Neuroimaging PPS in the human brain

More recently, brain imaging techniques have been employed to unravel the anatomical underpinnings and functional mechanisms of human PPS as well as to emphasize the homologies with the electrophysiological findings in the monkey brain. Before introducing this issue, I wish highlighting that caution should be exerted when comparing studies in nonhuman and human primates, especially with respect to possible homology relations between areas in the association cortices.

Although brain activations have most often been reported in premotor and posterior parietal cortex (see Grivaz et al., 2017 for a meta-analysis, see also Figure 1.8), they also encompassed a larger network containing areas such as to the lateral occipital cortex (e.g. Makin et al., 2007), the parietal operculum (e.g. Tyll et al., 2013), the insula (e.g. Schaefer et al., 2012), the cerebellar cortex (e.g. Brozzoli et al., 2011), and the putamen (e.g. Gentile et al., 2011). Furthermore, while only few investigations examined neural correlates of the space surrounding the face, many of these studies have focused on the processing of hand-centred multisensory space.

Figure 1.8 Cortical regions involved in human PPS. Visualization of the results from one of the meta-analysis performed by Grivaz et al., (2017, see the paper for methodological details) with approximate location of cytoachitectonically and functionally defined regions (surrounded by white dashed lines). SPL superior parietal lobule, S1primary somatosensory cortex, IPL inferior parietal lobule, IPS intraparietal sulcus, PMv/d ventral/dorsal premotor cortex.

An early study disclosed an overlap between brain activity related to tactile stimuli delivered dorsal parieto-occipital sulcus (dPOS). In this study, subjects viewed looming and receding moving visual stimuli presented close to (from 13 to 17 cm), at an intermediate distance (from 33 to 43 cm) or far away from their face (from 73 to 95). In dPOS, blood oxygen level–dependent (BOLD) contrast increased for closer stimuli. Interestingly, this was not the case in the putative human VIP, which was activated by moving stimuli irrespectively of their distance from the face.

Similar cortical activations were displayed for the multisensory representation of the hand space. Makin and co-workers (2007) identified regions within IPS, lateral occipital complex (LOC), and PMv (ventral premotor cortex) showing significantly stronger activation in response to a ball approaching the subject's hand (near condition), compared to when the same stimulus moving away from the subject's hand (far condition, up to 70 cm from the hand). This differential near-far activation (i.e., within or outside the hand PPS) was further modulated by proprioceptive hand position signals as well as body-related visual information, compatible with coding in a hand-centred reference frame. When the hand was retracted, the preferential activation for the near vs. far condition disappeared, thereby indicating that these brain regions do not simply respond to low -level visual differences in the near and far ball conditions. Moreover, the selective activation for the near ball condition in IPS was also present when viewing a fake hand at the near location (even if the participant’s real hand was retracted), but was absent in LOC and PMv, if participants positioned their hand far from the location of the near stimulus.

Gentile and colleagues (2011) examined how these regions of the brain integrate visual and tactile stimuli delivered in the near hand space. While participants were in the scanner gazing at their hand, unisensory and multisensory stimuli were presented in the space immediately surrounding the hand. Superadditive, nonlinear BOLD responses during multisensory visual –tactile stimulation were observed in the cortex lining IPS, the insula, the dorsal premotor cortex, and the putamen, similarly to multisensory integration regions in animals (Avillac et al., 2005; Stein and Stanford, 2008). Such effects further depended on the spatial and temporal coherence between visuo-tactile inputs. In a second investigation the same authors (Gentile et al., 2013) joined tactile

stimulation of the participant’s real hand with the visual presentation of a virtual hand while manipulating spatial congruency (i.e., manipulating the direction of visual and tactile stimulation) and temporal synchrony of stimulation (i.e., with synchronous or asynchronous visuo-tactile stimulation). Activations in IPS, in ventral and dorsal PM, in LOC, and in the cerebellum varied as a function of the spatial and temporal congruency of visuo-tactile hand stimulation and were modulated by proprioceptive and visual signals related to the hand (similarly to Makin at al., 2007, see Figure 1.9).

Figure 1.9 Bar charts displaying the parameter estimates for all significant peaks of activation as a function of visuo-tactile temporal and spatial congruency. The coordinates are given in MNI space. For display purposes only, the anatomical location of the peak is indicated by a red circle on an activation map displayed on a coronal, sagittal, or axial section from the average structural image. L/R, left/right; PMv/d, ventral/dorsal premotor cortex; SMG, supramarginal gyrus. Adapted from Gentile et al., 2013.

In a series of neuroimaging studies, Brozzoli and colleagues used a BOLD adaptation parading for revealing neuronal population with a visual selective response for events occurring within the space near the hand. Compared to the standard neuroimaging approach, fMRI adaptation has the capacity to reveal population of neurons selective to specific stimulus features within a single voxel and, therefore, is perhaps more closely related to electrophysiological recordings (Grill-Spector et al., 2006). In the first study Brozzoli and colleagues (2011) found that IPS, the inferior parietal lobe (supramarginal gyrus), the dorsal and ventral PM, the cerebellum, and the putamen showed reduced activation (adaptation) to consecutive visual stimulation near the hand, but not for consecutive far stimuli, compatible with their role in multisensory perception within PPS. Indeed, these areas displayed a reduction in the BOLD response specifically when the object was repeatedly moved in

the near location with respect to the outstretched hand. By contrast, such significant reduction in the BOLD signal was not detected when the hand was retracted. Presenting the object in the far location did not produce a differential BOLD adaptation across the conditions, regardless of whether the hand was stretched out in view or retracted. A follow-up study of the same group (Brozzoli et al., 2012) exploited fMRI adaption to investigate whether regions in the intraparietal and premotor cortices remap the PPS of the hand as it is moved in space, that is to say whether the visual selectivity for the space near the hand is “anchored” to the hand. In line with the hypothesis, IPS and premotor areas showed adaptation effects when the stimulus was presented near the hand.

Critically, the effect followed the hand when it was moved across two positions in space. These results further revealed that inducing illusory ownership for a fake hand through prolonged synchronous visuo-tactile stimulation remaps the space around the fake hand as PPS, thus paralleling earlier neurophysiological findings in the monkey brain (Graziano et al., 2000).

Lastly, in keeping with previous studies, Ferri and colleagues (2015) identified a region of the premotor cortex that responded to tactile stimulation on the hand depending on the sound (near vs far) location. Interestingly, the extent of individuals’ PPS was not predicted by the level of neural activity (i.e., mean BOLD) elicited by near versus far stimulation. Rather, the inter-trial variability (i.e., the modulation of the standard deviation of the BOLD signal after stimulus onset) in the responses to far stimuli predicted the location of PPS extent at the individual level. Specifically, PPS was closer to the body in participants whose neural activity in the premotor cortex was more variable when the sound was presented in the far space. This result is especially interesting because it suggests that the processing of far stimuli is also critical in defining PPS and because it represents the first attempt to actually investigate the neural mechanisms explaining how PPS differs among individuals.

1.3.4 In a nutshell…

More recent research has corroborated, built on and extended the findings described through the electrophysiological approach. Neuropsychological observations support the claim that space is divided into separable regions. For example, deficits in the orienting of visuospatial attentio n in PPS have been reported after brain damage, while visuospatial orienting in extrapersonal space remains intact (or vice versa, e.g., Aimola et al., 2012; Halligan and Marshall, 1991, Cowey et al., 1994). The results of studies of cross-modal extinction also point to a similar conclusion.

Differences in the magnitude of cross-modal extinction have been observed in right brain-damaged

patients when visual stimuli are presented from either close to, or further away from, body parts (di Pellegrino et al., 1997). Moreover, PPS can be ‘extended’ by simply modulating the area that an individual can reach by means of, say, the use of a tool (Berti and Frassinetti, 2000; Farnè and Ladavas, 2000). A visual stimulus located in far space, when repeatedly reached with the tool, may be processed as if it is close(r) to the body and, thus, have an stronger influence over PPS multisensory interactions (Maravita and Iriki 2004; Di Pellegrino and Lavadas, 2015).

Similarly to what found in brain-damaged patients, a series of behavioural experiments in neurotypical humans has shown that the PPS representation in the healthy brain reflect the same principles of multisensory interaction. Typically these studies measure the strength of the effects induced by visual or auditory stimulation over the performance on tactile tasks to probe the layout of PPS (Spence el al., 2004b, Serino et al., 2007). A selective review of this literature reveals that the strength of multisensory interactions appears to decay as a function of the distance between visual (or auditory) and tactile information (Spence et al., 2004a), to follow a body part–centred frame of reference (Spence et al., 2004b), and to be remapped after the use of a tool that functionally extends action capabilities (Maravita et al., 2002; see also Holmes, 2012).

Functional brain imaging findings in healthy humans provide further support for the homologies between neurophysiological research and the neural bases of PPS in the human brain. A recent meta-analysis of functional neuroimaging studies identifies a bilateral PPS network, including superior parietal, temporo-parietal and ventral premotor regions, that nicely fits with the anatomical locations of the monkey visuo-tactile network (Grivaz et al., 2017). In particular, brain areas representing near-face and near-hand space in body-centred coordinates through visual and tactile maps have been reported in the anterior section of the intraparietal sulcus and in the ventral premotor cortex (Bremmer et al., 2001; Makin et al., 2007; Sereno and Huang 2006; Gentile et al., 2013). Furthermore, some studies have additionally identified the superior parietal occipital junction as a potential site for representing near-face and near-hand visual space (Gallivan et al.

2009; Quinlan and Culham 2007). This new line of research not only extends our current knowledge of the PPS neural network but may also guide further electrophysiological studies to come.