Four-dimensional map of direct effective connectivity from posterior visual areas

Abstract

Lower- and higher-order visual cortices in the posterior brain, ranging from the medial- and lateral-occipital to fusiform regions, are suggested to support visual object recognition, whereas the frontal eye field (FEF) plays a role in saccadic eye movements which optimize visual processing. Previous studies using electrophysiology and functional MRI techniques have reported that tasks requiring visual object recognition elicited cortical activation sequentially in the aforementioned posterior visual regions and FEFs. The present study aims to provide unique evidence of direct effective connectivity outgoing from the posterior visual regions by measuring the early component (10-50 ​ms) of cortico-cortical spectral responses (CCSRs) elicited by weak single-pulse direct cortical electrical stimulation. We studied 22 patients who underwent extraoperative intracranial EEG recording for clinical localization of seizure foci and functionally-important brain regions. We used animations to visualize the spatiotemporal dynamics of gamma band CCSRs elicited by stimulation of three different posterior visual regions. We quantified the strength of CCSR-defined effective connectivity between the lower- and higher-order posterior visual regions as well as from the posterior visual regions to the FEFs. We found that effective connectivity within the posterior visual regions was larger in the feedforward (i.e., lower-to higher-order) direction compared to the opposite direction. Specifically, connectivity from the medial-occipital region was largest to the lateral-occipital region, whereas that from the lateral-occipital region was largest to the fusiform region. Among the posterior visual regions, connectivity to the FEF was largest from the lateral-occipital region and the mean peak latency of CCSR propagation from the lateral-occipital region to FEF was 26 ​ms. Our invasive study of the human brain using a stimulation-based intervention supports the model that the posterior visual regions have direct cortico-cortical connectivity pathways in which neural activity is transferred preferentially from the lower-to higher-order areas. The human brain has direct cortico-cortical connectivity allowing a rapid transfer of neural activity from the lateral-occipital region to the FEF.

Keywords: Animation movie; Cortico-cortical evoked potentials (CCEPs); Intracranial electroencephalography (iEEG); Neuronal propagation; Pediatric epilepsy surgery; Ventral visual pathways.

Figure 1.. Visual object recognition-related cortical activations which motivated the hypotheses tested in the present study.

(A) Our previous iEEG study of 79 patients with focal epilepsy (Nakai et al., 2019) demonstrated that picture naming-related high-gamma augmentation involved the medial- and lateral-occipital regions bilaterally at 70 ms after the stimulus onset. (B) Sustained high-gamma augmentation subsequently involved the fusiform regions bilaterally in addition to the medial- and lateral-occipital regions. These findings motivated our hypothesis that the posterior visual regions would have established the cortico-cortical connectivity capable of directly transfer neuronal activity in a feedforward direction.

Figure 2.. Stimulus and recording electrode sites.

The extent of stimulus sites in the (A) medial-occipital (39 stimulus pairs from 14 patients), (B) lateral-occipital (46 pairs from 18 patients), and (C) fusiform regions (41 pairs from 20 patients). The extent of sites recording CCSRs propagated from the (D) medial-occipital (3944 sites), (E) lateral-occipital (4782 sites), and (F) fusiform regions (4163 sites). Note that electrode sites within 1 cm from the stimulus site were excluded from a given CCSR analysis to minimize the potential effects of stimulation artifacts on the iEEG signals (Swann et al., 2012). Areas marked in red color had iEEG data derived from at least six patients.

Figure 3.. Regions defined as the frontal eye fields in the present study.

Regions marked in red color were defined as the frontal eye fields (FEFs) based on the results of electrical stimulation mapping (ESM) as previously employed in 84 patients with focal epilepsy (Nakai et al., 2017).

Figure 4.. Time-frequency analysis to measure early gamma band CCSRs.

(A) Cortico-cortical evoked potentials (CCEPs) elicited by stimulation of a fusiform pair and recorded at an inferior-temporal lobe site. The initial negative deflection (N1) denoted by an arrowhead is time-locked with gamma band augmentation on CCSRs. (B) The time-frequency plot shows the temporal dynamics of iEEG amplitude changes at the same site. Augmentation of gamma band activity at 30–40 Hz took place maximally around 40 ms after stimulus onset. Augmentation of high-gamma activity at >50 Hz took place maximally around the time zero and is attributed to the unwanted effect of a stimulus artifact. +100% indicates that the timing of maximum amplitude augmentation within a given spectral frequency band within a period between −10 and 50 ms relative to stimulus onset. Broken line: The amplitude changes at 30–40 Hz between 10–50 ms poststimulus were used for the measurement of CCSR-based effective connectivity in the present study.

Figure 5.. The spatiotemporal dynamics of CCSRs elicited by stimulation of medial-occipital sites.

The video snapshots demonstrate the percent change of early gamma band activity relative to the baseline period (100–150 ms prior to the single-pulse stimulation). The extent of stimulus sites is presented in Figure 2A, whereas that of recording sites in Figure 2D. Note that the snapshots demonstrate the CCSRs on the hemisphere ipsilateral to the stimulus site.

Figure 6.. The spatiotemporal dynamics of CCSRs elicited by stimulation of adjacent lateral-occipital sites.

The video snapshots demonstrate the percent change of early gamma band activity relative to the baseline period (100–150 ms prior to the single-pulse stimulation). The extent of stimulus sites is presented in Figure 2B, whereas that of recording sites in Figure 2E. Note that the snapshots demonstrate the CCSRs on the hemisphere ipsilateral to the stimulus site.

Figure 7.. The spatiotemporal dynamics of CCSRs elicited by stimulation of fusiform sites.

The video snapshots demonstrate the percent change of early gamma band activity relative to the baseline period (100–150 ms prior to the single-pulse stimulation). The extent of stimulus sites is presented in Figure 2C, whereas that of recording sites in Figure 2F. Note that the snapshots demonstrate the CCSRs on the hemisphere ipsilateral to the stimulus site.