Biology subjects

Parra, L. C.

Publications and source records attributed to Parra, L. C..

34 records · Page 2Linked to original sources

bioRxiv2019

Temporal interference stimulation targets deep brain regions by modulating neural oscillations

Temporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range. A validated current-flow model of the human head estimates that amplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. The electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05-2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1-2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms. Experiment and model confirm the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. This selectivity is governed by network adaption (e.g. GABAb) that is faster than the amplitude-modulation frequency. The applied current required depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency of temporal interference stimulation.

neuroscience↗

bioRxiv2019

Eye movements predict test scores in online video education

Experienced teachers pay close attention to their students, adjusting their teaching when students seem lost. This dynamic interaction is missing in online education. We propose to measure attention to online videos remotely by tracking eye movements, as we hypothesize that attentive students follow videos similarly with their eyes. Here we show that inter-subject correlation of eye-movements during instructional video presentation is substantially higher for attentive students, and that synchronized eye movement are predictive of individual test scores on the material presented in the video. These findings replicate for videos in a variety of production styles, learning scenarios and for recall and comprehension questions alike. We reproduce the result using standard web cameras to capture eye-movements in a classroom setting, and with over 1,000 participants at-home without the need to transmit user data. Our results suggest that online education could be made adaptive to a students level of attention in real-time.

neuroscience↗

bioRxiv2019

Optimized Interferential Stimulation of Human Brains

ObjectiveInterferential stimulation (IFS) has generated considerable interest recently because of its potential to achieve focal electric fields in deep brain areas with transcranial currents. Conventionally, IFS applies sinusoidal currents through two electrode pairs with close-by frequencies. Here we propose to use an array of electrodes instead of just two electrode pairs; and to use algorithmic optimization to identify the currents required at each electrode to target a desired location in the brain. ApproachWe formulate rigorous optimization criteria for IFS to achieve either maximal modulation-depth or maximally focal stimulation. We find the solution for optimal modulation-depth analytically and maximize for focal stimulation numerically. Main resultsMaximal modulation is achieved when IFS equals conventional high-definition multi-electrode transcranial electrical stimulation (HD-TES) with a modulated current source. This optimal solution can be found directly from a current-flow model, i.e. the "lead field" without the need for algorithmic optimization. Once currents are optimized numerically to achieve optimal focal stimulation, we find that IFS can indeed be more focal than conventional HD-TES, both at the cortical surface and deep in the brain. Generally, however, stimulation intensity of IFS is weak and the locus of highest intensity does not match the locus of highest modulation. SignificanceThis proof-of-principle study shows the potential of IFS over HD-TES for focal non-invasive deep brain stimulation. Future work will be needed to improve on intensity of stimulation and convergence of the optimization procedure.

biophysics↗

bioRxiv2019

Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness

Severe brain injuries can lead to long-lasting disorders of consciousness (DoC) such as vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS). While behavioral assessment remains the gold standard to determine conscious state, EEG has proven to be a promising complementary tool to monitor the effect of new therapeutics. Encouraging results have been obtained with invasive electrical stimulation of the brain, and recent studies identified transcranial direct current stimulation (tDCS) as an effective approach in randomized controlled trials. This non-invasive and inexpensive tool may turn out to be the preferred treatment option. However, its mechanisms of action and physiological effects on brain activity remain unclear and debated. Here, we stimulated 60 DoC patients with the anode placed over left-dorsolateral prefrontal cortex in a prospective open-label study. Clinical behavioral assessment improved in twelve patients (20%) and none deteriorated. This behavioral response after tDCS coincided with an enhancement of putative EEG markers of consciousness: in comparison with non-responders, responders showed increases of power and long-range cortico-cortical functional connectivity in the theta-alpha band, and a larger and more sustained P300 suggesting improved conscious access to auditory novelty. The EEG changes correlated with electric fields strengths in prefrontal cortices, and no correlation was found on the scalp. Taken together, this prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.

neuroscience↗

bioRxiv2019

Action enhances perception: Visually evoked neural responses are enhanced when engaging in a motor task

While it is well known that vision guides movement, less appreciated is that the motor cortex also provides input to the visual system. Here we asked whether neural processing of visual stimuli is acutely modulated during motor activity, hypothesizing that visual evoked responses are enhanced when engaged in a motor task that depends on the visual stimulus. To test this, we told participants that their brain activity was controlling a video game that was in fact the playback of a prerecorded game. The deception, which was effective in half of participants, aimed to engage the motor system while avoiding evoked responses related to actual movement or somatosensation. In other trials, subjects actively played the game with keyboard control or passively watched a playback. The strength of visually evoked responses was measured as the temporal correlation between the continuous stimulus and the evoked potentials on the scalp. We found reduced correlation during passive viewing, but no difference between active and sham play. Alpha band (8-12 Hz) activity was reduced over central electrodes during sham play, indicating recruitment of motor cortex despite the absence of overt movement. To account for the potential increase of attention during game play, we conducted a second study with subjects counting screen items during viewing. We again found increased correlation during sham play, but no difference between counting and passive viewing. While we cannot fully rule out the involvement of attention, our findings do demonstrate an enhancement of visual evoked responses during active vision.

neuroscience↗

bioRxiv2019

Direct current stimulation boosts associative Hebbian synaptic plasticity and maintains its pathway specificity

There is evidence that transcranial direct current stimulation can boost learning performance. Arguably, this boost is related to synaptic plasticity. However, the precise effects on synaptic plasticity and its underlying mechanisms are not known. We hypothesized that direct current stimulation modulates endogenous Hebbian plasticity mechanisms due to its ability to polarize cellular membrane. To test this we induced long term plasticity (LTP) using theta-burst stimulation (TBS) in rat hippocampus, and measured the effects of concurrent direct current stimulation (DCS). Soma-depolarizing DCS increased TBS-induced LTP. Oscillating current stimulation is equally effective provided the soma-depolarizing phase is time-aligned with the theta-bursts, suggesting that only instantaneous depolarization is relevant. Importantly, the effect is pathway-specific and associative. These findings are consistent with classic theory on the role of post-synaptic membrane potential in Hebbian plasticity. These data suggest that the effects of direct current stimulation are specific because they modulate endogenous Hebbian plasticity, thus inheriting its exquisite functional specificity.

neuroscience↗

bioRxiv2018

Can transcranial electric stimulation with multiple electrodes reach deep targets?

To reach a deep target in the brain with transcranial electric stimulation (TES), currents have to pass also through the cortical surface. Thus, it is generally thought that TES cannot achieve focal deep brain stimulation. Recent efforts with interfering waveforms and pulsed stimulation have argued that one can achieve deeper or more intense stimulation in the brain. Here we argue that conventional transcranial stimulation with multiple current sources is just as effective as these new approaches. The conventional multi-electrode approach can be numerically optimized to maximize intensity or focality at a desired target location. Using such optimal electrode configurations we find in a detailed and realistic head model that deep targets may in fact be strongly stimulated, with cerebro-spinal fluid guiding currents deep into the brain.\n\nO_LSTHighlightsC_LSTO_LIDeep targets can be reached with intensities comparable to the cortical surface.\nC_LIO_LIMulti-electrode montages increase intensity with the same current limits per electrode.\nC_LIO_LIHigh-definition and intersectional pulsed stimulation are largely equivalent.\nC_LIO_LIInterferential stimulation is generally weaker than conventional stimulation.\nC_LI

biophysics↗

bioRxiv2018

Multiway Canonical Correlation Analysis of Brain Signals

Brain signals recorded with electroencephalography (EEG), magnetoencephalography (MEG) and related techniques often have poor signal-to-noise ratio due to the presence of multiple competing sources and artifacts. A common remedy is to average over repeats of the same stimulus, but this is not applicable for temporally extended stimuli that are presented only once (speech, music, movies, natural sound). An alternative is to average responses over multiple subjects that were presented with the same identical stimuli, but differences in geometry of brain sources and sensors reduce the effectiveness of this solution. Multiway canonical correlation analysis (MCCA) brings a solution to this problem by allowing data from multiple subjects to be fused in such a way as to extract components common to all. This paper reviews the method, offers application examples that illustrate its effectiveness, and outlines the caveats and risks entailed by the method.

neuroscience↗

bioRxiv2018

Neural engagement with online educational videos predicts learning performance for individual students

Online educational materials are largely disseminated through videos, and yet there is little understanding of how these videos engage students and fuel academic success. We hypothesized that components of the electroencephalogram (EEG), previously shown to reflect video engagement, would be predictive of academic performance in the context of educational videos. Two groups of subjects watched educational videos in either an intentional learning paradigm, in which they were aware of an upcoming test, or in an incidental learning paradigm, in which they were unaware that they would be tested. \"Neural engagement\" was quantified by the inter-subject correlation (ISC) of the EEG that was evoked by the videos. In both groups, students with higher neural engagement retained more information. Neural engagement also discriminated between attentive and inattentive video viewing. These results suggest that this EEG metric is a marker of the stimulus-related attentional mechanisms necessary to retain information. In the future, EEG may be used as a tool to design and assess online educational content.

neuroscience↗

bioRxiv2017

Realistic vOlumetric-Approach to Simulate Transcranial Electric Stimulation -- ROAST -- a fully automated open-source pipeline

Research in the area of transcranial electrical stimulation (TES) often relies on computational models of current flow in the brain. Models are built based on the magnetic resonance images (MRI) of the human head to capture detailed individual anatomy. To simulate current flow on an individual, the subjects MRI is segmented, virtual electrodes are placed on this anatomical model, the volume is tessellated into a mesh, and a finite element model (FEM) is solved numerically to estimate the current flow. Various software tools are available for each step, as well as processing pipelines that connect these tools for automated or semi-automated processing. The goal of the present tool - ROAST - is to provide an end-to-end pipeline that can automatically process individual heads with realistic volumetric anatomy leveraging open-source software and custom scripts to improve segmentation and execute electrode placement. The electric field estimated with the open-source tools used by ROAST differ little from the results obtained with commercial meshing and FEM solving software. We also do not find large differences between the various automated segmentation methods used by ROAST and SimNIBS, a well-established open-source modeling pipeline. However, we do find large differences when volumetric segmentation are converted into surfaces that are used in SimNIBS to generate volumetric meshes. Evaluation on intracranial recordings from human subjects suggests that ROAST outperforms newer versions of SimNIBS in predicting field distribution and magnitudes, but that an older version of SimNIBS performs similarly. We hope that the detailed comparisons presented here of various choices in this modeling pipeline can provide guidance for future tool development. We release ROAST as an open-source, easy-to-install and fully-automated pipeline for individualized TES modeling at https://www.parralab.org/roast/.

biophysics↗

bioRxiv2017

Elucidating relations between fMRI, ECoG and EEG through a common natural stimulus

Human brain mapping relies heavily on fMRI, ECoG and EEG, which capture different physiological signals. Relationships between these signals have been established in the context of specific tasks or during resting state, often using spatially confined concurrent recordings in animals. But it is not certain whether these correlations generalize to other contexts relevant for human cognitive neuroscience. Here, we address the case of complex naturalistic stimuli and ask two basic questions. First, how reliable are the responses evoked by a naturalistic audio-visual stimulus in each of these imaging methods, and second, how similar are stimulus-related responses across methods? To this end, we investigated a wide range of brain regions and frequency bands. We presented the same movie clip twice to three different cohorts of subjects (NEEG = 45, NfMRI = 11, NECoG = 5) and assessed stimulus-driven correlations across viewings and between imaging methods, thereby ruling out task-irrelevant confounds. All three imaging methods had similar repeat-reliability across viewings when fMRI and EEG data were averaged across subjects, highlighting the potential to achieve large signal-to-noise ratio by leveraging large sample sizes. The fMRI signal correlated positively with high-frequency ECoG power across multiple task-related cortical structures but positively with low-frequency EEG and ECoG power. In contrast to previous studies, these correlations were as strong for low-frequency as for high frequency ECoG. We also observed links between fMRI and infra-slow EEG voltage fluctuations. These results extend previous findings to the case of natural stimulus processing.

neuroscience↗

bioRxiv2017

Award or Reward? Which comes first, NIH funding or research impact?

Which comes first, funding or research impact? We use causal inference to determine the direction of influence in a record of 70,000 NIH-funded investigators, which was recently released. Contrary to the basic premise of many funding policies, we find that the number of citations of an investigator determine funding levels, but not the other way around.

scientific communication and education↗

bioRxiv2017

Common neural responses to narrative speech indisorders of consciousness

ObjectiveClinical assessment of auditory attention in patients with disorders of consciousness is often limited by motor impairment. Here, we employ inter-subject correlations among electroencephalography responses to naturalistic speech in order to assay auditory attention among patients and healthy controls.\n\nMethodsElectroencephalographic data were recorded from 20 subjects with disorders of consciousness and 14 healthy controls during of two narrative audio stimuli, presented both forwards and time-reversed. Inter-subject correlation of evoked electroencephalography signals were calculated, comparing responses of both groups to those of the healthy control subjects. This analysis was performed blinded and subsequently compared to the diagnostic status of each patient based on the Coma Recovery Scale-Revised.\n\nResultsSubjects with disorders of consciousness exhibit significantly lower inter-subject correlation than healthy controls during narrative speech. Additionally, while healthy subjects had higher inter-subject correlation values in forward vs. backwards presentation, neural responses did not vary significantly with the direction of playback in subjects with disorders of consciousness. Increased inter-subject correlation values in the backward speech condition were noted with improving disorder of consciousness diagnosis, both in cross-sectional analysis and in a subset of patients with longitudinal data.\n\nInterpretationInter-subject correlation of neural responses to narrative speech audition differentiates healthy controls from patients and appears to index clinical diagnoses in disorders of consciousness.

neuroscience↗

bioRxiv2017

Engaging narratives evoke similar neural activity and lead to similar time perception

It is said that we lose track of time - that \"time flies\" - when we are engrossed in a story. How does engagement with the story cause this distorted perception of time, and what are its neural correlates? People commit both time and attentional resources to an engaging stimulus. For narrative videos, attentional engagement can be represented as the level of similarity between the electroencephalographic responses of different viewers. Here we show that this measure of neural engagement predicted the duration of time that viewers were willing to commit to narrative videos. Contrary to popular wisdom, engagement did not distort the average perception of time duration. Rather, more similar brain responses resulted in a more uniform perception of time across viewers. These findings suggest that by capturing the attention of an audience, narrative videos bring both neural processing and the subjective perception of time into synchrony.

neuroscience↗

bioRxiv2016

A Resource for Assessing Information Processing in the Developing Brain Using EEG and Eye Tracking

We present a dataset combining electrophysiology and eye tracking intended as a resource for the investigation of information processing in the developing brain. The dataset includes high-density task-based and task-free EEG, eye tracking, and cognitive and behavioral data collected from 126 individuals (ages: 6-44). The task battery spans both the simple/complex and passive/active dimensions to cover a range of approaches prevalent in modern cognitive neuroscience. The active task paradigms facilitate principled deconstruction of core components of task performance in the developing brain, whereas the passive paradigms permit the examination of intrinsic functional network activity during varying amounts of external stimulation. Alongside these neurophysiological data, we include an abbreviated cognitive test battery and questionnaire-based measures of psychiatric functioning. We hope that this dataset will lead to the development of novel assays of neural processes fundamental to information processing, which can be used to index healthy brain development as well as detect pathologic processes.

neuroscience↗

bioRxiv2016

Age and sex affect intersubject correlation of EEGthroughout development

Neural development is generally marked by an increase in the efficiency and diversity of neural processes. In a large sample (N = 114) of children and adults with ages ranging from 5 -44 years, we investigated the neural responses to naturalistic video stimuli. Videos from both real-life classroom settings and Hollywood feature films were used to probe different aspects of attention and engagement. For all stimuli, older ages were marked by more variable neural responses. Variability was assessed by the inter-subject correlation of evoked electroencephalographic (EEG) responses. Young males also had more variable responses than young females. These results were replicated in an independent cohort (N = 303). When interpreted in the context of neural maturation, we conclude that neural function becomes more variable with maturity, at least in during the passive viewing of real-world stimuli.\n\nSignificance StatementNaturalistic videos were used to measure how a large sample of children and adults process environmentally meaningful stimuli. As age increased, neural responses were more variable, and females responded more variably than males - a difference that disappeared with age. These results are consistent with developmental theories positing that neural variability increases with maturation, and that neural maturation typically occurs earlier in females. This is the first study to investigate neural variability under naturalistic conditions in a developmental sample.

neuroscience↗