Functional re-organization of hippocampal-cortical gradients during naturalistic memory processes.

The functional organization of the hippocampus mirrors that of the cortex, changing smoothly along connectivity gradients and abruptly at inter-areal boundaries. Hippocampal-dependent cognitive processes require flexible integration of these hippocampal gradients into functionally related cortical networks. To understand the cognitive relevance of this functional embedding, we acquired fMRI data while participants viewed brief news clips, either containing or lacking recently familiarized cues. Participants were 188 healthy mid-life adults and 31 adults with mild cognitive impairment (MCI) or Alzheimer's disease (AD). We employed a recently developed technique - connectivity gradientography - to study gradually changing patterns of voxel to whole brain functional connectivity and their sudden transitions. We observed that functional connectivity gradients of the anterior hippocampus map onto connectivity gradients across the default mode network during these naturalistic stimuli. The presence of familiar cues in the news clips accentuates a stepwise transition across the boundary from the anterior to the posterior hippocampus. This functional transition is shifted in the posterior direction in the left hippocampus of individuals with MCI or AD. These findings shed new light on the functional integration of hippocampal connectivity gradients into large-scale cortical networks, how these adapt with memory context and how these change in the presence of neurodegenerative disease.

A systematic review of modified electroconvulsive therapy (ECT) to treat delirium.

BACKGROUND: Delirium is costly for patients, carers, and healthcare systems. In addition, non-pharmacological and pharmacological management of delirium is challenging. Electroconvulsive therapy (ECT) has been proposed and used as an anecdotal treatment of delirium in clinical practice. However, the efficacy and safety of this approach are not well understood. OBJECTIVE: To synthesise and review the evidence relating to the safety and efficacy of ECT as a treatment for delirium. METHODS: A systematic review was completed according to PRISMA guidelines using the PubMed, CINAHL, Cochrane Library, and PsycINFO databases. Studies were eligible for inclusion if modified ECT was used to treat delirium symptoms. ECT for delirium in people with neuroleptic malignant syndrome, catatonia, or confusional states associated with acute primary psychiatric conditions were excluded. All included records were first ranked using the hierarchy of evidence-based medicine; quality was then assessed using the Joanna Briggs critical appraisal checklists. Pooled data across the cases identified were analysed using descriptive statistics. RESULTS: Of 1226 records screened, 10 studies met inclusion criteria: six case reports, three case series, and one quasi-experimental study. The literature base was of mixed quality. A single quasi-experimental study was assessed to be of 'fair' quality, the remainder of the case series and case reports were rated as 'poor' to 'fair' quality. A total of only 40 individual people with delirium who were treated with ECT were identified. In 33/40 cases, the aetiology of delirium was substance withdrawal. The number of ECT treatments administered ranged from 1 to 13. ECT was reported to positively contribute towards treatment of delirium in all cases, although objective measures of improvement were reported in only 6/13 patient cases from case reports and case series (46%). The singular quasi-experimental study reported a statistically significant decrease in duration of delirium, time spent in physical restraint, and in benzodiazepine requirement when ECT was used as an adjunct in benzodiazepine withdrawal delirium. When adverse events were described these included mild confusion and memory deficits; all were reported as time limited and reversible. Considerable limitations in the quality of the evidence base were identified, including the risk of selection, publication and reporting bias. Much data reporting on safety and efficacy of ECT in delirium was missing. CONCLUSION: There is insufficient literature to support modified ECT as a clinical treatment for delirium. The few studies identified were generally of weak evidence lacking important data on safety and objective outcome measures, and not including populations with broad delirium aetiologies. Further research using more robust methodologies and broader populations (age, aetiology) of people with delirium treated with ECT is needed.

The Role of Apathy in Spontaneous Verbal and Nonverbal Behaviors: A Transdiagnostic Pilot Study in Neurodegeneration.

BACKGROUND: Apathy, characterized by a quantifiable reduction in motivation or goal-directed behavior, is a multidimensional syndrome that has been observed across many neurodegenerative diseases. OBJECTIVE: To develop a novel task measuring spontaneous action initiation (ie, a nonverbal equivalent to spontaneous speech tasks) and to investigate the association between apathy and executive functions such as the voluntary initiation of speech and actions and energization (ie, ability to initiate and sustain a response). METHOD: We compared the energization and executive functioning performance of 10 individuals with neurodegenerative disease and clinically significant apathy with that of age-matched healthy controls (HC). We also investigated the association between self-reported scores on the Apathy Evaluation Scale (AES) and performance on energization tasks. RESULTS: The individuals with apathy made significantly fewer task-related actions than the HC on the novel spontaneous action task, and their scores on the AES were negatively correlated with spontaneous task-related actions, providing preliminary evidence for the task's construct validity. In addition, the individuals with apathy performed more poorly than the HC on all of the energization tasks, regardless of task type or stimulus modality, suggesting difficulty in sustaining voluntary responding over time. Most of the tasks also correlated negatively with the AES score. However, the individuals with apathy also performed more poorly on some of the executive function tasks, particularly those involving self-monitoring. CONCLUSION: Our work presents a novel experimental task for measuring spontaneous action initiation-a key symptom of apathy-and suggests a possible contribution of apathy to neuropsychological deficits such as poor energization.

Hypnotic benzodiazepine receptor agonist exposure during pregnancy and the risk of congenital malformations and other adverse pregnancy outcomes: A systematic review and meta-analysis.

OBJECTIVE: To determine if there is an association between antenatal hypnotic benzodiazepine receptor agonist exposure and congenital malformations or other adverse pregnancy outcomes in the offspring. METHODS: Databases were searched to January 31, 2021. Cohort studies published in English on congenital malformations or other adverse pregnancy outcomes in infants following exposure compared with those unexposed, were summarized and meta-analyzed where possible. RESULTS: Following screening, 25 studies were assessed for eligibility and seven included in the meta-analyses. Five studies were pooled for congenital malformations following first trimester exposure and not statistically significant (OR 0.87, 95% CI 0.56-1.36). The five studies that assessed for preterm birth following anytime exposure did pool to a statistically significant effect (OR 1.49, 95% CI 1.19-1.86); study quality, control for other psychotropic drugs and psychiatric diagnosis did not appear to be moderators. There were two missing studies when examining for publication bias in both of the main analyses above but the revised estimates were similar to the original. Low birth weight (LBW) was significant (three studies, any time exposure, OR 1.51, 1.27-1.78) as was small for gestational age (SGA) (three studies with anytime exposure, OR 1.34, 1.22-1.48). There were too few studies to summarize birth weight, gestational age, respiratory difficulties, APGAR score at 5 min and NICU admission. CONCLUSIONS: Pregnancy exposure to hypnotics was not associated with a higher risk for congenital malformations but was associated with an increased risk for preterm birth, LBW and SGA compared with those infants who were not exposed. These findings are consistent with the antidepressant and benzodiazepine literature.

The Mental and Physical Health Impacts of Overturning Roe v Wade.

ABSTRACT: The overturning of Roe v Wade has resulted in the loss of reproductive rights for millions of women in the United States. It has also put these women at risk of severe mental and physical health consequences. When legal abortions are restricted, there is a rise in illegal abortion with the risk of hemorrhage, infection, infertility, and death. There are many more risks of carrying a pregnancy to term than health or psychological risks of a legal abortion. Women who have a miscarriage risk having to prove they did not abort. In cases of medical emergencies, doctors may be restricted from performing life-saving abortions for fear of penalties. Women or children who have been victims of rape or incest will have to either have an illegal abortion or carry an unwanted pregnancy to term. In states that allow an abortion in cases of severe risk to a mother's health, panels of internists and psychiatrist may, again, be charged with deciding whether her risks are valid. Women's physical and mental health will suffer.

Age of Onset and Length of Survival of Queensland Patients with Amyotrophic Lateral Sclerosis: Details of Subjects with Early Onset and Subjects with Long Survival.

INTRODUCTION: The aims of the study were to document the characteristics of amyotrophic lateral sclerosis (ALS) patients in Queensland, to examine factors influencing age of onset, and survival, and to study those with early-onset (<45 years) disease and those with long (>5 years) survival. METHODS: We studied subjects seen at the ALS Clinic at the Royal Brisbane and Women's Hospital. We recorded sex, age of onset, region of onset, length of survival, presence of family history, type of disease, and evidence of cognitive involvement. We analysed the influence of these features on age of onset and survival. We analysed the features of patients with early onset of disease and patients with long survival. RESULTS: There were 855 ALS patients (505 males) in the cohort. The age of onset was lower in males than females, in patients with a family history of ALS compared to those without, and in patients with spinal onset compared to bulbar onset. Early-onset disease was seen in 10% of patients, and had a greater proportion of males, spinal onset, and classical ALS phenotype compared to late-onset disease. Survival was shorter in females, in patients with bulbar onset, and in patients with classical ALS. Long survival was seen in 18% of patients. Patients with long survival had younger age of onset, greater proportion of males, spinal onset, and fewer patients with classical ALS. CONCLUSION: Our study confirms that ALS is more prevalent in males and that spinal onset is more common than bulbar onset. Males have earlier onset but longer survival. We found that overall, patients with classical ALS have worse survival than ALS variants, but some patients who were considered to have classical ALS had long survival. This study confirms the similarity of ALS in our region to ALS in other geographical regions.

Screening for obstructive sleep apnoea in patients with serious mental illness.

OBJECTIVE: Patients with serious mental illness (SMI) are at increased risk of obstructive sleep apnoea (OSA). Despite this, OSA is frequently under-recognised in the psychiatric population. This study describes the results of OSA screening in SMI patients. METHOD: Patients with SMI attending a metropolitan mental health clinic were screened for OSA using the OSA50, STOP-BANG Questionnaire (SBQ), Epworth Sleep Score (ESS) and the Pittsburgh Sleep Quality Index (PSQI). They were then offered diagnostic sleep testing via ResMed ApneaLinkTM and polysomnography. RESULTS: Of the 65 patients recruited, 65% had a primary diagnosis of schizophrenia or schizoaffective disorder, 85% were on antipsychotic medications and the majority were obese. Approximately 50% of patients reported poor sleep quality via the PSQI, in contrast to 12% with elevated daytime sleepiness via the ESS. 46% of our cohort were at risk of OSA due to an elevated OSA50 or SBQ. Of the five patients who agreed to proceed to diagnostic sleep testing, three were diagnosed with OSA. CONCLUSION: A high proportion of patients with psychiatric illness are at risk of sleep-disordered breathing. Sleep dissatisfaction is high. The low uptake of sleep investigation requires improved patient engagement to improve OSA diagnosis in this high-risk group.

Verbal Adynamia and Conceptualization in Partial Rhombencephalosynapsis and Corpus Callosum Dysgenesis.

Verbal adynamia is characterized by markedly reduced spontaneous speech that is not attributable to a core language deficit such as impaired naming, reading, repetition, or comprehension. In some cases, verbal adynamia is severe enough to be considered dynamic aphasia. We report the case of a 40-year-old, left-handed, male native English speaker who presented with partial rhombencephalosynapsis, corpus callosum dysgenesis, and a language profile that is consistent with verbal adynamia, or subclinical dynamic aphasia, possibly underpinned by difficulties selecting and generating ideas for expression. This case is only the second investigation of dynamic aphasia in an individual with a congenital brain malformation. It is also the first detailed neuropsychological report of an adult with partial rhombencephalosynapsis and corpus callosum dysgenesis, and the only known case of superior intellectual abilities in this context.

Subthalamic deep brain stimulation identifies frontal networks supporting initiation, inhibition and strategy use in Parkinson's disease.

Initiation and inhibition are executive functions whose disruption in Parkinson's disease impacts substantially on everyday activities. Management of Parkinson's disease with subthalamic deep brain stimulation (DBS) modifies initiation and inhibition, with prior work suggesting that these effects may be mediated via the connectivity of the subthalamic nucleus (STN) with the frontal cortex. Here, we employed high-resolution structural neuroimaging to investigate the variability in initiation, inhibition and strategy use in a cohort of twenty-five (ten females, mean age 62.5, mean Hoehn and Yahr stage 2.5) participants undertaking subthalamic DBS for Parkinson's disease. Neuropsychological assessment of initiation and inhibition was performed preoperatively and at six months postoperatively. We first reconstructed the preoperative connectivity of the STN with a frontal network of anterior and superior medial cortical regions. We then modelled the postoperative site of subthalamic stimulation and reconstructed the connectivity of the stimulation field within this same network. We found that, at both pre- and postoperative intervals, inter-individual variability in inhibition and initiation were strongly associated with structural network connectivity. Measures of subcortical atrophy and local stimulation effects did not play a significant role. Preoperatively, we replicated prior work, including a role for the right inferior frontal gyrus in inhibition and strategy use, as well as the left inferior frontal gyrus in tasks requiring selection under conditions of maintained inhibition. Postoperatively, greater connectivity of the stimulation field with right anterior cortical regions was associated with greater rule violations and suppression errors, supporting prior work implicating right-hemispheric STN stimulation in disinhibition. Our findings suggest that, in Parkinson's disease, connectivity of the frontal cortex with the STN is an important mediator of individual variability in initiation and inhibition,. Personalised information on brain network architecture could guide individualised brain circuit manipulation to minimise neuropsychological disruption after STN-DBS.

Idea Formulation for Spoken Language Production: The Interface of Cognition and Language.

BACKGROUND: Language and communication are fundamental to the human experience, and, traditionally, spoken language is studied as an isolated skill. However, before propositional language (i.e., spontaneous, voluntary, novel speech) can be produced, propositional content or 'ideas' must be formulated. OBJECTIVE: This review highlights the role of broader cognitive processes, particularly 'executive attention', in the formulation of propositional content (i.e., 'ideas') for propositional language production. CONCLUSIONS: Several key lines of evidence converge to suggest that the formulation of ideas for propositional language production draws on executive attentional processes. Larger-scale clinical research has demonstrated a link between attentional processes and language, while detailed case studies of neurological patients have elucidated specific idea formulation mechanisms relating to the generation, selection and sequencing of ideas for expression. Furthermore, executive attentional processes have been implicated in the generation of ideas for propositional language production. Finally, neuroimaging studies suggest that a widely distributed network of brain regions, including parts of the prefrontal and parietal cortices, supports propositional language production. IMPLICATIONS: Theoretically driven experimental research studies investigating mechanisms involved in the formulation of ideas are lacking. We suggest that novel experimental approaches are needed to define the contribution of executive attentional processes to idea formulation, from which comprehensive models of spoken language production can be developed. Clinically, propositional language impairments should be considered in the context of broader executive attentional deficits.

Callosal agenesis and congenital mirror movements: outcomes associated with DCC mutations.

Pathogenic variants in the gene encoding deleted in colorectal cancer (DCC) are the first genetic cause of isolated agenesis of the corpus callosum (ACC). Here we present the detailed neurological, brain magnetic resonance imaging (MRI), and neuropsychological characteristics of 12 individuals from three families with pathogenic variants in DCC (aged 8-50y), who showed ACC and mirror movements (n=5), mirror movements only (n=2), ACC only (n=3), or neither ACC nor mirror movements (n=2). There was heterogeneity in the neurological and neuroimaging features on brain MRI, and performance across neuropsychological domains ranged from extremely low (impaired) to within normal limits (average). Our findings show that ACC and/or mirror movements are associated with low functioning in select neuropsychological domains and a DCC pathogenic variant alone is not sufficient to explain the disability. WHAT THIS PAPER ADDS: Neuropsychological impairment severity is related to presence of mirror movements and/or agenesis of the corpus callosum. A DCC pathogenic variant in isolation is associated with the best prognosis.

Revisiting the role of electroconvulsive therapy in schizophrenia: Where are we now?

OBJECTIVE: The purpose of this opinion article is to review the recent evidence base in relation to the role of electroconvulsive therapy (ECT) in the management of patients with schizophrenia. Specifically, we explore the efficacy and safety of ECT. Furthermore, consideration is given to the profile of patients who benefit most from ECT, the role of maintenance ECT and what happens when ECT is not given. CONCLUSION: Our brief review of the evidence suggests that clinical practice in developing countries has not kept up with the growing literature supporting ECT use in schizophrenia. As such, we advocate that ECT should not be a treatment of last resort. Rather, it should be considered more readily as an add-on therapy when there has been a poor response to antipsychotic medications or concerns exist about side effects. Further research is needed into the efficacy of maintenance ECT.

DCC mutation update: Congenital mirror movements, isolated agenesis of the corpus callosum, and developmental split brain syndrome.

The deleted in colorectal cancer (DCC) gene encodes the netrin-1 (NTN1) receptor DCC, a transmembrane protein required for the guidance of commissural axons. Germline DCC mutations disrupt the development of predominantly commissural tracts in the central nervous system (CNS) and cause a spectrum of neurological disorders. Monoallelic, missense, and predicted loss-of-function DCC mutations cause congenital mirror movements, isolated agenesis of the corpus callosum (ACC), or both. Biallelic, predicted loss-of-function DCC mutations cause developmental split brain syndrome (DSBS). Although the underlying molecular mechanisms leading to disease remain poorly understood, they are thought to stem from reduced or perturbed NTN1 signaling. Here, we review the 26 reported DCC mutations associated with abnormal CNS development in humans, including 14 missense and 12 predicted loss-of-function mutations, and discuss their associated clinical characteristics and diagnostic features. We provide an update on the observed genotype-phenotype relationships of congenital mirror movements, isolated ACC and DSBS, and correlate this to our current understanding of the biological function of DCC in the development of the CNS. All mutations and their associated phenotypes were deposited into a locus-specific LOVD (https://databases.lovd.nl/shared/genes/DCC).

Novel cognitive insights from the first year after bi-thalamic infarct.

Neuropsychological consequences of bi-thalamic damage are scarcely known. This case study documents cognitive (in particular memory and executive) functioning in a man with a medial bi-thalamic infarct in the first year (8 and 12 months) post injury. NG showed persistent memory (including autobiographical) impairment, but improved executive functions at one year post injury. On a response inhibition task his speed of response improved but his ability to inhibit a "prepotent" automatic response declined, corresponding to an increase in behavioral disinhibition. Despite this, he showed intact performances on several social cognition tasks. This case contributes to our understanding of the role of the thalamus in mediating retrograde memory, executive, and social cognition functions.

Executive Dysfunction After Fourth-Ventricle Epidermoid Cyst Resection.

Intracranial epidermoid cysts are rare, comprising 0.2% to 1.8% of all primary intracranial expanding lesions, of which <5% occur within the fourth ventricle. Epidermoid cysts are frequently congenital, and patients often present in the fourth decade of life. These cysts produce symptoms as a result of mass effect on surrounding structures, most commonly the cerebellum and cranial nerves. Symptoms can include hearing impairment, trigeminal neuralgia (severe facial pain), facial tics, headaches, double vision, and facial palsy. However, no research has focused on the neuropsychological effects on a patient after surgical resection of these cysts. This case report presents the cognitive profile of a woman after resection of an epidermoid cyst in the fourth ventricle. The 49-year-old patient underwent neuropsychological assessment after removal of the cyst, completing a comprehensive set of cognitive tests of estimated premorbid intelligence, attention, memory, social cognition, language, visual perception, and executive functioning. Test results indicated executive dysfunction and reduced visuospatial memory in the acute stage after surgical removal of the epidermoid cyst. These findings suggest that cognitive deficits can occur after resection of space-occupying lesions in brain regions not typically associated with cognition. To our knowledge, this is the first report of the neuropsychological consequences of surgical removal of a congenital epidermoid cyst in the fourth ventricle. An understanding of the neuropsychological sequelae of this rare cerebral cyst will allow patients, families, and health professionals to better anticipate and manage postoperative difficulties.

Trends and repetition of non-fatal suicidal behaviour: analyses of the Gold Coast University Hospital's Emergency Department.

Objective The aim of the current paper is to analyse time trends of non-fatal suicidal behaviour (NFSB) and its repetition at the Gold Coast in 2005-2015. Methods Data on presentations for NFSB were obtained from the Emergency Department (ED) Information System. Potential cases were identified through keyword searches, which were further scrutinised and coded. Annual person-based age-standardised rates for NFSB were calculated. Chi-square test, Poisson regression and Cox proportional hazards regression were used. RESULTS: There was a significant increase in the age-standardised rates of NFSB for males (incidence Rate Ratio = 1.05; 95% confidence interval (CI): 1.04-1.07) and females (iRR = 1.06; 95% CI: 1.04-1.07). Age-specific rates showed significant increases for all age groups, except 25-34 and 55+ for females. Different types of poisoning were the predominant method of NFSB (poisoning only - 61.7% of episodes), followed by cutting (23%). Within the first year after the index episode, 13.4% of subjects repeated NFSB. Multivariate Cox regression model showed that sex, age and method predicted repetition. CONCLUSION: The increasing trends of NFSB and relatively high repetition rates emphasise the need for preventative actions. Monitoring of NFSB at the ED level should be further extended in Australia.

The language we use - the effect of writing mental health care plans in the first person.

OBJECTIVE: This study describes the impact of Motivational Aftercare Planning (MAP) - an intervention to increase consumer/clinician collaboration on the content of mental health recovery plans. The intervention focussed on enhancing existing discharge processes in psychiatric inpatient wards and supporting nursing staff in using motivational interviewing techniques to facilitate the completion of these plans. METHODS: We conducted a qualitative thematic content analysis of the recovery plans completed throughout the study ( n = 110). Chi-squared tests were then used to compare the occurrence of themes and content identified in recovery plans pre and post the intervention ( n = 55). RESULTS: The thematic content of the recovery plans shifted in focus following the intervention, with a change from third to first person language. Those completed prior to the intervention generally mentioned: decreasing symptoms of mental illness; acceptance of the illness; achieving clinical stability; risk management and treatment compliance. The recovery plans completed after the intervention focussed on: general wellness; participate in meaningful activities; community life; social roles and connections with others. CONCLUSIONS: This study demonstrated that a simple time-limited, facilitated intervention resulted in a change of thematic content in recovery plans. The use of these plans and its effect on care planning will need further evaluation.

Antipsychotic prescribing for vulnerable populations: a clinical audit at an acute Australian mental health unit at two-time points.

BACKGROUND: Antipsychotics are recognised as a critical intervention for schizophrenia and bipolar disorder. Guidelines globally endorse the routine practice of antipsychotic monotherapy, at the minimum effective dose. Even in treatment-resistant schizophrenia, clozapine use is endorsed before combining antipsychotics. This aim of this study was to review antipsychotic polytherapy alone, high-dose therapy alone, polytherapy and high-dose prescribing patterns in adults discharged from an inpatient mental health unit at two time-points, and the alignment of this prescribing with clinical guideline recommendations. Additionally, associations with polytherapy and high-dose antipsychotic prescribing, including patient and clinical characteristics, were explored. METHODS: A retrospective clinical audit of 400 adults (200 patients at two different time-points) discharged with at least one antipsychotic. Preliminary findings and education sessions were provided to physicians between Cohorts. Outcomes (polytherapy alone, high-dose therapy alone, polytherapy and high-dose therapy) were compared between study Cohorts using chi-squared and rank-sum tests. Associations between outcomes and covariates were assessed using multivariable logistic regression. RESULTS: Most patients (62.5%) were discharged on a single antipsychotic within the recommended dose range. There was a clear preference for prescribing second generation antipsychotics, and in this respect, prescribing is aligned with current evidence-based guidelines. However, sub-optimal prescribing practices were identified for both Cohorts in relation to polytherapy and high-dose antipsychotic rates. Involuntary treatment, frequent hospitalisations and previous clozapine use significantly increased the risk of all three prescribing outcomes at discharge. CONCLUSIONS: In a significant minority, antipsychotic prescribing did not align with clinical guidelines despite increased training, indicating that the education program alone was ineffective at positively influencing antipsychotic prescribing practices. Further consideration should be given when prescribing antipsychotics for involuntary patients, people with frequent hospitalisations, and those who have previously trialled clozapine.