Dual Feedback Streams and Laminar integration of Long-range Inter-areal Processes in Primate Cortex – Dual_Streams

We combine the skill of all three teams to improve our understanding of the roles of different feedback pathways in nonhuman and human primate early visual cortex. We use laminar-resolution fMRI to visualize the influence of feedback processes on different layers of early visual cortex while subjects are performing visual and cognitive tasks. Using a combination of optogenetics stimulation in one area with electrophysiological recording in two areas, frequency specific activity will be studied in a layer specific fashion. Optogenetics will be used to insert experimentally controlled rhythmic activity into lower or higher visual areas and electrophysiologic recordings will be used to investigate the responses of the target areas of the respective feedforward or feedback projections. Monosynaptic circuit tracing with glycoprotein (G)-deleted rabies viruses (RVdG) and retrograde tracing will be used to characterize GABAergic projection neurons linking white matter to overlaying gray matter and long-distance inter-areal GABAergic connectivity in the frontal cortex. If the anatomical investigation reveals a significant number of long-range GABAergic projections from area V1 to area V6, their role in the gamma-band synchronization between V1 and V6 will be investigated using optogenetic techniques.

High intensity fMRI has permitted the visualization of activity at the laminar level in human cortex. We will use this to characterize the differential influence of visual and cognitive tasks on feedback influences of different cortical layers in human. By comparing different tasks that are expected to engage short and long-range processes, we expect to see differential activity in superficial and deep cortical layers. We are currently analyzing the results from experiments to evaluate how early visual areas decode low and high-level motion integration phenomena. In the awake and behaving marmoset, a method was developed to record neural activity from two visual cortical areas simultaneously in combination with optogenetic stimulation. Thus far, the application has shown that optogenetic activation of excitatory neurons in area V6 can influence behavior in a detection task. Using retrograde tracing, we have identified numerous long-distance connections from interstitial neurons in the vicinity of the claustrum, and temporal lobe underlying the entorhinal cortex. We conceive of these layer 6B neurons as manifestations of a claustrum complex. The comparison of these results across methods and species will permit clarification of the two feedback streams and will lead to major progress in determining predictive coding mechanisms in the cortex.

The major impact of this project will concern inter-areal processing in the cerebral cortex in primates including human. Progress in the field will impact on theories of brain function, and the role of descending predictions in mental disorders. We predict that the major contribution for understanding the neurobiology of feedback pathways will strengthen the biological substrate for progress in the field of computational pyschiatry.

1. Vezoli, J, Magrou, L, Goebel, R, Wang, XJ, Knoblauch, K, Vinck, M, Kennedy, H (2021). Cortical hierarchy, dual counterstream architecture and the importance of top-down generative networks. Neuroimage, 225:117479.
Reviews the structural and functional bases of the cortical hierarchy and describes the Dual Counterstream Architecture.

2. Abbatecola C, Gerardin P, Beneyton K, Kennedy H and Knoblauch K (2021) The Role of Unimodal Feedback Pathways in Gender Perception During Activation of Voice and Face Areas. Front. Syst. Neurosci. 15:669256. doi: 10.3389/fnsys.2021.669256.
Describes behavioral and neuroimaging results that show two types of top-down influences in a high-level multimodal perceptual task.

3. Jendritza, P., Klein, F. J., Rohenkohl, G. and Fries, P. (2021) Visual Neuroscience Methods for Marmosets: Efficient Receptive Field Mapping and Hand-Free Eye Tacking. eNeuro 8:ENEURO.0489-20.2021et. doi.org/10.1523/ENEURO.0489-20.2021
Presents methodological advancements in the recording of behavior and receptive field properties of awake and behaving marmosets.

4. Lewis, C. M., Ni, J., Wunderle, T., Jendritza, P., Diester, I. and Fries, P. (2021) Cortical gamma-band resonance preferentially transmits coherent input. Cell. Rep. 35:109083 doi.org/10.1016/j.celrep.2021.109083
Shows that optogenetically generated depolarizing currents in pyramidal cells generates strong gamma-band synchronization and demonstrates that cortical gamma-band resonance preferentially transmits coherent input components.

Cortical feedback plays a critical role in perceptual-cognitive integration and in major hypotheses on brain function, including predictive coding theory. We aim to investigate the integrative roles of two feedback pathways that have been identified in the inter-areal projections of primate cerebral cortex in the framework of a multidisciplinary project that will use neuroimaging, electrophysiology and anatomy. The two feedback pathways in supra- and infragranular cortical layers show distinct topographical features: a long-distance, diffusely projecting pathway in infragranular layers and a short-distance pathway whose projections are more focal and confined to supragranular layers. Importantly, the specific functions of these two pathways are unknown. Objectives 1 and 2 probes these pathways by studying laminar dependent activity in early visual areas during cognitive tasks requiring perceptual integration and attention in human and nonhuman primates while performing tasks requiring long-range cortical interaction: contextual effects on perception, motion coherence and spatial vs feature selective attention. Objective 1, in human, uses laminar-resolution functional imaging with fMRI at 7T to explore what stimulus conditions generate differential activation of supra and infragranular layers and causal modeling to infer directed inter-areal effective connectivity. We will explore three tasks: (1) contextual effects on surface color perception that influence (i) the visual stream of origin of feedback signals and (ii) stimulus predictability; (2) the influence of motion coherence and stimulus expectation on feedback to early visual areas; (3) the role of spatial and feature selective attention on the laminar profile of activity. We expect that these experiments will reveal conditions that differentially affect the two feedback streams, thus, informing us about their different functional roles. Objective 2, in marmoset uses multi-site depth electrodes to assess layer-specific activation patterns and directed inter-areal interactions via layer-specific optogenetic activation of the two feedback pathways to probe their causal relevance. We expect that the results will inform us about the differential roles of the two feedback pathways in cortical processing, which will allow more accurate models of cortical processing to be developed in a predictive coding framework. Objective 3 addresses the nature and frequency of long-distance inhibitory connections between cortical areas and interstitial neurons and cortex, investigating if they are preferentially associated with a particular circuit. Such inhibitory processes are predicted to have profound impact on inter-areal processing through effects on oscillation and synchrony. We predict the proposed work will contribute to understanding the canonical cortical microcircuits and the computations they support in a predictive coding framework and thereby furthering understanding the neuronal basis of psychiatric disorders.