The Microbiota-Gut-Brain Axis.

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.

Pathological laughter and crying: insights from lesion network-symptom-mapping.

The study of pathological laughter and crying (PLC) allows insights into the neural basis of laughter and crying, two hallmarks of human nature. PLC is defined by brief, intense and frequent episodes of uncontrollable laughter or crying provoked by trivial stimuli. It occurs secondary to CNS disorders such as stroke, tumours or neurodegenerative diseases. Based on case studies reporting various lesions locations, PLC has been conceptualized as dysfunction in a cortico-limbic-subcortico-thalamo-ponto-cerebellar network. To test whether the heterogeneous lesion locations are indeed linked in a common network, we applied 'lesion network-symptom-mapping' to 70 focal lesions identified in a systematic literature search for case reports of PLC. In lesion network-symptom-mapping normative connectome data (resting state functional MRI, n = 100) is used to identify the brain regions that are likely affected by diaschisis based on the lesion locations. With lesion network-symptom-mapping we were able to identify a common network specific for PLC when compared with a control cohort (n = 270). This bilateral network is characterized by positive connectivity to the cingulate and temporomesial cortices, striatum, hypothalamus, mesencephalon and pons, and negative connectivity to the primary motor and sensory cortices. In the most influential pathophysiological model of PLC, a centre for the control and coordination of facial expressions, respiration and vocalization in the periaqueductal grey is assumed, which is controlled via two pathways: an emotional system that exerts excitatory control of the periaqueductal grey descending from the temporal and frontal lobes, basal ganglia and hypothalamus; and a volitional system descending from the lateral premotor cortices that can suppress laughter or crying. To test whether the positive and negative PLC subnetworks identified in our analyses can indeed be related to an emotional system and a volitional system, we identified lesions causing emotional (n = 15) or volitional facial paresis (n = 46) in a second literature search. Patients with emotional facial paresis show preserved volitional movements but cannot trigger emotional movements in the affected hemiface, while the reverse is true for volitional facial paresis. Importantly, these lesions map differentially onto the PLC subnetworks: the 'positive PLC subnetwork' is part of the emotional system and the 'negative PLC subnetwork' overlaps with the volitional system for the control of facial movements. Based on this network analysis we propose a two-hit model of PLC: a combination of direct lesion and indirect diaschisis effects cause PLC through the loss of inhibitory cortical control of a dysfunctional emotional system.

Morphometrical Brain Markers of Sex Difference.

Many major neuropsychiatric pathologies, some of which appear in adolescence, show differentiated prevalence, onset, and symptomatology across the biological sexes. Therefore, mapping differences in brain structure between males and females during this critical developmental period may provide information about the neural mechanisms underlying the dimorphism of these pathologies. Utilizing a large dataset collected through the Adolescent Brain Cognitive Development study, we investigated the differences of adolescent (9-10 years old) male and female brains (n = 8325) by using a linear Support-Vector Machine Classifier to predict sex based on morphometry and image intensity values of structural brain imaging data. The classifier correctly classified the sex of 86% individuals with the insula, the precentral and postcentral gyri, and the pericallosal sulcus as the most discernable features. These results demonstrate the existence of complex, yet robustly measurable morphometrical brain markers of sex difference.

What are the epileptic encephalopathies?

PURPOSE OF REVIEW: To review the evolution of the concept of epileptic encephalopathy during the course of past years and analyze how the current definition might impact on both clinical practice and research. RECENT FINDINGS: Developmental delay in children with epilepsy could be the expression of the cause, consequence of intense epileptiform activity (seizures and EEG abnormalities), or because of the combination of both factors. Therefore, the current International League Against Epilepsy classification identified three electroclinical entities that are those of developmental encephalopathy, epileptic encephalopathy, and developmental and epileptic encephalopathy (DEE). Many biological pathways could be involved in the pathogenesis of DEEs. DNA repair, transcriptional regulation, axon myelination, metabolite and ion transport, and peroxisomal function could all be involved in DEE. Also, epilepsy and epileptiform discharges might impact on cognition via several mechanisms, although they are not fully understood. SUMMARY: The correct and early identification of cause in DEE might increase the chances of a targeted treatment regimen. Interfering with neurobiological processes of the disease will be the most successful way in order to improve both the cognitive disturbances and epilepsy that are the key features of DEE.

Replicable brain signatures of emotional bias and memory based on diffusion kurtosis imaging of white matter tracts.

Diffusion MRI (dMRI) is sensitive to anisotropic diffusion within bundles of nerve axons and can be used to make objective measurements of brain networks. Many brain disorders are now recognised as being caused by network dysfunction or are secondarily associated with changes in networks. There is therefore great potential in using dMRI measures that reflect network integrity as a future clinical tool to help manage these conditions. Here, we used dMRI to identify replicable, robust and objective markers that meaningfully reflect cognitive and emotional performance. Using diffusion kurtosis analysis and a battery of cognitive and emotional tests, we demonstrated strong relationships between white matter structure across networks of anatomically and functionally specific brain regions with both emotional bias and emotional memory performance in a large healthy cohort. When the connectivity of these regions was examined using diffusion tractography, the terminations of the identified tracts overlapped precisely with cortical loci relating to these domains, drawn from an independent spatial meta-analysis of available functional neuroimaging literature. The association with emotional bias was then replicated using an independently acquired healthy cohort drawn from the Human Connectome Project. These results demonstrate that, even in healthy individuals, white matter dMRI structural features underpin important cognitive and emotional functions. Our robust cross-correlation and replication supports the potential of structural brain biomarkers from diffusion kurtosis MRI to characterise early neurological changes and risk in individuals with a reduced threshold for cognitive dysfunction, with further testing required to demonstrate clinical utility.

Recommendations for the Nonpharmacological Treatment of Apathy in Brain Disorders.

Apathy is a common neuropsychiatric syndrome observed across many neurocognitive and psychiatric disorders. Although there are currently no definitive standard therapies for the treatment of apathy, nonpharmacological treatment (NPT) is often considered to be at the forefront of clinical management. However, guidelines on how to select, prescribe, and administer NPT in clinical practice are lacking. Furthermore, although new Information and Communication Technologies (ICT) are beginning to be employed in NPT, their role is still unclear. The objective of the present work is to provide recommendations for the use of NPT for apathy, and to discuss the role of ICT in this domain, based on opinions gathered from experts in the field. The expert panel included 20 researchers and healthcare professionals working on brain disorders and apathy. Following a standard Delphi methodology, experts answered questions via several rounds of web-surveys, and then discussed the results in a plenary meeting. The experts suggested that NPT are useful to consider as therapy for people presenting with different neurocognitive and psychiatric diseases at all stages, with evidence of apathy across domains. The presence of a therapist and/or a caregiver is important in delivering NPT effectively, but parts of the treatment may be performed by the patient alone. NPT can be delivered both in clinical settings and at home. However, while remote treatment delivery may be cost and time-effective, it should be considered with caution, and tailored based on the patient's cognitive and physical profile and living conditions.

COVID-19-related encephalopathy: a case series with brain FDG-positron-emission tomography/computed tomography findings.

AIM: The aim of this paper is to describe the clinical features of COVID-19-related encephalopathy and their metabolic correlates using brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) imaging. BACKGROUND AND PURPOSE: A variety of neurological manifestations have been reported in association with COVID-19. COVID-19-related encephalopathy has seldom been reported and studied. METHODS: We report four cases of COVID-19-related encephalopathy. The diagnosis was made in patients with confirmed COVID-19 who presented with new-onset cognitive disturbances, central focal neurological signs, or seizures. All patients underwent cognitive screening, brain magnetic resonance imaging (MRI), lumbar puncture, and brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) (FDG-PET/CT). RESULTS: The four patients were aged 60 years or older, and presented with various degrees of cognitive impairment, with predominant frontal lobe impairment. Two patients presented with cerebellar syndrome, one patient had myoclonus, one had psychiatric manifestations, and one had status epilepticus. The delay between first COVID-19 symptoms and onset of neurological symptoms was between 0 and 12 days. None of the patients had MRI features of encephalitis nor significant cerebrospinal fluid (CSF) abnormalities. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. All patients presented with a consistent brain FDG-PET/CT pattern of abnormalities, namely frontal hypometabolism and cerebellar hypermetabolism. All patients improved after immunotherapy. CONCLUSIONS: Despite varied clinical presentations, all patients presented with a consistent FDG-PET pattern, which may reflect an immune mechanism.

Neurocovid: Pharmacological Recommendations for Delirium Associated With COVID-19.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the biggest health threats of our generation. A significant portion of patients are presenting with delirium and neuropsychiatric sequelae of the disease. Unique examination findings and responses to treatment have been identified. OBJECTIVE: In this article, we seek to provide pharmacologic and treatment recommendations specific to delirium in patients with COVID-19. METHODS: We performed a literature search reviewing the neuropsychiatric complications and treatments in prior coronavirus epidemics including Middle Eastern respiratory syndrome and severe acute respiratory syndrome coronaviruses, as well as the emerging literature regarding COVID-19. We also convened a work group of consultation-liaison psychiatrists actively managing patients with COVID-19 in our hospital. Finally, we synthesized these findings to provide preliminary pharmacologic recommendations for treating delirium in these patients. RESULTS: Delirium is frequently found in patients who test positive for COVID-19, even in the absence of respiratory symptoms. There appears to be a higher rate of agitation, myoclonus, abulia, and alogia. No data are currently available on the treatment of delirium in patients with COVID-19. Extrapolating from general delirium treatment, Middle Eastern respiratory syndrome/severe acute respiratory syndrome case reports, and our experience, preliminary recommendations for pharmacologic management have been assembled. CONCLUSIONS: COVID-19 is associated with neuropsychiatric symptoms. Low-potency neuroleptics and alpha-2 adrenergic agents may be especially useful in this setting. Further research into the pathophysiology of COVID-19 will be key in developing more targeted treatment guidelines.

Physicians' and Attorneys' Beliefs and Attitudes Related to the Brain Disease Model of Addiction.

BACKGROUND AND OBJECTIVES: Addiction is increasingly considered a chronic, relapsing brain disease; however, many scholars still disagree with the brain disease model of addiction. We set out to provide evidence of attorneys' and physicians' beliefs regarding the model. First, we asked the following question: do attorneys and physicians affirm the full brain disease model, or its modified form, or do they believe that addiction is driven by deficits in self-control or moral weakness? Second, we evaluated the extent to which such beliefs correspond to attitudes toward individuals with substance use disorders (SUDs). METHODS: A questionnaire was sent to resident physicians (N = 301) and criminal defense attorneys (N = 483) practicing in the United States. It was comprised of (i) an attitudes measure, (ii) a measure regarding conceptions of addiction, and (iii) demographic questions. RESULTS: Attorneys were more likely to believe that individuals with SUDs had "practically no choice" about whether to seek and use, whereas physicians were more likely to believe that such individuals had "genuine choice." For both groups of participants, the rejection of the full brain disease model of addiction was associated with more negative attitudes toward individuals with SUDs. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These results represent an important advance, as past research has neglected attorneys' attitudes and is inconclusive regarding the manner in which beliefs about the brain disease model of addiction are related to attitudes toward individuals with SUDs. Educating practitioners regarding this relationship would raise awareness regarding when and to what extent stigma is likely to be present, which may in turn provide a foundation from which to address stigma. (Am J Addict 2020;00:00-00).

Behavioural activation treatment for depression in individuals with neurological conditions: a systematic review.

OBJECTIVE: To evaluate the effectiveness of behavioural activation interventions for people with neurological conditions with comorbid depression, and explore content and adaptations. DATA SOURCES: PsycINFO, MEDLINE, CINAHL, AMED, and EMBASE databases were searched on the 19 November 2019. Reference lists of selected full-texts were screened by title. REVIEW METHODS: We included peer-reviewed studies published in English that used behavioural activation for treatment of depression in adults with a neurological condition. Single-case reports, reviews, and grey literature were excluded. Methodological quality was assessed by two authors independently, and quality was appraised using Critical Appraisal Skills Programme checklists. RESULTS: From 2714 citations, 10 articles were included comprising 590 participants. Behavioural activation was used to treat depression in people with dementia (n = 4), stroke (n = 3), epilepsy (n = 1), Parkinson's disease (n = 1), and brain injury (n = 1). Sample size ranged from 4 to 105 participants. There were seven randomized controlled studies; however, no studies compared behavioural activation to an alternative psychological therapy. The effect sizes varied between small and large in the studies where effect size could be calculated (d = 0.24-1.7). Methodological quality of the included studies was variable. Intervention components were identifying and engaging in pleasurable activities, psychoeducation, and problem-solving. Adaptations included delivering sessions via telephone, delivering interventions via primary caregivers, and giving psychoeducation to caregivers. CONCLUSION: The effectiveness of behavioural activation in randomized controlled trials varied from small to large (d = 0.24-1.7) in reducing depression. The content of behavioural activation was comparable to established treatment manuals. Adaptations appeared to support individuals to engage in therapy. REVIEW REGISTRATION: PROSPERO 2018, CRD42018102604.

Encephalopathy only stroke codes (EoSC) do not result in rt-PA treatments.

BACKGROUND: Isolated mental status changes as a presenting sign (EoSC+), are not uncommon stroke code triggers. As stroke alerts, they still require the same intensive resources be applied. We previously showed that EoSC+ strokes (EoSC+ Stroke+) account for 0.1-0.2% of all codes. Whether these result in thrombolytic treatment (rt-PA), and the characteristics/ risk factor profiles of EoSC+ Stroke+ patients, have not been reported. METHODS: Retrospective analysis of stroke codes from an IRB approved registry, from 2004 to 2018, was performed. EoSC+ was defined as a NIHSS>0 for Q1a, 1b, or 1c with remaining elements scored 0. Characteristics and risk factors were compared for EoSC+, EoSC-, EoSC+ Stroke+, and rt-PA (EoSC+ Stroke+TPA+) patients. RESULTS: EoSC+ occurred in 55/2982 (1.84%) of all stroke codes. EoSC+ Stroke+ occurred in 8/55 (14.5%) of EoSC+ codes and 8/2982 (0.27%) of all stroke codes. 6/8 (75%) of EoSC+ Stroke+ scored NIHSS=1. When comparing EoSC++versus EoSC-, Hispanic ethnicity (p=0.009), hypertension (p=0.02), and history of stroke/TIA (p=0.002) were less common in EoSC+. No demographic/risk factor differences were noted for EoSC+ Stroke+ vs. EoSC+ Stroke-. No cases of rt-PA eligibility/treatment were noted. In EoSC+ Stroke+ analysis, imaging positive stroke/intracranial hemorrhage was noted on only 3 cases (3/2982=0.10% of all stroke codes) and none were posterior stroke. CONCLUSIONS: EoSC+ rarely results in stroke/TIA (0.27%) or stroke (0.10%), and in our analysis never (0%) resulted in rt-PA. Sub-analysis did not show missed rt-PA or posterior strokes. Understanding characteristics, and knowing that EoSC+ Stroke+ patients are unlikely to receive rt-PA, may help triage stroke resources.

Pseudobulbar Affect: An Overview.

Pseudobulbar affect (PBA) is a disorder that develops in the context of a brain injury or underlying neurological dysfunction. It is characterized as an affective disorder of emotional expression. PBA manifests as frequent uncontrollable outbursts of laughing or crying, incongruent with the individual's internal emotional state. It can be challenging for clinicians to differentiate PBA from mood disorders, contributing to its high rate of misdiagnosis. This lack of recognition leads to ineffective and insufficient treatment, impacting patients' quality of life. The current article provides an overview of PBA, including its history, prevalence, pathophysiology, diagnostic criteria, clinical implications, and treatment. [Journal of Psychosocial Nursing and Mental Health Services, 58(9), 19-24.].

Fluoxetine reverses brain radiation and temozolomide-induced anxiety and spatial learning and memory defect in mice.

Radiation therapy and concomitant temozolomide chemotherapy are commonly used in treatment of brain tumors, but they may also result in behavioral impairments such as anxiety and cognitive deficit. The present study sought to investigate the effect of fluoxetine on the behavioral impairments caused by radiation and temozolomide treatment. C57BL/6J mice were subjected to a single cranial radiation followed by 6-wk cyclic temozolomide administration and were then treated with chronic administration of fluoxetine. Behavioral tests were carried out to determine the anxiety-like behavior and cognition function of these animals. Long-term potentiation (LTP) in the hippocampus was measured by electrophysiology, and neurogenesis in the dentate gyrus was evaluated by immunohistochemistry. Mice treated with radiation and temozolomide showed increased anxiety-like behavior and cognitive impairment, along with LTP impairment and neurogenesis deficit. Chronic fluoxetine administration could reverse the behavioral dysfunction, enhance LTP, and increase neurogenesis in the hippocampus. NEW & NOTEWORTHY Mice treated with radiation and temozolomide showed increased anxiety-like behavior and cognitive impairment. Chronic fluoxetine administration could reverse the behavioral dysfunction. The effect of fluoxetine might be via rescuing the neurogenesis deficit caused by radiation and temozolomide treatment.

An empirical evaluation of multivariate lesion behaviour mapping using support vector regression.

Multivariate lesion behaviour mapping based on machine learning algorithms has recently been suggested to complement the methods of anatomo-behavioural approaches in cognitive neuroscience. Several studies applied and validated support vector regression-based lesion symptom mapping (SVR-LSM) to map anatomo-behavioural relations. However, this promising method, as well as the multivariate approach per se, still bears many open questions. By using large lesion samples in three simulation experiments, the present study empirically tested the validity of several methodological aspects. We found that (i) correction for multiple comparisons is required in the current implementation of SVR-LSM, (ii) that sample sizes of at least 100-120 subjects are required to optimally model voxel-wise lesion location in SVR-LSM, and (iii) that SVR-LSM is susceptible to misplacement of statistical topographies along the brain's vasculature to a similar extent as mass-univariate analyses.

Differential impact of ventromedial prefrontal cortex damage on "hot" and "cold" decisions under risk.

The ventromedial prefrontal cortex (vmPFC) is known to play a key role in reward processing and decision making. However, its relative contribution to affect-rich ("hot") and affect-poor ("cold") decisions is not fully understood. Damage to vmPFC is associated with impaired performance on laboratory tasks of decision making under ambiguity and risk. In the current study, we tested the hypothesis that vmPFC is critical for adaptive risk taking under "hot" conditions specifically. Participants included patients with focal lesions in vmPFC, patient controls with damage in regions not including vmPFC, and healthy controls. They completed hot and cold versions of a dynamic risk-taking task, the Columbia Card Task (CCT). Relative to healthy controls and patient controls, vmPFC patients showed a strong overall increase in risk taking in the hot version of the CCT, despite preserved sensitivity to trial-level variation in risk. In the cold version, overall risk taking was similar among all three groups, even though vmPFC patients showed reduced sensitivity to trial-level variation in risk. Sensitivity to gain and loss magnitudes did not differ significantly among the groups, in either the hot or the cold CCT. These findings lend novel support to the hypothesis that the vmPFC is critical for adaptive decision making under affect-rich conditions.

Brain mechanisms underlying apathy.

The past few decades have seen growing interest in the neuropsychiatric syndrome of apathy, conceptualised as a loss of motivation manifesting as a reduction of goal-directed behaviour. Apathy occurs frequently, and with substantial impact on quality of life, in a broad range of neurological and psychiatric conditions. Apathy is also consistently associated with neuroimaging changes in specific medial frontal cortex and subcortical structures, suggesting that disruption of a common systems-level mechanism may underlie its development, irrespective of the condition that causes it. In parallel with this growing recognition of the clinical importance of apathy, significant advances have been made in understanding normal motivated behaviour in humans and animals. These developments have occurred at several different conceptual levels, from work linking neural structures and neuromodulatory systems to specific aspects of motivated behaviour, to higher order computational models that aim to unite these findings within frameworks for normal goal-directed behaviour. In this review we develop a conceptual framework for understanding pathological apathy based on this current understanding of normal motivated behaviour. We first introduce prominent theories of motivated behaviour-which often involves sequences of actions towards a goal that needs to be maintained across time. Next, we outline the behavioural effects of disrupting these processes in animal models, highlighting the specific effects of these manipulations on different components of motivated behaviour. Finally, we relate these findings to clinical apathy, demonstrating the homologies between this basic neuroscience work and emerging behavioural and physiological evidence from patient studies of this syndrome.

Idiopathic encephalopathy related to status epilepticus during slow sleep (ESES) as a "pure" model of epileptic encephalopathy. An electroclinical, genetic, and follow-up study.

OBJECTIVE: The objective of the study was to investigate electroclinical and neuropsychological features, genetic background, and evolution of children with idiopathic encephalopathy with status epilepticus during slow sleep (ESES), including Landau-Kleffner syndrome (LKS). MATERIAL AND METHODS: All children diagnosed with idiopathic ESES at the Danish Epilepsy Centre between March 2003 and December 2014 were retrospectively reviewed. Repeated 24-hour electroencephalography (24-h EEG) recordings, neuropsychological assessments, and clinical-neurological evaluation were performed throughout the follow-up in all patients. In 13 children, genetic investigations were performed. RESULTS: We collected 24 children (14 males and 10 females). Mean age at ESES diagnosis was 6 years, and mean ESES duration was 2 years and 7 months. Twenty-one children had epileptic seizures. Three children had LKS. Topography of sleep-related EEG epileptic abnormalities was diffuse in 3 subjects, hemispheric in 6, multifocal in 9, and focal in 6. During the active phase of ESES, all children presented with a heterogeneous combination of behavioral and cognitive disturbances. In 14 children, a parallel between severity of the clinical picture and spike-wave index (SWI) was observed. We could not find a strict correlation between the type and severity of neurobehavioral impairment and the side/topography of sleep-related EEG discharges during the active phase of ESES. At the last follow-up, 21 children were in remission from ESES. Complete recovery from neurobehavioral disorders was observed in 5 children. Genetic assessment, performed in 13 children, showed GRIN2A variant in two (15.4%). SIGNIFICANCE: Our patients with idiopathic ESES showed a heterogeneous pattern of epileptic seizures, neurobehavioral disorders, and sleep EEG features. Only one-fourth of children completely recovered from the neuropsychological disturbances after ESES remission. Lack of correlation between severity/type of cognitive derangement and SWI and/or topography of sleep EEG epileptic abnormalities may suggest the contribution of additional factors (including impaired sleep homeostasis due to epileptic activity) in the neurobehavioral derangement that characterize ESES.

The ambiguity of loss affects some, but not all autobiographical memories: redemption and contamination, agency and communion.

Compared with clear-cut loss by death, ambiguous loss is defined as a loss that is not definite because the person is missing or mentally absent but physically present (e.g., through Alzheimer's disease). We expected the ambiguity of loss to show in psychologically more compromised loss memories and self-defining memories, but not in autobiographical memories in general. Thirty Chinese adults who had lost a parent through death, thirty whose parent had gone missing, and thirty who cared for a demented parent narrated their loss experiences and memories of sad and turning-point events as well as self-defining memories. Individuals with ambiguous loss narrated the loss and a self-defining memory with more contamination and fewer redemption sequences, and only the loss memory with fewer themes of agency and communion than individuals with definite loss, but not in memories of sad and turning point events. Effects of ambiguity of loss were independent of prolonged grief, which in turn independently predicted some of these effects. Thus the ambiguous quality of loss predicts effects on loss memories and self-defining memories independently of psychiatric symptoms.

Review: Post-Intensive Care Syndrome: Unique Challenges in the Neurointensive Care Unit.

Within the last couple of decades, advances in critical care medicine have led to increased survival of critically ill patients, as well as the discovery of notable, long-term health challenges in survivors and their loved ones. The terms post-intensive care syndrome (PICS) and PICS-family (PICS-F) have been used in non-neurocritical care populations to characterize the cognitive, psychiatric, and physical sequelae associated with critical care hospitalization in survivors and their informal caregivers (e.g., family and friends who provide unpaid care). In this review, we first summarize the literature on the cognitive, psychiatric, and physical correlates of PICS and PICS-F in non-neurocritical patient populations and draw attention to their long-term negative health consequences. Next, keeping in mind the distinction between disease-related neurocognitive changes and those that are associated directly with the experience of a critical illness, we review the neuropsychological sequelae among patients with common neurocritical illnesses. We acknowledge the clinical factors contributing to the difficulty in studying PICS in the neurocritical care patient population, provide recommendations for future lines of research, and encourage collaboration among critical care physicians in all specialties to facilitate continuity of care and to help elucidate mechanism(s) of PICS and PICS-F in all critical illness survivors. Finally, we discuss the importance of early detection of PICS and PICS-F as an opportunity for multidisciplinary interventions to prevent and treat new neuropsychological deficits in the neurocritical care population.

Bridging the Great Divide: What Can Neurology Learn From Psychiatry?

Neurology and psychiatry share common historical origins and rely on similar tools to study brain disorders. Yet the practical integration of medical and scientific approaches across these clinical neurosciences remains elusive. Although much has been written about the need to incorporate emerging systems-level, cellular-molecular, and genetic-epigenetic advances into a science of mind for psychiatric disorders, less attention has been given to applying clinical neuroscience principles to conceptualize neurologic conditions with an integrated neurobio-psycho-social approach. In this perspective article, the authors briefly outline the historically interwoven and complicated relationship between neurology and psychiatry. Through a series of vignettes, the authors then illustrate how some traditional psychiatric conditions are being reconceptualized in part as disorders of neurodevelopment and awareness. They emphasize the intersection of neurology and psychiatry by highlighting conditions that cut across traditional diagnostic boundaries. The authors argue that the divide between neurology and psychiatry can be narrowed by moving from lesion-based toward circuit-based understandings of neuropsychiatric disorders, from unidirectional toward bidirectional models of brain-behavior relationships, from exclusive reliance on categorical diagnoses toward transdiagnostic dimensional perspectives, and from silo-based research and treatments toward interdisciplinary approaches. The time is ripe for neurologists and psychiatrists to implement an integrated clinical neuroscience approach to the assessment and management of brain disorders. The subspecialty of behavioral neurology & neuropsychiatry is poised to lead the next generation of clinicians to merge brain science with psychological and social-cultural factors. These efforts will catalyze translational research, revitalize training programs, and advance the development of impactful patient-centered treatments.