Perception is associated with the brain's metabolic response to sensory stimulation

  1. Mauro DiNuzzo
  2. Silvia Mangia
  3. Marta Moraschi
  4. Daniele Mascali
  5. Gisela E Hagberg
  6. Federico Giove  Is a corresponding author
  1. Museo Storico della Fisica e Centro Studi e Ricerche Enrico Fermi, Italy
  2. University of Minnesota, United States
  3. Campus Bio-Medico University of Rome, Italy
  4. Università Gabriele D'Annunzio, Italy
  5. Max Planck Institute for Biological Cybernetics and Biomedical Magnetic Resonance, Germany

Abstract

Processing of incoming sensory stimulation triggers an increase of cerebral perfusion and blood oxygenation (neurovascular response) as well as an alteration of the metabolic neurochemical profile (neurometabolic response). Here we show in human primary visual cortex (V1) that perceived and unperceived isoluminant chromatic flickering stimuli designed to have similar neurovascular responses as measured by blood oxygenation level dependent functional MRI (BOLD-fMRI) have markedly different neurometabolic responses as measured by functional MRS. In particular, a significant regional buildup of lactate, an index of aerobic glycolysis, and glutamate, an index of malate-aspartate shuttle, occurred in V1 only when the flickering was perceived, without any relation with behavioral or physiological variables. Whereas the BOLD-fMRI signal in V1, a proxy for input to V1, was insensitive to flickering perception by design, the BOLD-fMRI signal in secondary visual areas was larger during perceived than unperceived flickering, indicating increased output from V1. These results demonstrate that the upregulation of energy metabolism induced by visual stimulation depends on the type of information processing taking place in V1, and that 1H-fMRS provides unique information about local input/output balance that is not measured by BOLD fMRI.

Data availability

The study was developed using SPM12 (https://www.fil.ion.ucl.ac.uk/spm/software/spm12/), LCmodel (http://s-provencher.com/lcmodel.shtml), jMRUI (http://www.jmrui.eu/) and AFNI (https://afni.nimh.nih.gov/). Data used for all the figures and for Tables 2-3 is available as source data to each element. Source data include also custom Matlab code for processing related to each figure. The raw data include sensitive data. The raw dataset cannot be made available in a public repository because of constraints originally set by the Ethics Committee and included in the informed consent signed by participants. Raw data that support the findings of this study are available from the corresponding author upon signing a MTA that would include: a list of authorized researchers; a commitment to not disclose the raw data to persons not included in the list; and a commitment to destroy the raw data when legitimate use is finished. Commercial use of the raw data is not permitted.

Article and author information

Author details

  1. Mauro DiNuzzo

    Museo Storico della Fisica e Centro Studi e Ricerche Enrico Fermi, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  2. Silvia Mangia

    Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Marta Moraschi

    Department of Radiation Oncology, Campus Bio-Medico University of Rome, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniele Mascali

    Dipartimento di Neuroscienze, Università Gabriele D'Annunzio, Chieti, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Gisela E Hagberg

    High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics and Biomedical Magnetic Resonance, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Federico Giove

    Museo Storico della Fisica e Centro Studi e Ricerche Enrico Fermi, Rome, Italy
    For correspondence
    federico.giove@uniroma1.it
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6934-3146

Funding

Ministero della Salute (Ricerca Corrente)

  • Federico Giove

Max Planck Institute for Biological Cybernetics (Open Access funding)

  • Gisela E Hagberg

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This study included human subjects and was performed by the authors in compliance with all applicable ethical standards, including the Helsinki declaration and its amendments, institutional/national standards, and international/national/institutional guidelines. The study was approved by the Ethics Committee of Fondazione Santa Lucia (Rome). All subjects gave informed consent before being enrolled in the study.

Copyright

© 2022, DiNuzzo 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.

Metrics

  • 2,658
    views
  • 404
    downloads
  • 16
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Mauro DiNuzzo
  2. Silvia Mangia
  3. Marta Moraschi
  4. Daniele Mascali
  5. Gisela E Hagberg
  6. Federico Giove
(2022)
Perception is associated with the brain's metabolic response to sensory stimulation
eLife 11:e71016.
https://doi.org/10.7554/eLife.71016

Share this article

https://doi.org/10.7554/eLife.71016

Further reading

    1. Neuroscience
    Gergely F Turi, Sasa Teng ... Yueqing Peng
    Research Article

    Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.

    1. Neuroscience
    Ulrike Pech, Jasper Janssens ... Patrik Verstreken
    Research Article

    The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson’s disease patients confirms these findings. Indeed, the disturbances lead to early synaptic dysfunction, notably affecting cholinergic olfactory projection neurons crucial for olfactory function in flies. Correcting these defects specifically in olfactory cholinergic interneurons in flies or inducing cholinergic signaling in Parkinson mutant human induced dopaminergic neurons in vitro using nicotine, both rescue age-dependent dopaminergic neuron decline. Hence, our research uncovers that one of the earliest indicators of disease in five different models of familial Parkinsonism is synaptic dysfunction in higher-order cholinergic projection neurons and this contributes to the development of hyposmia. Furthermore, the shared pathways of synaptic failure in these cholinergic neurons ultimately contribute to dopaminergic dysfunction later in life.