Biology subjects

Engel, A. K.

Publications and source records attributed to Engel, A. K..

8 recordsLinked to original sources

bioRxiv2018

Alpha-band oscillations reflect external spatial coding for tactile stimuli in sighted, but not in congenitally blind humans

We investigated the function of oscillatory alpha-band activity in the neural coding of spatial information during tactile processing. Sighted humans concurrently encode tactile location in skin-based and, after integration with posture, external spatial reference frames, whereas congenitally blind humans preferably use skin-based coding. Accordingly, lateralization of alpha-band activity in parietal regions during attentional orienting in expectance of tactile stimulation reflected external spatial coding in sighted, but skin-based coding in blind humans. Here, we asked whether alpha-band activity plays a similar role in spatial coding for tactile processing, that is, after the stimulus has been received. Sighted and congenitally blind participants were cued to attend to one hand in order to detect rare tactile deviant stimuli at this hand while ignoring tactile deviants at the other hand and tactile standard stimuli at both hands. The reference frames encoded by oscillatory activity during tactile processing were probed by adopting either an uncrossed or crossed hand posture. In sighted participants, attended relative to unattended standard stimuli suppressed the power in the alpha-band over ipsilateral centro-parietal and occipital cortex. Hand crossing attenuated this attentional modulation predominantly over ipsilateral posterior-parietal cortex. In contrast, although contralateral alpha-activity was enhanced for attended versus unattended stimuli in blind participants, no crossing effects were evident in the oscillatory activity of this group. These findings suggest that oscillatory alpha-band activity plays a pivotal role in the neural coding of external spatial information for touch.

neuroscience↗

bioRxiv2018

Synchronised spiking activity underlies phase amplitude coupling in the subthalamic nucleus of Parkinson’s disease patients

Both phase-amplitude coupling (PAC) and beta-bursts in the subthalamic nucleus have been significantly linked to symptom severity in Parkinsons disease (PD) in humans and emerged independently as competing biomarkers for closed-loop deep brain stimulation (DBS). However, the underlying nature of subthalamic PAC is poorly understood and its relationship with transient beta burst-events has not been investigated. To address this, we studied macro- and micro electrode recordings of local field potentials (LFPs) and single unit activity from 15 hemispheres in 10 PD patients undergoing DBS surgery. PAC between beta phase and high frequency oscillation (HFO) amplitude was compared to single unit firing rates, spike triggered averages, power spectral densities and phase-spike locking, and was studied in periods of beta-bursting. We found a significant synchronisation of spiking to HFOs and correlation of mean firing rates with HFO-amplitude when the latter was coupled to beta phase (i.e. in the presence of PAC). In the presence of PAC, single unit power spectra displayed peaks in the beta and HFO frequency range and the HFO frequency was correlated with that in the LFP. Finally, PAC significantly increased with beta burst-duration. Our findings offer new insight in the pathology of Parkinsons disease by providing evidence that subthalamic PAC reflects the locking of spiking activity to network beta oscillations and that this coupling progressively increases with beta-burst duration. These findings suggest that beta-bursts capture periods of increased subthalamic input/output synchronisation in the beta frequency range and have important implications for therapeutic closed-loop DBS.\n\nSignificance statementIdentifying biomarkers for closed-loop deep brain stimulation (DBS) has become an increasingly important issue in Parkinsons Disease (PD) research. Two such biomarkers, phase-amplitude coupling (PAC) and beta-bursts, recorded from the implanted electrodes in subthalamic nucleus in PD patients, correlate with motor impairment. However, the physiological basis of PAC, and it relationship to beta bursts, is unclear. We provide multiple lines of evidence that PAC in the human STN reflects the locking of spiking activity to network beta oscillations and that this coupling progressively increases with the duration of beta-bursts. This suggests that beta-bursts capture increased subthalamic input/output synchronisation and provides new insights in PD pathology with direct implications for closed-loop DBS therapy strategies.

neuroscience↗

bioRxiv2018

Phase-dependent suppression of beta oscillations in Parkinson’s disease patients

Synchronized oscillations within and between brain areas facilitate normal processing, but are often amplified in disease. A prominent example is the abnormally sustained beta-frequency (~20Hz) oscillations recorded from the cortex and subthalamic nucleus of Parkinson's Disease patients. Computational modelling suggests that the amplitude of such oscillations could be modulated by applying stimulation at a specific phase. Such a strategy would allow selective targeting of the oscillation, with relatively little effect on other activity parameters. Here we demonstrate in awake, parkinsonian patients undergoing functional neurosurgery, that electrical stimulation arriving on consecutive cycles of a specific phase of the subthalamic oscillation can suppress its amplitude and coupling to cortex. Stimulus-evoked changes in spiking did not have a consistent time course, suggesting that the oscillation was modulated independently of net output. Phase-dependent stimulation could thus be a valuable strategy for treating brain diseases and probing the function of oscillations in the healthy brain.

neuroscience↗

bioRxiv2018

Short-term aerobic training does not improve memory functioning in relapsing remitting multiple sclerosis - a randomized controlled trial

BackgroundOnly few aerobic exercise intervention trials specifically targeting cognitive functioning have been performed in MS.\n\nObjective and methodsThis randomized controlled trial aimed to determine the effects of aerobic exercise on cognition in relapsing-remitting MS. The primary outcome was verbal memory (Verbal learning and memory test, VLMT). Patients were randomized to an intervention group (IG) program or a waitlist control group (CG). Patients in the IG exercised according to an individually tailored training schedule (with 2-3 sessions per week for 12 weeks). The primary analysis was carried out using the intention-to-treat (ITT) sample with ANCOVA adjusting for baseline scores.\n\nResults77 RRMS patients were screened and 68 participants randomized (CG n=34; IG n=34). The sample comprised 68% females, had a mean age of 39 years, a mean disease duration of 6.3 years, and a mean EDSS of 1.8. No significant effects were detected in the ITT analysis for the primary endpoint VLMT or any other cognitive measures. Moreover, no significant treatment effects were observed for quality of life, fatigue, or depressive symptoms.\n\nConclusionThis study failed to demonstrate beneficial effects of aerobic exercise on cognition in RRMS.\n\nThe trial was prospectively registered at clinicaltrials.gov (NCT02005237).

clinical trials↗

bioRxiv2018

Synchrony surfacing: epicortical recording of correlated action potentials

Synchronous spiking of multiple neurons is a key phenomenon in normal brain function and pathologies. Recently, approaches to record spikes from the intact cortical surface using small high-density arrays of microelectrodes have been reported. It remained unaddressed how epicortical spiking relates to intracortical unit activity. We introduce a mesoscale approach using an array of 64 electrodes with intermediate diameter (250 {micro}m) and combined large-coverage epicortical recordings in ferrets with intracortical recordings via laminar probes. Empirical data and modeling strongly suggest that our epicortical electrodes selectively captured synchronized spiking of neurons in the subjacent cortex. As a result, responses to sensory stimulation were more robust and less noisy as compared to intracortical activity, and receptive field properties were well preserved in epicortical recordings. This should promote insights into assembly-coding beyond the informative value of subdural EEG or single-unit spiking, and be advantageous to real-time applications in brain-machine interfacing.\n\nSignificance statementElectrocorticography allows chronic, low-noise recordings from the intact cortical surface - a prerequisite for investigations into brain network dynamics and brain-machine interfaces. Novel electrodes can capture spiking activity at the surface, which should boost precision in the spatial - and time domain, compared to conventional EEG-like measurements. To clarify how surface spiking relates to intracortically fired action potentials, we recorded both types of signal simultaneously from sensory cortices in anesthetized ferrets. Results suggest that mesoscale (250 {micro}m) surface electrodes can selectively capture synchronized spiking from nearby cortical columns, which reduces contamination by non-representative, jittering spikes. Given the high relevance of neural synchrony for sensorimotor and cognitive processing, the novel methodology may improve signal decoding in brain-machine interface approaches.\n\nAuthor contributionsE.G.L., T.B. and A.K.E. conceptualized the research; E.G.L. and F.P. performed experiments; T.B. and E.G.L. wrote Matlab routines for data analysis; T.B. and E.G.L. analyzed the data; T.S. provided technical resources; T.B., E.G.L. and A.K.E. wrote the manuscript; G.E. administrated the project; A.K.E. acquired funding.

neuroscience↗

bioRxiv2018

Surprise About Sensory Event Timing Drives Cortical Transients in the Beta Frequency Band

Understanding the statistical structure of the environment is crucial for adaptive behavior. Humans and non-human decision-makers seem to track such structure through a process of probabilistic inference, which enables predictions about behaviorally relevant events. Deviations from such predictions cause surprise, which in turn helps improve the inference. Surprise about the timing of behaviorally relevant sensory events drives phasic responses of neuromodulatory brainstem systems, which project to the cerebral cortex. Here, we developed a computational model-based magnetoencephalography (MEG) approach for mapping the resulting cortical transients across space, time, and frequency, in the human brain. We used a Bayesian updating model to estimate the predicted timing of the next stimulus change in a simple visual detection task. This model yielded quantitative trial-by-trial estimates of temporal surprise. The model-based surprise variable predicted trial-by-trial variations in reaction time more strongly than the externally observable interval timings alone. Trial-by-trial variations in surprise were negatively correlated with the power of cortical population activity measured with MEG. This surprise-related power suppression occurred transiently around the behavioral response, specifically in the beta frequency band. It peaked in left lateral prefrontal as well as in frontal midline regions, and its cortical distribution was distinct from the movement-related suppression of beta power in motor cortex. Our results indicate that surprise about sensory event timing transiently suppresses ongoing beta-band oscillations in association cortex. This transient suppression of frontal beta-band oscillations might reflect an active reset triggered by surprise, and is in line with the idea that beta-oscillations help maintain cognitive sets.\n\nSignificance statementAgents continuously track the statistical structure of the environment, in order to make predictions about behaviorally relevant sensory events. Deviations from such predictions cause surprise, which in turn drives phasic responses of neuromodulatory brainstem systems that project to the cerebral cortex. We developed a computational model-based magnetoencephalography approach, which enabled us to map out transients changes in cortical population dynamics elicited by surprise about sensory event timing, across space, time, and frequency, in the human brain. The model-based estimates of surprise predicted behavior as well as a transient suppression of beta frequency-band oscillations in frontal cortical regions. Our results are in line with conceptual accounts that have linked neural oscillations in the beta-band to the maintenance of cognitive sets.

neuroscience↗

bioRxiv2017

Working Memory Training Integrates Visual Cortex into Beta-Band Networks in Congenitally Blind Individuals

Congenitally blind individuals activate the visual cortex during non-visual tasks. Such crossmodal reorganization is likely associated with changes in large-scale functional connectivity, the spectral characteristics of which can be assessed by analysis of neural oscillations. To test visual cortical integration into working memory networks, we recorded magnetoencephalographic data from congenitally blind and sighted individuals during resting state as well as during a voice-based working memory task prior to and following working memory training with voices, or tactile stimuli or a training-control condition. Auditory training strengthened beta-band (17.5-22.5 Hz) connectivity (imaginary coherency) in the blind and theta-band (2.5-5 Hz) connectivity in the sighted during the task, suggesting different neural coupling mechanisms. In the sighted, theta-band connectivity increased between brain areas involved in auditory working memory (inferior frontal, superior temporal, insular cortex). In the blind, beta-band networks largely emerged during the training, and connectivity increased between brain areas involved in auditory working memory and the visual cortex. The prominent involvement of the right fusiform face area in this beta-band network suggests a task-specific integration of visual cortex. Our findings highlight large-scale interactions as a key mechanism of functional reorganization following congenital blindness, and provide new insights into the spectral characteristics of the mechanism.

neuroscience↗

bioRxiv2017

Catecholamines, not acetylcholine, alter cortical and perceptual dynamics in line with increased excitation inhibition ratio

The ratio between excitatory and inhibitory neurons (E/I ratio) is vital for cortical circuit dynamics, computation, and behavior. This ratio may be under the dynamic control of neuromodulatory systems, which are in turn implicated in several neuropsychiatric disorders. In particular, the catecholaminergic (dopaminergic and noradrenergic) and cholinergic systems have highly specific effects on excitatory and inhibitory cortical neurons, which might translate into changes in the local net E/I ratio. Here, we assessed and compared their net effects on net E/I ratio in human cortex, through an integrated application of computational modeling, placebo-controlled pharmacological intervention, magnetoencephalographic recordings of cortical activity dynamics, and perceptual psychophysics. We found that catecholamines, but not acetylcholine, altered both the temporal structure of intrinsic activity fluctuations in visual and parietal cortex, and the volatility of perceptual inference based on ambiguous visual input. Both effects indicate that catecholamines increase the net E/I ratio in visual and parietal cortex.

neuroscience↗