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Does neural input or processing play a greater role in the magnitude of neuroimaging signals?

Harris S, Jones M, Zheng Y, Berwick J - Front Neuroenergetics (2010)

Bottom Line: Pre-muscimol infusion whisker stimuli elicited the expected neural and accompanying hemodynamic responses to that reported previously.Following infusion of muscimol, although the temporal profile of neural responses to each pulse of the stimulus train was similar, the average response was reduced in magnitude by approximately 79% compared to that elicited pre-infusion.The whisker-evoked hemodynamic responses were reduced by a commensurate magnitude suggesting that, although the neurovascular coupling relationships were similar for synaptic input as well as for cortical processing, the magnitude of the overall response is dominated by processing rather than from that produced from the thalamocortical input alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Sheffield Sheffield, UK.

ABSTRACT
An important constraint on how hemodynamic neuroimaging signals such as fMRI can be interpreted in terms of the underlying evoked activity is an understanding of neurovascular coupling mechanisms that actually generate hemodynamic responses. The predominant view at present is that the hemodynamic response is most correlated with synaptic input and subsequent neural processing rather than spiking output. It is still not clear whether input or processing is more important in the generation of hemodynamics responses. In order to investigate this we measured the hemodynamic and neural responses to electrical whisker pad stimuli in rat whisker barrel somatosensory cortex both before and after the local cortical injections of the GABA(A) agonist muscimol. Muscimol would not be expected to affect the thalamocortical input into the cortex but would inhibit subsequent intra-cortical processing. Pre-muscimol infusion whisker stimuli elicited the expected neural and accompanying hemodynamic responses to that reported previously. Following infusion of muscimol, although the temporal profile of neural responses to each pulse of the stimulus train was similar, the average response was reduced in magnitude by approximately 79% compared to that elicited pre-infusion. The whisker-evoked hemodynamic responses were reduced by a commensurate magnitude suggesting that, although the neurovascular coupling relationships were similar for synaptic input as well as for cortical processing, the magnitude of the overall response is dominated by processing rather than from that produced from the thalamocortical input alone.

No MeSH data available.


Hemodynamic responses in a representative animal before and after local cortical infusion of muscimol. (A) In vivo gray level CCD camera image of the somatosensory cortical surface. The electrode with drug infusion probe attached is visible on the right hand side of the image. (B) An image of combined photomicrographs of post-mortem histological sections of the cortical surface and the underling cortical barrels from Layer IV. (C) Total blood volume (Hbt), Deoxyhemoglobin (Hbr) and Oxyhemoglobin (HbO2) responses to 16-s electrical stimulation of the whisker pad. Each image represents an average change in micromolar concentration from baseline over the 16-s stimulation period. (D) Time series of hemodynamics response prior to muscimol infusion from a region of interest around the electrode tip (solid lines) and an additional ROI distal to the electrode in the more anterior whisker barrels (dotted lines). (E) Hemodynamic response images post muscimol injection. (F) Time series of hemodynamics response post muscimol infusion from a region of interest around the electrode tip (solid lines) and an additional ROI distal to the electrode in the more anterior whisker barrels (dotted lines).
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Figure 1: Hemodynamic responses in a representative animal before and after local cortical infusion of muscimol. (A) In vivo gray level CCD camera image of the somatosensory cortical surface. The electrode with drug infusion probe attached is visible on the right hand side of the image. (B) An image of combined photomicrographs of post-mortem histological sections of the cortical surface and the underling cortical barrels from Layer IV. (C) Total blood volume (Hbt), Deoxyhemoglobin (Hbr) and Oxyhemoglobin (HbO2) responses to 16-s electrical stimulation of the whisker pad. Each image represents an average change in micromolar concentration from baseline over the 16-s stimulation period. (D) Time series of hemodynamics response prior to muscimol infusion from a region of interest around the electrode tip (solid lines) and an additional ROI distal to the electrode in the more anterior whisker barrels (dotted lines). (E) Hemodynamic response images post muscimol injection. (F) Time series of hemodynamics response post muscimol infusion from a region of interest around the electrode tip (solid lines) and an additional ROI distal to the electrode in the more anterior whisker barrels (dotted lines).

Mentions: Hemodynamic responses were recorded from the right somatosensory whisker barrel cortex of urethane anesthetized rats following presentation of 16 s electrical stimulation of the left whisker pad. The electrode (with fluidic port attached) placement was accurately placed into the cortex as demonstrated by an in vivo CCD camera “gray-level” image of the cortical surface (Figure 1A). An image of combined photomicrographs of post-mortem histology of the cortical surface and the underling cortical barrels is shown for comparison (Figure 1B). It can be seen the electrode and fluidic port have been inserted into the cortex in the region of whisker barrel B1. For this representative animal two regions of interest (ROI) were chosen from which to examine the resultant time series of cortical hemodynamics following pixel averaging. One ROI was selected near to the electrode tip and a second from anterior whisker barrels distal to electrode placement. To assess the spatial extent of the hemodynamic response prior and post muscimol infusion, an average response image was created by averaging all images collected during the entire stimulus presentation period (16 s) for Hbt, HbO2 and Hbr (Figures 1C,E). For the whisker-evoked hemodynamics collected prior to muscimol infusion (control, Figure 1C) a large increase over the whole whisker barrel cortical region can be observed for both Hbt and HbO2; whereas Hbr showed a large decrease over the whole whisker region particularly in the “draining” cortical veins. Examination of the time series of the response for the two ROI selected (Figure 1D) demonstrates that the response in the anterior barrels (dotted lines) distal to the electrode is only slightly larger than from the region immediately surrounding the electrode tip (solid lines). Following infusion of muscimol the spatial extent and magnitude of the hemodynamic response elicited by whisker stimuli was altered compared to that observed prior to muscimol infusion. By observation of spatial images calculated by averaging images collected during stimulus presentation (Figure 1E), Hbt, HbO2 and Hbr around the electrode tip were attenuated compared to those elicited prior to muscimol infusion and with respect to the ROI distal to the electrode. This can also be observed in the time series responses from the two ROI (Figure 1F) which demonstrate that the hemodynamic response around the electrode tip has been substantially reduced following muscimol infusion whereas the response from the distal region of interest being relatively unaffected.


Does neural input or processing play a greater role in the magnitude of neuroimaging signals?

Harris S, Jones M, Zheng Y, Berwick J - Front Neuroenergetics (2010)

Hemodynamic responses in a representative animal before and after local cortical infusion of muscimol. (A) In vivo gray level CCD camera image of the somatosensory cortical surface. The electrode with drug infusion probe attached is visible on the right hand side of the image. (B) An image of combined photomicrographs of post-mortem histological sections of the cortical surface and the underling cortical barrels from Layer IV. (C) Total blood volume (Hbt), Deoxyhemoglobin (Hbr) and Oxyhemoglobin (HbO2) responses to 16-s electrical stimulation of the whisker pad. Each image represents an average change in micromolar concentration from baseline over the 16-s stimulation period. (D) Time series of hemodynamics response prior to muscimol infusion from a region of interest around the electrode tip (solid lines) and an additional ROI distal to the electrode in the more anterior whisker barrels (dotted lines). (E) Hemodynamic response images post muscimol injection. (F) Time series of hemodynamics response post muscimol infusion from a region of interest around the electrode tip (solid lines) and an additional ROI distal to the electrode in the more anterior whisker barrels (dotted lines).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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Figure 1: Hemodynamic responses in a representative animal before and after local cortical infusion of muscimol. (A) In vivo gray level CCD camera image of the somatosensory cortical surface. The electrode with drug infusion probe attached is visible on the right hand side of the image. (B) An image of combined photomicrographs of post-mortem histological sections of the cortical surface and the underling cortical barrels from Layer IV. (C) Total blood volume (Hbt), Deoxyhemoglobin (Hbr) and Oxyhemoglobin (HbO2) responses to 16-s electrical stimulation of the whisker pad. Each image represents an average change in micromolar concentration from baseline over the 16-s stimulation period. (D) Time series of hemodynamics response prior to muscimol infusion from a region of interest around the electrode tip (solid lines) and an additional ROI distal to the electrode in the more anterior whisker barrels (dotted lines). (E) Hemodynamic response images post muscimol injection. (F) Time series of hemodynamics response post muscimol infusion from a region of interest around the electrode tip (solid lines) and an additional ROI distal to the electrode in the more anterior whisker barrels (dotted lines).
Mentions: Hemodynamic responses were recorded from the right somatosensory whisker barrel cortex of urethane anesthetized rats following presentation of 16 s electrical stimulation of the left whisker pad. The electrode (with fluidic port attached) placement was accurately placed into the cortex as demonstrated by an in vivo CCD camera “gray-level” image of the cortical surface (Figure 1A). An image of combined photomicrographs of post-mortem histology of the cortical surface and the underling cortical barrels is shown for comparison (Figure 1B). It can be seen the electrode and fluidic port have been inserted into the cortex in the region of whisker barrel B1. For this representative animal two regions of interest (ROI) were chosen from which to examine the resultant time series of cortical hemodynamics following pixel averaging. One ROI was selected near to the electrode tip and a second from anterior whisker barrels distal to electrode placement. To assess the spatial extent of the hemodynamic response prior and post muscimol infusion, an average response image was created by averaging all images collected during the entire stimulus presentation period (16 s) for Hbt, HbO2 and Hbr (Figures 1C,E). For the whisker-evoked hemodynamics collected prior to muscimol infusion (control, Figure 1C) a large increase over the whole whisker barrel cortical region can be observed for both Hbt and HbO2; whereas Hbr showed a large decrease over the whole whisker region particularly in the “draining” cortical veins. Examination of the time series of the response for the two ROI selected (Figure 1D) demonstrates that the response in the anterior barrels (dotted lines) distal to the electrode is only slightly larger than from the region immediately surrounding the electrode tip (solid lines). Following infusion of muscimol the spatial extent and magnitude of the hemodynamic response elicited by whisker stimuli was altered compared to that observed prior to muscimol infusion. By observation of spatial images calculated by averaging images collected during stimulus presentation (Figure 1E), Hbt, HbO2 and Hbr around the electrode tip were attenuated compared to those elicited prior to muscimol infusion and with respect to the ROI distal to the electrode. This can also be observed in the time series responses from the two ROI (Figure 1F) which demonstrate that the hemodynamic response around the electrode tip has been substantially reduced following muscimol infusion whereas the response from the distal region of interest being relatively unaffected.

Bottom Line: Pre-muscimol infusion whisker stimuli elicited the expected neural and accompanying hemodynamic responses to that reported previously.Following infusion of muscimol, although the temporal profile of neural responses to each pulse of the stimulus train was similar, the average response was reduced in magnitude by approximately 79% compared to that elicited pre-infusion.The whisker-evoked hemodynamic responses were reduced by a commensurate magnitude suggesting that, although the neurovascular coupling relationships were similar for synaptic input as well as for cortical processing, the magnitude of the overall response is dominated by processing rather than from that produced from the thalamocortical input alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Sheffield Sheffield, UK.

ABSTRACT
An important constraint on how hemodynamic neuroimaging signals such as fMRI can be interpreted in terms of the underlying evoked activity is an understanding of neurovascular coupling mechanisms that actually generate hemodynamic responses. The predominant view at present is that the hemodynamic response is most correlated with synaptic input and subsequent neural processing rather than spiking output. It is still not clear whether input or processing is more important in the generation of hemodynamics responses. In order to investigate this we measured the hemodynamic and neural responses to electrical whisker pad stimuli in rat whisker barrel somatosensory cortex both before and after the local cortical injections of the GABA(A) agonist muscimol. Muscimol would not be expected to affect the thalamocortical input into the cortex but would inhibit subsequent intra-cortical processing. Pre-muscimol infusion whisker stimuli elicited the expected neural and accompanying hemodynamic responses to that reported previously. Following infusion of muscimol, although the temporal profile of neural responses to each pulse of the stimulus train was similar, the average response was reduced in magnitude by approximately 79% compared to that elicited pre-infusion. The whisker-evoked hemodynamic responses were reduced by a commensurate magnitude suggesting that, although the neurovascular coupling relationships were similar for synaptic input as well as for cortical processing, the magnitude of the overall response is dominated by processing rather than from that produced from the thalamocortical input alone.

No MeSH data available.