rudyvdbrink/CitationDatabase huggingface dataset:
Mouse Visual Cortex Is Modulated by Distance Traveled and by Theta Oscillations.
Current biology : CB, 2020

The visual responses of neurons in the primary visual cortex (V1) are influenced by the animal's position in the environment [1-5]. V1 responses encode positions that co-fluctuate with those encoded by place cells in hippocampal area CA1 [2, 5]. This correlation might reflect a common influence of non-visual spatial signals on both areas. Place cells in CA1, indeed, do not rely only on vision; their place preference depends on the physical distance traveled [6-11] and on the phase of the 6-9 Hz theta oscillation [12, 13]. Are V1 responses similarly influenced by these non-visual factors? We recorded V1 and CA1 neurons simultaneously while mice performed a spatial task in a virtual corridor by running on a wheel and licking at a reward location. By changing the gain that couples the wheel movement to the virtual environment, we found that ∼20% of V1 neurons were influenced by the physical distance traveled, as were ∼40% of CA1 place cells. Moreover, the firing rate of ∼24% of V1 neurons was modulated by the phase of theta oscillations recorded in CA1 and the response profiles of ∼7% of V1 neurons shifted spatially across the theta cycle, analogous to the phase precession observed in ∼37% of CA1 place cells. The influence of theta oscillations on V1 responses was more prominent in putative layer 6. These results reveal that, in a familiar environment, sensory processing in V1 is modulated by the key non-visual signals that influence spatial coding in the hippocampus.
Retraction: Borroto-Escuela et al., The existence of FGFR1-5-HT1A receptor heterocomplexes in midbrain 5-HT neurons of the rat: relevance for neuroplasticity.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

The Journal of Neuroscience has received a report describing an investigation by the Karolinska Institutet, which found substantial data misrepresentation in the article "The Existence of FGFR1-5-HT1A Receptor Heterocomplexes in Midbrain 5-HT Neurons of the Rat: Relevance for Neuroplasticity" by Dasiel O. Borroto-Escuela, Wilber Romero-Fernandez, Mileidys Pérez-Alea, Manuel Narvaez, Alexander O. Tarakanov, Giuseppa Mudó , Luigi F. Agnati, Francisco Ciruela, Natale Belluardo, and Kjell Fuxe, which appeared on pages 6295-6303 of the May 2, 2012 issue. Because the results cannot be considered reliable, the editors of The Journal are retracting the paper.
Neural Activation Patterns Associated with Maternal Mouthbrooding and Energetic State in an African Cichlid Fish.
Neuroscience, 2020

Parental care is widespread in the animal kingdom, but for many species, provisioning energetic resources must be balanced with trade-offs between self-promoting and offspring-promoting behaviors. However, little is known about the neural mechanisms underlying these motivational decisions. Mouthbrooding is an extreme form of parental care most common in fishes that provides an ideal opportunity to examine which brain regions are involved in parenting and energetics. The African cichlid fish Astatotilapia burtoni is a maternal mouthbrooder in which females hold developing young inside their mouths for 2 weeks. This brood care makes feeding impossible, so females undergo obligatory starvation. We used immunohistochemistry for the neural activation marker pS6 to examine which brain regions were involved in processing salient information in mouthbrooding, starved, and fed females. We identified brain regions more associated with maternal brood care (TPp, Dc-4/-5), and others reflective of energetic state (Dl-v, NLTi). Most nuclei examined, however, were involved in both maternal care and energetic status. Placement of each of the 16 examined nuclei into these functional categories was supported by node by node comparisons, co-activity networks, hierarchical clustering, and discriminant function analysis. These results reveal which brain regions are involved in parental care and food intake in a species where provisioning is skewed towards the offspring when parental feeding is not possible. This study provides support for both distinct and shared circuitry involved in regulation of maternal care, food intake, and energy balance, and helps put the extreme parental case of mouthbrooding into a comparative and evolutionary context.
Sex, stress, and prefrontal cortex: influence of biological sex on stress-promoted cocaine seeking.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020

Clinical reports suggest that females diagnosed with substance use disorder experience enhanced relapse vulnerability compared with males, particularly during stress. We previously demonstrated that a stressor (footshock) can potentiate cocaine seeking in male rats via glucocorticoid-dependent cannabinoid type-1 receptor (CB1R)-mediated actions in the prelimbic prefrontal cortex (PrL-PFC). Here, we investigated the influence of biological sex on stress-potentiated cocaine seeking. Despite comparable self-administration and extinction, females displayed a lower threshold for cocaine-primed reinstatement than males. Unlike males, footshock, tested across a range of intensities, failed to potentiate cocaine-primed reinstatement in females. However, restraint potentiated reinstatement in both sexes. While sex differences in stressor-induced plasma corticosterone (CORT) elevations and defensive behaviors were not observed, differences were evident in footshock-elicited ultrasonic vocalizations. CORT administration, at a dose which recapitulates stressor-induced plasma levels, reproduced stress-potentiated cocaine-primed reinstatement in both sexes. In females, CORT effects varied across the estrous cycle; CORT-potentiated reinstatement was only observed during diestrus and proestrus. As in males, CORT-potentiated cocaine seeking in females was localized to the PrL-PFC and both CORT- and restraint-potentiated cocaine seeking required PrL-PFC CB1R activation. In addition, ex vivo whole-cell electrophysiological recordings from female layer V PrL-PFC pyramidal neurons revealed CB1R-dependent CORT-induced suppression of inhibitory synaptic activity, as previously observed in males. These findings demonstrate that, while stress potentiates cocaine seeking via PrL-PFC CB1R in both sexes, sensitivity to cocaine priming injections is greater in females, CORT-potentiating effects vary with the estrous cycle, and whether reactivity to specific stressors may manifest as drug seeking depends on biological sex.
The therapeutic potential of targeting exchange protein directly activated by cyclic adenosine 3',5'-monophosphate (Epac) for central nervous system trauma.
Neural regeneration research, 2021

Millions of people worldwide are affected by traumatic spinal cord injury, which usually results in permanent sensorimotor disability. Damage to the spinal cord leads to a series of detrimental events including ischaemia, haemorrhage and neuroinflammation, which over time result in further neural tissue loss. Eventually, at chronic stages of traumatic spinal cord injury, the formation of a glial scar, cystic cavitation and the presence of numerous inhibitory molecules act as physical and chemical barriers to axonal regrowth. This is further hindered by a lack of intrinsic regrowth ability of adult neurons in the central nervous system. The intracellular signalling molecule, cyclic adenosine 3',5'-monophosphate (cAMP), is known to play many important roles in the central nervous system, and elevating its levels as shown to improve axonal regeneration outcomes following traumatic spinal cord injury in animal models. However, therapies directly targeting cAMP have not found their way into the clinic, as cAMP is ubiquitously present in all cell types and its manipulation may have additional deleterious effects. A downstream effector of cAMP, exchange protein directly activated by cAMP 2 (Epac2), is mainly expressed in the adult central nervous system, and its activation has been shown to mediate the positive effects of cAMP on axonal guidance and regeneration. Recently, using ex vivo modelling of traumatic spinal cord injury, Epac2 activation was found to profoundly modulate the post-lesion environment, such as decreasing the activation of astrocytes and microglia. Pilot data with Epac2 activation also suggested functional improvement assessed by in vivo models of traumatic spinal cord injury. Therefore, targeting Epac2 in traumatic spinal cord injury could represent a novel strategy in traumatic spinal cord injury repair, and future work is needed to fully establish its therapeutic potential.
Electrophoretic Delivery of γ-aminobutyric Acid (GABA) into Epileptic Focus Prevents Seizures in Mice.
Journal of visualized experiments : JoVE, 2019

Epilepsy is a group of neurological disorders which affects millions of people worldwide. Although treatment with medication is helpful in 70% of the cases, serious side effects affect the quality of life of patients. Moreover, a high percentage of epileptic patients are drug resistant; in their case, neurosurgery or neurostimulation are necessary. Therefore, the major goal of epilepsy research is to discover new therapies which are either capable of curing epilepsy without side effects or preventing recurrent seizures in drug-resistant patients. Neuroengineering provides new approaches by using novel strategies and technologies to find better solutions to cure epileptic patients at risk. As a demonstration of a novel experimental protocol in an acute mouse model of epilepsy, a direct in situ electrophoretic drug delivery system is used. Namely, a neural probe incorporating a microfluidic ion pump (µFIP) for on-demand drug delivery and simultaneous recording of local neural activity is implanted and demonstrated to be capable of controlling 4-aminopyridine-induced (4AP-induced) seizure-like event (SLE) activity. The γ-aminobutyric acid (GABA) concentration is kept in the physiological range by the precise control of GABA delivery to reach an antiepileptic effect in the seizure focus but not to cause overinhibition-induced rebound bursts. The method allows both the detection of pathological activity and intervention to stop seizures by delivering inhibitory neurotransmitters directly to the epileptic focus with precise spatiotemporal control. As a result of the developments to the experimental method, SLEs can be induced in a highly localized manner that allows seizure control by the precisely tuned GABA delivery at the seizure onset.
Neural alignment during face-to-face spontaneous deception: Does gender make a difference?
Human brain mapping, 2020

This study investigated the gender differences in deception and their neural basis in the perspective of two-person neuroscience. Both male and female dyads were asked to perform a face-to-face spontaneous sender-receiver deception task, while their neural activities in the prefrontal cortex (PFC) and right temporal parietal junction (rTPJ) were recorded simultaneously using functional near-infrared spectroscopy (fNIRS)-based hyperscanning. Male and female dyads displayed similar deception rate, successful deception rate, and eye contact in deception trials. Moreover, eye contact in deception trials was positively correlated with the success rate of deception in both genders. The fNIRS data showed that the interpersonal neural synchronization (INS) in PFC was significantly enhanced only in female dyads when performed the deception task, while INS in rTPJ was increased only in male dyads. Such INS was correlated with the success rate of deception in both dyads. Granger causality analysis showed that no significant directionality between time series of PFC (or rTPJ) in each dyad, which could indicate that sender and receiver played equally important role during deception task. Finally, enhanced INS in PFC in female dyads mediated the contribution of eye contact to the success rate of deception. All findings in this study suggest that differential patterns of INS are recruited when male and female dyads perform the face-to-face deception task. To our knowledge, this is the first interbrain evidence for gender difference of successful deception, which could make us a deeper understanding of spontaneous face-to-face deception.
Cardiac cycle gated cognitive-emotional control in superior frontal cortices.
NeuroImage, 2020

Accumulating evidence suggests that peripheral physiological processes, such as the cardiac cycle, impact the individual's ability to appropriately exert control over behavior and emotional responses. We examine, whether response selection processes during cognitive-emotional control and its neurophysiological correlates, can be experimentally controlled in a cardiac-cycle dependent manner. To this end, we designed an experimental setup in which the EEG experiment, an emotional Stroop task, was controlled by the individual's electrocardiogram (ECG). Since theoretical considerations suggest that the effects of the cardiac cycle may affect only specific aspects during information processing, we apply EEG signal decomposition before examining functional neuroanatomical regions associated with cardiac-cycle dependent effects with EEG-beamforming approaches. Analyzing N = 27 healthy participants, we show that the cardiac-cycle specifically affects response selection processes, when demands on cognitive-emotional control are low. Response execution processes are sped up when trials are presented shortly after the ECG R peak. These effects were confined to conditions were response selection is not modulated by cognitive-emotional conflicts, which is in line with theoretical concepts on response selection. Corroborating the behavioural data, the EEG data show that particularly motor response-related processes encoded in the theta frequency band in middle and superior frontal regions (BA6) are differentially modulated by cardiac phase and difficulty to select a response. The presented work has an essential methodological focus in cognitive neuroscience for investigating brain-body interaction. It shows how peripheral-physiological parameters can be used to control EEG experiments and that the cardiac cycle has very specific effects in neurophysiological processes and associated functional neuroanatomical structures.
The mitochondrial type IB topoisomerase drives mitochondrial translation and carcinogenesis.
Nature communications, 2019

Mitochondrial topoisomerase IB (TOP1MT) is a nuclear-encoded topoisomerase, exclusively localized to mitochondria, which resolves topological stress generated during mtDNA replication and transcription. Here, we report that TOP1MT is overexpressed in cancer tissues and demonstrate that TOP1MT deficiency attenuates tumor growth in human and mouse models of colon and liver cancer. Due to their mitochondrial dysfunction, TOP1MT-KO cells become addicted to glycolysis, which limits synthetic building blocks and energy supply required for the proliferation of cancer cells in a nutrient-deprived tumor microenvironment. Mechanistically, we show that TOP1MT associates with mitoribosomal subunits, ensuring optimal mitochondrial translation and assembly of oxidative phosphorylation complexes that are critical for sustaining tumor growth. The TOP1MT genomic signature profile, based on Top1mt-KO liver cancers, is correlated with enhanced survival of hepatocellular carcinoma patients. Our results highlight the importance of TOP1MT for tumor development, providing a potential rationale to develop TOP1MT-targeted drugs as anticancer therapies.
Key emerging issues in frontotemporal dementia.
Journal of neurology, 2016

Frontotemporal dementia (FTD) encompasses the syndromes of behavioural variant FTD (bvFTD) and primary progressive aphasia (PPA) and refers to those neurodegenerative diseases characterised by predominant pathological involvement of the frontal and temporal lobes. Recent years have witnessed major advances in the clinical characterisation of FTD, reflected in the publication of updated diagnostic criteria for bvFTD and PPA, and the discovery of new pathogenic mutations has added to the understanding of genotype-phenotype interactions and of disease mechanisms. Emerging results from longitudinal studies of familial FTD show that imaging and cognitive changes occur years before symptom onset and such studies may yield biomarkers of early disease that in turn will facilitate earlier diagnosis. The hope and (guarded) expectation is that these advances may together herald the beginning of the end of the chapter in which FTD is considered an inexorably progressive and untreatable condition.
Are we training psychiatrists to develop skills in intellectual disability psychiatry? Current European context and future directions.
European psychiatry : the journal of the Association of European Psychiatrists, 2020

The majority of people with intellectual disabilities (ID) and psychiatric disorders access mainstream mental health services across Europe. However, only 56% of countries provide postgraduate psychiatric training in ID according to a survey across 42 European countries. We explore the challenges of ID training and make recommendations for education and health policymakers.
Personality driven alcohol and drug abuse: New mechanisms revealed.
Neuroscience and biobehavioral reviews, 2020

While the majority of the regular consumers of alcohol controls their consumption well over life span and even takes instrumentalization benefits from it, a minority, but yet high total number of users develops an alcohol addiction. It has long been known that particular personality types are more addiction prone than others. Here we review recent progress in the understanding of neurobiological pathways that determine personality and facilitate drug abuse. Novel approaches to characterize personality traits leading to addiction proneness in social settings in mice are discussed. A common genetic and neurobiological base for the behavioural traits of sensation seeking or a depressed phenotype and escalating alcohol consumption are reviewed. Furthermore, recent progress on how social and cognitive factors, including impulsivity and decision making, act at brain level to make an individual more vulnerable to alcohol abuse, are discussed. Altogether, this review provides an update on brain mechanisms underlying a broad spectrum of personality traits that make an individual more prone to alcohol and drug abuse and addiction.
Targeting Pancreatic Ductal Adenocarcinoma (PDAC).
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2021

Pancreatic cancers are among the most ominous, and among the most studied. Their complexities have provided ample material for a huge investigative effort, which is briefly surveyed in this review. Eradication by surgery has proven extremely difficult, and a successful chemotherapeutic approach is desperately needed. Treatment with "traditional" anticancer drugs, such as benchmark gemcitabine or the current standard-of-care FOLFIRINOX quaternary combination increase the mean overall survival by only a few months and often leads to chemoresistance. Much work is therefore currently devoted to potentiating our pharmacological weapons by accurate targeting and, in particular, by acting on the dense tumoral stroma, a distinctive feature of PDAC accounting for much of the therapeutic difficulty. We give an overview of recent developments, touching on the major aspects of PDAC physiology and biochemistry, currently-used and experimental drugs, and targeting technologies under development. A few papers are discussed in some detail to help provide a sense of how the field is moving.
Quantitative Identification of Functional Connectivity Disturbances in Neuropsychiatric Lupus Based on Resting-State fMRI: A Robust Machine Learning Approach.
Brain sciences, 2020

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an autoimmune entity comprised of heterogenous syndromes affecting both the peripheral and central nervous system. Research on the pathophysiological substrate of NPSLE manifestations, including functional neuroimaging studies, is extremely limited. The present study examined person-specific patterns of whole-brain functional connectivity in NPSLE patients (
Mental Health, Quality of Life and Violence Exposure in Low-Socioeconomic Status Children and Adolescents of Guatemala.
International journal of environmental research and public health, 2020

Growing up in vulnerable conditions has an impact on children and adolescents' mental health and well-being outcomes. However, this evidence has rarely been obtained in middle and low-income countries like Guatemala, where food insecurity and exposure to violence frequently threaten childhood development. The aim of this study was to analyse the relations that sociodemographic and socioeconomic factors have with psychological adjustment of low-socioeconomic status (SES) Guatemalan children and adolescents, and how these relations were mediated by food insecurity and exposure to violence. A total of 185 participants (50.8% girls; aged between 6 to 17, M = 11.82, SD = 3.7) from three vulnerable schools located in rural and urban areas of Guatemala were assessed. The results indicated that exposure to violence significantly moderates the effect of sociodemographic and socioeconomic variables in measures of depression, anxiety and health-related quality of life. Adolescents more exposed to violence reported higher levels of depression and anxiety, as well as lower levels of health-related quality of life. In contrast, food insecurity did not seem to influence psychological adjustment outcomes in this low-SES sample. These findings highlight the relevance of exposure to violence for mental health and well-being, and is a factor that should be considered when designing public health policies to promote children and adolescents' welfare.
Oncology Referral Concerning Paediatric Neurosurgery? Analysis of the Situation between 2008-2013 in the North of Portugal.
Acta medica portuguesa, 2016

Primary central nervous system tumours represent the second most frequent neoplasm and are the leading cause of death from solid tumours in children. Our study aimed to provide the most up-to-date epidemiological analysis of primary central nervous system tumours in children living in the north of Portugal and to explore a possible effect of the centralisation of care on outcomes.
Rest-Activity Pattern Alterations in Idiopathic REM Sleep Behavior Disorder.
Annals of neurology, 2020

The purpose of this study was to investigate the differences in actigraphy-measured rest-activity patterns (eg, sleep-wake cycle, circadian rest-activity rhythm, and physical activity) across different stages of α-synucleinopathy.
BrightFocus Alzheimer's Fast Track 2019.
Molecular neurodegeneration, 2019

The 3 day workshop "Alzheimer's Fast Track" is a unique opportunity for graduate students, postdoctoral fellows, or other early-career scientists, focused on Alzheimer's disease research, to gain new knowledge and become an expert in where this emerging scientific field is moving. In addition, it is not only about receiving a good overview, but also learning to write and defend a successful application for securing funding for Alzheimer's disease research projects.