rudyvdbrink/CitationDatabase huggingface dataset:
Physiological variation of retinal layer thickness is not caused by hydration: a randomised trial.
Journal of the neurological sciences, 2014

There is evidence for physiological variation of retinal thicknesses as determined by optical coherence tomography (OCT). We tested if such changes could be explained by hydration and would exceed what may be expected from normal ageing. Subjects (n=26) of a previous study were re-assessed and were randomised to 3 groups of a hydration escalation trial (no hydration, 1× hydration, 2× hydration). Automated retinal layer segmentations were performed for the macular retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear layer (ONL). The averaged volumes were calculated for the central foveola, 3 mm and 6 mm circles of the ETDRS grid. Following oral hydration there were no significant differences of retinal layer thicknesses between the three randomised groups in any of the ETDRS regions at any time-point. Ageing related changes were significant over an 18 month period for the GCL. The negative outcome of this trial implies that, until the causes for the observed variation are resolved, investigators may need to accept, and include into trial power calculations, a small degree of variation (<1%) of quantitative SD-OCT imaging either due to human physiology or instrument/software related factors.
Maintenance of antidepressant and antisuicidal effects by D-cycloserine among patients with treatment-resistant depression who responded to low-dose ketamine infusion: a double-blind randomized placebo-control study.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2019

Increasing evidence supports a rapid antidepressant and antisuicidal effect of a single subanesthetic dose of ketamine infusion for treatment-resistant depression (TRD). Maintaining the initial clinical response after ketamine infusion in TRD is a crucial next-step challenge. D-cycloserine (DCS), a partial agonist of the glycine co-agonist of the N-methyl-D-aspartate (NMDA) glutamate receptor, is potentially effective as a depression augmentation treatment. However, whether DCS maintains the antidepressant and antisuicidal effects of ketamine infusion remains unknown. In all, 32 patients with TRD (17 with major depression and 15 with bipolar depression) who responded to ketamine infusion with an average 17-item Hamilton Depression Rating Scale (HAMD) score of 9.47 ± 4.11 at baseline were randomly divided to 6-week DCS treatment (250 mg for 2 days, 500 mg for 2 days, 750 mg for 3 days, and 1000 mg for 5 weeks) and placebo groups. Depression symptoms were rated at timepoints of dose titration and weekly. During the 6-week treatment, the total scores of HAMD did not differ between the DCS and placebo groups. The results remained consistent when stratified by disorder. A mixed model analysis indicated that the DCS group exhibited lower scores of HAMD item 3 (suicide) compared with the placebo group throughout the follow-up period (p = 0.01). A superior maintenance of the antisuicidal effect of ketamine was observed in the DCS group than in the placebo group. DCS may be therapeutically beneficial for patients with TRD who responded to ketamine infusion but have a residual suicidal risk.
Episodic withdrawal promotes psychomotor sensitization to morphine.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2010

The relative intermittency or continuity of drug delivery is a major determinant of addictive liability, and also influences the impact of drug exposure on brain function and behavior. Events that occur during the offset of drug action (ie, acute withdrawal) may have an important role in the consequences of intermittent drug exposure. We assessed whether recurrent episodes of acute withdrawal contribute to the development of psychomotor sensitization in rodents during daily morphine exposure. The acoustic startle reflex--a measure of anxiety induced by opiate withdrawal-was used to resolve and quantify discrete withdrawal episodes, and pharmacological interventions were used to manipulate withdrawal severity. Startle potentiation was observed during spontaneous withdrawal from a single morphine exposure, and individual differences in initial withdrawal severity positively predicted the subsequent development of sensitization. Manipulations that reduce or exacerbate withdrawal severity also produced parallel changes in the degree of sensitization. These results demonstrate that the episodic experience of withdrawal during daily drug exposure has a novel role in promoting the development of psychomotor sensitization--a prominent model of drug-induced neurobehavioral plasticity. Episodic withdrawal may have a pervasive role in many effects of intermittent drug exposure and contribute to the development of addiction.
Time scales of memory, learning, and plasticity.
Biological cybernetics, 2012

After only about 10 days would the storage capacity of our nervous system be reached if we stored every bit of input. The nervous system relies on at least two mechanisms that counteract this capacity limit: compression and forgetting. But the latter mechanism needs to know how long an entity should be stored: some memories are relevant only for the next few minutes, some are important even after the passage of several years. Psychology and physiology have found and described many different memory mechanisms, and these mechanisms indeed use different time scales. In this prospect we review these mechanisms with respect to their time scale and propose relations between mechanisms in learning and memory and their underlying physiological basis.
GPR30 differentially regulates short latency responses of luteinising hormone and prolactin secretion to oestradiol.
Journal of neuroendocrinology, 2009

Rapid, nongenomic actions of 17beta-oestradiol (E(2)) on hypothalamic neurones that may be relevant to reproductive function were described decades ago. The orphan G protein-coupled receptor, GPR30, was recently shown to bind oestrogens and to trigger rapid signalling in vitro, and is expressed in several rat and human brain regions, including the hypothalamus. We used two complementary approaches to investigate the role of GPR30 in hypothalamic responses to E(2) that are relevant to reproductive physiology. Serial blood sampling after the acute administration of the selective GPR30 agonist G1 was used to assess the role of GPR30 in short latency negative-feedback inhibition of luteinising hormone (LH) secretion and facilitation of prolactin secretion in ovariohysterectomised female rats. In vivo RNA interference (RNAi), mediated by adeno-associated virus-expressing small hairpin RNA (shRNA) infused into the mediobasal hypothalamus, was used to study the effects of GPR30 knockdown on these rapid responses to E(2). Longer-term actions of E(2) on female sexual behaviour (lordosis) were also examined in female rats subjected to in vivo RNAi. Administration of E(2) or G1 triggered a short latency surge of prolactin secretion, and animals subjected to GPR30 RNAi showed significantly less E(2)-dependent prolactin release than animals receiving control virus. G1 did not mimic E(2) negative-feedback inhibition of LH secretion, and GPR30 RNAi did not interfere with E(2) suppression of LH or facilitation of lordosis behaviour. These findings suggest that activation of GPR30 promotes short latency prolactin secretion but does not mediate E(2) negative-feedback inhibition of LH secretion or E(2) facilitation of female reproductive behaviour.
The role of cannabis in treating anxiety: an update.
Current opinion in psychiatry, 2020

Cannabis use for medical purposes has become increasingly common, including as treatment for mental health disorders such as anxiety. Unfortunately, the evidence examining its use in mental health has been slow to evolve, but is emerging. Given the widespread use of cannabis, it is important for both clinicians and those who suffer with anxiety to understand the effects of cannabis on symptoms of anxiety. In this review, we present recent, available evidence from animal models, clinical trials, and survey studies and evaluate the contribution of these studies to the current understanding of the role of cannabis in treating anxiety.
Blood acetylcholinesterase level is a potential biomarker for the early detection of cerebral amyloid deposition in cognitively normal individuals.
Neurobiology of aging, 2019

Cerebral β-amyloid (cAβ) deposition and cholinergic dysfunction have been considered as major pathological and functional hallmarks of Alzheimer's disease (AD). Acetylcholinesterase (AChE) is one of the major cholinergic enzymes, and there is no report to show the relationship between cAβ accumulation and peripheral AChE alteration in early stage of AD pathogenesis. Recent studies demonstrate that cAβ starts to deposit 15-20 years ahead of symptomatic appearance and this preclinical AD is important for early diagnosis of disease. In this study, we investigated the link between cAβ deposition and the peripheral AChE in cognitively normal (CN) individuals. A total of 407 individuals who underwent Pittsburgh compound B (PiB)-positron emission tomography participated in our study. Lower levels of plasma AChE and its enzymatic activity were detected in CN individuals with cAβ deposition than in those without cAβ. Plasma AChE levels and enzymatic activity were negatively correlated with the degree of cAβ deposition. Our results suggest that blood AChE can be used as a potential blood biomarker for the prediction of cAβ deposition in CN individuals.
From micro- to macro-structures in multiple sclerosis: what is the added value of diffusion imaging.
NMR in biomedicine, 2019

Diffusion imaging has been instrumental in understanding damage to the central nervous system as a result of its sensitivity to microstructural changes. Clinical applications of diffusion imaging have grown exponentially over the past couple of decades in many neurological and neurodegenerative diseases, such as multiple sclerosis (MS). For several reasons, MS has been extensively researched using advanced neuroimaging techniques, which makes it an 'example disease' to illustrate the potential of diffusion imaging for clinical applications. In addition, MS pathology is characterized by several key processes competing with each other, such as inflammation, demyelination, remyelination, gliosis and axonal loss, enabling the specificity of diffusion to be challenged. In this review, we describe how diffusion imaging can be exploited to investigate micro-, meso- and macro-scale properties of the brain structure and discuss how they are affected by different pathological substrates. Conclusions from the literature are that larger studies are needed to confirm the exciting results from initial investigations before current trends in diffusion imaging can be translated to the neurology clinic. Also, for a comprehensive understanding of pathological processes, it is essential to take a multiple-level approach, in which information at the micro-, meso- and macroscopic scales is fully integrated.
Basal forebrain chemogenetic inhibition disrupts the superior complex movement control of goal-tracking rats.
Behavioral neuroscience, 2019

Sign- and goal-tracking behavior signifies the influence of opposed cognitive-motivational styles, with the former being characterized by a tendency for approaching and contacting reward cues, including a readiness for attending, bottom-up, to salient cues, and a relatively greater vulnerability for developing and maintaining addiction-like behaviors. We previously demonstrated that these styles also impact the cognitive-motor interactions that are taxed during traversal of dynamic surfaces, with goal-trackers (GTs) making less movement errors and falling less frequently than sign-trackers (STs). The present experiment tested the hypothesis that complex movement control in GTs, but not STs, depends on activation of the basal forebrain projection system to telencephalic regions. Chemogenetic inhibition of the basal forebrain increased movement errors and falls in GTs during traversal of a rotating zigzag rod but had no significant effect on the relatively lower performance of STs. Neurochemical evidence confirmed the efficacy of the inhibitory designer receptor exclusively activated by designer drug (DREADD). Administration of clozapine-N-oxide (CNO) had no significant effect in GTs not expressing the DREADD. These results indicate that GTs, but not STs, activate the basal forebrain projection system to mediate their relatively superior ability for complex movement control. STs may also serve as an animal model in research on the role of basal forebrain systems in aging- and Parkinson's disease-associated falls. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
A three-groups model for high-throughput survival screens.
Biometrics, 2016

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive deterioration of motor neurons in the cortex and spinal cord. Using an automated robotic microscope platform that enables the longitudinal tracking of thousands of single neurons, we examine the effects a large library of compounds on modulating the survival of primary neurons expressing a mutation known to cause ALS. The goal of our analysis is to identify the few potentially beneficial compounds among the many assayed, the vast majority of which do not extend neuronal survival. This resembles the large-scale simultaneous inference scenario familiar from microarray analysis, but transferred to the survival analysis setting due to the novel experimental setup. We apply a three-component mixture model to censored survival times of thousands of individual neurons subjected to hundreds of different compounds. The shrinkage induced by our model significantly improves performance in simulations relative to performing treatment-wise survival analysis and subsequent multiple testing adjustment. Our analysis identified compounds that provide insight into potential novel therapeutic strategies for ALS.
Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation.
American journal of physiology. Regulatory, integrative and comparative physiology, 2015

Psychological disorders are prevalent in patients with inflammatory bowel disease; the underlying mechanisms remain unknown. We tested the hypothesis that ulcerative colitis-like inflammation induced by dextran sodium sulfate (DSS) exacerbates the ongoing spontaneous activity in colon-projecting afferent neurons that induces abdominal discomfort and anxiety, and depressive-like behaviors in rats. In this study, we used the conditioned place preference and standard tests for anxiety- and depression-like behaviors. DSS rats developed anxiety- and depression-like behaviors 10 to 20 days after the start of inflammation. Single-fiber recordings showed an increase in the frequency of spontaneous activity in L6-S1 dorsal root ganglion (DRG) roots. Prolonged desensitization of transient receptor potential vanilloid 1 (TRPV1)-expressing colonic afferents by resiniferatoxin (RTX) suppressed the spontaneous activity, as well as the anxiety- and depressive-like behaviors. Reduction in spontaneous activity in colon afferents by intracolonic administration of lidocaine produced robust conditioned place preference (CPP) in DSS rats, but not in control rats. Patch-clamp studies demonstrated a significant decrease in the resting membrane potential, lower rheobase, and sensitization of colon-projecting L6-S1 DRG neurons to generate trains of action potentials in response to current injection in DSS rats. DSS inflammation upregulated the mRNA levels of transient receptor potential ankyrin 1 and TRPV1 channels and downregulated that of Kv1.1 and Kv1.4 channels. Ulcerative colitis-like inflammation in rats induces anxiety- and depression-like behaviors, as well as ongoing abdominal discomfort by exacerbating the spontaneous activity in the colon-projecting afferent neurons. Alterations in the expression of voltage- and ligand-gated channels are associated with the induction of mood disorders following colon inflammation.
Age dependence of primary motor cortex plasticity induced by paired associative stimulation.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2008

The increase of elderly population prompted growing research for the understanding of cerebral phenomena sustaining learning abilities, with inclusion of long-term potentiation (LTP)-like plasticity phenomena. Aim of the present study was to characterize LTP-like plasticity dependence on age and gender.
Neuregulin-1 (NRG1) polymorphisms linked with psychosis transition are associated with enlarged lateral ventricles and white matter disruption in schizophrenia.
Psychological medicine, 2018

Two single-nucleotide polymorphisms (SNPs) (rs4281084 and rs12155594) within the neuregulin-1 (NRG1) gene have been associated with psychosis transition. However, the neurobiological changes associated with these SNPs remain unclear. We aimed to determine what relationship these two SNPs have on lateral ventricular volume and white matter integrity, as abnormalities in these brain structures are some of the most consistent in schizophrenia.
Distinct cortical activity patterns in Parkinson's disease and essential tremor during a bimanual tapping task.
Journal of neuroengineering and rehabilitation, 2020

Parkinson's disease (PD) and essential tremor (ET) are neurodegenerative diseases characterized by movement deficits. Especially in PD, maintaining cyclic movement can be significantly disturbed due to pathological changes in the basal ganglia and the cerebellum. Providing external cues improves timing of these movements in PD and also affects ET. The aim of this study is to determine differences in cortical activation patterns in PD and ET patients during externally and internally cued movements.
The multistep hypothesis of ALS revisited: The role of genetic mutations.
Neurology, 2018

Amyotrophic lateral sclerosis (ALS) incidence rates are consistent with the hypothesis that ALS is a multistep process. We tested the hypothesis that carrying a large effect mutation might account for ≥1 steps through the effect of the mutation, thus leaving fewer remaining steps before ALS begins.
VGLUT2-dependent sensory neurons in the TRPV1 population regulate pain and itch.
Neuron, 2010

The natural response to itch sensation is to scratch, which relieves the itch through an unknown mechanism. Interaction between pain and itch has been frequently demonstrated, and the selectivity hypothesis of itch, based on data from electrophysiological and behavioral experiments, postulates the existence of primary pain afferents capable of repressing itch. Here, we demonstrate that deletion of vesicular glutamate transporter (VGLUT) 2 in a subpopulation of neurons partly overlapping with the vanilloid receptor (TRPV1) primary afferents resulted in a dramatic increase in itch behavior accompanied by a reduced responsiveness to thermal pain. The increased itch behavior was reduced by administration of antihistaminergic drugs and by genetic deletion of the gastrin-releasing peptide receptor, demonstrating a dependence on VGLUT2 to maintain normal levels of both histaminergic and nonhistaminergic itch. This study establishes that VGLUT2 is a major player in TRPV1 thermal nociception and also serves to regulate a normal itch response.
Attention Shifts Recruit the Monkey Default Mode Network.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018

A unifying function associated with the default mode network (DMN), which is more active during rest than under active task conditions, has been difficult to define. The DMN is activated during monitoring the external world for unexpected events, as a sentinel, and when humans are engaged in high-level internally focused tasks. The existence of DMN correlates in other species, such as mice, challenge the idea that internally focused, high-level cognitive operations, such as introspection, autobiographical memory retrieval, planning the future, and predicting someone else's thoughts, are evolutionarily preserved defining properties of the DMN. A recent human study demonstrated that demanding cognitive shifts could recruit the DMN, yet it is unknown whether this holds for nonhuman species. Therefore, we tested whether large changes in cognitive context would recruit DMN regions in female and male nonhuman primates. Such changes were measured as displacements of spatial attentional weights based on internal rules of relevance (spatial shifts) compared with maintaining attentional weights at the same location (stay events). Using fMRI in macaques, we detected that a cortical network, activated during shifts, largely overlapped with the DMN. Moreover, fMRI time courses sampled from independently defined DMN foci showed significant shift selectivity during the demanding attention task. Finally, functional clustering based on independent resting state data revealed that DMN and shift regions clustered conjointly, whereas regions activated during the stay events clustered apart. We therefore propose that cognitive shifting in primates generally recruits DMN regions. This might explain a breakdown of the DMN in many neurological diseases characterized by declined cognitive flexibility.
LRRTM1-deficient mice show a rare phenotype of avoiding small enclosures--a tentative mouse model for claustrophobia-like behaviour.
Behavioural brain research, 2013

The LRRTM family proteins have been shown to act as synaptogenic cell adhesion molecules via interaction with presynaptic neurexins and are associated with neuropsychiatric disorders. LRRTM1-knockout mice have subtle morphological deficits in excitatory hippocampal synapses and were suggested to have impaired cognitive function. Here we report that LRRTM1-knockout mice exhibit an extraordinary phenotype of avoiding small enclosures. In the light-dark box, the knockout mice escape to dark through a standard opening as quickly as wild-type littermates but avoid escaping through a small doorway. While all wild-type mice spontaneously enter a small tube, most knockout mice do not. This apparent aversion to enter narrow space may explain other abnormalities such as increased time in open arms in the elevated plus maze and less visits through a tunnel in the IntelliCage. Moreover, LRRTM1-knockout mice show increased social interaction, reduced nest building and MK801-induced locomotion, and slower swim speed but normal water maze learning. Since LRRTM1 is predominantly expressed in thalamus, hippocampus and limbic cortex, specific synaptic defects in those areas presumably cause these behavioural abnormalities.