Multi-channel infrared stimulation on mesoscale cortical units with ultra-high field 7T MRI

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Abstract Submission 

Yipeng Liu¹, Feiyan Tian^1,2, Meixuan Chen¹, Anna Roe^1,2,3,4

¹Department of Neurosurgery of the Second Affiliated Hospital, Interdisciplinary Institute of Neurosc, Hangzhou, China, ²College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China, ³MOE Frontier Science Center for Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China, ⁴Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, China

Yipeng Liu  
Department of Neurosurgery of the Second Affiliated Hospital, Interdisciplinary Institute of Neurosc
Hangzhou, China

Feiyan Tian  
Department of Neurosurgery of the Second Affiliated Hospital, Interdisciplinary Institute of Neurosc|College of Biomedical Engineering and Instrument Science, Zhejiang University
Hangzhou, China|Hangzhou, China

Meixuan Chen  
Department of Neurosurgery of the Second Affiliated Hospital, Interdisciplinary Institute of Neurosc
Hangzhou, China

Anna Roe  
Department of Neurosurgery of the Second Affiliated Hospital, Interdisciplinary Institute of Neurosc|College of Biomedical Engineering and Instrument Science, Zhejiang University|MOE Frontier Science Center for Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University|Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University
Hangzhou, China|Hangzhou, China|Hangzhou, China|Hangzhou, China

The cortex of primate is organized by submillimeter functional domains. But little is known about how these coordinated units form a highly organized network on a brain-wide scale. Recently, the use of holographic optogenetics to target multiple brain areas opens up the possibility to modulate cortical information flow with diverse spatiotemporal patterns. Here we develop another patterned illumination method by infrared neural stimulation (INS), which is capable of producing a spatially focal stimulation via heat transients. This effective field is smaller than the column width in cat (~700µm). Combined with BOLD functional MRI in ultrahigh field, coordinated connectivity of the whole-brain can be mapped and further manipulated with patterns.

Animal preparation
Three adult cats were anesthetized with sufentanil and vecutonium bromide and the brain state was examined by a grating visual stimulus. After localized the visual area by structural imaging with reference tubes, a cranial window fitting the size of bundle was opened. Then the bundle tip was attached to the cortical surface. Agar was applied to reduce the artifacts caused by air bubbles.
Infrared stimulation
Infrared laser was delivered by a solid-state laser generator (CW-1875±10nm) and a pulse modulator (Master-9). Each pulse train consisted of 250µs pulses at 200Hz for 0.5 seconds. Each channel block consisted of 9s stimulation with 3 pulse trains and 9s blank. One piezoelectric switch (Piezosystem) was customized by an Arduino (Mega-2560) to control channel switching. Radiant exposures were calibrated before every experiment (SD within one channel:4.51×10^(-6) J/cm^2; SD between channels: 0.082J/cm^2) and ranged from 0.2 to 0.7J/cm^2 per pulse train.
Data acquisition
A single-shot echo planar imaging (EPI) sequence (TR=2000ms, TE=17ms, resolution=1×1 mm2, 0.5-mm slice thickness, FA=78°) was acquired in a 7T MR scanner (Siemens Healthcare) with customized 2mm and 3mm surface coils (Suzhou, China). After canonical preprocessing, Fourier coherence analysis and general linear model (GLM) were applied to extract significant activations.

The spatiotemporal feature of local responses depends on the channel distance
After validated the tip location (area 18/19) by anatomical registration, we examined the local spatiotemporal feature by alternating pair channels with three distances (0.2, 2, and 3mm). Different components of the hemodynamic response can be distinguished by adjusting the frequency of interest and extracting phase values. Both 2mm- and 3mm- pairs evoked separable channel-specific clusters, whereas 0.2mm-pair had mostly responses of both channels. The channel-specific tuning curves showed alternative negative BOLD dips, indicating the possible surround modulation process.

The global activations of pair channels show integration and segregation patterns in diverse areas
Significant clusters were extracted by GLM and further categorized by PCA and KNN. The overall network distribution (PMLS, AMLS, 21a, 20a, SVA, 5) was similar to previous anatomical evidences but had variations between patterns. Most ipsilateral area 19 responded to both channels, while only distal areas (area 7a and 5) had separated activations. It might indicate different integrative properties of receptive field along the cortical hierarchy.

We developed a multi-channel infrared-fMRI system and demonstrated its feasibility of producing mesoscale stimulus with varying channel spacing and mapping static networks of two separated points. The overall network with separable channel-specific clusters suggests the possible coordinated columnar structure across the whole brain. And the network variability across the hierarchy indicates that, similar to the structural architecture, a regularity of functional connectivity at the mesoscale might exist.

Invasive Stimulation Methods Other ¹

Connectivity (eg. functional, effective, structural) ²

Cortex

Cortical Columns

FUNCTIONAL MRI

OPTICAL

Vision