rudyvdbrink/CitationDatabase huggingface dataset:
Acute memory deficits in chemotherapy-treated adults.
Memory (Hove, England), 2017

Data from research on amnesia and epilepsy are equivocal with regards to the dissociation, shown in animal models, between rapid and slow long-term memory consolidation. Cancer treatments have lasting disruptive effects on memory and on brain structures associated with memory, but their acute effects on synaptic consolidation are unknown. We investigated the hypothesis that cancer treatment selectively impairs slow synaptic consolidation. Cancer patients and their matched controls were administered a novel list-learning task modelled on the Rey Auditory Verbal Learning Test. Learning, forgetting, and retrieval were tested before, and one day after patients' first chemotherapy treatment. Due to difficulties recruiting cancer patients at that sensitive time, we were only able to study 10 patients and their matched controls. Patients exhibited treatment-dependent accelerated forgetting over 24 hours compared to their own pre-treatment performance and to the performance of control participants, in agreement with our hypothesis. The number of intrusions increased after treatment, suggesting retrieval deficits. Future research with larger samples should adapt our methods to distinguish between consolidation and retrieval causes for treatment-dependent accelerated forgetting. The presence of significant accelerated forgetting in our small sample is indicative of a potentially large acute effect of chemotherapy treatment on forgetting, with potentially clinically relevant implications.
A global needs assessment in times of a global crisis: world psychiatry response to the COVID-19 pandemic.
BJPsych open, 2020

The COVID-19 pandemic has stunned the global community with marked social and psychological ramifications. There are key challenges for psychiatry that require urgent attention to ensure mental health well-being for all - COVID-19-positive patients, healthcare professionals, first responders, people with psychiatric disorders and the general population. This editorial outlines some of these challenges and research questions, and serves as a preliminary framework of what needs to be addressed. Mental healthcare should be an integral component of healthcare policy and practice towards COVID-19. Collaborative efforts from psychiatric organisations and their members are required to maximise appropriate clinical and educational interventions while minimising stigma.
Experience moderates overlap between object and face recognition, suggesting a common ability.
Journal of vision, 2014

Some research finds that face recognition is largely independent from the recognition of other objects; a specialized and innate ability to recognize faces could therefore have little or nothing to do with our ability to recognize objects. We propose a new framework in which recognition performance for any category is the product of domain-general ability and category-specific experience. In Experiment 1, we show that the overlap between face and object recognition depends on experience with objects. In 256 subjects we measured face recognition, object recognition for eight categories, and self-reported experience with these categories. Experience predicted neither face recognition nor object recognition but moderated their relationship: Face recognition performance is increasingly similar to object recognition performance with increasing object experience. If a subject has a lot of experience with objects and is found to perform poorly, they also prove to have a low ability with faces. In a follow-up survey, we explored the dimensions of experience with objects that may have contributed to self-reported experience in Experiment 1. Different dimensions of experience appear to be more salient for different categories, with general self-reports of expertise reflecting judgments of verbal knowledge about a category more than judgments of visual performance. The complexity of experience and current limitations in its measurement support the importance of aggregating across multiple categories. Our findings imply that both face and object recognition are supported by a common, domain-general ability expressed through experience with a category and best measured when accounting for experience.
Effects of noradrenergic denervation by anti-DBH-saporin on behavioral responsivity to L-DOPA in the hemi-parkinsonian rat.
Behavioural brain research, 2014

Dopamine (DA) replacement with l-DOPA remains the most effective pharmacotherapy for motor symptoms of Parkinson's disease (PD) including tremor, postural instability, akinesia, and bradykinesia. Prolonged L-DOPA use frequently leads to deleterious side effects including involuntary choreic and dystonic movements known as L-DOPA induced dyskinesias (LID). DA loss in PD is frequently accompanied by concomitant noradrenergic (NE) denervation of the locus coeruleus (LC); however, the effects of NE loss on L-DOPA efficacy and LID remain controversial and are often overlooked in traditional animal models of PD. The current investigation examined the role of NE loss in L-DOPA therapy by employing the NE specific neurotoxin anti-DA-beta hydroxylase saporin (αDBH) in a rat model of PD. Rats received unilateral 6-hydroxydopamine lesions of the medial forebrain bundle to deplete nigral DA and intraventricular injection of vehicle (DA lesioned rats) or αDBH (DANE lesioned rats) to destroy NE neurons bilaterally. Results indicated that αDBH infusion drastically reduced NE neuron markers within the LC compared to rats that received vehicle treatment. Behaviorally, this loss did not alter the development or expression of L-DOPA- or DA agonist-induced dyskinesia. However, rats with additional NE lesions were less responsive to L-DOPA's pro-motor effects. Indeed, DANE lesioned animals rotated less and showed less attenuation of parkinsonian stepping deficits following high doses of L-DOPA than DA lesioned animals. These findings suggest that severe NE loss may reduce L-DOPA treatment efficacy and demonstrate that degradation of the NE system is an important consideration when evaluating L-DOPA effects in later stage PD.
Satellite glial cell proliferation in the trigeminal ganglia after chronic constriction injury of the infraorbital nerve.
Glia, 2013

We have examined satellite glial cell (SGC) proliferation in trigeminal ganglia following chronic constriction injury of the infraorbital nerve. Using BrdU labeling combined with immunohistochemistry for SGC specific proteins we positively confirmed proliferating cells to be SGCs. Proliferation peaks at approximately 4 days after injury and dividing SGCs are preferentially located around neurons that are immunopositive for ATF-3, a marker of nerve injury. After nerve injury there is an increase GFAP expression in SGCs associated with both ATF-3 immunopositive and immunonegative neurons throughout the ganglia. SGCs also express the non-glial proteins, CD45 and CD163, which label resident macrophages and circulating leukocytes, respectively. In addition to SGCs, we found some Schwann cells, endothelial cells, resident macrophages, and circulating leukocytes were BrdU immunopositive.
Inter-hemispheric plasticity in patients with median nerve injury.
Neuroscience letters, 2016

Peripheral nerve injuries result in reorganization within the contralateral hemisphere. Furthermore, recent animal and human studies have suggested that the plastic changes in response to peripheral nerve injury also include several areas of the ipsilateral hemisphere. The objective of this study was to map the inter-hemispheric plasticity in response to median nerve injury, to investigate normal differences in contra- and ipsilateral activation, and to study the impact of event-related or blocked functional magnetic resonance imaging (fMRI) design on ipsilateral activation. Four patients with median nerve injury at the wrist (injured and epineurally sutured >2 years earlier) and ten healthy volunteers were included. 3T fMRI was used to map the hemodynamic response to brain activity during tactile stimulation of the fingers, and a laterality index (LI) was calculated. Stimulation of Digits II-III of the injured hand resulted in a reduction in contralateral activation in the somatosensory area SI. Patients had a lower LI (0.21±0.15) compared to healthy controls (0.60±0.26) indicating greater ipsilateral activation of the primary somatosensory cortex. The spatial dispersion of the coordinates for areas SI and SII was larger in the ipsilateral than in the contralateral hemisphere in the healthy controls, and was increased in the contralateral hemisphere of the patients compared to the healthy controls. There was no difference in LI between the event-related and blocked paradigms. In conclusion, patients with median nerve injury have increased ipsilateral SI area activation, and spatially more dispersed contralateral SI activation during tactile stimulation of their injured hand. In normal subjects ipsilateral activation has larger spatial distribution than the contralateral. Previous findings in patients performed with the blocked fMRI paradigm were confirmed. The increase in ipsilateral SI activation may be due to an interhemispheric disinhibition associated with changes in the afferent signal inflow to the contralateral primary somatosensory cortex.
An investigation of cortical neuroplasticity following stroke in adults: is there evidence for a critical window for rehabilitation?
BMC neurology, 2015

Evidence in animal stroke models suggests that neuroplasticity takes place maximally in a specific time window after an ischaemic lesion, which may coincide with the optimal time to intervene with rehabilitation. The aim of this study is to investigate neurophysiological evidence for a "critical window" of enhanced neuroplasticity in patients following ischaemic stroke, and establish its duration. We will also investigate changes in cortical inhibition following stroke, and the influence this has on functional recovery.
Superior temporal sulcus and social cognition in dangerous drivers.
NeuroImage, 2013

Understanding the neural systems underpinning social cognition is a primary focus of contemporary social neuroscience. Using functional magnetic resonance imaging (fMRI), the present study asked if brain activity reflecting socio-cognitive processes differs between individuals according to their social behavior; namely, between a group of drivers with frequent traffic offenses and a group with none. Socio-cognitive processing was elicited by employing videos from a traffic awareness campaign, consisting of reckless and anti-social driving behavior ending in tragic consequences, and control videos with analogous driving themes but without such catastrophic endings. We investigated whether relative increases in brain function during the observation of these campaign stimuli compared with control videos differed between these two groups. To develop the results of our previous study we focused our analyses on superior temporal sulcus/gyrus (STS/STG). This revealed a bigger increase in brain activity within this region during the campaign stimuli in safe compared with dangerous drivers. Furthermore, by thematically coding drivers' verbal descriptions of the stimuli, we also demonstrate differences in STS reactivity according to drivers' scores on two indices of socio-cognitive processing: subjects' perceived consequences of actors' actions, and their affective evaluation of the clips. Our results demonstrate the influence of social behavior and socio-cognitive processing on STS reactivity to social stimuli, developing considerably our understanding of the role of this region in social cognition.
The spatiotemporal dynamics of early attention processes: a high-resolution electroencephalographic study of N2 subcomponent sources.
Neuroscience, 2014

The N2 subcomponents of event-related potentials are known to reflect early attentional processes. The anterior N2 may reflect conflict monitoring, whereas the posterior N2 may be involved in target detection. The aim of this study was to identify the brain areas involved in the generation of the N2 subcomponents, in order to define the spatiotemporal dynamics of these attentional processes. We recorded 128-channel electroencephalograms in 15 healthy controls performing a three-stimulus visual oddball task and identified standard-, distracter- and target-elicited N2 components. Individual N2 sources were localized using standardized-weighted-low-resolution-electromagnetic-tomography (swLORETA). Comparative analyses were performed with a non-parametric permutation technique. Common N2 generators were observed in the Brodmann area (BA) 24 of the anterior cingulate cortex (ACC). The posterior cingulate cortex and the central precuneus were more involved in distracter processing, whereas the anterior precuneus and BA 32 of the ACC were target-specific. In accordance with previous demonstration of the frontoparietal cortex's critical role in attentional processes, these new data shed light on the ACC's role in conflict monitoring and its interaction with other median and frontoparietal structures in early attentional processes.
Treatment strategies in Alzheimer's disease: a review with focus on selenium supplementation.
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 2016

Alzheimer's disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (Aβ) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce Aβ production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral Aβ plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.
The relation between insecure attachment and posttraumatic stress: Early life versus adulthood traumas.
Psychological trauma : theory, research, practice and policy, 2015

The present study examined the relations between insecure attachment and posttraumatic stress disorder (PTSD) symptoms among community-dwelling older adults with exposure to a broad range of traumatic events. Attachment anxiety and attachment avoidance predicted more severe symptoms of PTSD and explained unique variance in symptom severity when compared to other individual difference measures associated with an elevated risk of PTSD, including NEO neuroticism and event centrality. A significant interaction between the developmental timing of the trauma and attachment anxiety revealed that the relation between PTSD symptoms and attachment anxiety was stronger for individuals with current PTSD symptoms associated with early life traumas compared to individuals with PTSD symptoms linked to adulthood traumas. Analyses examining factors that account for the relation between insecure attachment and PTSD symptoms indicated that individuals with greater attachment anxiety reported stronger physical reactions to memories of their trauma and more frequent voluntary and involuntary rehearsal of their trauma memories. These phenomenological properties of trauma memories were in turn associated with greater PTSD symptom severity. Among older adults with early life traumas, only the frequency of involuntary recall partially accounted for the relation between attachment anxiety and PTSD symptoms. Our differential findings concerning early life versus adulthood trauma suggest that factors underlying the relation between attachment anxiety and PTSD symptoms vary according to the developmental timing of the traumatic exposure. Overall our results are consistent with attachment theory and with theoretical models of PTSD according to which PTSD symptoms are promoted by phenomenological properties of trauma memories.
The neuroscience of musical improvisation.
Neuroscience and biobehavioral reviews, 2015

Researchers have recently begun to examine the neural basis of musical improvisation, one of the most complex forms of creative behavior. The emerging field of improvisation neuroscience has implications not only for the study of artistic expertise, but also for understanding the neural underpinnings of domain-general processes such as motor control and language production. This review synthesizes functional magnetic resonance imagining (fMRI) studies of musical improvisation, including vocal and instrumental improvisation, with samples of jazz pianists, classical musicians, freestyle rap artists, and non-musicians. A network of prefrontal brain regions commonly linked to improvisatory behavior is highlighted, including the pre-supplementary motor area, medial prefrontal cortex, inferior frontal gyrus, dorsolateral prefrontal cortex, and dorsal premotor cortex. Activation of premotor and lateral prefrontal regions suggests that a seemingly unconstrained behavior may actually benefit from motor planning and cognitive control. Yet activation of cortical midline regions points to a role of spontaneous cognition characteristic of the default network. Together, such results may reflect cooperation between large-scale brain networks associated with cognitive control and spontaneous thought. The improvisation literature is integrated with Pressing's theoretical model, and discussed within the broader context of research on the brain basis of creative cognition.
S-nitrosylation-dependent proteasomal degradation restrains Cdk5 activity to regulate hippocampal synaptic strength.
Nature communications, 2015

Precise regulation of synaptic strength requires coordinated activity and functions of synaptic proteins, which is controlled by a variety of post-translational modification. Here we report that S-nitrosylation of p35, the activator of cyclin-dependent kinase 5 (Cdk5), by nitric oxide (NO) is important for the regulation of excitatory synaptic strength. While blockade of NO signalling results in structural and functional synaptic deficits as indicated by reduced mature dendritic spine density and surface expression of glutamate receptor subunits, phosphorylation of numerous synaptic substrates of Cdk5 and its activity are aberrantly upregulated following reduced NO production. The results show that the NO-induced reduction in Cdk5 activity is mediated by S-nitrosylation of p35, resulting in its ubiquitination and degradation by the E3 ligase PJA2. Silencing p35 protein in hippocampal neurons partially rescues the NO blockade-induced synaptic deficits. These findings collectively demonstrate that p35 S-nitrosylation by NO signalling is critical for regulating hippocampal synaptic strength.
Novel presenilin 1 and 2 double knock-out cell line for in vitro validation of PSEN1 and PSEN2 mutations.
Neurobiology of disease, 2020

Mutations in APP (amyloid precursor protein), PSEN1 (presenilin 1) or PSEN2 (presenilin 2) are the main cause of early-onset familial forms of Alzheimer's disease (autosomal dominant AD or ADAD). These genes affect γ-secretase-dependent generation of Amyloid β (Aβ) peptides, the main constituent of amyloid plaques and one of the pathological hallmarks of AD. Evaluation of patients with ADAD includes assessment of family history, clinical presentation, biomarkers, neuropathology when available and DNA sequencing data. These analyses frequently uncover novel variants of unknown significance in ADAD genes. This presents a barrier to recruitment of such individuals into clinical trials, unless a biochemical test can demonstrate that a novel mutation results in altered APP processing in a manner consistent with pathogenicity. Here we describe generation and characterization of a novel presenilin 1 and 2 double knock-out in N2A mouse neuroblastoma cells using CRISPR/Cas9, which results in complete ablation of Aβ production, decreased Pen-2 expression and Nicastrin glycosylation. Because of the absence of background Aβ secretion from endogenous γ-secretases, these cells can be used for validation of PSEN1 and PSEN2 variant effects on production of Aβ or other γ-secretase substrates and for biochemical studies of γ-secretase function using novel variants. We examined several PSEN1 and PSEN2 mutations of known and unknown pathogenicity. Known mutants increased Aβ42/Aβ40 ratio with varying effect on Aβ40, Aβ42, total Aβ levels and Pen-2 expression, which aligns with previous work on these mutants. Our data on novel PSEN1 V142F, G206V and G206D mutations suggest that these mutations underlie the reported clinical observations in ADAD patients. We believe our novel cell line will be valuable for the scientific community for reliable validation of presenilin mutations and helpful in defining their pathogenicity to improve and facilitate evaluation of ADAD patients, particularly in the context of enrollment in clinical trials.
Expression pattern of estroprogestinic receptors in sinonasal inverted papilloma.
Oncotarget, 2017

Inverted papilloma (IP) is a locally destructive, benign neoplasm of the nose and paranasal sinuses with a high tendency for recurrence, a significant potential for malignancy, and an etiology that today is still uncertain. The expression of hormonal receptors in neoplastic tissues has been the focus of intensive research for its potential diagnostic, prognostic, and therapeutic significance. The aim of this study was to assess the potential estroprogestinic receptor expression in patients undergoing sinus surgery for IP. A retrospective study was carried out, on surgical specimens of 73 patients who underwent endoscopic sinus surgery for first manifestation of sinonasal IP (primitive IP group) and in 21 subjects who had developed a recurrence (relapsed IP group). The results of the immunohistochemical analysis of the first group showed the absence of receptor expression for PGR in all cases analyzed and the presence of a low positivity for ER in 11 cases (P > 0.082). Similarly, in the second group the results showed a low presence of ER receptors in 3 of the 21 cases (P > 0.068), while there was no evidence of PGR receptors in the examined samples. In addition, in 11 of the cases only 3 were considered positive (27.2%) showing a recurrence during follow-up (P > 0.068).Our results suggest that the sinonasal IP is a benign tumor independent of estrogen and progesterone, and the receptors for these hormones are therefore unsuitable as predictors of relapse or possible prognostic indicators and therapeutic targets.