect quality of life, and vice versa. Conversely, some players may benefit from being part of a social community and from using it as a learning platform or as a safe space to explore gender-identity issues. Brain circuitry and metabolism are changed through problematic MMORPG use, with the affected areas including the ventral striatum and left angular gyrus.

Opioid use and schizophrenia.

PURPOSE OF REVIEW: To summarize the current literature regarding comorbid schizophrenia and opioid use disorder (OUD). RECENT FINDINGS: Epidemiological evidence is unclear on whether patients with schizophrenia have a higher rate of OUD. Patients with OUD have been shown to have a higher risk of developing schizophrenia. However, it is clear that patients with both schizophrenia and OUD are less likely to receive standard of care including medication-assisted treatment (MAT) for opiate use disorder and have worse outcomes compared with patients with schizophrenia who do not abuse opioids. OUD significantly increases the risk of converting patients from prodromal schizophrenia states to schizophrenia or schizoaffective disorder. Shared pathophysiology involving the kappa opioid receptor may help explain the relationships between schizophrenia and OUD. Second-generation antipsychotics, long-acting injectables, and MAT for OUD should be utilized in a dual-diagnosis and treatment approach for patients with schizophrenia and OUD. SUMMARY: Exploration into the relationship between schizophrenia and opiate abuse is still in its infancy and requires a significant amount of future attention to clarify the epidemiology of this comorbidity, neurobiological relationship, shared genetic underpinnings, and possible treatments for both the psychotic symptoms and substance abuse.

Antipsychotics and the microbiota.

PURPOSE OF REVIEW: The gut microbiota has been speculated to underpin metabolic changes associated with chronic antipsychotic use. The change in the gut microbiota can also cause abnormal absorbtion from the gut into the blood stream (leaky gut syndrome) that can lead to inflammatory reactions, and thus, secondary damage to the brain and central nervous system. Our article aims to highlight relevant research on antipsychotic's effect on the microbiota and to point out future directions. RECENT FINDINGS: Antipsychtoic use can result in specific microbiota changes, and it is important to differentiate this from the innate microbiota of the patient. It is important to treat these microbiota changes, as they are correlated with obesity, which is a negative contributor to the cardiovascular health of those suffering with schizophrenia. Ways to prevent antipsychotic-induced side-effects include antibiotic treatment, histamine 3 receptor blockade and metformin use. SUMMARY: Given the dearth of current literature, more research is needed, however, to determine, which comes first in people with schizophrenia--an abnormal gut microbiota that elevates one's risk for schizophrenia or psychopharmacologic treatment of schizophrenia leading to secondary microbiota abnormalities or the negative symptoms of schizophrenia leading to obesity and its associated microbiota changes.

Hypertensive Urgency and Emergency in Alcohol Withdrawal: A Literature Review.

OBJECTIVE: To help clinicians recognize that hypertension, hypertensive urgency, and hypertensive emergency can arise in patients detoxifying from alcohol. Diagnostic and treatment implications are reviewed to help clinicians manage blood pressure in these situations. DATA SOURCES: PubMed was searched with no restrictions on publication date or study type in June 2019 using the terms (alcohol withdrawal) AND hypertension. STUDY SELECTION: Of 531 studies retrieved, all were reviewed, and articles older than 20 years were excluded. Of the remaining 158 articles, all were reviewed by full-text reading, and 17 were selected based on relevance. Seven UpToDate articles and 2 older papers were also included for relevance. DATA EXTRACTION: Various other searches were also performed; however, no relevant hits resulted when the following terms were entered: (hypertensive urgency/emergency) AND alcohol withdrawal OR detoxification; (hypertensive urgency/emergency) AND (alcohol withdrawal OR detoxification) AND treatment-resistant hypertension. RESULTS: Hypertension is typically self-limited in alcohol withdrawal syndrome; however, treatment is important to prevent hypertensive urgency or emergency. There is a paucity of data on how best to manage hypertension in patients withdrawing from alcohol, with treatment often individualized. Patients with underlying treatment-resistant hypertension may have more difficult-to-control blood pressure, especially in the first 24 hours of withdrawal. CONCLUSIONS: Multiple medications may be used to treat hypertension in the setting of alcohol withdrawal, with selection based on side effect profile and the patient's other comorbidities. In patients for whom there is concern for hypertensive urgency versus emergency, full medical evaluation is indicated to identify any potential end-organ damage.

Meloxicam-desmopressin drug-drug interaction producing hyponatremia.

BACKGROUND: People with schizophrenia and medical comorbidities are often on multiple medications to manage their symptoms. Herein we present a case of drug-drug interaction (meloxicam and desmopressin), in a patient also on clozapine, that ultimately resulted in hyponatremia and seizure. METHODS: The patient provided consent to have his case published. We searched PubMed and after reviewing 321 articles, 11 were chosen for relevance. RESULTS: Meloxicam enhanced the adverse effect (hyponatremia) of desmopressin and was the likely culprit. CONCLUSIONS: In a patient with higher ADH levels, as in our patient taking desmopressin, the addition of an NSAID could further increase water retention and worsen hyponatremia; indeed, meloxicam was the only new medication added to the patient's regimen, and a drug interaction calculator supports the desmopressin-meloxicam drug-drug interaction as the culprit. We urge clinicians to avoid the use of desmopressin in patients with schizophrenia as this can lead to water intoxication. As meloxicam may worsen desmopressin-induced hyponatremia and could result in seizure, one should avoid using NSAIDs in patients with schizophrenia whom are also prescribed vasopressin/desmopressin. Serum sodium levels should be closely monitored in patients with schizophrenia whose regimen includes desmopressin.