rudyvdbrink/CitationDatabase huggingface dataset:
A temporal hierarchy for conspecific vocalization discrimination in humans.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

The ability to discriminate conspecific vocalizations is observed across species and early during development. However, its neurophysiologic mechanism remains controversial, particularly regarding whether it involves specialized processes with dedicated neural machinery. We identified spatiotemporal brain mechanisms for conspecific vocalization discrimination in humans by applying electrical neuroimaging analyses to auditory evoked potentials (AEPs) in response to acoustically and psychophysically controlled nonverbal human and animal vocalizations as well as sounds of man-made objects. AEP strength modulations in the absence of topographic modulations are suggestive of statistically indistinguishable brain networks. First, responses were significantly stronger, but topographically indistinguishable to human versus animal vocalizations starting at 169-219 ms after stimulus onset and within regions of the right superior temporal sulcus and superior temporal gyrus. This effect correlated with another AEP strength modulation occurring at 291-357 ms that was localized within the left inferior prefrontal and precentral gyri. Temporally segregated and spatially distributed stages of vocalization discrimination are thus functionally coupled and demonstrate how conventional views of functional specialization must incorporate network dynamics. Second, vocalization discrimination is not subject to facilitated processing in time, but instead lags more general categorization by approximately 100 ms, indicative of hierarchical processing during object discrimination. Third, although differences between human and animal vocalizations persisted when analyses were performed at a single-object level or extended to include additional (man-made) sound categories, at no latency were responses to human vocalizations stronger than those to all other categories. Vocalization discrimination transpires at times synchronous with that of face discrimination but is not functionally specialized.
A Systematic Review of Outcome Measures Employed in Aneurysmal Subarachnoid Hemorrhage (aSAH) Clinical Research.
Neurocritical care, 2019

Consensus on appropriate outcome measures to use in aneurysmal subarachnoid hemorrhage (aSAH) research has not been established, although the transition toward a core outcome set (COS) would provide significant benefits. To inform COS development, we conducted a systematic review to identify outcome measures included in reports of randomized clinical trials (RCTs) of interventions in patients with aSAH. Ovid Medline, EMBASE, CINAHL, and CENTRAL were searched. RCTs investigating aSAH published between January 1996 and May 2015 were included. The primary and secondary outcomes of RCTs were recorded and classified according to the OMERACT Consortium's framework. We identified 1093 potential studies of which 129 met inclusion criteria representing 24 238 patients. There were 285 unique outcome measures. The Glasgow Outcome Scale (GOS) was the most frequently used primary outcome (13/129, 10.1%). Mortality was reported in 84 trials (65.1%) with 3 months the most common time point (34/129, 26.4%). The GOS (65/129, 50.4%) and the Modified Rankin Scale (51/129, 39.5%) were the most commonly reported functional measures; however, these were reported at different time points and often dichotomized using different ranges. Patient-reported quality of life measures were used in 11 trials (8.5%). Transcranial Doppler was the most frequently used imaging modality (40/129, 31.0%). Definitions and reporting of vasospasm, delayed cerebral ischemia and imaging modality results were highly variable. The marked heterogeneity of outcomes in reports of RCTs supports the development of a core outcome set for aSAH trials. Our study has identified a wide range of outcomes for potential inclusion in a future aSAH COS.
Chemogenetic manipulation of parasympathetic neurons (DMV) regulates feeding behavior and energy metabolism.
Neuroscience letters, 2019

Parasympathetic nervous system (PNS) innervates with several peripheral organs such as liver, pancreas and regulates energy metabolism. However, the direct role of PNS on food intake has been poorly understood. In the present study, we investigated the role of parasympathetic nervous system in regulation of feeding by chemogenetic methods. Adeno associated virus carrying DREADD (designer receptors exclusively activated by designer drugs) infused into the target brain region by stereotaxic surgery. The stimulatory hM3Dq or inhibitory hM4Di DREADD was over-expressed in selective population of dorsal motor nucleus of the vagus (DMV) neurons by Cre-recombinase-dependent manners. Activation of parasympathetic neuron by intraperitoneal injection of the M3-muscarinic receptor ligand clozapine-N-oxide (CNO) (1 mg/kg) suppressed food intake and resulted in body weight loss in ChAT-Cre mice. Parasympathetic neurons activation resulted in improved glucose tolerance while inhibition of the neurons resulted in impaired glucose tolerance. Stimulation of parasympathetic nervous system by injection of CNO (1 mg/kg) increased oxygen consumption and energy expenditure. Within the hypothalamus, in the arcuate nucleus (ARC) changed AGRP/POMC neurons. These results suggest that direct activation of parasympathetic nervous system decreases food intake and body weight with improved glucose tolerance.
Potentiation of neurotoxicity in double-mutant mice with Pink1 ablation and A53T-SNCA overexpression.
Human molecular genetics, 2015

The common age-related neurodegeneration of Parkinson's disease can result from dominant causes like increased dosage of vesicle-associated alpha-synuclein (SNCA) or recessive causes like deficiency of mitophagy factor PINK1. Interactions between these triggers and their convergence onto shared pathways are crucial, but currently conflicting evidence exists. Here, we crossed previously characterized mice with A53T-SNCA overexpression and with Pink1 deletion to generate double mutants (DMs). We studied their lifespan and behavior, histological and molecular anomalies at late and early ages. DM animals showed potentiated phenotypes in comparison with both single mutants (SMs), with reduced survival and strongly reduced spontaneous movements from the age of 3 months onwards. In contrast to SMs, a quarter of DM animals manifested progressive paralysis at ages >1 year and exhibited protein aggregates immunopositive for pSer129-SNCA, p62 and ubiquitin in spinal cord and basal brain. Brain proteome quantifications of ubiquitination sites documented altered degradation of SNCA and the DNA-damage marker H2AX at the age of 18 months. Global brain transcriptome profiles and qPCR validation experiments identified many consistent transcriptional dysregulations already at the age of 6 weeks, which were absent from SMs. The observed downregulations for Dapk1, Dcaf17, Rab42 and the novel SNCA-marker Lect1 as well as the upregulations for Dctn5, Mrpl9, Tmem181a, Xaf1 and H2afx reflect changes in ubiquitination, mitochondrial/synaptic/microtubular/cell adhesion dynamics and DNA damage. Thus, our study confirmed that SNCA-triggered neurotoxicity is exacerbated by the absence of PINK1 and identified a novel molecular signature that is detectable early in the course of this double pathology.
Left inferior frontal gyrus mediates morphosyntax: ERP evidence from verb processing in left-hemisphere damaged patients.
Cortex; a journal devoted to the study of the nervous system and behavior, 2017

Neurocognitive models of language comprehension have proposed different mechanisms with different neural substrates mediating human language processing. Whether the left inferior frontal gyrus (LIFG) is engaged in morpho-syntactic information processing is currently still controversially debated. The present study addresses this issue by examining the processing of irregular verb inflection in real words (e.g., swim > swum > swam) and pseudowords (e.g., frim > frum > fram) by using event-related brain potentials (ERPs) in neurological patients with lesions in the LIFG involving Broca's area as well as healthy controls. Different ERP patterns in response to the grammatical violations were observed in both groups. Controls showed a biphasic negativity-P600 pattern in response to incorrect verb inflections whereas patients with LIFG lesions displayed a N400. For incorrect pseudoword inflections, a late positivity was found in controls, while no ERP effects were obtained in patients. These findings of different ERP patterns in the two groups strongly indicate an involvement of LIFG in morphosyntactic processing, thereby suggesting brain regions' specialization for different language functions.
Reduced perceptual narrowing in synesthesia.
Proceedings of the National Academy of Sciences of the United States of America, 2020

Synesthesia is a neurologic trait in which specific inducers, such as sounds, automatically elicit additional idiosyncratic percepts, such as color (thus "colored hearing"). One explanation for this trait-and the one tested here-is that synesthesia results from unusually weak pruning of cortical synaptic hyperconnectivity during early perceptual development. We tested the prediction from this hypothesis that synesthetes would be superior at making discriminations from nonnative categories that are normally weakened by experience-dependent pruning during a critical period early in development-namely, discrimination among nonnative phonemes (Hindi retroflex /d̪a/ and dental /ɖa/), among chimpanzee faces, and among inverted human faces. Like the superiority of 6-mo-old infants over older infants, the synesthetic groups were significantly better than control groups at making all the nonnative discriminations across five samples and three testing sites. The consistent superiority of the synesthetic groups in making discriminations that are normally eliminated during infancy suggests that residual cortical connectivity in synesthesia supports changes in perception that extend beyond the specific synesthetic percepts, consistent with the incomplete pruning hypothesis.
A tug of war: antagonistic effective connectivity patterns over the motor cortex and the severity of motor symptoms in Gilles de la Tourette syndrome.
The European journal of neuroscience, 2017

We tested the hypothesis that Gilles de la Tourette syndrome (GTS) is characterized by perturbed connectivity within cortico-subcortical motor networks. To this end, we performed a dynamic causal modelling (DCM) analysis of fMRI data collected during a finger opposition task in 24 normal controls and 24 GTS patients. The DCM analysis allowed us to assess whether any GTS-specific patterns of brain activity were related to intrinsic and/or to task-dependent connectivity. While no abnormalities were found for task-dependent connectivity, intrinsic connectivity was abnormally increased in the premotor network, with stronger connections from the supplementary motor area (SMA), from the dorsolateral premotor cortex and from the putamen to the right superior frontal gyrus, an area where GTS showed over-activation in a previous univariate analysis. We also found a positive correlation between the connectivity strength from the right basal ganglia to the right primary motor cortex (M1) and disease severity measured by the Yale Global Tic Severity Scale (YGTSS). This pattern was mirrored by a negative correlation between the connection strength from the right SMA to the right area M1 and the YGTSS score. These two reverse correlation effects showed a specific relationship with individual disease severity: the greater the imbalance between subcortical and premotor connectivity towards area M1, the higher the YGTSS score. These results reveal the existence of perturbed intrinsic connectivity patterns in the motor networks of GTS patients with two competing forces operating in a tug of war-like mechanism: aberrant subcortical afferents to M1, compensated for by inputs from the premotor cortex.
Increased functional connectivity in gambling disorder correlates with behavioural and emotional dysregulation: Evidence of a role for the cerebellum.
Behavioural brain research, 2020

Gambling disorder (GD) is a psychiatric disease that has been recently classified as a behavioural addiction. So far, a very few studies have investigated the alteration of functional connectivity in GD patients, thus the concrete interplay between relevant function-dependent circuitries in such disease has not been comprehensively assessed. The aim of this research was to investigate resting-state functional connectivity in GD patients, searching for a correlation with GD symptoms severity. GD patients were assessed for gambling behaviour, impulsivity, cognitive distortions, anxiety and depression, in comparison with healthy controls (HC). Afterwards, they were assessed for resting-state functional magnetic resonance imaging; functional connectivity was assessed through a data-driven approach, by using independent component analysis. The correlation between gambling severity and the strength of specific resting-state networks was also investigated. Our results show that GD patients displayed higher emotional and behavioural impairment than HC, together with an increased resting state functional connectivity in the network including anterior cingulate cortex, the caudate nucleus and nucleus accumbens, and within the cerebellum, in comparison with the control group. Moreover, a significant correlation between behavioural parameters and the strength of the resting-state cerebellar network was found. Overall, the functional alterations in brain connectivity involving the cerebellum observed in this study underpin the emotional and behavioural impairment recorded in GD patients. This evidence suggests the employment of novel neuromodulatory therapeutic approaches involving specific and salient targets such as the cerebellum in addictive disorders.
Is it safe to drive after acute mild stroke? A preliminary report.
Journal of the neurological sciences, 2015

Most guidelines recommend that patients should refrain from driving for at least one month after stroke. Despite these guidelines, and the fact that patients post-stroke may be at an increased risk for driving impairment, many patients report resuming driving within the acute phase of injury. The aim of this study was to investigate the driving performance of patients with acute mild stroke.
Eye dominance influences triggering action: the Poffenberger paradigm revisited.
Cortex; a journal devoted to the study of the nervous system and behavior, 2014

Our dominant eye (DE) is the one we unconsciously choose when performing a monocular task. Although it has been recognized for centuries, eye dominance and its behavioral consequences remain poorly understood. Here we used the simple and well-known Poffenberger paradigm (1912) in which participants press a button with the right or left index finger, in reaction to the appearance of a lateralized visual stimulus. By selecting participants according to their DE and handedness, we were able to decipher the impact of eye dominance on visuomotor transformation speed. We show, for the first time, that in right-handers simple reaction times (RT) in response to a lateralized visual target are shorter when it appears in the contralateral visual hemifield with respect to the DE. In left-handers, only those with a right DE exhibit a shorter RT with the left hand and they show no hemifield difference. Additionally, the Poffenberger paradigm has been used to estimate the interhemispheric transfer time (IHTT) in both directions, from the right to the left hemisphere or the reverse, by comparing hand RTs following stimulation of each visual hemifield. The present study demonstrates that this paradigm leads to biased estimations of these directionally considered IHTT and provides an explanation to the often reported IHTT negative values that otherwise appear implausible. These new findings highlight the need to consider eye dominance in studies investigating the neural processes underlying visually-guided actions. More generally, they demonstrate a substantial impact of eye dominance on the neural mechanisms involved in converting visual inputs into motor commands.
Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos.
Science (New York, N.Y.), 2019

Genome editing holds promise for correcting pathogenic mutations. However, it is difficult to determine off-target effects of editing due to single-nucleotide polymorphism in individuals. Here we developed a method named GOTI (genome-wide off-target analysis by two-cell embryo injection) to detect off-target mutations by editing one blastomere of two-cell mouse embryos using either CRISPR-Cas9 or base editors. Comparison of the whole-genome sequences of progeny cells of edited and nonedited blastomeres at embryonic day 14.5 showed that off-target single-nucleotide variants (SNVs) were rare in embryos edited by CRISPR-Cas9 or adenine base editor, with a frequency close to the spontaneous mutation rate. By contrast, cytosine base editing induced SNVs at more than 20-fold higher frequencies, requiring a solution to address its fidelity.
Metabolic implications of exposure to wastewater effluent in bluegill sunfish.
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 2019

Effluent from wastewater treatment plants (WWTP) contains a complex mixture of contaminants and is a major worldwide source of aquatic pollution. We examined the effects of exposure to treated effluent from a municipal WWTP on the metabolic physiology of bluegill sunfish (Lepomis macrochirus). We studied fish that were wild-caught or experimentally caged (28 d) downstream of the WWTP, and compared them to fish that were caught or caged at clean reference sites. Survival was reduced in fish caged at the effluent-contaminated site compared to those caged at the reference site. Resting rates of O
Ischemic LTP: NMDA-dependency and dorso/ventral distribution within the hippocampus.
Hippocampus, 2015

A transient ischemic episode causes a reduction in evoked EPSPs in hippocampal slices, followed by an NMDA dependent LTP. We explored the relations between ischemic LTP (iLTP) and the more conventional tetanic LTP (tLTP) in CA1 region of slices along the dorsal/ventral axis of the hippocampus. Dorsal hippocampal (DH) slices produced a much larger iLTP than their ventral hippocampal (VH) counterparts. In both regions, iLTP and tLTP shared the same NMDA mediated potentiation, such that one LTP saturated the ability of the other treatment to generate LTP. The smaller LTP in VH was correlated with a lower NMDA-mediated EPSP, and a parallel lower density of NMDA receptors. Calcium permeable AMPA receptors did not contribute to the DH/VH disparity. We conclude that a differential distribution of NMDA receptor subunits along the septotemporal axis of the hippocampus controls the diverse ability to evoke iLTP and tLTP in the two regions and may underlie their characteristic behavioral outputs as well as their differential sensitivity to ischemia.
Sleep in youth with autism spectrum disorders: systematic review and meta-analysis of subjective and objective studies.
Evidence-based mental health, 2018

Sleep problems are common and impairing in individuals with autism spectrum disorders (ASD). Evidence synthesis including both subjective (ie, measured with questionnaires) and objective (ie, quantified with neurophysiological tools) sleep alterations in youth with ASD is currently lacking.
Allopurinol augmentation in acute mania: A meta-analysis of placebo-controlled trials.
Journal of affective disorders, 2018

Allopurinol is a xanthine oxidase inhibitor commonly used in the treatment of gout. Recent studies have also shown its promise as an adjunctive treatment for manic episodes in bipolar 1 disorder, possibly through mechanisms involving the purinergic pathway. However, its efficacy across studies has been inconsistent, so we conducted a meta-analysis of the published controlled studies with the goal of determining the efficacy profile of allopurinol as an adjunctive treatment for mania in bipolar disorder.
Pharyngeal sense organs drive robust sugar consumption in Drosophila.
Nature communications, 2015

The fly pharyngeal sense organs lie at the transition between external and internal nutrient-sensing mechanisms. Here we investigate the function of pharyngeal sweet gustatory receptor neurons, demonstrating that they express a subset of the nine previously identified sweet receptors and respond to stimulation with a panel of sweet compounds. We show that pox-neuro (poxn) mutants lacking taste function in the legs and labial palps have intact pharyngeal sweet taste, which is both necessary and sufficient to drive preferred consumption of sweet compounds by prolonging ingestion. Moreover, flies putatively lacking all sweet taste show little preference for nutritive or non-nutritive sugars in a short-term feeding assay. Together, our data demonstrate that pharyngeal sense organs play an important role in directing sustained consumption of sweet compounds, and suggest that post-ingestive sugar sensing does not effectively drive food choice in a simple short-term feeding paradigm.
Epilepsy: Transition from pediatric to adult care. Recommendations of the Ontario epilepsy implementation task force.
Epilepsia, 2017

The transition from a pediatric to adult health care system is challenging for many youths with epilepsy and their families. Recently, the Ministry of Health and Long-Term Care of the Province of Ontario, Canada, created a transition working group (TWG) to develop recommendations for the transition process for patients with epilepsy in the Province of Ontario. Herein we present an executive summary of this work. The TWG was composed of a multidisciplinary group of pediatric and adult epileptologists, psychiatrists, and family doctors from academia and from the community; neurologists from the community; nurses and social workers from pediatric and adult epilepsy programs; adolescent medicine physician specialists; a team of physicians, nurses, and social workers dedicated to patients with complex care needs; a lawyer; an occupational therapist; representatives from community epilepsy agencies; patients with epilepsy; parents of patients with epilepsy and severe intellectual disability; and project managers. Three main areas were addressed: (1) Diagnosis and Management of Seizures; 2) Mental Health and Psychosocial Needs; and 3) Financial, Community, and Legal Supports. Although there are no systematic studies on the outcomes of transition programs, the impressions of the TWG are as follows. Teenagers at risk of poor transition should be identified early. The care coordination between pediatric and adult neurologists and other specialists should begin before the actual transfer. The transition period is the ideal time to rethink the diagnosis and repeat diagnostic testing where indicated (particularly genetic testing, which now can uncover more etiologies than when patients were initially evaluated many years ago). Some screening tests should be repeated after the move to the adult system. The seven steps proposed herein may facilitate transition, thereby promoting uninterrupted and adequate care for youth with epilepsy leaving the pediatric system.
Permanent work disability before and after ischaemic heart disease or stroke event: a nationwide population-based cohort study in Sweden.
BMJ open, 2017

We examined the risk of disability pension before and after ischaemic heart disease (IHD) or stroke event, the burden of stroke compared with IHD and which factors predicted disability pension after either event.