Effective connectivity within the neural system for object-directed action representation during aware and unaware tool processing

Previous work using single-cell recordings in monkeys and neuro-imaging studies in humans has shown that perceiving an object or imaging the action associated with the object recruits the same brain regions in the ventral premotor cortex as performing an action with the object. We used functional magnetic resonance imaging (fMRI) for examining whether similar brain regions are also activated while maintaining information about manipulable objects in working memory. Holding information about manipulable objects in working memory activated the left ventral premotor cortex and the left inferior frontal gyrus (Broca's area). Conversely, non-manipulable objects to be held in working memory co-activated Broca's area and the left angular gyrus. When contrasted directly, manipulable relative to non-manipulable objects activated the left ventral premotor cortex and the anterior intraparietal sulcus, a circuitry that is assumed to mediate the transformation of movement-relevant object properties into hand actions. These results indicate that visual working memory for manipulable objects is based on motor programmes associated with their use. Similar to speech motor programmes in verbal memory tasks, hand motor programmes may allow the maintenance of objects in working memory over short intervals.

How do airborne plumes of molecules docking on olfactory receptors emerge as conscious odors in the brain? How are they interpreted in space, time, and biological meaning? And how do they lead to fast and adaptive decisions and actions? In general, conscious (reportable) perception supports neural adaptation to novelty, judgments of self-relevance, and voluntary decision-making. Conscious processes have a number of established properties that are markedly different from unconscious ones (Seth et al., 2005). A growing experimental literature has explored conscious perception with a wide array of recording techniques. Similarly, conscious olfaction “as such” can be studied by comparing novel vs. habituated odors, attended vs. unattended ones, and rivaling olfactory percepts, comparable to visual rivalry (Stevenson and Mahmut, 2013). State comparisons of odor processing during waking vs. sleep, general anesthesia, and impaired consciousness are also important. Neural activity underlying conscious percepts should follow the known psychophysical features of the stimulus. A specific conscious odor should correspond to a specific trajectory in the olfactory perceptual space derived from psychophysical stimulus matching and discrimination (e.g., Berglund et al., 1973; Koulakov et al., 2011). Global workspace theory (GWT) has been used as a framework for experimental studies of conscious brain processes for more than two decades, leading to a family of related models and experimental predictions. GWT begins by analyzing a reliable set of properties of conscious events (Baars, 1988, 2002). For example, while conscious perception shows limited momentary capacity, it also supports access to non-conscious functions, like memory, executive control, and automatic skills (Baars and Franklin, 2003). By comparison, unconscious stimuli do not afford such very widespread access to unconscious brain capacities. In general terms, a global workspace (GW) is a functional hub of binding and propagation in a population of loosely coupled signaling elements, such as neurons (Izhikevich, 1999). A GW is commonly compared to the stage of a theater, or a playing field in a large football arena, allowing many specialized knowledge sources to compete and cooperate to resolve focal problems. GW architectures are useful to resolve ambiguous and novel stimuli, such as words in natural language. Conscious percepts often result from a process of ambiguity reduction, and GW architectures have therefore been proposed as models of conscious perception. They are also consistent with highly interactive information flow in the cortico-thalamic (C-T) system (Baars et al., 2013). Edelman et al. (2011) suggest that GW theory is consistent with Neural Darwinism and its many ramifications. GWT predicted widespread “broadcasting” of conscious events, a prediction that is now widely accepted. In a recent study of visual rivalry in the macaque, content-specific “global broadcasting” from temporal to lateral prefrontal cortex was observed for both oscillatory population signaling and multi-unit recordings (Panagiotaropoulos et al., 2012). Similarly, long-distance cortical phase-linking is associated with the waking state but not slow-wave sleep (see Baars et al., 2013 for a review). In general, conscious sensory input has been repeatedly found to evoke more widespread, high amplitude, and phase-linked oscillations in cortex. Baars et al. (2013) have proposed that neuronal source coalitions may emerge anywhere in cortex, becoming subjectively conscious and reportable when a convergent winner-take-all source coalition comes to a momentary equilibrium, able to drive many other regions. During the waking state the visual cortex shows reentrant signaling among more than 40 visuotopical maps (Steriade, 2006). In vision the occipito-temporal cortex identifies the perceptual features that emerge in consciousness, from high-resolution visual details to lower-resolution object and event representation (IT and MTL). For the sight of a visual coffee cup or a flower garden, input convergence is believed to occur at high levels of the visual hierarchy, including object perception in area IT and event perception in MTL. However, a simple stimulus, like the sight of a single star on a dark night, might equilibrate early in the visual hierarchy, since areas V1 and LGN have the highest spatial resolution. This highly flexible version of GWT in the C-T system has been called Dynamic GWT (dGWT). Thus, visual cortex may integrate visual gestalts and broadcast them to frontoparietal, anterior temporal, and subcortical regions. In contrast, non-sensory “feelings of knowing” (FOKs), including expectations and intentions, may arise and propagate from frontal and anterior-temporal regions to caudal sites (Cole et al., 2010; Baars et al., 2013). Direct brain recordings in human patients show widespread neocortical signaling by way of cross-frequency phase-linking among cortical arrays, especially theta-gamma and alpha-gamma signaling. Single neurons have been shown to phase-adapt to dominant theta oscillations, suggesting a mechanism by which individual neurons may be recruited by population oscillations. Such spatiotemporal coding allows for an extremely rich signaling vocabulary, but specific coding schemes are just beginning to be understood (see Baars et al., 2013 for a review).

THINGS-data reflects three large-scale neuroimaging and behavioral datasets of object processing in humans, comprising densely sampled functional MRI and magnetoencephalographic recordings, as well as 4.70 million similarity judgments in response to thousands of photographic images for up to 1854 objects.

Functional object use requires the integration of visuomotor representations processed in the dorsal visual pathway with representations of surface texture and material composition of objects, processed in the ventral visual pathway. Do regions in the ventral visual pathway project outputs to dorsal visual pathway action systems, or are the outputs of the dorsal visual pathway communicated to the ventral visual pathway to modulate processing? And what are the white matter pathways that mediate structural connectivity in support of functional object use? Here we show that the left inferior parietal cortex, a region within the dorsal visual pathway, exerts a direct effect on neural responses in ventral occipital-temporal cortex during visual processing of manipulable objects. We studied a series of consecutively enrolled participants in the pre-operative phase of their neurosurgical care (N = 109) with lesions principally distributed throughout the left hemisphere. Participants completed an object processing category localizer functional MRI experiment in which they viewed images of manipulable objects, animals, faces, and places. We then used Voxel-based Lesion-Activity Mapping (VLAM), a technique in which functional responses in a region-of-interest are used to predict variance in voxel-wise lesion incidence throughout the brain. In the VLAM analyses performed here, we found that lesions to the left anterior intraparietal sulcus and left supramarginal gyrus, two inferior parietal regions known to support object-directed grasping and manipulation, respectively, cause reduced neural responses for manipulable objects (compared to faces, places and animals) in the fusiform gyrus. Parietal lesions do not affect neural responses during visual processing of places in the same region of the fusiform gyrus, even though places elicit stronger responses in the fusiform gyrus than manipulable objects. Seventy-five of 109 participants took part in a common diffusion MRI protocol, permitting a connectome-wide analyses relating white matter fiber integrity to the strength of functional responses for manipulable objects in the left fusiform gyrus. This analysis demonstrated that the descending portion of the left arcuate fasciculus mediates parietal-totemporal lobe connectivity for manipulable objects, supporting the integration of action representations with conceptual and perceptual attributes of objects. By combining voxel-based and connectome-wide lesion-symptom mapping methods with functional MRI, we have demonstrated that structural connectivity to dorsal visual pathway areas supporting skilled manual action shape category-specific neural responses for manipulable objects within the ventral visual pathway.

Patients with semantic aphasia have impaired control of semantic retrieval, often accompanied by executive dysfunction following left hemisphere stroke. Many but not all of these patients have damage to the left inferior frontal gyrus, important for semantic and cognitive control. Yet semantic and cognitive control networks are highly distributed, including posterior as well as anterior components. Accordingly, semantic aphasia might not only reflect local damage but also white matter structural and functional disconnection. Here, we characterise the lesions and predicted patterns of structural and functional disconnection in individuals with semantic aphasia and relate these effects to semantic and executive impairment. Impaired semantic cognition was associated with infarction in distributed left-hemisphere regions, including in the left anterior inferior frontal and posterior temporal cortex. Lesions were associated with executive dysfunction within a set of adjacent but distinct left frontoparietal clusters. Performance on executive tasks was also associated with interhemispheric structural disconnection across the corpus callosum. In contrast, poor semantic cognition was associated with small left-lateralized structurally disconnected clusters, including in the left posterior temporal cortex. Little insight was gained from functional disconnection symptom mapping. These results demonstrate that while left-lateralized semantic and executive control regions are often damaged together in stroke aphasia, these deficits are associated with distinct patterns of structural disconnection, consistent with the bilateral nature of executive control and the left-lateralized yet distributed semantic control network.

The hierarchical organization between 25 ventral stream visual cortical regions and 180 cortical regions was measured with magnetoencephalography using the Human Connectome Project Multimodal Parcellation atlas in 83 Human Connectome Project participants performing a visual memory task. The aim was to reveal the hierarchical organization using a whole-brain model based on generative effective connectivity with this fast neuroimaging method. V1-V4 formed a first group of interconnected regions. Especially V4 had connectivity to a ventrolateral visual stream: V8, the fusiform face cortex, and posterior inferior temporal cortex PIT. These regions in turn had effectivity connectivity to inferior temporal cortex visual regions TE2p and TE1p. TE2p and TE1p then have connectivity to anterior temporal lobe regions TE1a, TE1m, TE2a, and TGv, which are multimodal. In a ventromedial visual stream, V1-V4 connect to ventromedial regions VMV1-3 and VVC. VMV1-3 and VVC connect to the medial parahippocampal gyrus PHA1-3, which, with the VMV regions, include the parahippocampal scene area. The medial parahippocampal PHA1-3 regions have connectivity to the hippocampal system regions the perirhinal cortex, entorhinal cortex, and hippocampus. These effective connectivities of two ventral visual cortical streams measured with magnetoencephalography provide support to the hierarchical organization of brain systems measured with fMRI, and new evidence on directionality.

To determine the degree of pathological change in the primary visual cortex (area V1) in patients with Creutzfeldt-Jakob disease. The vacuolation, surviving neurons, glial cells, and deposits of prion protein were quantified in area V1 obtained postmortem in nine cases of the sporadic type of Creutzfeldt-Jakob disease. Variations in the density of glial cells and in prion protein deposition were particularly evident between patients. In the upper and lower cortical laminae, vacuoles and prion protein deposits were regularly distributed in clusters with a mean dimensions of 450 to 1000 microm. Vacuolation in area V1 was most severe in lamina III and the glial cell reaction in lamina V or VI. Surviving neurons were most abundant in lamina II or III, whereas prion protein deposition either affected all laminae equally or was maximal in lamina II or III. The data suggest that pathological changes in area V1 in sporadic type of Creutzfeldt-Jakob disease may affect the transmission of visual information from area V1 to V2 and to subcortical visual areas. In addition, the data suggest an association between the developing pathology and the functional domains of area V1.

We recorded responses in 107 cells in the primary visual area V1 and 113 cells in the extrastriate visual area V2 while presenting a kinetically defined edge or a luminance contrast edge. Cells meeting statistical criteria for responsiveness and orientation selectivity were classified as selective for the orientation of the kinetic edge if the preferred orientation for a kinetic boundary stimulus remained essentially the same even when the directions of the two motion components defining that boundary were changed by 90 degrees. In area V2, 13 of the 113 cells met all three requirements, whereas in V1, only 4 cells met the criteria of 107 that were tested, and even these demonstrated relatively weak selectivity. Correlation analysis showed that V1 and V2 populations differed greatly (P < 1.0 x 10(-6), Student's t-test) in their selectively for specific orientations of kinetic edge stimuli. Neurons in V2 that were selective for the orientation of a kinetic boundary were further distinguished from their counterparts in V1 in displaying a strong, sharply tuned response to a luminance edge of the same orientation. We concluded that selectivity for the orientation of kinetically defined boundaries first emerges in area V2 rather than in primary visual cortex. An analysis of response onset latencies in V2 revealed that cells selective for the orientation of the motion-defined boundary responded about 40 ms more slowly, on average, to the kinetic edge stimulus than to a luminance edge. In nonselective cells, that is, those presumably responding only to the local motion in the stimulus, this difference was only about 20 ms. Response latencies for the luminance edge were indistinguishable in KE-selective and -nonselective neurons. We infer that while responses to luminance edges or local motion are indigenous to V2, KE-selective responses may involve feedback entering the ventral stream at a point downstream with respect to V2.

Visual perception depends strongly on spatial context. A classic example is the tilt illusion where the perceived orientation of a central stimulus differs from its physical orientation when surrounded by tilted spatial contexts. Here we show that such contextual modulation of orientation perception exhibits trait-like interindividual diversity that correlates with interindividual differences in effective connectivity within human primary visual cortex. We found that the degree to which spatial contexts induced illusory orientation perception, namely, the magnitude of the tilt illusion, varied across healthy human adults in a trait-like fashion independent of stimulus size or contrast. Parallel to contextual modulation of orientation perception, the presence of spatial contexts affected effective connectivity within human primary visual cortex between peripheral and foveal representations that responded to spatial context and central stimulus, respectively. Importantly, this effective connectivity from peripheral to foveal primary visual cortex correlated with interindividual differences in the magnitude of the tilt illusion. Moreover, this correlation with illusion perception was observed for effective connectivity under tilted contextual stimulation but not for that under iso-oriented contextual stimulation, suggesting that it reflected the impact of orientation-dependent intra-areal connections. Our findings revealed an interindividual correlation between intra-areal connectivity within primary visual cortex and contextual influence on orientation perception. This neurophysiological-perceptual link provides empirical evidence for theoretical proposals that intra-areal connections in early visual cortices are involved in contextual modulation of visual perception.

The Hayling Sentence Completion Task (HSCT) is known to activate left hemisphere frontal and temporal language regions. However, the effective connectivity between frontal and temporal language regions associated with the task has yet to be examined. The aims of the study were to examine activation and effective connectivity during the HSCT using a functional magnetic resonance imaging (fMRI) paradigm in which participants made overt verbal responses. We predicted that producing an incongruent response (response suppression), compared to a congruent one (response initiation), would be associated with greater activation in the left prefrontal cortex and an increase in the effective connectivity between temporal and frontal regions. Fifteen participants were scanned while completing 80 sentence stems. The congruency and constraint of sentences varied across trials. Dynamic Causal Modeling (DCM) and Bayesian Model Selection (BMS) were used to compare a set of alternative DCMs of fronto-temporal connectivity. The HSCT activated regions in the left temporal and prefrontal cortices, and the cuneus. Response suppression was associated with greater activation in the left middle and orbital frontal gyri and the bilateral precuneus than response initiation. Left middle temporal and frontal regions identified by the conventional fMRI analyses were entered into the DCM analysis. Using a systematic BMS procedure, the optimal DCM showed that the connection from the left middle temporal gyrus, which was driven by verbal stimuli per se, was significantly increased in strength during response suppression compared to initiation. Greater effective connectivity between left temporal and prefrontal regions during response suppression may reflect the transfer of information from posterior temporal regions where semantic and lexical information is stored to prefrontal regions where it is manipulated in preparation for an appropriate response.

In recent years, several functional imaging studies have shown that the hypothalamus is closely associated with migraine and have suggested that the hypothalamus may be a potential site of migraine generation. Studying the characteristics of the functional network of the hypothalamus in persons with migraines may help to understand the neural mechanisms of migraine. We thus used resting-state functional magnetic resonance imaging (rsfMRI) and Granger causal analysis to investigate the effective connectivity (EC) of the hypothalamus in persons with migraines. The study included 17 healthy volunteers and 39 persons with migraines. The EC calculation was based on rsfMRI data from a 3-T magnetic resonance imaging scanner. The brain networks of the hypothalamus were compared using a general linear model to determine if there were any differences between the two groups. We used Pearson correlation analysis to examine the correlation between EC values in abnormal brain regions and clinical variables. Compared with healthy controls, those with migraines showed decreased EC from the hypothalamus to the left fusiform and increased EC from the hypothalamus to the medial frontal gyrus/orbital part, right lingual gyrus, left superior frontal gyrus, and right middle frontal gyrus (P<0.05). Meanwhile, persons with migraines also showed decreased EC from the left middle frontal gyrus and right medial frontal gyrus/orbital part to the hypothalamus (P<0.05). EC from the hypothalamus to the left superior frontal gyrus correlated significantly and positively with the visual analogue scale in those with migraines (r=-0.3820; P=0.0164). Disturbances in the EC between the hypothalamus and the prefrontal gyrus and visual cortex may play a key role in the neuropathological features of persons with migraines. The current study adds to our understanding of the complexity of migraine mechanisms.

In the past, we demonstrated that the neural system which supports both the generation of an action and the perception of the same action performed by another subject encompasses widespread areas in a parieto-frontal cortical network. In the present study we examined whether this system that helps match action perception to action generation extends beyond these areas to early visual cortices. We applied the quantitative autoradiographic method of [14C]- deoxyglucose, combined with cytoarchitectonic identification of cortical areas, to explore early visual cortical areas throughout the cortex of the occipital operculum, lunate and inferior occipital sulci of twelve adult female monkeys (Macaca mulatta) performing three behavioural tasks: (a) grasping-in-the-light (Gl), (b) grasping-observation (O), and (c) grasping-in-the-dark (Gd). In order to disambiguate the effects of the purposely reaching/grasping action from the effects of (a) the non-goal-directed biological-motion elicited by a purposelessly moving forelimb in front of the monkey, and (b) the visual stimulation induced by mere presentation of the 3D-object, we compared the functional activity in the Gl and O monkeys with that in two arm-motion control (Cm) monkeys. To reveal the effects induced by reaching-to-grasp in the dark, we compared the functional activity in the two Gd monkeys with that in two control-in-the-dark monkeys (Cd). In order to reveal the effects induced by the behavioural tasks, we produced and compared twodimensional reconstructions (2D-maps) of the spatio-intensive pattern of metabolic activity (LCGU values in #mol/100 g/min) throughout the full extent of the visual areas V1, V2, V3, V3A, and V4. During grasping-in-the-light increased metabolic activity was evident in extrastriate areas V3d, V3A and V4 with the two segments of area V3d, the occipito-parietal reflecting peripheral vision and the occipito-temporal reflecting central vision being equally activated. During grasping-observation, area V4 was not activated, marginal activation was displayed in the representation of the central visual field of area V1 and significant activation was displayed in areas V3d and V3A with the occipito-temporal region of area V3d being more activated than the occipito-parietal. During grasping-in-the-dark activation was observed in areas V1, V2, V3A, and V3v. Area V3d was markedly activated in its occipito-parietal segment, contrary to the occipito-temporal which was not activated. According to our previous proposal, the activations induced by grasping-observation in the parietal and motor cortex imply that observation of an action corresponds to simulation of its overt counterpart. Based on our present findings, we suggest that the activation of areas V3d and V3A for action-observation and for action-execution in the dark reflects the processing of visual information xv Summary related to the mental simulation of the action. Area V3 may relay to the motor system, via the parieto-frontal visuo-motor stream, visuospatial information required for the reaching component of the action and 3D-object-related information useful for the grasping constituent. Therefore, as the somatotopic activation of the primary somatosensory cortex during action-observation in our previous study supported an introspective kinesthetic feeling of the movement by the observer in a first person perspective, the activation of the early visual cortices during action-generation in the dark in the present study supports an internalized visual representation of the spatial-location and the 3D-form of the invisible object to be reached and grasped, i.e. visual imagery during action control.

Background: Habituation is considered to have protective and filtering mechanisms. The present study is aim to find the casual relationship and mechanisms of excitatory–inhibitory (E/I) dysfunctions in schizophrenia (SCZ) via habituation.Methods: A dichotic listening paradigm was performed with simultaneous EEG recording on 22 schizophrenia patients and 22 gender- and age-matched healthy controls. Source reconstruction and dynamic causal modeling (DCM) analysis were performed to estimate the effective connectivity and casual relationship between frontal and temporal regions before and after habituation.Results: The schizophrenia patients expressed later habituation onset (p < 0.01) and hyper-activity in both lateral frontal–temporal cortices than controls (p = 0.001). The patients also showed decreased top-down and bottom-up connectivity in bilateral frontal–temporal regions (p < 0.01). The contralateral frontal–frontal and temporal–temporal connectivity showed a left to right decreasing (p < 0.01) and right to left strengthening (p < 0.01).Conclusions: The results give causal evidence for E/I imbalance in schizophrenia during dichotic auditory processing. The altered effective connectivity in frontal–temporal circuit could represent the trait bio-marker of schizophrenia with auditory hallucinations.

The callosal connectivity of areas V1 and V2 in the newborn monkey has been investigated with the neuroanatomical tracers wheat germ agglutinin conjugated to horseradish peroxidase and free horseradish peroxidase. In the adult, callosal projecting neurons in cortex subserving the lower parafoveal visual field were found to extend from the V1/V2 border for a distance of 1-2.5 mm into V1 and 8 mm into V2. In the newborn, the tangential extent and total number of callosal projecting neurons were the same as in the adult. Within area V1, callosal projecting neurons in the adult and newborn were limited to supragranular layers. In the adult, axon terminals of callosal projections were located in layers 4B and 5 and were excluded from layer 4C. In the newborn, axon terminals were more extensively distributed than in the adult and invaded layer 4C. In area V2, the laminar distribution and the patchy location of callosal connections in regions of high cytochrome oxidase activity were similar in the newborn and adult animals. In both newborns and adults, the patchy distribution of callosal projections persisted when the neuroanatomical tracers were injected over extensive regions of the contralateral striate and extrastriate cortex. In the adult, area V1 and V2 project contralaterally to two heterotopic sites located in the fundus of the lunate sulcus and the superior temporal sulcus. This was also found to be the case in the newborn. In the adult the terminals of these heterotopic projections were focused in layer 4. This was not the case in the newborn, where after injection limited to the contralateral V1/V2 border they were more evenly distributed among the different cortical layers. Following extensive contralateral injection of tracer, terminals in cortex anterior to V2 were focused over layer 5 and the bottom of layer 4.

Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57–100%), than to area V4 (25–36%). In contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70–80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and VI in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II–III and V–VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of corticocortically projecting neurons with distinct regional and laminar distribution in the monkey visual system. It is possible that the preferential distribution of neurofilament protein within feedforward connections to area MT and all feedback projections is related to other distinctive properties of these corticocortical projection neurons. © 1996 Wiley-Liss, Inc.