rudyvdbrink/CitationDatabase huggingface dataset:
The Role of Amantadine Withdrawal in 3 Cases of Treatment-Refractory Altered Mental Status.
Journal of psychiatric practice, 2017

Amantadine, which was originally developed as an antiviral medication, functions as a dopamine agonist in the central nervous system and consequently is utilized in the treatment of Parkinson disease, drug-induced extrapyramidal reactions, and neuroleptic malignant syndrome. For reasons that are not entirely understood, abrupt changes in amantadine dosage can produce a severe withdrawal syndrome. Existing medical literature describes case reports of amantadine withdrawal leading to delirium, which at times has progressed to neuroleptic malignant syndrome. Amantadine withdrawal may be under-recognized by mental health clinicians, which has the potential to lead to protracted hospital courses and suboptimal outcomes. The goal of this case series is to highlight the role of amantadine withdrawal in the cases of 3 medically complex patients with altered mental status. In the first case, the cognitive side effects of electroconvulsive therapy masked acute amantadine withdrawal in a 64-year-old man with Parkinson disease. In the second case, a 75-year-old depressed patient developed a catatonic delirium when amantadine was discontinued. Finally, a refractory case of neuroleptic malignant syndrome in a 57-year-old patient with schizoaffective disorder rapidly resolved with the reintroduction of outpatient amantadine. These cases highlight several learning objectives regarding amantadine withdrawal syndrome: First, it may be concealed by co-occurring causes of delirium in medically complex patients. Second, its symptoms are likely to be related to a cortical and limbic dopamine shortage, which may be reversed with electroconvulsive therapy or reintroduction of amantadine. Third, its clinical presentation may occur on a spectrum and may include features suggestive of delirium, catatonia, or neuroleptic malignant syndrome.
Determinants of quality of life after epilepsy surgery: systematic review and evidence summary.
Epilepsy & behavior : E&B, 2011

We systematically reviewed evidence-based determinants of health-related quality of life (QOL) in adults undergoing epilepsy surgery and assessed the effect of study methods. Medline, Embase, and the Cochrane library (1950-2008) were searched systematically. Two authors independently performed every step of the review. We obtained the proportion of studies reporting statistically significant positive or negative impact on QOL. Of 39 eligible studies, 32 assessed the impact of surgery on QOL and 29 (90.6%) found a significant positive effect. The most prevalent preoperative determinant was psychological function. Seizure freedom was the most prevalent postoperative determinant (80% of studies), followed by antiepileptic drug adverse events, employment status, and psychological function. Psychosocial (95%), physical (91%), and overall QOL (90%) domains improved most frequently, whereas role limitation (63%) and cognition (78%) improved least frequently. Methods, choice of instrument, and time of measurement influenced QOL outcomes and should be carefully chosen in future studies.
Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze.
BMC neuroscience, 2017

The possibility of using deep brain stimulation (DBS) for memory enhancement has recently been reported, but the precise underlying mechanisms of its effects remain unknown. Our previous study suggested that spatial memory improvement by medial septum (MS)-DBS may be associated with cholinergic regulation and neurogenesis. However, the affected stage of memory could not be distinguished because the stimulation was delivered during the execution of all memory processes. Therefore, this study was performed to determine the stage of memory affected by MS-DBS. Rats were administered 192 IgG-saporin to lesion cholinergic neurons. Stimulation was delivered at different times in different groups of rats: 5 days before the Morris water maze test (pre-stimulation), 5 days during the training phase of the Morris water maze test (training-stimulation), and 2 h before the Morris water maze probe test (probe-stimulation). A fourth group of rats was lesioned but received no stimulation. These four groups were compared with a normal (control) group.
Neurochemical effects of quetiapine in patients with bipolar mania: a proton magnetic resonance spectroscopy study.
Journal of clinical psychopharmacology, 2013

Although the neurophysiology underlying pharmacotherapy for bipolar disorder remains poorly understood, recent studies suggest that therapeutic mechanisms may be reflected in changes in concentrations of N-acetylaspartate (NAA), a putative measure of neuronal integrity and metabolism. In this study, we used magnetic resonance spectroscopy (MRS) to examine prefrontal NAA in patients receiving quetiapine for bipolar mania. On the basis of previous findings, we hypothesized that remission would be associated with increased NAA concentrations in the prefrontal cortex. Thirty-one manic bipolar patients and 13 healthy subjects were recruited to participate in this prospective study. All subjects participated in MRS at baseline and after 8 weeks of treatment. Bipolar subjects received open-label quetiapine monotherapy (mean dose [SD], 584 [191] mg). Fourteen patients remitted (Young Mania Rating Scale ≤ 12) ("remitters"), 11 patients did not ("nonremitters"), and 6 patients were lost to follow-up. Bipolar and healthy subjects did not significantly differ in baseline NAA or degree of change during the 8 weeks. Remitters showed greater mean baseline NAA concentrations in the right ventrolateral prefrontal cortex compared with nonremitters (P < 0.05). In the anterior cingulate, remitters showed near significantly decreased baseline NAA concentrations at baseline (P < 0.06), and significant differences in NAA change during the 8 weeks of treatment (P < 0.03). Manic patients who remitted with quetiapine treatment in the course of this study exhibited distinct patterns of baseline prefrontal NAA concentration, coupled with decreased NAA in the anterior cingulate with treatment; the latter possibly reflecting disparate effects of quetiapine on neuronal metabolism. These data support suggestions that therapeutic effects of quetiapine involve metabolic effects on specific prefrontal regions.
Standardized Reporter Systems for Purification and Imaging of Human Pluripotent Stem Cell-derived Motor Neurons and Other Cholinergic Cells.
Neuroscience, 2020

Reliable and consistent pluripotent stem cell reporter systems for efficient purification and visualization of motor neurons are essential reagents for the study of normal motor neuron biology and for effective disease modeling. To overcome the inherent noisiness of transgene-based reporters, we developed a new series of human induced pluripotent stem cell lines by knocking in tdTomato, Cre, or CreERT2 recombinase into the HB9 (MNX1) or VACHT (SLC18A3) genomic loci. The new lines were validated by directed differentiation into spinal motor neurons and immunostaining for motor neuron markers HB9 and ISL1. To facilitate efficient purification of spinal motor neurons, we further engineered the VACHT-Cre cell line with a validated, conditional CD14-GFP construct that allows for both fluorescence-based identification of motor neurons, as well as magnetic-activated cell sorting (MACS) to isolate differentiated motor neurons at scale. The targeting strategies developed here offer a standardized platform for reproducible comparison of motor neurons across independently derived pluripotent cell lines.
Morphine exposure before conception affects anxiety-like behavior and CRF level (in the CSF and plasma) in the adult male offspring.
Brain research bulletin, 2019

It has been proven that exposure to some drugs even before gestation had transgenerational effects. To investigate the changes which induced by parental morphine exposure before gestation; mainly the anxiety-like behavior, Corticotropin Releasing Factor (CRF) level in the CSF and plasma, CRF Receptor 1 (CRFR1), and the level of protein kinase C (PKC-α) were evaluated in the male offspring. Male and female Wistar rats were exposed to morphine for 21 following days. Ten days after last drug exposure, animals were prepared for mating in 4 distinct groups as follow: drug-naïve female and male (used as control), drug-naïve female and morphine-abstinent male, drug-naïve male and morphine-abstinent female, and morphine abstinent male and female. Offspring were subjected to assess anxiety-like behavior (using elevated plus maze test). CSF and plasma were gathered, and the CRF level was evaluated by ELISA. Using real-time PCR, the CRFR1 level in the brain was evaluated. Results showed that anxiety-like behavior increased in the offspring of morphine-abstinent parent(s) compared with the control group. CRF level in the plasma and CSF also increased in the litter of morphine-abstinent parent(s). CRFR1 mRNA level was upregulated in the brain of offspring with one and/or two morphine-abstinent parent(s). Furthermore, the level of PKC-α was decreased in the brain of offspring which had one and/or two morphine-abstinent parent(s). Taken together, our findings indicated that morphine exposure even before gestation induced transgenerational effects via dysregulation of HPA axis which results in anxiety in the adult male offspring.
Automatic detection of generalized paroxysmal fast activity in interictal EEG using time-frequency analysis.
Computers in biology and medicine, 2021

Markup of generalized interictal epileptiform discharges (IEDs) on EEG is an important step in the diagnosis and characterization of epilepsy. However, manual EEG markup is a time-consuming, subjective, and the specialized task where the human reviewer needs to visually inspect a large amount of data to facilitate accurate clinical decisions. In this study, we aimed to develop a framework for automated detection of generalized paroxysmal fast activity (GPFA), a generalized IED seen in scalp EEG recordings of patients with the severe epilepsy of Lennox-Gastaut syndrome (LGS).
Hierarchical reinforcement learning and decision making.
Current opinion in neurobiology, 2012

The hierarchical structure of human and animal behavior has been of critical interest in neuroscience for many years. Yet understanding the neural processes that give rise to such structure remains an open challenge. In recent research, a new perspective on hierarchical behavior has begun to take shape, inspired by ideas from machine learning, and in particular the framework of hierarchical reinforcement learning. Hierarchical reinforcement learning builds on traditional reinforcement learning mechanisms, extending them to accommodate temporally extended behaviors or subroutines. The resulting computational paradigm has begun to influence both theoretical and empirical work in neuroscience, conceptually aligning the study of hierarchical behavior with research on other aspects of learning and decision making, and giving rise to some thought-provoking new findings.
Network mechanisms of grid cells.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2014

One of the major breakthroughs in neuroscience is the emerging understanding of how signals from the external environment are extracted and represented in the primary sensory cortices of the mammalian brain. The operational principles of the rest of the cortex, however, have essentially remained in the dark. The discovery of grid cells, and their functional organization, opens the door to some of the first insights into the workings of the association cortices, at a stage of neural processing where firing properties are shaped not primarily by the nature of incoming sensory signals but rather by internal self-organizing principles. Grid cells are place-modulated neurons whose firing locations define a periodic triangular array overlaid on the entire space available to a moving animal. The unclouded firing pattern of these cells is rare within the association cortices. In this paper, we shall review recent advances in our understanding of the mechanisms of grid-cell formation which suggest that the pattern originates by competitive network interactions, and we shall relate these ideas to new insights regarding the organization of grid cells into functionally segregated modules.
Radiotracer properties determined by high performance liquid chromatography: a potential tool for brain radiotracer discovery.
Nuclear medicine and biology, 2012

Previously, development of novel brain radiotracers has largely relied on simple screening tools. Improved selection methods at the early stages of radiotracer discovery and an increased understanding of the relationships between in vitro physicochemical and in vivo radiotracer properties are needed. We investigated if high performance liquid chromatography (HPLC) methodologies could provide criteria for lead candidate selection by comparing HPLC measurements with radiotracer properties in humans.
Next-generation sequencing analysis of multiplex families with atypical psychosis.
Translational psychiatry, 2018

Atypical psychosis (similar to acute and transient psychotic disorder, brief psychotic disorder) is highly heritable, but the causal genes remain unidentified. We conducted whole-genome sequencing on multiplex Japanese families with atypical psychosis. The patient group of interest shows acute psychotic features including hallucinations, delusions, and catatonic symptoms while they often show good prognosis after the onset. In addition to the next-generation analysis, HLA typing has been conveyed to check the similarity with autoimmune disease, such as systemic lupus erythematosus (SLE). Shared causal polymorphisms in the Deleted in Colorectal Carcinoma, Netrin 1 receptor (DCC) gene were found in one multiplex family with three patients, and variants in the RNA 3'-Terminal Phosphate Cyclase (RTCA) and One Cut Homeobox 2 (ONECUT2) genes were found to be shared in seven patients. Next-generation sequencing analysis of the MHC region (previously suggested to be a hot region in atypical psychosis) using HLA typing (HLA-DRB1) revealed a common vulnerability with SLE (systemic lupus erythematosus) among five patients. This finding demonstrates the shared etiology between psychotic symptoms and autoimmune diseases at the genetic level. Focusing on a specific clinical phenotype is key for elucidating the genetic factors that underlie the complex traits of psychosis.
Modulation of hippocampal synaptic transmission by the kynurenine pathway member xanthurenic acid and other VGLUT inhibitors.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013

Xanthurenic acid (XA), an endogenous kynurenine, is a known vesicular glutamate transport (VGLUT) inhibitor and has also been proposed as an mGlu2/3 receptor agonist. Changes in these systems have been implicated in the pathophysiology of schizophrenia and other psychiatric disorders; however, little is known of how XA affects synaptic transmission. We therefore investigated the effects of XA on synaptic transmission at two hippocampal glutamatergic pathways and evaluated the ability of XA to bind to mGlu2/3 receptors. Field excitatory postsynaptic potentials (fEPSPs) were recorded from either the dentate gyrus (DG) or CA1 region of mouse hippocampal slices in vitro. Addition of XA to the bathing medium (1-10 mM) resulted in a dose-related reduction of fEPSP amplitudes (up to 52% reduction) in both hippocampal regions. In the DG, the VGLUT inhibitors Congo Red and Rose Bengal, and the mGlu2/3 agonist LY354740, also reduced fEPSPs (up to 80% reduction). The mGlu2/3 antagonist LY341495 reversed the LY354740 effect, but not the XA effect. LY354740, but not XA, also reduced DG paired-pulse depression. XA had no effect on specific binding of 1 nM [(3)H]LY341495 to membranes with human mGlu2 receptors. We conclude that XA can modulate synaptic transmission via a mechanism that may involve VGLUT inhibition rather than activation of mGlu2/3 receptors. This could be important in the pathophysiology of nervous system disorders including schizophrenia and might represent a target for developing novel pharmacological therapies.
Morphine enhances microglial migration through modulation of P2X4 receptor signaling.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

Opioids, although fundamental to the treatment of pain, are limited in efficacy by side effects including tolerance and hyperalgesia. Using an in vitro culture system, we report that morphine increased microglial migration via a novel interaction between mu-opioid and P2X(4) receptors, which is dependent upon PI3K/Akt pathway activation. Morphine at 100 nm enhanced migration of primary microglial cells toward adenosine diphosphate by 257, 247, 301, 394, and 345% following 2, 6, 12, 24, and 48 h of stimulation, respectively. This opioid-dependent migration effect was inhibited by naloxone and confirmed to be mu-opioid receptor-dependent through the use of selective agonists and antagonists. PPADS [pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid)], a P2X(1-3,5-7) antagonist, had no effect on microglial migration; however, TNP-ATP [2',3'-O-(2,4,6-trinitrophenyl)-ATP], a P2X(1-7) antagonist, inhibited morphine-induced migration, suggesting a P2X(4) receptor-mediated effect. The PI3K inhibitors wortmannin and LY294002 decreased morphine-induced microglial migration. Iba1 protein, a microglial marker, and P2X(4) receptor expression were significantly increased after 6, 12, 24, and 48 h of morphine stimulation. Together, these results provide evidence for two phases of morphine effects on microglia. The initial phase takes place in minutes, involves PI3K/Akt pathway activation and leads to acutely enhanced migration. The longer-term phase occurs on the order of hours and involves increased expression of Iba1 and P2X(4) receptor protein, which imparts a promigratory phenotype and is correlated with even greater migration. These data provide the first necessary step in supporting microglial migration as an attractive target for the prevention or attenuation of morphine-induced side effects including tolerance and hyperalgesia.
Comparative assessment of phototherapy protocols for reduction of oxidative stress in partially transected spinal cord slices undergoing secondary degeneration.
BMC neuroscience, 2016

Red/near-infrared light therapy (R/NIR-LT) has been developed as a treatment for a range of conditions, including injury to the central nervous system (CNS). However, clinical trials have reported variable or sub-optimal outcomes, possibly because there are few optimized treatment protocols for the different target tissues. Moreover, the low absolute, and wavelength dependent, transmission of light by tissues overlying the target site make accurate dosing problematic.
Descriptive experiences and sexual vs. nurturant aspects of cuddling between adult romantic partners.
Archives of sexual behavior, 2013

Touch is a critical factor in intimate bonds between romantic partners. Although cuddling is a key expression of intimacy, it has received little empirical attention. Past research suggests that cuddling has some sexual aspects (e.g., it increases testosterone [T]), but there are theoretical reasons to expect cuddling to also involve nurturant intimacy (which should decrease T). In this article, we examined the phenomenon of partner cuddling to: (1) provide a descriptive examination; (2) determine if cuddling involved only nurturant intimacy or also sexual intimacy; and (3) test whether cuddling was perceived as nurturant but experienced as sexual. Via an online questionnaire, 514 participants (338 women) responded to quantitative and qualitative questions about cuddling with their romantic partners. Results suggested that cuddling occurred frequently and for relatively long durations, and was viewed very positively. Findings also showed that cuddling was perceived as nurturant and non-sexual but was experienced as at least somewhat sexual, which may explain why past research had found that cuddling increased T. Correlational analyses linked cuddling frequency and enjoyment positively with partnered sexual activities, but negatively with solitary sexuality. Results were discussed relative to evolutionary theories of distinct but overlapping neurobiological systems underlying pair bonding that involve sexual and nurturant intimacy.
Optimizing the delivery of interventions for harmful alcohol use in primary healthcare: an update.
Current opinion in psychiatry, 2018

Alcohol is a leading risk factor for ill health and premature death. Regardless of poor levels of implementation achieved after more than 30 years of research and policy advice, alcohol screening and brief advice (SBA) remains one of the best policy options. This study updates the evidence by considering recent publications on SBA for heavy drinking and alcohol use disorder in primary healthcare at a timely moment, because researchers are, at present, debating future direction of research and policy in this field.
Foraging in an unsteady world: bumblebee flight performance in field-realistic turbulence.
Interface focus, 2017

Natural environments are characterized by variable wind that can pose significant challenges for flying animals and robots. However, our understanding of the flow conditions that animals experience outdoors and how these impact flight performance remains limited. Here, we combine laboratory and field experiments to characterize wind conditions encountered by foraging bumblebees in outdoor environments and test the effects of these conditions on flight. We used radio-frequency tags to track foraging activity of uniquely identified bumblebee (
Failure is not an option: Risk-taking is moderated by anxiety and also by cognitive ability in children and adolescents diagnosed with an autism spectrum disorder.
Journal of autism and developmental disorders, 2011

Understanding hetereogeneity in symptom expression across the autism spectrum disorders (ASD) is a major challenge for identifying causes and effective treatments. In 40 children and adolescents diagnosed with ASD and 37 IQ-and age-matched comparison participants (the TYP group), we found no differences in summary measures on an experimental risk-taking task. However, anxiety and IQ predicted risk-taking only in the ASD group. Risk-taking was correlated with behavioral inhibition in the ASD group and behavioral activation in the TYP group. We suggest that performance on the task was motivated by fear of failure in the ASD group and by sensitivity to reward in the TYP group. Behavioral markers of anxiety and cognitive ability may improve conceptualization of heterogeneity in ASD.