Previously, using simultaneous resting-state functional magnetic resonance imaging (fMRI) and photometry-based neuronal calcium recordings in the anesthetized rat, we identified blood oxygenation level-dependent (BOLD) responses directly related to slow calcium waves, revealing a cortex-wide and spatially organized correlate of locally recorded neuronal activity (Schwalm et al., 2017). Here, using the same techniques, we investigate two distinct cortical activity states: persistent activity, in which compartmentalized network dynamics were observed; and slow wave activity, dominated by a cortex-wide BOLD component, suggesting a strong functional coupling of inter-cortical activity. During slow wave activity, we find a correlation between the occurring slow wave events and the strength of functional connectivity between different cortical areas. These findings suggest that down-up transitions of neuronal excitability can drive cortex-wide functional connectivity. This study provides further evidence that changes in functional connectivity are dependent on the brain’s current state, directly linked to the generation of slow waves.

Dopamine dysfunction is associated with a wide range of neuropsychiatric disorders commonly treated pharmacologically or invasively. Recent studies provide evidence for a nonpharmacological and noninvasive alternative that allows similar manipulation of the dopaminergic system: transcranial direct current stimulation (tDCS). In rodents, tDCS has been shown to increase neural activity in subcortical parts of the dopaminergic system, and recent studies in humans provide evidence that tDCS over prefrontal regions induces striatal dopamine release and affects reward-related behavior. Based on these findings, we used fMRI in healthy human participants and measured the fractional amplitude of low-frequency fluctuations to assess spontaneous neural activity strength in regions of the mesostriatal dopamine system before and after tDCS over prefrontal regions (n ϭ 40, 22 females). In a second study, we examined the effect of a single dose of the dopamine precursor levodopa (L-DOPA) on mesostriatal fractional amplitude of low-frequency fluctuation values in male humans (n ϭ 22) and compared the results between both studies. We found that prefrontal tDCS and L-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. We furthermore assessed the spatial similarity of whole-brain statistical parametric maps, indicating tDCS-andL-DOPA-inducedactivation,andϾ100neuronalreceptorgeneexpressionmapsbasedontranscriptionaldatafromtheAllenInstitute forBrainScience.Inlinewithaspecificactivationofthedopaminergicsystem,wefoundthatbothinterventionspredominantlyactivatedregions with high expression levels of the dopamine receptors D2 and D3.

The interaction between the primary visual cortex (V1) and extrastriate visual areas provides the first building blocks in our perception of the world. V2, in particular, seems to play a crucial role in shaping contextual modulation information through feedback projections to V1. However, whether this feedback is inhibitory or excitatory is still unclear. In order to test the nature of V2 feedback to V1, we used neuronavigation-guided offline inhibitory transcranial magnetic stimulation (TMS) on V2 before testing participants on collinear facilitation, a contrast detection task with lateral masking. This contextual modulation task is thought to rely on horizontal connections in V1 and possibly extrastriate feedback. Results showed that when inhibitory TMS was delivered over V2, contrast thresholds decreased for targets presented in the contralateral hemifield, consistent with the retinotopic mapping of this area, while having no effect for targets presented in the ipsilateral hemifield or after control (CZ) stimulation. These results suggest that feedback from V2 to V1 during contextual modulation is mostly inhibitory, corroborating recent observations in monkey electrophysiology and extending this mechanism to human visual system. Moreover, we provide for the first time direct evidence of the involvement of extrastriate visual areas in collinear facilitation.Electronic supplementary materialThe online version of this article (10.1007/s00429-019-01964-z) contains supplementary material, which is available to authorized users.

Contrast detection thresholds for a central Gabor patch (target) can be modulated by the presence of co-oriented and collinear high contrast Gabors flankers. In foveal vision collinear facilitation can be observed for target-to-flankers relative distances beyond two times the wavelength (λ) of the Gabor’s carrier, while for shorter relative distances (<2λ) there is suppression. These modulatory influences seem to disappear after 12λ. In this study, we measured contrast detection thresholds for different spatial frequencies (1, 4 and 6 cpd) and target-to-flankers relative distances ranging from 6 to 16λ, but with collinear configurations presented in near periphery at 4° of eccentricity. Results showed that in near periphery collinear facilitation extends beyond 12λ for the higher spatial frequencies tested (4 and 6 cpd), while it decays already at 10λ for the lowest spatial frequency used (i.e., 1 cpd). In addition, we found that increasing the spatial frequency the peak of collinear facilitation shifts towards larger target-to-flankers relative distances (expressed as multiples of the stimulus wavelength), an effect never reported neither for near peripheral nor for central vision. The results suggest that the peak and the spatial extent of collinear facilitation in near periphery depend on the spatial frequency of the stimuli used.

Accurate time perception is crucial in peripheral vision especially for the spatial perception during actions. To investigate the dynamics of time perception in peripheral vision, parvocellular-biased and magnocellular-biased flashes were presented at different eccentricities (0-48 degrees ) in an interflash interval discrimination task. Results showed an increase in time compression with eccentricity for both stimuli (magnocellular-biased and parvocellular-biased flashes). Nevertheless, when stimulus visibility was 'equalized' across the visual field, the increase in time compression was only found for magnocellular-biased stimuli. Thus, we suggest that the magnocellular pathway accounts for time underestimation. Moreover, its increase with eccentricity could be an inherent property of the magnocellular system more than a result of a decrease in stimulus visibility.

Visuo-vestibular integration is crucial for locomotion, yet the cortical mechanisms involved remain poorly understood. We combined binaural monopolar galvanic vestibular stimulation (GVS) and functional magnetic resonance imaging (fMRI) to characterize the cortical networks activated during antero-posterior and lateral stimulations in humans. We focused on functional areas that selectively respond to egomotion-consistent optic flow patterns: the human middle temporal complex (hMT+), V6, the ventral intraparietal (VIP) area, the cingulate sulcus visual (CSv) area and the posterior insular cortex (PIC). Areas hMT+, CSv, and PIC were equivalently responsive during lateral and anteroposterior GVS while areas VIP and V6 were highly activated during antero-posterior GVS, but remained silent during lateral GVS. Using psychophysiological interaction (PPI) analyses, we confirmed that a cortical network including areas V6 and VIP is engaged during antero-posterior GVS. Our results suggest that V6 and VIP play a specific role in processing multisensory signals specific to locomotion during navigation.

Previously, using simultaneous task-free fMRI and optic-fiber-based neuronal calcium recordings in the anesthetized rat, we identified BOLD responses directly related to slow calcium waves, revealing a cortex-wide and spatially organized BOLD correlate (Schwalm et al. 2017). Here, with these bimodal recordings, we reveal two distinct brain states: persistent state, in which compartmentalized network activity was observed, including defined subsets such as the default mode network; and slow wave state, dominated by a cortex-wide component, suggesting a strong functional coupling of brain activity. In slow wave state we find a correlation between slow wave events and the strength of functional connectivity. These findings suggest that indeed down-up transitions of neuronal excitability drive cortex-wide functional connectivity. This study provides strong evidence that previously reported changes in functional connectivity are highly dependent on the brain's current state and directly linked with cortical excitability and slow waves generation.

Visuo-vestibular integration is crucial for locomotion, yet cortical mechanisms involved remain poorly understood. We combined binaural monopolar galvanic vestibular stimulation (GVS) and functional magnetic resonance imaging (fMRI) to characterize the cortical networks activated during antero-posterior and lateral stimulations in humans. We focused on functional areas that selectively respond to egomotion-consistent optic flow patterns: the human middle temporal complex (hMT+), V6, the ventral intraparietal (VIP) area, the cingulate sulcus visual (CSv) area and the posterior insular cortex (PIC). Areas hMT+, CSv, and PIC were equivalently responsive during lateral and antero-posterior GVS while areas VIP and V6 were highly activated during antero-posterior GVS but remained silent during lateral GVS. Using psychophysiological interaction (PPI) analyses, we confirmed that a cortical network including areas V6 and VIP is engaged during antero-posterior GVS. Our results suggest that V6 and VIP play a specific role in processing multisensory signals specific to locomotion during navigation.