Uncovering the fast, directional signal flow through the human temporal pole during semantic processing.

The temporal pole (TP) plays a central role in semantic memory, yet its neural machinery is unknown. Intracerebral recordings in patients discriminating visually the gender or actions of an actor, yielded gender discrimination responses in the ventrolateral (VL) and tip (T) regions of right TP. Granger causality revealed task-specific signals travelling first forward from VL to T, under control of orbitofrontal cortex (OFC) and neighboring prefrontal cortex, and then, strongly, backwards from T to VL. Many other cortical regions provided inputs to or received outputs from both TP regions, often with longer delays, with ventral temporal afferents to VL signaling the actor's physical appearance. The TP response timing reflected more that of the connections to VL, controlled by OFC, than that of the input leads themselves. Thus, visual evidence for gender categories, collected by VL, activates category labels in T, and consequently, category features in VL, indicating a two-stage representation of semantic categories in TP.

From Observed Action Identity to Social Affordances.

Others' observed actions cause continuously changing retinal images, making it challenging to build neural representations of action identity. The monkey anterior intraparietal area (AIP) and its putative human homologue (phAIP) host neurons selective for observed manipulative actions (OMAs). The neuronal activity of both AIP and phAIP allows a stable readout of OMA identity across visual formats, but human neurons exhibit greater invariance and generalize from observed actions to action verbs. These properties stem from the convergence in AIP of superior temporal signals concerning: (i) observed body movements; and (ii) the changes in the body-object relationship. We propose that evolutionarily preserved mechanisms underlie the specification of observed-actions identity and the selection of motor responses afforded by them, thereby promoting social behavior.

Histological assessment of a chronically implanted cylindrically-shaped, polymer-based neural probe in the monkey.

Objective.Previous studies demonstrated the possibility to fabricate stereo-electroencephalography probes with high channel count and great design freedom, which incorporate macro-electrodes as well as micro-electrodes offering potential benefits for the pre-surgical evaluation of drug resistant epileptic patients. These new polyimide probes allowed to record local field potentials, multi- and single-unit activity (SUA) in the macaque monkey as early as 1 h after implantation, and yielded stable SUA for up to 26 d after implantation. The findings opened new perspectives for investigating mechanisms underlying focal epilepsy and its treatment, but before moving to possible human application, safety data are needed. In the present study we evaluate the tissue response of this new neural interface by assessing post-mortem the reaction of brain tissue along and around the probe implantation site.Approach.Three probes were implanted, independently, in the brain of one monkey (Macaca mulatta) at different times. We used specific immunostaining methods for visualizing neuronal cells and astrocytes, for measuring the extent of damage caused by the probe and for relating it with the implantation time.Main results.The size of the region where neurons cannot be detected did not exceed the size of the probe, indicating that a complete loss of neuronal cells is only present where the probe was physically positioned in the brain. Furthermore, around the probe shank, we observed a slightly reduced number of neurons within a radius of 50µm and a modest increase in the number of astrocytes within 100µm.Significance.In the light of previous electrophysiological findings, the present data suggest the potential usefulness and safety of this probe for human applications.

A shared neural substrate for action verbs and observed actions in human posterior parietal cortex.

High-level sensory and motor cortical areas are activated when processing the meaning of language, but it is unknown whether, and how, words share a neural substrate with corresponding sensorimotor representations. We recorded from single neurons in human posterior parietal cortex (PPC) while participants viewed action verbs and corresponding action videos from multiple views. We find that PPC neurons exhibit a common neural substrate for action verbs and observed actions. Further, videos were encoded with mixtures of invariant and idiosyncratic responses across views. Action verbs elicited selective responses from a fraction of these invariant and idiosyncratic neurons, without preference, thus associating with a statistical sampling of the diverse sensory representations related to the corresponding action concept. Controls indicated that the results are not the product of visual imagery or arbitrary learned associations. Our results suggest that language may activate the consolidated visual experience of the reader.

Multiple time courses of somatosensory responses in human cortex.

Here we show how anatomical and functional data recorded from patients undergoing stereo-EEG can be used to decompose the cortical processing following nerve stimulation in different stages characterized by specific topography and time course. Tibial, median and trigeminal nerves were stimulated in 96 patients, and the increase in gamma power was evaluated over 11878 cortical sites. All three nerve datasets exhibited similar clusters of time courses: phasic, delayed/prolonged and tonic, which differed in topography, temporal organization and degree of spatial overlap. Strong phasic responses of the three nerves followed the classical somatotopic organization of SI, with no overlap in either time or space. Delayed responses presented overlaps between pairs of body parts in both time and space, and were confined to the dorsal motor cortices. Finally, tonic responses occurred in the perisylvian region including posterior insular cortex and were evoked by the stimulation of all three nerves, lacking any spatial and temporal specificity. These data indicate that the somatosensory processing following nerve stimulation is a multi-stage hierarchical process common to all three nerves, with the different stages likely subserving different functions. While phasic responses represent the neural basis of tactile perception, multi-nerve tonic responses may represent the neural signature of processes sustaining the capacity to become aware of tactile stimuli.

Decomposing Tool-Action Observation: A Stereo-EEG Study.

A description of the spatiotemporal dynamics of human cortical activity during cognitive tasks is a fundamental goal of neuroscience. In the present study, we employed stereo-EEG in order to assess the neural activity during tool-action observation. We recorded from 49 epileptic patients (5502 leads) implanted with intracerebral electrodes, while they observed tool and hand actions. We deconstructed actions into 3 events-video onset, action onset, and tool-object contact-and assessed how different brain regions respond to these events. Video onset, with actions not yet visible, recruited only visual areas. Aligning the responses at action onset, yielded activity in the parietal-frontal manipulation circuit and, selectively for tool actions, in the left anterior supramarginal gyrus (aSMG). Finally, by aligning to the tool-object contact that signals the achievement of the main goal of the observed action, activations were found in SII and dorsal premotor cortex. In conclusion, our data show that during tool-action observation, in addition to the general action observation network there is a selective activation of aSMG, which exhibits internally different patterns of responsiveness. In addition, neural responses selective for the contact between the tool and the object were also observed.

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites.

OBJECTIVE: Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. APPROACH: Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 µm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. MAIN RESULTS: Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. SIGNIFICANCE: With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the brain of a monkey, which suggests the potential usefulness of this probe for human applications.

Stereoscopically Observing Manipulative Actions.

The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors "stimulus type" (action, static control, and dynamic control), "stereopsis" (present, absent) and "viewpoint" (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior.

A human homologue of monkey F5c.

Area F5c is a monkey premotor area housing mirror neurons which responds more strongly to grasping observation when the actor is visible than when only the actor's hand is visible. Here we used this characteristic fMRI signature of F5c in seven imaging experiments - one in macaque monkeys and six in humans - to identify the human homologue of monkey F5c. By presenting the two grasping actions (actor, hand) and varying the low level visual characteristics, we localized a putative human homologue of area F5c (phF5c) in the inferior part of precentral sulcus, bilaterally. In contrast to monkey F5c, phF5c is asymmetric, with a right-sided bias, and is activated more strongly during the observation of the later stages of grasping when the hand is close to the object. The latter characteristic might be related to the emergence, in humans, of the capacity to precisely copy motor acts performed by others, and thus imitation.

Fabrication and characterization of a high-resolution neural probe for stereoelectroencephalography and single neuron recording.

This paper reports on the design, fabrication, and characterization of neural probes for stereoelectroencephalography (SEEG). The probe specifically targets focal epilepsy as key application. However, probes of this type can also be used for the diagnosis and treatment of other neural dysfunctions such as Parkinson's disease or tremor, typically requiring deep brain probes. The probe fabrication, of which most processes are parallel batch processes, relies on a novel fabrication concept for rolling and gluing thin film polyimide sheets with integrated electrodes into permanent cylindrical shapes with diameters down to 800 µm. The SEEG probes, comprise several macro-electrodes designed to record local field potentials, and micro-electrodes positioned in-between, dedicated to monitoring single unit activity, with a total channel count of 32, despite the small diameter. While platinum micro-electrodes with a diameter of 35 µm have impedances of about 255 kΩ at 1 kHz, impedance values down to about 1.5 kΩ have been measured for the macro-electrodes. The devices have shown good compatibility with magnetic resonance imaging in a 9.4 T magnet, enabling the precise post-operative probe localization within the brain.

The overlap of the EBA and the MT/V5 cluster.

The extrastriate body area (EBA) is located in the lateral occipito-temporal cortex, in the vicinity of the motion-sensitive region hMT/V5+. To investigate the relationship of EBA to the recently mapped retinotopic areas of the MT/V5 cluster (Kolster et al., 2010), we evaluated the proportion of voxels responsive to the presentation of static human bodies (EBA voxels) in each of the four areas of the MT/V5 cluster and neighboring LO and phPIT areas. We evaluated this proportion as both a function of the number of voxels in a given area and the total number of voxels in a broader lateral occipito-temporal cortex (LOTC) ROI. We observed that each of the four retinotopic areas of the MT/V5 cluster includes substantial fractions of EBA voxels, in contrast to the LO and phPIT areas. This proportion was slightly greater in the right than left hemisphere, and did not depend on the control condition. While most EBA voxels in MT/V5 were only body-sensitive, those in pMSTv and pFST were also motion-sensitive. The main locus of EBA voxels outside the MT/V5 cluster was in the LOTC cortex just rostral to the MT/V5 cluster. Although this region contained more EBA voxels than the MT/V5 cluster, the proportion as a function of areal size was much reduced compared to the MT/V5 cluster. Our results show that EBA is not a single cortical area as EBA voxels are located in all four areas of the MT/V5 cluster, and that body-sensitivity is a key feature of the MT/V5 cluster, in keeping with its exquisite sensitivity to observed actions of others.

Retinotopic coding of extraretinal pursuit signals in early visual cortex.

During smooth pursuit, the image of the target is stabilized on the fovea, implying that speed judgments made during pursuit must rely on an extraretinal signal providing precise eye speed information. To characterize the introduction of such extraretinal signal into the human visual system, we performed a factorial, functional magnetic resonance imaging experiment, in which we manipulated the factor eye movement, with "fixation" and "pursuit" as levels, and the factor task, with "speed" and "form" judgments as levels. We hypothesized that the extraretinal speed signal is reflected as an interaction between speed judgments and pursuit. Random effects analysis yielded an interaction only in dorsal early visual cortex. Retinotopic mapping localized this interaction on the horizontal meridian (HM) between dorsal areas visual 2 and 3 (V2/V3) at 1-2 degrees azimuth. This corresponded to the position the pursuit target would have reached, if moving retinotopically, at the time of the subject's speed judgment. Because the 2 V2/V3 HMs are redundant, both may be involved in speed judgments, the ventral one involving judgments based on retinal motion and the dorsal one judgments requiring an internal signal. These results indicate that an extraretinal speed signal is injected into early visual cortex during pursuit.

The representation of tool use in humans and monkeys: common and uniquely human features.

Though other species of primates also use tools, humans appear unique in their capacity to understand the causal relationship between tools and the result of their use. In a comparative fMRI study, we scanned a large cohort of human volunteers and untrained monkeys, as well as two monkeys trained to use tools, while they observed hand actions and actions performed using simple tools. In both species, the observation of an action, regardless of how performed, activated occipitotemporal, intraparietal, and ventral premotor cortex, bilaterally. In humans, the observation of actions done with simple tools yielded an additional, specific activation of a rostral sector of the left inferior parietal lobule (IPL). This latter site was considered human-specific, as it was not observed in monkey IPL for any of the tool videos presented, even after monkeys had become proficient in using a rake or pliers through extensive training. In conclusion, while the observation of a grasping hand activated similar regions in humans and monkeys, an additional specific sector of IPL devoted to tool use has evolved in Homo sapiens, although tool-specific neurons might reside in the monkey grasping regions. These results shed new light on the changes of the hominid brain during evolution.

Specificity of regions processing biological motion.

Using functional magnetic resonance imaging and point light displays portraying six different human actions, we were able to show that several visual cortical regions, including human MT/V5 complex, posterior inferior temporal gyrus and superior temporal sulcus, are differentially active in the subtraction comparing biological motion to scrambled motion. Comparison of biological motion to three-dimensional rotation (of a human figure), articulated motion and translation suggests that human superior temporal sulcus activity reflects the action portrayed in the biological motion stimuli, whereas posterior inferior temporal gyrus responds to the figure and hMT/V5+ to the complex motion pattern present in biological motion stimuli. These results were confirmed with implied action stimuli.

Attentional responses to unattended stimuli in human parietal cortex.

Right-sided parietal lesions lead to lateralized attentional deficits which are most prominent with bilateral stimulation. We determined how an irrelevant stimulus in the unattended hemifield alters attentional responses in parietal cortex during unilateral orienting. A trial consisted of a central spatial cue, a delay and a test phase during which a grating was presented at 9 degrees eccentricity. Subjects had to discriminate the orientation of the grating. The unattended hemifield was either empty or contained a second, irrelevant grating. We carried out a series of functional MRI (fMRI) studies in 35 healthy volunteers (13 men and 22 women, aged between 19 and 30 years) as well as a behavioural and structural lesion mapping study in 17 right-hemispheric lesion patients, 11 of whom had neglect. In the patients with but not in those without neglect, the addition of a distractor in the unattended hemifield significantly impaired performance if attention was directed contralesionally but not if it was directed ipsilesionally. In the healthy volunteers, we discerned two functionally distinct areas along the posterior-anterior axis of the intraparietal sulcus (IPS). The posterior, descending IPS segment in both hemispheres showed attentional enhancement of responses during contralateral attentional orienting and was unaffected by the presence of an irrelevant stimulus in the ignored hemifield. In contrast, the right-sided horizontal IPS segment showed a strong attentional response when subjects oriented to a stimulus in the relevant hemifield and an irrelevant stimulus was simultaneously present in the ignored hemifield, compared with unilateral stimulation. This effect was independent of the direction of attention. The symmetrical left-sided horizontal IPS segment showed the highest responses under the same circumstances, in combination with a contralateral bias during unilateral stimulation conditions. None of the six patients without neglect had a lesion of the horizontal IPS segment. In four of the 11 neglect patients, the lesion overlapped with the horizontal IPS activity cluster and lay in close proximity to it in another four. The remaining three patients had a lesion at a distance from the parietal cortex. Our findings reconcile the role of the IPS in endogenous attentional control with the clinically significant interaction between direction of attention and bilateral stimulation in right parietal lesion patients. Functional imaging in neglect patients will be necessary to assess IPS function in those cases where the structural lesion spares the middle IPS segment.

Using functional magnetic resonance imaging to assess adaptation and size invariance of shape processing by humans and monkeys.

Functional magnetic resonance imaging in awake monkeys and humans was used to compare object adaptation in shape-sensitive regions of these two species under identical and different size conditions. Object adaptation was similar in humans and monkeys under both conditions. Neither species showed complete size invariance, in agreement with single-cell studies. Both the macaque inferotemporal (IT) complex and human lateral occipital complex (LOC) displayed an anteroposterior gradient in object adaptation and size invariance, with the more anterior regions being more adaptable and size invariant. The results provide additional evidence for the homology between the macaque IT cortex and human LOC but also add to the growing list of differences between human and monkey intraparietal sulcus regions.

Cerebral regions processing first- and higher-order motion in an opposed-direction discrimination task.

Using PET, we studied the processing of different types of motion in an opposed-direction discrimination task. We used first-order motion and two types of higher-order motion (presented as moving gratings with stripes defined by flickering texture and kinetic boundaries, respectively). In these experiments, we found that all types of motion activate a common set of cortical regions when comparing a direction discrimination task to a detection of the dimming of the fixation point. This set includes left hV3A, bilateral hMT/V5+ and regions in the middle occipital gyrus, bilateral activations in the posterior and anterior parts of the intraparietal sulcus, bilateral precentral gyrus, medial frontal cortex and regions in the cerebellum. No significant differences were observed between different types of motion, even at low statistical thresholds. From this we conclude that, under our experimental conditions, the same cerebral regions are involved in the processing of first-order and higher-order motion in an opposed-direction discrimination task.

Extracting 3D from motion: differences in human and monkey intraparietal cortex.

We compared three-dimensional structure-from-motion (3D-SFM) processing in awake monkeys and humans using functional magnetic resonance imaging. Occipital and midlevel extrastriate visual areas showed similar activation by 3D-SFM stimuli in both species. In contrast, intraparietal areas showed significant 3D-SFM activation in humans but not in monkeys. This suggests that human intraparietal cortex contains visuospatial processing areas that are not present in monkeys.

The neural substrate of orientation short-term memory and resistance to distractor items.

We used Positron Emission Tomography to map the neural substrate of human short-term memory for orientation, defined as retaining a single orientation in memory over a long delay, by comparing a successive discrimination task with a 6-s delay to the same task with a brief 0.3 s delay and to an identification control task. Short-term memory engaged the superior parietal lobe bilaterally, the middle occipital gyrus bilaterally and the left dorsolateral prefrontal cortex. In addition, we studied the resistance to a distractor item by comparing the successive discrimination task with long delay, with and without an intervening distractor stimulus. This manipulative process engaged left ventral premotor cortex and left dorsolateral prefrontal cortex. The activation of left dorsolateral prefrontal cortex is interpreted as reflecting co-ordination between task components. These results, combined with those of two previous studies using an identical reduction strategy, underscore the functional heterogeneity in the prefrontal cortex during short-term and working memory.

Visual motion processing investigated using contrast agent-enhanced fMRI in awake behaving monkeys.

To reduce the information gap between human neuroimaging and macaque physiology and anatomy, we mapped fMRI signals produced by moving and stationary stimuli (random dots or lines) in fixating monkeys. Functional sensitivity was increased by a factor of approximately 5 relative to the BOLD technique by injecting a contrast agent (monocrystalline iron oxide nanoparticle [MION]). Areas identified as motion sensitive included V2, V3, MT/V5, vMST, FST, VIP, and FEF (with moving dots), as well as V4, TE, LIP, and PIP (with random lines). These regions sensitive for moving dots are largely in agreement with monkey single unit data and (except for V3A) with human fMRI results. Moving lines activate some regions that have not been previously implicated in motion processing. Overall, the results clarify the relationship between the motion pathway and the dorsal stream in primates.