Neuronal substrates of gaze following in monkeys

Human and non-human primates follow the gaze of their respective conspecific to identify objects of common interest. Whereas humans rely on eye-gaze for such purposes, monkeys preferentially use head-gaze information. Functional magnetic resonance imaging (fMRI) studies have delineated an area in the human superior temporal sulcus (STS), which is specifically activated when subjects actively follow the eye-gaze of others. Similarly, using fMRI, we have identified an analogous region in the monkey's middle STS responding to gaze following. Hence, although humans and monkeys might rely on different directional cues guiding their attention, they seem to deploy a similar and possibly homologous cortical area to follow the gaze of a conspecific. Our results support the idea that the eyes developed a new social function in human evolution, most likely to support cooperative mutual social interactions building on a phylogenetically old STS module for the processing of head cues.     

The Mona Lisa effect: Neural correlates of centered and off‐centered gaze

The Mona Lisa effect describes the phenomenon when the eyes of a portrait appear to look at the observer regardless of the observer's position. Recently, the metaphor of a cone of gaze has been proposed to describe the range of gaze directions within which a person feels looked at. The width of the gaze cone is about five degrees of visual angle to either side of a given gaze direction. We used functional magnetic resonance imaging to investigate how the brain regions involved in gaze direction discrimination would differ between centered and decentered presentation positions of a portrait exhibiting eye contact. Subjects observed a given portrait's eyes. By presenting portraits with varying gaze directions—eye contact (0°), gaze at the edge of the gaze cone (5°), and clearly averted gaze (10°), we revealed that brain response to gaze at the edge of the gaze cone was similar to that produced by eye contact and different from that produced by averted gaze. Right fusiform gyrus and right superior temporal sulcus showed stronger activation when the gaze was averted as compared to eye contact. Gaze sensitive areas, however, were not affected by the portrait's presentation location. In sum, although the brain clearly distinguishes averted from centered gaze, a substantial change of vantage point does not alter neural activity, thus providing a possible explanation why the feeling of eye contact is upheld even in decentered stimulus positions. Hum Brain Mapp 36:619–632, 2015. © 2014 Wiley Periodicals, Inc .     

Human MT/V5 activity on viewing eye gaze changes in others: A magnetoencephalographic study

The present study used magnetoencephalography (MEG) to investigate human MT/V5 activity when observing changes in eye gaze. Subjects viewed a face in which the eyes changed to look either directly at (BACK) or away from (AWAY) the subject in a series of apparent motion conditions. BACK involved 2 directions, from left to center (LC) and from right to center (RC). Likewise, AWAY involved 2 directions, from center to left (CL) and from center to right (CR). A clear MEG component, 1M, was elicited with all eye gaze changes. Mean peak latency was 157 ms and was unaffected by stimulus condition. The equivalent current dipole (ECD) was localized to human MT/V5. Two main effects were noted: (1) ECD moment was significantly larger for BACK than for AWAY; and (2) 1M ECD locations were more posterior for AWAY than for BACK. Gaze direction, with LEFT involving CL and RC and RIGHT involving CR and LC, showed no significant effects. These data indicate that MT/V5 responds to gaze direction rather than eye position, and that eye movements directed at the viewer elicit the strongest effects. Processing of gaze change is NOT sensitive to eye direction per se but rather is modulated by eye gaze relative to the viewer.     

Brain activation evoked by perception of gaze shifts: the influence of context

Prior studies from our laboratory [Journal of Neuroscience 18 (1998) 2188; Cognitive Neuropsychology 17 (2000) 221] have demonstrated that discrete regions of the superior temporal sulcus (STS) are activated when a subject views a face in which the eyes shift their gaze. Here we investigated the degree to which activity in the STS and other brain regions is modulated by the context of the perceived gaze shift; that is, when the shift correctly or incorrectly acquires a visual target. Fifteen subjects participated in an event-related functional magnetic resonance imaging experiment in which they viewed an animated face that remained present throughout each run. On each of 21 trials within each run, a small checkerboard appeared and flickered at one of six locations within the character's visual field. On "correct" trials, the character shifted its gaze towards the checkerboard after a delay of 1 or 3s. On "incorrect" trials, the character shifted its gaze towards empty space after the same delays. On "no shift" trials, the character's eyes did not move. Significantly larger hemodynamic responses (HDR) were evoked by gaze shifts compared to no gaze shifts in primarily right hemisphere STS. The gaze-evoked HDR was significantly delayed in peak amplitude for 3s compared to 1s shifts. For 1s shifts, a strong effect of context was observed in which errors evoked a HDR with extended duration. Although this study focused upon STS, similar effects were also observed in the intraparietal sulcus and fusiform gyrus.     

GABA metabolism and its role in gamma‐band oscillatory activity during auditory processing: An MRS and EEG study

Gamma‐aminobutyric acid (GABA) and glutamate are believed to have inhibitory and exhibitory neuromodulatory effects that regulate the brain's response to sensory perception. Furthermore, frequency‐specific synchronization of neuronal excitability within the gamma band (30–80 Hz) is attributable to a homeostatic balance between excitation and inhibition. However, our understanding of the physiological mechanism underlying gamma rhythms is based on animal models. Investigations of the relationship between GABA concentrations, glutamate concentrations, and gamma band activity in humans were mostly restricted to the visual cortex and are conflicting. Here, we performed a multimodal imaging study combining magnetic resonance spectroscopy (MRS) with electroencephalography (EEG) in the auditory cortex. In 14 healthy subjects, we investigated the impact of individual differences in GABA and glutamate concentration on gamma band response (GBR) following auditory stimulus presentation. We explored the effects of bulk GABA on the GBR across frequency (30–200 Hz) and time (?200 to 600 ms) and found no significant relationship. Furthermore, no correlations were found between gamma peak frequency or power measures and metabolite concentrations (GABA, glutamate, and GABA/glutamate ratio). These findings suggest that, according to MRS measurements, and given the auditory stimuli used in this study, GABA and glutamate concentrations are unlikely to play a significant role in the inhibitory and excitatory drive in the generation of gamma band activity in the auditory cortex. Hum Brain Mapp 38:3975–3987, 2017 . © 2017 Wiley Periodicals, Inc.     

A quantitative study of gamma-band activity in human intracranial recordings triggered by visual stimuli

This paper studies gamma-band responses from two implanted epileptic patients during a simple visual discrimination task. Our main aim was to ascertain, in a reliable manner, whether evoked (stimulus-locked) and induced (triggered by, but not locked to, stimuli) responses are present in intracranial recordings. For this purpose, we introduce new methods adapted to detect the presence of gamma responses at this level of recording, intermediary between EEG-scalp and unicellular responses. The analysis relies on a trial-by-trial time-frequency analysis and on the use of surrogate data for statistical testing. We report that visual stimulation reliably elicits evoked and induced responses in human intracranial recordings. Induced intracranial gamma activity is significantly present in short oscillatory bursts (a few cycles) following visual stimulation. These responses are highly variable from trial to trial, beginning after 200 ms and lasting up to 500 ms. In contrast, intracranial-evoked gamma responses concentrate around 100 ms latencies corresponding to evoked responses observed on the scalp. We discuss our results in relation to scalp gamma response in a similar protocol [Tallon-Baudry et al. (1996) J. Neurosci., 16, 4240-4249] and draw some conclusions for bridging the gap between gamma oscillations observed on the scalp surface and their possible cortical sources.     

Social perception in the infant brain: gamma oscillatory activity in response to eye gaze

Gamma band oscillatory brain activity was measured to examinethe neural basis of 4-month-old infants’ perception ofeye gaze direction. Infants were presented with photographicimages of upright and inverted female faces directing theirgaze towards them or to the side. Direct gaze compared to avertedgaze in upright faces elicited increased early evoked gammaactivity at occipital channels indicating enhanced neural processingduring the earliest steps of face encoding. Direct gaze alsoelicited a later induced gamma burst over right prefrontal channels,suggesting that eye contact detection might recruit very similarcortical regions as in adults. An induced gamma burst in responseto averted gaze was observed over right posterior regions, whichmight reflect neural processes associated with shifting spatialattention. Inverted faces did not produce such effects, confirmingthat the gamma band oscillations observed in response to gazedirection are specific to upright faces. These data demonstratethe use of gamma band oscillations in examining the developmentof social perception and suggest an early specialization ofbrain regions known to process eye gaze.     

Specifying the brain anatomy underlying temporo‐parietal junction activations for theory of mind: A review using probabilistic atlases from different imaging modalities

In this quantitative review, we specified the anatomical basis of brain activity reported in the Temporo‐Parietal Junction (TPJ) in Theory of Mind (ToM) research. Using probabilistic brain atlases, we labeled TPJ peak coordinates reported in the literature. This was carried out for four different atlas modalities: (i) gyral‐parcellation, (ii) sulco‐gyral parcellation, (iii) cytoarchitectonic parcellation and (iv) connectivity‐based parcellation. In addition, our review distinguished between two ToM task types (false belief and social animations) and a nonsocial task (attention reorienting). We estimated the mean probabilities of activation for each atlas label, and found that for all three task types part of TPJ activations fell into the same areas: (i) Angular Gyrus (AG) and Lateral Occpital Cortex (LOC) in terms of a gyral atlas, (ii) AG and Superior Temporal Sulcus (STS) in terms of a sulco‐gyral atlas, (iii) areas PGa and PGp in terms of cytoarchitecture and (iv) area TPJp in terms of a connectivity‐based parcellation atlas. Beside these commonalities, we also found that individual task types showed preferential activation for particular labels. Main findings for the right hemisphere were preferential activation for false belief tasks in AG/PGa, and in Supramarginal Gyrus (SMG)/PFm for attention reorienting. Social animations showed strongest selective activation in the left hemisphere, specifically in left Middle Temporal Gyrus (MTG). We discuss how our results (i.e., identified atlas structures) can provide a new reference for describing future findings, with the aim to integrate different labels and terminologies used for studying brain activity around the TPJ. Hum Brain Mapp 38:4788–4805, 2017. © 2017 Wiley Periodicals, Inc.     

Time course of superior temporal sulcus activity in response to eye gaze: a combined fMRI and MEG study

The human superior temporal sulcus (STS) has been suggested to be involved in gaze processing, but temporal data regarding this issue are lacking. We investigated this topic by combining fMRI and MEG in four normal subjects. Photographs of faces with either averted or straight eye gazes were presented and subjects passively viewed the stimuli. First, we analyzed the brain areas involved using fMRI. A group analysis revealed activation of the STS for averted compared to straight gazes, which was confirmed in all subjects. We then measured brain activity using MEG, and conducted a 3D spatial filter analysis. The STS showed higher activity in response to averted versus straight gazes during the 150–200 ms period, peaking at around 170 ms, after stimulus onset. In contrast, the fusiform gyrus, which was detected by the main effect of stimulus presentations in fMRI analysis, exhibited comparable activity across straight and averted gazes at about 170 ms. These results indicate involvement of the human STS in rapid processing of the eye gaze of another individual.     

Differences in cortical coding of heat evoked pain beyond the perceived intensity: An fMRI and EEG study

Imaging studies have identified a wide network of brain areas activated by nociceptive stimuli and revealed differences in somatotopic representation of highly distinct stimulation sites (foot vs. hand) in the primary (S1) and secondary (S2) somatosensory cortices. Somatotopic organization between adjacent dermatomes and differences in cortical coding of similarly perceived nociceptive stimulation are less well studied. Here, cortical processing following contact heat nociceptive stimulation of cervical (C4, C6, and C8) and trunk (T10) dermatomes were recorded in 20 healthy subjects using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Stimulation of T10 compared with the C6 and C8 revealed significant higher response intensity in the left S1 (contralateral) and the right S2 (ipsilateral) even when the perceived pain was equal between stimulation sites. Accordingly, contact heat evoked potentials following stimulation of T10 showed significantly higher N2P2 amplitudes compared to C6 and C8. Adjacent dermatomes did not reveal a distinct somatotopical representation. Within the assessed cervical and trunk dermatomes, nociceptive cortical processing to heat differs significantly in magnitude even when controlling for pain perception. This study provides evidence that controlling for pain perception is not sufficient to compare directly the magnitude of cortical processing [blood oxygen level dependence (BOLD) response and amplitude of evoked potentials] between body sites. Hum Brain Mapp 35:1379–1389, 2014. © 2013 Wiley Periodicals, Inc.     

Auditory stroop and absolute pitch: An fMRI study

To date, the underlying cognitive and neural mechanisms of absolute pitch (AP) have remained elusive. In the present fMRI study, we investigated verbal and tonal perception and working memory in musicians with and without absolute pitch. Stimuli were sine wave tones and syllables (names of the scale tones) presented simultaneously. Participants listened to sequences of five stimuli, and then rehearsed internally either the syllables or the tones. Finally participants indicated whether a test stimulus had been presented during the sequence. For an auditory stroop task, half of the tonal sequences were congruent (frequencies of tones corresponded to syllables which were the names of the scale tones) and half were incongruent (frequencies of tones did not correspond to syllables). Results indicate that first, verbal and tonal perception overlap strongly in the left superior temporal gyrus/sulcus (STG/STS) in AP musicians only. Second, AP is associated with the categorical perception of tones. Third, the left STG/STS is activated in AP musicians only for the detection of verbal‐tonal incongruencies in the auditory stroop task. Finally, verbal labelling of tones in AP musicians seems to be automatic. Overall, a unique feature of AP appears to be the similarity between verbal and tonal perception. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Brain regions involved in human movement perception: a quantitative voxel-based meta-analysis

Face, hands, and body movements are powerful signals essential for social interactions. In the last 2 decades, a large number of brain imaging studies have explored the neural correlates of the perception of these signals. Formal synthesis is crucially needed, however, to extract the key circuits involved in human motion perception across the variety of paradigms and stimuli that have been used. Here, we used the activation likelihood estimation (ALE) meta-analysis approach with random effect analysis. We performed meta-analyses on three classes of biological motion: movement of the whole body, hands, and face. Additional analyses of studies of static faces or body stimuli and sub-analyses grouping experiments as a function of their control stimuli or task employed allowed us to identify main effects of movements and forms perception, as well as effects of task demand. In addition to specific features, all conditions showed convergence in occipito-temporal and fronto-parietal regions, but with different peak location and extent. The conjunction of the three ALE maps revealed convergence in all categories in a region of the right posterior superior temporal sulcus as well as in a bilateral region at the junction between middle temporal and lateral occipital gyri. Activation in these regions was not a function of attentional demand and was significant also when controlling for non-specific motion perception. This quantitative synthesis points towards a special role for posterior superior temporal sulcus for integrating human movement percept, and supports a specific representation for body parts in middle temporal, fusiform, precentral, and parietal areas.     

Focal cortical high-frequency oscillations trigger epileptic spasms: Confirmation by digital video subdural EEG

OBJECTIVE: To localize high-frequency oscillations (HFOs) on the cortex during epileptic spasms using video subdural EEG and Multiple Band Frequency Analysis (MBFA). METHODS: Using video subdural EEG sampled at 1 kHz, we studied a 14-year-old boy with asymmetric epileptic spasms of possible left frontal origin. We identified HFOs, then analyzed and localized their distributions by MBFA. We correlated HFO distribution to clinical spasm intensity. RESULTS: Ictal subdural EEG recorded HFOs at 60-150 Hz lasting 0.3-4 s. MBFA showed extensive but noncontiguous distribution of HFOs predominantly over the left frontal and temporal regions. HFOs began and became quasiperiodic before manifestation of clinical spasms. As clinical spasms intensified, HFOs persisted in regions where they initiated subclinically but were of higher frequency and greater power than HFOs in other regions. We performed cortical resections over the left frontal and temporal regions with predominant HFOs. Six months after surgery, the patient remained seizure free. CONCLUSIONS: HFOs were present over the ictal onset zone during epileptic spasms. Periodic spasms in this patient had the characteristics of partial seizures. SIGNIFICANCE: We show that HFOs occurred over the cerebral cortex during epileptic spasms, and we suggest that these focal cortical HFOs triggered the spasms.     

The attracting power of the gaze of politicians is modulated by the personality and ideological attitude of their voters: a functional magnetic resonance imaging study

Observing someone rapidly moving their eyes induces reflexive shifts of overt and covert attention in the onlooker. Previous studies have shown that this process can be modulated by the onlooker's personality, as well as by the social features of the person depicted in the cued face. Here, we investigated whether an individual's preference for social dominance orientation, in‐group perceived similarity (PS), and political affiliation of the cued‐face modulated neural activity within specific nodes of the social attention network. During functional magnetic resonance imaging, participants were requested to perform a gaze‐following task to investigate whether the directional gaze of various Italian political personages might influence the oculomotor behaviour of in‐group or out‐group voters. After scanning, we acquired measures of PS in personality traits with each political personage and preference for social dominance orientation. Behavioural data showed that higher gaze interference for in‐group than out‐group political personages was predicted by a higher preference for social hierarchy. Higher blood oxygenation level‐dependent activity in incongruent vs. congruent conditions was found in areas associated with orienting to socially salient events and monitoring response conflict, namely the left frontal eye field, right supramarginal gyrus, mid‐cingulate cortex and left anterior insula. Interestingly, higher ratings of PS with the in‐group and less preference for social hierarchy predicted increased activity in the left frontal eye field during distracting gaze movements of in‐group as compared with out‐group political personages. Our results suggest that neural activity in the social orienting circuit is modulated by higher‐order social dimensions, such as in‐group PS and individual differences in ideological attitudes.     

Transient human cortical responses during the observation of simple finger movements: a high-resolution EEG study

High-resolution event-related potentials (ERPs) were used to model the hemispherical representation of the transient cortical responses relating to the observation of movement during execution (right or left aimless finger extension). Subjects were seated in front of the observed person and looked at both their own and the observer's hand to receive similar visual feedback during the two conditions. In a visual control condition, a diode light moved at the observed person's hand. A first potential accompanying the movement execution peaked at about +110 msec over the contralateral somatomotor areas. It was followed by a potential (P300) peaking at about +350 msec over the central midline. In contrast, the potentials accompanying the movement observation peaked later over parietal-occipital other than somatomotor areas (N200 peak, +200 msec; P300 peak, +400 msec). Notably, the N200 was maximum in left parietal area whereas the P300 was maximum in right parietal area regardless the side of the movement. They markedly differed by the potentials following the displacement of the diode light. These results suggest a rapid time evolution (approximately 200-400 msec) of the cortical responses characterizing the observation of aimless movements (as opposite to grasping or handling). The execution of these movements would mainly involve somatomotor cortical responses and would be scarcely founded on the visual feedback. In contrast, the observation of the same movements carried out by others would require dynamical responses of somatomotor and parietal-occipital areas (especially of the right hemisphere), possibly for a stringent visuospatial analysis of the motor event.     

Cortical projections to the nucleus of the optic tract and dorsal terminal nucleus and to the dorsolateral pontine nucleus in macaques: a dual retrograde tracing study

The nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN) along with the dorsolateral pontine nucleus (DLPN) have been shown to play a role in controlling slow eye movements and in maintaining stable vision during head movements. Both nuclei are known to receive cortical input from striate and extrastriate cortex. To determine to what degree this cortical input arises from the same areas and potentially from the same individual neurons, we placed different retrograde tracers into the NOT-DTN and the DLPN. In the ipsilateral cortical hemisphere the two projections mainly overlapped in the posterior part of the superior temporal sulcus (STS) comprising the middle temporal area (MT), the middle superior temporal area (MST), and the visual area in the fundus of the STS (FST) and the surrounding cortex. In these areas, neurons projecting to the NOT-DTN or the DLPN were closely intermingled. Nevertheless, only 3-11% of the labeled neurons in MT and MST were double-labeled in our various cases. These results indicate that the cortical input to the NOT-DTN and DLPN arises from largely separate neuronal subpopulations in the motion sensitive areas in the posterior STS. Only a small percentage of the projection neurons bifurcate to supply both targets. These findings are discussed in relation to the optokinetic and the smooth pursuit system.     

Human brain oscillatory activity phase-locked to painful electrical stimulations: a multi-channel EEG study

The main aims of this study were 1) a fine spatial analysis of electroencephalographic (EEG) oscillations after galvanic painful stimulation (nonpainful stimulation as a reference) and 2) a comparative evaluation of phase- and nonphase-locked component of these EEG oscillations. Preliminary surface Laplacian transformation of EEG data (31 channels) reduced head volume conductor effects. EEG phase values were computed by FFT analysis and the statistical evaluation of these values was performed by Rayleigh test (P < 0.05). About 50% of the EEG single trials presented statistically the same FFT phase value of the evoked EEG oscillations (phase-locked single trials), indicating a preponderant phase-locked compared to nonphase-locked component. The remaining single trials showed random FFT phase values (nonphase-locked single trials), indicating a preponderant nonphase-locked compared to phase-locked component. Compared to nonpainful stimulation, painful stimulation increased phase-locked theta to gamma band responses in the contralateral hemisphere and decreased the phase-locked beta band response in the ipsilateral hemisphere. Furthermore, nonphase-locked alpha band response decreased in the ipsilateral fronto-central area. In conclusion, both decreased and increased EEG oscillatory responses to galvanic painful stimulation would occur in parallel in different cortical regions and in the phase- and nonphase-locked EEG data sets. This enriches the actual debate on the mapping of event-related oscillatory activity of human brain.     

Voluntary tic suppression and the normalization of motor cortical beta power in Gilles de la Tourette syndrome: an EEG study

Gilles de la Tourette syndrome (GTS) is a neurological condition characterized by motor and vocal tics. Previous studies suggested that this syndrome is associated with abnormal sensorimotor cortex activity at rest, as well as during the execution of voluntary movements. It has been hypothesized that this abnormality might be interpreted as a form of increased tonic inhibition, probably to suppress tics; however, this hypothesis has not been tested so far. The present study was designed to formally test how voluntary tic suppression in GTS influences the activity of the sensorimotor cortex during the execution of a motor task. We used EEG to record neural activity over the contralateral sensorimotor cortex during a finger movement task in adult GTS patients, in both free ticcing and tic suppression conditions; these data were then compared with those collected during the same task in age‐matched healthy subjects. We focused on the levels of activity in the beta frequency band, which is typically associated with the activation of the motor system, during three different phases: a pre‐movement, a movement, and a post‐movement phase. GTS patients showed decreased levels of beta modulation with respect to the healthy controls, during the execution of the task; however, this abnormal pattern returned to be normal when they were explicitly asked to suppress their tics while moving. This is the first demonstration that voluntary tic suppression in GTS operates through the normalization of the EEG rhythm in the beta frequency range during the execution of a voluntary finger movement.     

Hand somatosensory subcortical and cortical sources assessed by functional source separation: an EEG study

We propose a novel electroencephalographic application of a recently developed cerebral source extraction method (Functional Source Separation, FSS), which starts from extracranial signals and adds a functional constraint to the cost function of a basic independent component analysis model without requiring solutions to be independent. Five ad-hoc functional constraints were used to extract the activity reflecting the temporal sequence of sensory information processing along the somatosensory pathway in response to the separate left and right median nerve galvanic stimulation. Constraints required only the maximization of the responsiveness at specific latencies following sensory stimulation, without taking into account that any frequency or spatial information. After source extraction, the reliability of identified FS was assessed based on the position of single dipoles fitted on its retroprojected signals and on a discrepancy measure. The FS positions were consistent with previously reported data (two early subcortical sources localized in the brain stem and thalamus, the three later sources in cortical areas), leaving negligible residual activity at the corresponding latencies. The high-frequency component of the oscillatory activity (HFO) of the extracted component was analyzed. The integrity of the low amplitude HFOs was preserved for each FS. On the basis of our data, we suggest that FSS can be an effective tool to investigate the HFO behavior of the different neuronal pools, recruited at successive times after median nerve galvanic stimulation. As FSs are reconstructed along the entire experimental session, directional and dynamic HFO synchronization phenomena can be studied.