rudyvdbrink/CitationDatabase huggingface dataset:
Probing Mechanical Properties of Brain in a Tuberous Sclerosis Model of Autism.
Journal of biomechanical engineering, 2019

Causes of autism spectrum disorders (ASD) are understood poorly, making diagnosis and treatment challenging. While many studies have investigated the biochemical and genetic aspects of ASD, whether and how mechanical characteristics of the autistic brain can modulate neuronal connectivity and cognition in ASD are unknown. Previously, it has been shown that ASD brains are characterized by abnormal white matter and disorganized neuronal connectivity; we hypothesized that these significant cellular-level structural changes may translate to changes in the mechanical properties of the autistic brain or regions therein. Here, we focused on tuberous sclerosis complex (TSC), a genetic disorder with a high penetrance of ASD. We investigated mechanical differences between murine brains obtained from control and TSC cohorts at various deformation length- and time-scales. At the microscale, we conducted creep-compliance and stress relaxation experiments using atomic force microscope(AFM)-enabled indentation. At the mesoscale, we conducted impact indentation using a pendulum-based instrumented indenter to extract mechanical energy dissipation metrics. At the macroscale, we used oscillatory shear rheology to quantify the frequency-dependent shear moduli. Despite significant changes in the cellular organization of TSC brain tissue, we found no corresponding changes in the quantified mechanical properties at every length- and time-scale explored. This investigation of the mechanical characteristics of the brain has broadened our understanding of causes and markers of TSC/ASD, while raising questions about whether any mechanical differences can be detected in other animal models of ASD or other disease models that also feature abnormal brain structure.
Sleep after learning aids the consolidation of factual knowledge, but not relearning.
Sleep, 2021

Sleep strengthens and reorganizes declarative memories, but the extent to which these processes benefit subsequent relearning of the same material remains unknown. It is also unclear whether sleep-memory effects translate to educationally realistic learning tasks and improve long-term learning outcomes.
Social behaviors and contextual memory of 
iScience, 2021

Both genetic variations and nutritional deficiency are associated with autism spectrum disorders and other neurological disorders. However, it is less clear whether or how nutritional deficiency and genetic variations influence each other under pathogenic conditions. "Valosin-containing protein" (
Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants.
Brain pathology (Zurich, Switzerland), 2021

Cognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP-43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concomitant pathologies on cognitive impairment in ALS patients. We analyzed a postmortem series of 104 ALS patients and retrospectively reviewed clinical and neuropathological data. We assessed the burden and extent of concomitant pathologies, the role of APOE ε4 and mutations, and correlated these findings with cognitive status. We performed a logistic regression model to identify which pathologies are related to cognitive impairment. Cognitive decline was recorded in 38.5% of the subjects. Neuropathological features of frontotemporal lobar degeneration (FTLD) were found in 32.7%, explaining most, but not all, cases with cognitive impairment. Extent of TDP-43 pathology and the presence of hippocampal sclerosis were associated with cognitive impairment. Mutation carriers presented a higher burden of TDP-43 pathology and FTLD more frequently than sporadic cases. Most cases (89.4%) presented some degree of concomitant pathologies. The presence of concomitant pathologies was associated with older age at death. FTLD, but also Alzheimer's disease, were the predominant underlying pathologies explaining the cognitive impairment in ALS patients. In sum, FTLD explained the presence of cognitive decline in most but not all ALS cases, while other non-FTLD related findings can influence the cognitive status, particularly in older age groups.
Transcriptional regulation of photoreceptor development and homeostasis in the mammalian retina.
Nature reviews. Neuroscience, 2010

In the developing vertebrate retina, diverse neuronal subtypes originate from multipotent progenitors in a conserved order and are integrated into an intricate laminated architecture. Recent progress in mammalian photoreceptor development has identified a complex relationship between six key transcription-regulatory factors (RORbeta, OTX2, NRL, CRX, NR2E3 and TRbeta2) that determine rod versus M cone or S cone cell fate. We propose a step-wise 'transcriptional dominance' model of photoreceptor cell fate determination, with the S cone representing the default state of a generic photoreceptor precursor. Elucidation of gene-regulatory networks that dictate photoreceptor genesis and homeostasis will have wider implications for understanding the development of nervous system function and for the treatment of neurodegenerative diseases.
Synergistic protective effects of humanin and necrostatin-1 on hypoxia and ischemia/reperfusion injury.
Brain research, 2010

Since several different pathways are involved in cerebral ischemia/reperfusion injury, combination therapy rather than monotherapy may be required for efficient neuroprotection. In this study, we examined the protective effects of an apoptosis inhibitor Gly(14)-humanin (HNG) and a necroptosis inhibitor necrostatin-1 (Nec-1) on hypoxia/ischemia/reperfusion injury. Cultured mouse primary cortical neurons were incubated with Nec-1, HNG or both in a hypoxia chamber for 60 min. Cell viability was determined by MTS assay at 24h after oxygen-glucose deprivation (OGD) treatment. Mice underwent middle cerebral artery occlusion for 75 min followed by 24h reperfusion. Mice were administered HNG and/or Nec-1 (i.c.v.) at 4h after reperfusion. Neurological deficits were evaluated and the cerebral infarct volume was determined by TTC staining. Nec-1 or HNG alone had protective effects on OGD-induced cell death. Combined treatment with Nec-1 and HNG resulted in more neuroprotection than Nec-1 or HNG alone. Treatment with HNG or Nec-1 reduced cerebral infarct volume from 59.3 ± 2.6% to 47.0 ± 2.3% and 47.1 ± 1.5%, respectively. Combined treatment with HNG and Nec-1 improved neurological scores and decreased infarct volume to 38.6 ± 1.5%. In summary, we demonstrated that the combination treatment of HNG and Nec-1 conferred synergistic neuroprotection on hypoxia/ischemia/reperfusion injury in vitro and in vivo. These findings provide a novel therapeutic strategy for the treatment of stroke by combining anti-apoptosis and anti-necroptosis therapy.
Gabor Than Award Lecture 2008: pre-eclampsia - from placental oxidative stress to maternal endothelial dysfunction.
Placenta, 2009

Pre-eclampsia is the most important complication of human pregnancy worldwide and a major contributor to maternal and fetal morbidity and mortality. Strong evidence exists that generation of placental oxidative stress, secondary to deficient spiral artery remodelling, is a key intermediary event, triggering the secretion of a mixture of placental factors that culminate in an enhanced maternal inflammatory response. Reactive oxygen species (ROS) have been recognised as secondary messengers in intracellular signalling cascades. Experiments studying placental ischaemia-reperfusion in vitro or in vivo during labour provide strong evidence suggesting that oxidative stress and ROS production can activate downstream stress-signalling pathways, p38 and SAPK/JNK MAPK, and the pro-inflammatory NF-kappaB signalling pathway, culminating in the release of inflammatory mediators, apoptotic debris, anti-angiogenic factors and other mediators, which then stimulate a maternal inflammatory reaction that manifests in endothelial dysfunction and the symptoms of pre-eclampsia. Addition of anti-oxidants or blocking the stress or inflammatory pathways in vitro attenuates these effects and opens possibilities for therapeutic intervention.
State-dependent bidirectional modification of somatic inhibition in neocortical pyramidal cells.
Neuron, 2008

Cortical pyramidal neurons alter their responses to input signals depending on behavioral state. We investigated whether changes in somatic inhibition contribute to these alterations. In layer 5 pyramidal neurons of rat visual cortex, repetitive firing from a depolarized membrane potential, which typically occurs during arousal, produced long-lasting depression of somatic inhibition. In contrast, slow membrane oscillations with firing in the depolarized phase, which typically occurs during slow-wave sleep, produced long-lasting potentiation. The depression is mediated by L-type Ca2+ channels and GABA(A) receptor endocytosis, whereas potentiation is mediated by R-type Ca2+ channels and receptor exocytosis. It is likely that the direction of modification is mainly dependent on the ratio of R- and L-type Ca2+ channel activation. Furthermore, somatic inhibition was stronger in slices prepared from rats during slow-wave sleep than arousal. This bidirectional modification of somatic inhibition may alter pyramidal neuron responsiveness in accordance with behavioral state.
Psychological therapies for post-traumatic stress disorder and comorbid substance use disorder.
The Cochrane database of systematic reviews, 2016

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that may develop after exposure to traumatic events. Substance use disorder (SUD) is a behavioural disorder in which the use of one or more substances is associated with heightened levels of distress, clinically significant impairment of functioning, or both. PTSD and SUD frequently occur together. The comorbidity is widely recognised as being difficult to treat and is associated with poorer treatment completion and poorer outcomes than for either condition alone. Several psychological therapies have been developed to treat the comorbidity, however there is no consensus about which therapies are most effective.
High-density EEG mobile brain/body imaging data recorded during a challenging auditory gait pacing task.
Scientific data, 2019

In this report we present a mobile brain/body imaging (MoBI) dataset that allows study of source-resolved cortical dynamics supporting coordinated gait movements in a rhythmic auditory cueing paradigm. Use of an auditory pacing stimulus stream has been recommended to identify deficits and treat gait impairments in neurologic populations. Here, the rhythmic cueing paradigm required healthy young participants to walk on a treadmill (constant speed) while attempting to maintain step synchrony with an auditory pacing stream and to adapt their step length and rate to unanticipated shifts in tempo of the pacing stimuli (e.g., sudden shifts to a faster or slower tempo). High-density electroencephalography (EEG, 108 channels), surface electromyography (EMG, bilateral tibialis anterior), pressure sensors on the heel (to register timing of heel strikes), and goniometers (knee, hip, and ankle joint angles) were concurrently recorded in 20 participants. The data is provided in the Brain Imaging Data Structure (BIDS) format to promote data sharing and reuse, and allow the inclusion of the data into fully automated data analysis workflows.
Sensitization of the trigeminovascular pathway: perspective and implications to migraine pathophysiology.
Journal of clinical neurology (Seoul, Korea), 2012

Migraine headache is commonly associated with signs of exaggerated intracranial and extracranial mechanical sensitivities. Patients exhibiting signs of intracranial hypersensitivity testify that their headache throbs and that mundane physical activities that increase intracranial pressure (such as bending over or coughing) intensify the pain. Patients exhibiting signs of extracranial hypersensitivity testify that during migraine their facial skin hurts in response to otherwise innocuous activities such as combing, shaving, letting water run over their face in the shower, or wearing glasses or earrings (termed here cephalic cutaneous allodynia). Such patients often testify that during migraine their bodily skin is hypersensitive and that wearing tight cloth, bracelets, rings, necklaces and socks or using a heavy blanket can be uncomfortable and/or painful (termed her extracephalic cutaneous allodynia). This review summarizes the evidence that support the view that activation of the trigeminovascular pathway contribute to the headache phase of a migraine attack, that the development of throbbing in the initial phase of migraine is mediated by sensitization of peripheral trigeminovascular neurons that innervate the meninges, that the development of cephalic allodynia is propelled by sensitization of second-order trigeminovascular neurons in the spinal trigeminal nucleus which receive converging sensory input from the meninges as well as from the scalp and facial skin, and that the development of extracephalic allodynia is mediated by sensitization of third-order trigeminovascular neurons in the posterior thalamic nuclei which receive converging sensory input from the meninges, facial and body skin.
Distance disintegration delineates the brain connectivity failure of Alzheimer's disease.
Neurobiology of aging, 2020

Alzheimer's disease (AD) is associated with brain network dysfunction. Network-based investigations of brain connectivity have mainly focused on alterations in the strength of connectivity; however, the network breakdown in AD spectrum is a complex scenario in which multiple pathways of connectivity are affected. To integrate connectivity changes that occur under AD-related conditions, here we developed a novel metric that computes the connectivity distance between cortical regions at the voxel level (or nodes). We studied 114 individuals with mild cognitive impairment, 24 with AD, and 27 healthy controls. Results showed that areas of the default mode network, salience network, and frontoparietal network display a remarkable network separation, or greater connectivity distances, from the rest of the brain. Furthermore, this greater connectivity distance was associated with lower global cognition. Overall, the investigation of AD-related changes in paths and distances of connectivity provides a novel framework for characterizing subjects with cognitive impairment; a framework that integrates the overall network topology changes of the brain and avoids biases toward unreferenced connectivity effects.
Flexible shaping: how learning in small steps helps.
Cognition, 2009

Humans and animals can perform much more complex tasks than they can acquire using pure trial and error learning. This gap is filled by teaching. One important method of instruction is shaping, in which a teacher decomposes a complete task into sub-components, thereby providing an easier path to learning. Despite its importance, shaping has not been substantially studied in the context of computational modeling of cognitive learning. Here we study the shaping of a hierarchical working memory task using an abstract neural network model as the target learner. Shaping significantly boosts the speed of acquisition of the task compared with conventional training, to a degree that increases with the temporal complexity of the task. Further, it leads to internal representations that are more robust to task manipulations such as reversals. We use the model to investigate some of the elements of successful shaping.
Sphingolipid Metabolism: New Insight into Ceramide-Induced Lipotoxicity in Muscle Cells.
International journal of molecular sciences, 2019

Insulin-resistance is a characteristic feature of type 2 diabetes (T2D) and plays a major role in the pathogenesis of this disease. Skeletal muscles are quantitatively the biggest glucose users in response to insulin and are considered as main targets in development of insulin-resistance. It is now clear that circulating fatty acids (FA), which are highly increased in T2D, play a major role in the development of muscle insulin-resistance. In healthy individuals, excess FA are stored as lipid droplets in adipocytes. In situations like obesity and T2D, FA from lipolysis and food are in excess and eventually accumulate in peripheral tissues. High plasma concentrations of FA are generally associated with increased risk of developing diabetes. Indeed, ectopic fat accumulation is associated with insulin-resistance; this is called lipotoxicity. However, FA themselves are not involved in insulin-resistance, but rather some of their metabolic derivatives, such as ceramides. Ceramides, which are synthetized de novo from saturated FA like palmitate, have been demonstrated to play a critical role in the deterioration of insulin sensitivity in muscle cells. This review describes the latest progress involving ceramides as major players in the development of muscle insulin-resistance through the targeting of selective actors of the insulin signaling pathway.
Team reasoning: Solving the puzzle of coordination.
Psychonomic bulletin & review, 2018

In many everyday activities, individuals have a common interest in coordinating their actions. Orthodox game theory cannot explain such intuitively obvious forms of coordination as the selection of an outcome that is best for all in a common-interest game. Theories of team reasoning provide a convincing solution by proposing that people are sometimes motivated to maximize the collective payoff of a group and that they adopt a distinctive mode of reasoning from preferences to decisions. This also offers a compelling explanation of cooperation in social dilemmas. A review of team reasoning and related theories suggests how team reasoning could be incorporated into psychological theories of group identification and social value orientation theory to provide a deeper understanding of these phenomena.
Low intensity white noise improves performance in auditory working memory task: An fMRI study.
Heliyon, 2019

Research suggests that white noise may facilitate auditory working memory performance via stochastic resonance. Stochastic resonance is quantified by plotting cognitive performance as a function of noise intensity. The plot would appear as an inverted U-curve, that is, a moderate noise is beneficial for performance whereas too low and too much noise attenuates performance. However, knowledge about the optimal signal-to-noise ratio (SNR) needed for stochastic resonance to occur in the brain, particularly in the neural network of auditory working memory, is limited and demand further investigation. In the present study, we extended previous works on the impact of white noise on auditory working memory performance by including multiple background noise levels to map out the inverted U-curve for the stochastic resonance. Using functional magnetic resonance imaging (fMRI), twenty healthy young adults performed a word-based backward recall span task under four signal-to-noise ratio conditions: 15, 10, 5, and 0-dB SNR. Group results show significant behavioral improvement and increased activation in frontal cortices, primary auditory cortices, and anterior cingulate cortex in all noise conditions, except at 0-dB SNR, which decreases activation and performance. When plotted as a function of signal-to-noise ratio, behavioral and fMRI data exhibited a noise-benefit inverted U-shaped curve. Additionally, a significant positive correlation was found between the activity of the right superior frontal gyrus (SFG) and performance in 5-dB SNR. The predicted phenomenon of SR on auditory working memory performance is confirmed. Findings from this study suggest that the optimal signal-to-noise ratio to enhance auditory working memory performance is within 10 to 5-dB SNR and that the right SFG may be a strategic structure involved in enhancement of auditory working memory performance.
Apolipoprotein M-bound sphingosine-1-phosphate regulates blood-brain barrier paracellular permeability and transcytosis.
eLife, 2019

The blood-brain barrier (BBB) is formed by the endothelial cells lining cerebral microvessels, but how blood-borne signaling molecules influence permeability is incompletely understood. We here examined how the apolipoprotein M (apoM)-bound sphingosine 1-phosphate (S1P) signaling pathway affects the BBB in different categories of cerebral microvessels using ApoM deficient mice (
Enduring deficits in contextual and auditory fear conditioning after adolescent, not adult, social instability stress in male rats.
Neurobiology of learning and memory, 2011

Adolescence is a time of developmental changes and reorganization in the brain and stress systems, thus, adolescents may be more vulnerable than adults to the effects of chronic mild stressors. Most studies, however, have not directly compared stress experienced in adolescence to the same stress experience in adulthood. In the present study, adolescent (n=46) and adult (n=48) male rats underwent 16 days of social instability stress (daily 1h isolation and change of cage partners) or were non-stress controls. Rats were then tested on the strength of acquired contextual and cued fear conditioning, as well as extinction learning, beginning either the day after the stress procedure or 3 weeks later. No difference was found among the groups during the Training Phase of conditioning. Irrespective of the time between the social stress experience and fear conditioning, rats stressed in adolescence had decreased context and cue memory, and cue generalization compared to control rats, as measured by the percentage of time spent freezing in tests. Social instability stress in adulthood had no effect on any measure of fear conditioning. The results support the hypothesis that adolescence is a time of heightened vulnerability to stressors.
Differential compromise of prospective and retrospective metamemory monitoring and their dissociable structural brain correlates.
Cortex; a journal devoted to the study of the nervous system and behavior, 2016

Metamemory refers to personal knowledge about one's own memory ability that invokes cognitive processes relevant to monitoring and controlling memory. An impaired monitoring system can potentially result in unawareness of symptoms as can occur in addiction denial. Monitoring processes can be assessed with prospective measures such as Feeling-Of-Knowing (FOK) judgments on prediction of future recognition performance, or retrospective confidence judgments (RCJ) made on previous memory performance. Alcoholic patients with amnesia showed poor FOK but intact RCJ. The neuropsychological continuum from mild to moderate deficits in nonamnesic to amnesic alcoholism raised the possibility that alcoholics uncomplicated by clinically-detectable amnesia may suffer anosognosia for their mild memory deficits. Herein 24 abstinent alcoholics and 26 age-matched controls completed an episodic memory paradigm including prospective FOK and retrospective RCJ monitoring measures and underwent 3T structural magnetic resonance imaging. Alcoholics were less accurate than controls in recognition and in assessing their future recognition performance, which was marked by overestimation, but were as accurate as controls on confidence ratings of actual recognition performance. Examination of brain structure-function relations revealed a double dissociation where FOK accuracy was selectively related to insular volume, and retrospective confidence accuracy was selectively related to frontolimbic structural volumes. Impaired FOK with intact RCJ was consistent with mild anosognosia and suggested evidence for neuropsychological and neural mechanisms of unawareness in addiction.