Parieto-frontal network in humans studied by cortico-cortical evoked potential

Abstract

Parieto-frontal network is essential for sensorimotor integration in various complex behaviors, and its disruption is associated with pathophysiology of apraxia and visuo-spatial disorders. Despite advances in knowledge regarding specialized cortical areas for various sensorimotor transformations, little is known about the underlying cortico-cortical connectivity in humans. We investigated inter-areal connections of the lateral parieto-frontal network in vivo by means of cortico-cortical evoked potentials (CCEPs). Six patients with epilepsy and one with brain tumor were studied. With the use of subdural electrodes implanted for presurgical evaluation, network configuration was investigated by tracking the connections from the parietal stimulus site to the frontal site where the maximum CCEP was recorded. It was characterized by (i) a near-to-near and distant-to-distant, mirror symmetric configuration across the central sulcus, (ii) preserved dorso-ventral organization (the inferior parietal lobule to the ventral premotor area and the superior parietal lobule to the dorsal premotor area), and (iii) projections to more than one frontal cortical sites in 56% of explored connections. These findings were also confirmed by the standardized parieto-frontal CCEP connectivity map constructed in reference to the Jülich cytoarchitectonic atlas in the MNI standard space. The present CCEP study provided an anatomical blueprint underlying the lateral parieto-frontal network and demonstrated a connectivity pattern similar to non-human primates in the newly developed inferior parietal lobule in humans.

Figure 1

Schematic diagram illustrating the coordinates for displaying the sites of stimulation and maximum CCEP response in the lateral parietal and frontal area. A: Distances from the central sulcus along the rostro‐caudal dimension are plotted for the parietal stimulus sites in the abscissa and for the frontal recording sites in the ordinate. The distance from the central sulcus was measured on a line drawn parallel to the AC‐PC line. B: Along the dorso‐ventral dimension, the parietal stimulus sites were measured from the intraparietal sulcus (IPS, dotted line) and the frontal recording sites were measured from the border between the dorsal and ventral premotor areas (broken line). CS, central sulcus; IFS, inferior frontal sulcus; IPS, intraparietal sulcus; PrCS, precentral sulcus; PMd, dorsal premotor area; PMv, ventral premotor area; SFS, superior frontal sulcus.

Figure 2

CCEPs recorded from the lateral premotor area in a representative case (Patient 1). CCEPs are plotted with subaverages (black and grey waveforms) in reference to the major sulci identified on 3D MRI (left lower corner of each figure). The vertical line corresponds to the time of single pulse stimulation. On 3D MRI, each parietal stimulus site is shown as a pair of interconnected black electrodes and the whole area covered by the recording electrodes is shaded white. Maximum response of the main CCEP field is plotted as a white circle, while that of smaller, separate CCEP fields, if present, as a black circle. CCEPs elicited by parietal stimulation of the same dorso‐ventral division are displayed in the same row (A‐C and D‐F, respectively). Note that the more caudal the parietal stimulus site is located, the more rostral the frontal maximum response site is located (i.e., more distant from CS). Other conventions are the same as for Figure 1 except for Sylv = Sylvian fissure.

Figure 3

Spatial relationship between the sites of stimulation and maximum CCEP response in the rostro‐caudal coordinate (A) and in the dorso‐ventral coordinate (B). In (A), the distance of the parietal stimulus sites (abscissa) and of the frontal response sites (ordinate) was measured from the central sulcus. In (B), the distance of the parietal stimulus sites (abscissa) was measured from the intraparietal sulcus (IPS) that is the border between SPL and IPL, and that of the frontal response sites (ordinate) was measured from the border between PMv and PMd (see text for more details). In terms of the distance from the stimulus and response sites, regression analysis showed a positive correlation between the sites of stimulation and maximum response both for the rostrocaudal (A) and dorsoventral (B) axes. Consistent with the mirror‐symmetric configuration across the central sulcus as shown in (A), a positive correlation was observed between the surface distance from the parietal stimulus sites to the frontal response sites and the N1 peak latency of the maximum response (C). Conventions are the same as for Figure 1.

Figure 4

Representative CCEP distribution indicative of multiple parieto‐frontal connections in Patient 2 (left) and 3 (right). Besides the predominant parieto‐frontal connection as judged by the prominent CCEP field (maximum response shown in white circle), additional connections were identified based on spatially separate fields (maximum response in black circle). Three separate connections were traced from the supramarginal gyrus to the ventral premotor area in Patient 2, while in Patient 3 stimulation of the postcentral gyrus revealed two separate connections to the adjacent precentral gyrus and ventral premotor area. Implanted hemispheres are shown on the same side for the sake of presentation by flipping the sides (Patient 2). See Figure 2 also for multiple connections in Patient 1. Conventions are the same as for Fig. 2.

Figure 5

Functional connections from the ventral parietal area to the premotor area revealed in the vicinity of astrocytoma (shadowed) located in the precentral gyrus in Patient 5. Stimulation at the supramarginal gyrus elicited CCEP ventral to the tumor at around the ventral ramus of the precentral sulcus. CCEP was not observed rostral to the tumor. Note the network configuration was similar to that seen in an epilepsy patient (e.g., Fig. 2E), in whom epileptic foci were away from the area of investigation. Conventions are the same as for Figure 2.

Figure 6

3D display of the stimulus and response sites in the MNI standard space. The stimulus and response sites are accumulated from all the patients and coregistered into the MNI standard space. All the stimulus and response sites are collapsed onto the left convexity for a display purpose. Stimulus sites are labeled and displayed together according to the Jülich cytoarchitectonic atlas on the same 3D brain (see the label in the left upper corner of each 3D brain). Regarding the frontal CCEP responses, a large sphere represents the location of the electrode showing the maximum CCEP response, i.e., the target site of the predominant connection from the stimulus site. A small sphere represents the electrode showing the maximum response of the additional, separate CCEP field, i.e., the target site of the additional divergent connection from the stimulus site. Note the location of the maximum and additional response sites may be overlapped within the lateral frontal area. Also note that the parieto‐frontal connections were not equally distributed along the central sulcus partly due to the less electrode coverage in the dorsal part than the ventral part. The lateral view of the 3D brain in the right lower corner indicates the parietal segmentations of the Jülich atlas where electrical stimuli were applied.