What we can do and what we cannot do with fMRI

Logothetis, Nikos K.

doi:10.1038/nature06976

Cited by 2,854 publications

(2,151 citation statements)

References 68 publications

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“…Neuroimaging of spontaneous infraslow activity has been the focus of tremendous research interest, but has typically relied upon imaging modalities that indirectly reflect neuronal activity [45][46][47][48] and have thus raised questions about the underlying nature and interpretation of these data 22,36 . Innovative efforts to directly assess the neurophysiological basis of fMRI BOLD signal fluctuations have revealed much about the best electrophysiological correlates of these signals, but these approaches require specialized recording equipment and technical analysis to remove electrical artifacts and are limited in their spatial coverage.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, alterations in its structure have been linked with neurodegenerative and psychiatric disease [19][20][21] suggesting the potential for the identification of novel biomarkers and a greater understanding of both disease progression and recovery. Because neuroimaging studies of infraslow functional connectivity are dominated by fMRI which reports on a surrogate signal of neuronal activity, blood oxygen level dependent (BOLD) contrast, the interpretation of the underlying neurophysiology is indirect and nuanced 22 , particularly, in light of evidence illustrating instances of dissociation between neuronal activity and hemodynamic responses [23][24][25][26] such as ipsilateral or non-crossed sensory responses where increases in neuronal activity are followed by reductions in blood flow 26 . Furthermore, the temporal resolution of fMRI is limited and questions of the underlying neuronal activity correlate cannot be directly assessed by these means.…”

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confidence: 99%

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Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

et al. 2015

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Neuroimaging of spontaneous, resting-state infraslow (o0.1 Hz) brain activity has been used to reveal the regional functional organization of the brain and may lead to the identification of novel biomarkers of neurological disease. However, these imaging studies generally rely on indirect measures of neuronal activity and the nature of the neuronal activity correlate remains unclear. Here we show, using wide-field, voltage-sensitive dye imaging, the mesoscale spatiotemporal structure and pharmacological dependence of spontaneous, infraslow cortical activity in anaesthetized and awake mice. Spontaneous infraslow activity is regionally distinct, correlates with electroencephalography and local field potential recordings, and shows bilateral symmetry between cortical hemispheres. Infraslow activity is attenuated and its functional structure abolished after treatment with voltage-gated sodium channel and glutamate receptor antagonists. Correlation analysis reveals patterns of infraslow regional connectivity that are analogous to cortical motifs observed from higher-frequency spontaneous activity and reflect the underlying framework of intracortical axonal projections.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

et al. 2015

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“…These changes arise from local changes in neuronal activity and metabolism. The relationship between BOLD signals and excitatory neuro‐metabolic processes has been studied extensively; however, the relationship between BOLD signals and inhibitory neuro‐metabolic processes is less well understood 3, 4, 5. One of the key inhibitory metabolites is γ‐aminobutyric acid (GABA), which is the main inhibitory neurotransmitter of the brain and is believed to have a direct impact on BOLD contrast through regulation of neuronal firing rates 6, 7, 8.…”

Section: Introductionmentioning

confidence: 99%

Maximizing sensitivity for fast GABA edited spectroscopy in the visual cortex at 7 T

et al. 2018

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The combination of functional MRI (fMRI) and MRS is a promising approach to relate BOLD imaging to neuronal metabolism, especially at high field strength. However, typical scan times for GABA edited spectroscopy are of the order of 6‐30 min, which is long compared with functional changes observed with fMRI.The aim of this study is to reduce scan time and increase GABA sensitivity for edited spectroscopy in the human visual cortex, by enlarging the volume of activated tissue in the primary visual cortex. A dedicated setup at 7 T for combined fMRI and GABA MRS is developed. This setup consists of a half volume multi‐transmit coil with a large screen for visual cortex activation, two high density receive arrays and an optimized single‐voxel MEGA‐sLASER sequence with macromolecular suppression for signal acquisition.The coil setup performance as well as the GABA measurement speed, SNR, and stability were evaluated. A 2.2‐fold gain of the average SNR for GABA detection was obtained, as compared with a conventional 7 T setup. This was achieved by increasing the viewing angle of the participant with respect to the visual stimulus, thereby activating almost the entire primary visual cortex, allowing larger spectroscopy measurement volumes and resulting in an improved GABA SNR. Fewer than 16 signal averages, lasting 1 min 23 s in total, were needed for the GABA fit method to become stable, as demonstrated in three participants. The stability of the measurement setup was sufficient to detect GABA with an accuracy of 5%, as determined with a GABA phantom. In vivo, larger variations in GABA concentration are found: 14‐25%. Overall, the results bring functional GABA detections at a temporal resolution closer to the physiological time scale of BOLD cortex activation.

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“…Such a behavior may suggest an interplay between excitatory and inhibitory neurons, which is force‐dependent. Interestingly, inhibition and negative BOLD signal have been observed previously, although not in relation to variable applied GFs [Logothetis, 2008; Logothetis et al, 2001; Newton et al, 2005; Singh, 2012]. …”

Section: Discussionmentioning

confidence: 86%

Cerebellar lobules and dentate nuclei mirror cortical force‐related‐BOLD responses: Beyond all (linear) expectations

Alahmadi

Pardini

Samson

et al. 2017

Human Brain Mapping

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The relationship between the BOLD response and an applied force was quantified in the cerebellum using a power grip task. To investigate whether the cerebellum responds in an on/off way to motor demands or contributes to motor responses in a parametric fashion, similarly to the cortex, five grip force levels were investigated under visual feedback. Functional MRI data were acquired in 13 healthy volunteers and their responses were analyzed using a cerebellum‐optimized pipeline. This allowed us to evaluate, within the cerebellum, voxelwise linear and non‐linear associations between cerebellar activations and forces. We showed extensive non‐linear activations (with a parametric design), covering the anterior and posterior lobes of the cerebellum with a BOLD‐force relationship that is region‐dependent. Linear responses were mainly located in the anterior lobe, similarly to the cortex, where linear responses are localized in M1. Complex responses were localized in the posterior lobe, reflecting its key role in attention and executive processing, required during visually guided movement. Given the highly organized responses in the cerebellar cortex, a key question is whether deep cerebellar nuclei show similar parametric effects. We found positive correlations with force in the ipsilateral dentate nucleus and negative correlations on the contralateral side, suggesting a somatotopic organization of the dentate nucleus in line with cerebellar and cortical areas. Our results confirm that there is cerebellar organization involving all grey matter structures that reflect functional segregation in the cortex, where cerebellar lobules and dentate nuclei contribute to complex motor tasks with different BOLD response profiles in relation to the forces. Hum Brain Mapp 38:2566–2579, 2017. © 2017 Wiley Periodicals, Inc.

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What we can do and what we cannot do with fMRI

Cited by 2,854 publications

References 68 publications

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

Maximizing sensitivity for fast GABA edited spectroscopy in the visual cortex at 7 T

Cerebellar lobules and dentate nuclei mirror cortical force‐related‐BOLD responses: Beyond all (linear) expectations

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