Neural representation of newly instructed rule identities during early implementation trials
- Technische Universität Dresden, Germany
Abstract
By following explicit instructions, humans instantaneously get the hang of tasks they have never performed before. We used a specially calibrated multivariate analysis technique to uncover the elusive representational states during the first few implementations of arbitrary rules such as 'for coffee, press red button' following their first-time instruction. Distributed activity patterns within the ventrolateral prefrontal cortex (VLPFC) indicated the presence of neural representations specific of individual stimulus-response (S-R) rule identities, preferentially for conditions requiring the memorization of instructed S-R rules for correct performance. Identity-specific representations were detectable starting from the first implementation trial and continued to be present across early implementation trials. The increasingly fluent application of novel rule representations was channelled through increasing cooperation between VLPFC and anterior striatum. These findings inform representational theories on how the prefrontal cortex supports behavioural flexibility specifically by enabling the ad-hoc coding of newly instructed individual rule identities during their first-time implementation.
Data availability
Preprocessed single subject data and unthresholded whole-brain maps underlying the main results visualized in Fig. 4, Fig. 5, Fig. 6, Fig. 7, and Fig. 8 are publicly available here: https://osf.io/vsbx8/
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Neural representation of individual rules after first-time instructionOpen Science Framework, osf.io/vsbx8/.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (SFB940 A2)
- Hannes Ruge
- Uta Wolfensteller
Deutsche Forschungsgemeinschaft (SFB940 Z2)
- Hannes Ruge
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- David Badre, Brown University, United States
Ethics
Human subjects: The experimental protocol was approved by the Ethics Committee of the Technische Universität Dresden (approval identifier: EK 545122015) and conformed to the World Medical Association's Declaration of Helsinki.All participants gave written informed consent before taking part in the experiment and were paid 10 Euros per hour for their participation or received course credit.
Version history
- Received: May 8, 2019
- Accepted: November 16, 2019
- Accepted Manuscript published: November 18, 2019 (version 1)
- Version of Record published: November 29, 2019 (version 2)
- Version of Record updated: December 4, 2019 (version 3)
Copyright
© 2019, Ruge et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Neural representation of newly instructed rule identities during early implementation trials
eLife 8:e48293.
https://doi.org/10.7554/eLife.48293
Further reading
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- Neuroscience
The presence of global synchronization of vasomotion induced by oscillating visual stimuli was identified in the mouse brain. Endogenous autofluorescence was used and the vessel ‘shadow’ was quantified to evaluate the magnitude of the frequency-locked vasomotion. This method allows vasomotion to be easily quantified in non-transgenic wild-type mice using either the wide-field macro-zoom microscopy or the deep-brain fiber photometry methods. Vertical stripes horizontally oscillating at a low temporal frequency (0.25 Hz) were presented to the awake mouse, and oscillatory vasomotion locked to the temporal frequency of the visual stimulation was induced not only in the primary visual cortex but across a wide surface area of the cortex and the cerebellum. The visually induced vasomotion adapted to a wide range of stimulation parameters. Repeated trials of the visual stimulus presentations resulted in the plastic entrainment of vasomotion. Horizontally oscillating visual stimulus is known to induce horizontal optokinetic response (HOKR). The amplitude of the eye movement is known to increase with repeated training sessions, and the flocculus region of the cerebellum is known to be essential for this learning to occur. Here, we show a strong correlation between the average HOKR performance gain and the vasomotion entrainment magnitude in the cerebellar flocculus. Therefore, the plasticity of vasomotion and neuronal circuits appeared to occur in parallel. Efficient energy delivery by the entrained vasomotion may contribute to meeting the energy demand for increased coordinated neuronal activity and the subsequent neuronal circuit reorganization.
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- Medicine
- Neuroscience
Background:
Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine’s molecular mechanisms connect to its neural and behavioral effects.
Methods:
We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets.
Results:
We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine’s data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level.
Conclusions:
These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry.
Funding:
This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1–190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016–0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 – 2056) (FXV).
Clinical trial number:
