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Introduction There is a need for novel anxiolytics with improved side effect profiles compared to benzodiazepines. A promising candidate with alternative pharmacodynamics is the translocator protein ligand, etifoxine. Methods To get further insight into its mechanisms of action and side effects compared to the benzodiazepine alprazolam, we performed a double-blind, placebo-controlled, repeated-measures study in 36 healthy male subjects. Participants were examined for trait anxiety and side effects and underwent repeated transcranial magnetic stimulation (TMS) assessments, including motor evoked potentials (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). Results We observed attenuation of MEPs by alprazolam but not by etifoxine. SICI was not significantly affected by alprazolam or etifoxine. However, the response pattern indicated a lowered SICI threshold after the administration of etifoxine and alprazolam compared to the placebo. ICF and CSP were influenced by neither medication. Alprazolam led to higher sedation and subjective impairment of concentration compared to etifoxine. Individual anxiety trait scores did not affect TMS parameters. Discussion This study indicated a favorable side effect profile of etifoxine in healthy volunteers. Moreover, it revealed differential GABA-related effects on neuromuscular function by means of TMS. The side effects and TMS profile of etifoxine are compatible with the involvement of neurosteroidogenesis and a predominant α3 subunit modulation compared to alprazolam.

There is need for novel fast acting treatment options in affective disorders. 3α-reduced neurosteroids such as allopregnanolone are powerful positive allosteric modulators of GABA

Although the somatosensory homunculus is a classically used description of the way somatosensory inputs are processed in the brain, the actual contributions of primary (SI) and secondary (SII) somatosensory cortices to the spatial coding of touch remain poorly understood. We studied adaptation of the fMRI BOLD response in the somatosensory cortex by delivering pairs of vibrotactile stimuli to the finger tips of the index and middle fingers. The first stimulus (adaptor) was delivered either to the index or to the middle finger of the right or left hand, and the second stimulus (test) was always administered to the left index finger. The overall BOLD response evoked by the stimulation was primarily contralateral in SI and was more bilateral in SII. However, our fMRI adaptation approach also revealed that both somatosensory cortices were sensitive to ipsilateral as well as to contralateral inputs. SI and SII adapted more after subsequent stimulation of homologous as compared with nonhomologous fingers, showing a distinction between different fingers. Most importantly, for both somatosensory cortices, this finger-specific adaptation occurred irrespective of whether the tactile stimulus was delivered to the same or to different hands. This result implies integration of contralateral and ipsilateral somatosensory inputs in SI as well as in SII. Our findings suggest that SI is more than a simple relay for sensory information and that both SI and SII contribute to the spatial coding of touch by discriminating between body parts (fingers) and by integrating the somatosensory input from the two sides of the body (hands).

The effects of transcranial magnetic stimulation (TMS) vary depending on the brain state at the stimulation moment. Four mechanisms have been proposed to underlie these effects: (1) virtual lesion—TMS suppresses neural signals; (2) preferential activation of less active neurons—TMS drives up activity in the stimulated area, but active neurons are saturating; (3) noise generation—TMS adds random neuronal activity, and its effect interacts with stimulus intensity; and (4) noise generation—TMS adds random neuronal activity, and its effect depends on TMS intensity. Here we explore these hypotheses by investigating the effects of TMS on early visual cortex by assessing the contrast response function while varying the adaptation state of the observers. We tested human participants in an orientation discrimination task, in which performance is contingent upon contrast sensitivity. Before each trial, neuronal activation of visual cortex was altered through contrast adaptation to two flickering gratings. In a factorial design, with or without adaptation, a single TMS pulse was delivered simultaneously with targets of varying contrast. Adaptation decreased contrast sensitivity. The effect of TMS on performance was state dependent: TMS decreased contrast sensitivity in the absence of adaptation but increased it after adaptation. None of the proposed mechanisms can account for the results in their entirety, in particular, for the facilitatory effect at intermediate to high contrasts after adaptation. We propose an alternative hypothesis: TMS effects are activity dependent, so that TMS suppresses the most active neurons and thereby changes the balance between excitation and inhibition.

The posterior superior temporal sulcus (pSTS) is active when observing biological motion. We investigated the functional connections of the pSTS node within the action observation network by measuring the after-effect of focal repetitive transcranial magnetic stimulation (rTMS) with whole-brain functional magnetic resonance imaging (fMRI). Participants received 1-Hz rTMS over the pSTS region for 10 min and underwent fMRI immediately after. While scanned, they were shown short video clips of a hand grasping an object (grasp clips) or moving next to it (control clips). rTMS-fMRI was repeated for four consecutive blocks. In two blocks we stimulated the left pSTS region and in the other two the right pSTS region. For each side TMS was applied with an effective intensity (95 % of motor threshold) or with ineffective intensity (50 % of motor threshold). Brain regions showing interactive effects of (clip type) × (TMS intensity) were identified in the lateral temporo-occipital cortex, in the anterior intraparietal region and in the ventral premotor cortex. Remote effects of rTMS were mostly limited to the stimulated hemisphere and consisted in an increase of blood oxygen level-dependent responses to grasp clips compared to control clips. We show that the pSTS occupies a pivotal relay position during observation of goal-directed actions.

The cognitive neurosciences combine behavioral experiments with acquiring physiological data from different modalities, such as electroencephalography, magnetoencephalography, transcranial magnetic stimulation, and functional magnetic resonance imaging, all of which require excellent timing. A simple framework is proposed in which uni- and multimodal experiments can be conducted with minimal adjustments when one switches between modalities. The framework allows the beginner to quickly become productive and the expert to be flexible and not constrained by the tool by building on existing software such as MATLAB and the Psychophysics Toolbox, which already are serving a large community. The framework allows running standard experiments but also supports and facilitates exciting new possibilities for real-time neuroimaging and state-dependent stimulation.

We present an experiment designed to test whether experienced regret and rejoicing evoked in a risk choice have an impact on subsequent intertemporal choice. We found that regret and rejoicing experienced prior to an intertemporal choice influenced considerably the way people relate to future: when regret was experienced participants preferred not to wait, whereas when rejoicing was experienced, participants were willing to wait longer. We show that in the framework of the discounted utility model experienced regret lowered and experienced rejoicing increased the discount factor.

Tool use depends on processes represented in distinct regions of left parietal cortex. We studied the role of visual experience in shaping neural specificity for tools in parietal cortex by using functional magnetic resonance imaging with sighted, late-blind, and congenitally blind participants. Using a region-of-interest approach in which tool-specific areas of parietal cortex were identified in sighted participants viewing pictures, we found that specificity in blood-oxygen-level-dependent responses for tools in the left inferior parietal lobule and the left anterior intraparietal sulcus is independent of visual experience. These findings indicate that motor- and somatosensory-based processes are sufficient to drive specificity for representations of tools in regions of parietal cortex. More generally, some aspects of the organization of the dorsal object-processing stream develop independently of the visual information that forms the major sensory input to that pathway in sighted individuals.

A transcranial magnetic stimulation (TMS) adaptation paradigm was used to investigate the neural representation of observed motor behavior in the inferior parietal lobule (IPL), ventral premotor cortex (PMv), and in the cortex around the superior temporal sulcus (STS). Participants were shown adapting movies of a hand or a foot acting on different objects and were asked to compare to the movie, a motor act shown in test pictures. The invariant features between adapting and test stimuli fitted a 2 x 2 design: same or different action made by the same or different effector. Neuronavigated TMS pulses were delivered at the onset of each test picture. TMS over the left and right PMv and over the left IPL induced a selective shortening of reaction times (RTs) to stimuli showing a repeated (adapted) action, regardless of the effector performing it. In a second experiment, TMS applied over the left STS induced shortening of RTs for adapted actions but only if also the effector was repeated. The results indicate that observed motor behavior is encoded with the body part that performs it in the temporal lobe. A hierarchically higher level of representation is carried by neural populations in the parietofrontal regions, where acts are encoded in an abstract way.

Recent psychophysics studies suggest that the behavioral impact of a visual stimulus and its conscious visual recognition underlie two functionally dissociated neuronal processes. Previous TMS studies have demonstrated that certain features of a visual stimulus can still be processed despite TMS-induced disruption of perception. Here, we tested whether symbolic action priming also remains intact despite TMS-induced masking of the prime. We applied single-pulse TMS over primary visual cortex at various temporal intervals from 20 ms to 120 ms during a supraliminal action priming paradigm. This TMS protocol enabled us to identify at what exact time point a TMS-induced activity disruption of primary visual cortex interferes with conscious visual perception of the prime versus (un)conscious behavioral priming of the visual target stimulus. We also introduced spatial uncertainty by presenting visual stimuli either above or below the fixation cross, while the TMS pulse was always targeting the prime presented below fixation. We revealed that TMS over primary visual cortex interferes with both conscious visual perception and symbolic behavioral priming in a temporarily and spatially specific manner, i.e., only when disrupting primary visual cortex at approximately the same temporal stage between 60 and 100 ms after prime onset, and only for those prime stimuli presented below fixation. These findings are in disagreement with the idea of subliminal action priming being mediated by neural pathways bypassing striate cortex, and rather suggest that symbolic action priming relies on an intact neural transmission along the retino-geniculo-striate pathway. The implications of our findings for previous reports of residual visual processing during striate TMS are discussed.

Written language comprehension at the word and the sentence level was analysed by the combination of spatial and temporal analysis of functional magnetic resonance imaging (fMRI). Spatial analysis was performed via general linear modelling (GLM). Concerning the temporal analysis, local differences in neurovascular coupling may confound a direct comparison of blood oxygenation level-dependent (BOLD) response estimates between regions. To avoid this problem, we parametrically varied linguistic task demands and compared only task-induced within-region BOLD response differences across areas. We reasoned that, in a hierarchical processing system, increasing task demands at lower processing levels induce delayed onset of higher-level processes in corresponding areas. The flow of activation is thus reflected in the size of task-induced delay increases. We estimated BOLD response delay and duration for each voxel and each participant by fitting a model function to the event-related average BOLD response. The GLM showed increasing activations with increasing linguistic demands dominantly in the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG). The combination of spatial and temporal analysis allowed a functional differentiation of IFG subregions involved in written language comprehension. Ventral IFG region (BA 47) and STG subserve earlier processing stages than two dorsal IFG regions (BA 44 and 45). This is in accordance with the assumed early lexical semantic and late syntactic processing of these regions and illustrates the complementary information provided by spatial and temporal fMRI data analysis of the same data set.

Our visual world can be thought of as organised in a hierarchical manner. Studies on hierarchical letter stimuli (a large letter composed of smaller letters) suggest that processing of a visual scene is global to local, a phenomenon known as the global-precedence effect. Elaborating on this global-to-local hypothesis we tested whether global interference will increase with increasing level of globality. For this, we used three-level hierarchical letter stimuli with a global, middle, and local level. When attending to the local level of the stimulus, only the middle level showed an interference effect, whereas the global level did not interfere at all. We argue that, considering the perceptual and attentional contributions to this effect, the hypothesis of global-to-local processing of a visual scene may only hold within a limited spatial attentional window.

The blood oxygen level dependent (BOLD) response, as measured with fMRI, offers good spatial resolution compared to other non-invasive neuroimaging methods. The use of a spin echo technique rather than the conventional gradient echo technique may further improve the resolution by refocusing static dephasing effects around the larger vessels, so sensitizing the signal to the microvasculature. In this work the width of the point spread function (PSF) of the BOLD response at a field strength of 3 Tesla is compared for these two approaches. A double echo EPI pulse sequence with simultaneous collection of gradient echo and spin echo signal allows a direct comparison of the techniques. Rotating multiple-wedge stimuli of different spatial frequencies are used to estimate the width of the BOLD response. Waves of activation are created on the surface of the visual cortex, which begin to overlap as the wedge separation decreases. The modulation of the BOLD response decreases with increasing spatial frequency in a manner dependent on its width. The spin echo response shows a 13% reduction in the width of the PSF, but at a cost of at least 3-fold reduction in contrast to noise ratio.

Visual attention is a mechanism by which observers select relevant or important information from the current visual array. Previous investigations have focused primarily on the ability to select a region of space for further visual analysis. These studies have revealed a distributed frontoparietal circuit that is responsible for the control of spatial attention. However, vision must ultimately represent objects and in real scenes objects often overlap spatially; thus attention must be capable of selecting objects and their properties nonspatially. Little is known about the neural basis of object-based attentional control. In two experiments, human observers shifted attention between spatially superimposed faces and houses. Event-related functional magnetic resonance imaging (fMRI) revealed attentional modulation of activity in face- and house-selective cortical regions. Posterior parietal and frontal regions were transiently active when attention was shifted between spatially superimposed perceptual objects. The timecourse of activity provides insight into the functional role that these brain regions play in attentional control processes.

Visual stimuli may remain invisible but nevertheless produce strong and reliable effects on subsequent actions. How well features of a masked prime are perceived depends crucially on its physical parameters and those of the mask. We manipulated the visibility of masked stimuli and contrasted it with their influence on the speed of motor actions, comparing the temporal dynamics of visual awareness in metacontrast masking with that of action priming under the same conditions. We observed priming with identical time course for reportable and invisible prime stimuli, despite qualitative changes in the masking time course. Our findings indicate that experimental variations that modify the subjective visual experience of masked stimuli have no effect on motor effects of those stimuli in early processing. We propose a model that provides a quantitative account of priming effects on response speed and accuracy.

Observers viewing a complex visual scene selectively attend to relevant locations or objects and ignore irrelevant ones. Selective attention to an object enhances its neural representation in extrastriate cortex, compared with those of unattended objects, via top-down attentional control signals. The posterior parietal cortex is centrally involved in this control of spatial attention. We examined brain activity during attention shifts using rapid, event-related fMRI of human observers as they covertly shifted attention between two peripheral spatial locations. Activation in extrastriate cortex increased after a shift of attention to the contralateral visual field and remained high during sustained contralateral attention. The time course of activity was substantially different in posterior parietal cortex, where transient increases in activation accompanied shifts of attention in either direction. This result suggests that activation of the parietal cortex is associated with a discrete signal to shift spatial attention, and is not the source of a signal to continuously maintain the current attentive state.

Neuropsychological studies have described patients with a selective impairment of finger identification in association with posterior parietal lesions. However, evidence of the role of these areas in finger gnosis from studies of the healthy human brain is still scarce. Here we used functional magnetic resonance imaging to identify the brain network engaged in a novel finger gnosis task, the intermanual in-between task (IIBT), in healthy participants. Several brain regions exhibited a stronger blood oxygenation level-dependent (BOLD) response in IIBT than in a control task that did not explicitly rely on finger gnosis but used identical stimuli and motor responses as the IIBT. The IIBT involved stronger signal in the left inferior parietal lobule (IPL), bilateral precuneus (PCN), bilateral premotor cortex, and left inferior frontal gyrus. In all regions, stimulation of nonhomologous fingers of the two hands elicited higher BOLD signal than stimulation of homologous fingers. Only in the left anteromedial IPL (a-mIPL) and left PCN did signal strength decrease parametrically from nonhomology, through partial homology, to total homology with stimulation delivered synchronously to the two hands. With asynchronous stimulation, the signal was stronger in the left a-mIPL than in any other region, possibly indicating retention of task-relevant information. We suggest that the left PCN may contribute a supporting visuospatial representation via its functional connection to the right PCN. The a-mIPL may instead provide the core substrate of an explicit bilateral body structure representation for the fingers that when disrupted can produce the typical symptoms of finger agnosia.

We typically fixate targets such that they are projected onto the fovea for best spatial resolution. Macular degeneration patients often develop fixation strategies such that targets are projected to an intact eccentric part of the retina, called pseudofovea. A longstanding debate concerns which pseudofovea-location is optimal for non-foveal vision. We examined how pseudofovea position and eccentricity affect performance in visual search, when vision is restricted to an off-foveal retinal region by a gaze-contingent display that dynamically blurs the stimulus except within a small viewing window (forced field location). Trained normally sighted participants were more accurate when forced field location was congruent with the required scan path direction; this contradicts the view that a single pseudofovea location is generally best. Rather, performance depends on the congruence between pseudofovea location and scan path direction.

Neuropsychological evidence has highlighted the role of the anterior temporal lobes in the processing of conceptual knowledge. That putative role is only beginning to be investigated with fMRI as methodological advances are able to compensate for well-known susceptibility artifacts that affect the quality of the BOLD signal. In this article, we described differential BOLD activation for pictures of animals and manipulable objects in the anterior temporal lobes, consistent with previous neuropsychological findings. Furthermore, we found that the pattern of BOLD signal in the anterior temporal lobes is qualitatively different from that in the fusiform gyri. The latter regions are activated to different extents but always above baseline by images of the preferred and of the nonpreferred categories, whereas the anterior temporal lobes tend to be activated by images of the preferred category and deactivated (BOLD below baseline) by images of the nonpreferred category. In our experimental design, we also manipulated the decision that participants made over stimuli from the different semantic categories. We found that in the right temporal pole, the BOLD signal shows some evidence of being modulated by the task that participants were asked to perform, whereas BOLD activity in more posterior regions (e.g., the fusiform gyri) is not modulated by the task. These results reconcile the fMRI literature with the neuropsychological findings of deficits for animals after damage to the right temporal pole and suggest that anterior and posterior regions within the temporal lobes involved in object processing perform qualitatively different computations.

Theoretical and empirical body of research have exposed the powerful role of experiencing regret in guiding choice behavior. In this paper, we examined the impact of experienced regret and rejoicing induced by feedback provided on a risk decision prior to a two-period intertemporal choice. To our knowledge, this is the first attempt to bring together experienced regret and choice over time. We used the two-component discounted utility model approach as a framework. We applied previous research findings on the effect of experienced regret on utility, and we performed an experiment to test whether experienced regret and rejoicing have an impact on the discount factor. We found that both experienced regret and rejoicing have an impact on the way people discount future: when regret is experienced the discount factor decreases, whereas when rejoicing is experienced the discount factor increases.

Written language comprehension at the word and the sentence level was analysed by the combination of spatial and temporal analysis of functional magnetic resonance imaging (fMRI). Spatial analysis was performed via general linear modelling (GLM). Concerning the temporal analysis, local differences in neurovascular coupling may confound a direct comparison of blood oxygenation level-dependent (BOLD) response estimates between regions. To avoid this problem, we parametrically varied linguistic task demands and compared only task-induced within-region BOLD response differences across areas. We reasoned that, in a hierarchical processing system, increasing task demands at lower processing levels induce delayed onset of higher-level processes in corresponding areas. The flow of activation is thus reflected in the size of task-induced delay increases. We estimated BOLD response delay and duration for each voxel and each participant by fitting a model function to the event-related average BOLD response. The GLM showed increasing activations with increasing linguistic demands dominantly in the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG). The combination of spatial and temporal analysis allowed a functional differentiation of IFG subregions involved in written language comprehension. Ventral IFG region (BA 47) and STG subserve earlier processing stages than two dorsal IFG regions (BA 44 and 45). This is in accordance with the assumed early lexical semantic and late syntactic processing of these regions and illustrates the complementary information provided by spatial and temporal fMRI data analysis of the same data set.

Forcing normal-sighted participants to use a distinct parafoveal retinal location for reading, we studied which part of the visual field is best suited to take over functions of the fovea during early stages of macular degeneration (MD). A region to the right of fixation lead to best reading performance and most natural gaze behavior, whereas reading performance was severely impaired when a region to the left or below fixation had to be used. An analysis of the underlying oculomotor behavior revealed that practice effects were accompanied by a larger number of saccades in text direction and decreased fixation durations, whereas no adjustment of saccade amplitudes was observed. We provide an explanation for the observed performance differences at different retinal locations based on the interplay of attention and eye movements. Our findings have important implications for the development of training methods for MD patients targeted at reading, suggesting that it would be beneficial for MD patients to use a region to the right of their central scotoma.

Because our brain cannot process all visual information that enters it, we usually pay attention to only a specific aspect of our visual world. Selective visual attention modulates brain activation in cortical areas corresponding to the attended spatial location. However, visual attention has also been associated with the modulation of activation in different brain areas depending on the relevant spatial scale. In this study, we establish a link between attended spatial scale and receptive field size. We demonstrate that attention to a large or a small object in a visual scene increases activation specifically in brain regions with correspondingly large or small receptive field sizes. To analyze and visualize differential brain activation in contiguous cortical areas we used a mapping strategy evaluating the modelling parameters (beta) from functional magnetic resonance imaging data analysis. Assessment of the course of these parameters along traces in different directions in the visual cortex strengthens our conclusion that selective visual attention modulates brain areas with specific neuronal receptive field size properties corresponding to the task at hand. This also confirms predictions of models of selective attention, that attentional modulation of visual processing critically depends on the receptive field size of neurons across the visual cortex.

We used event-related functional magnetic resonance imaging (erfMRI) to investigate the neural basis of biological and syntactic gender integration during pronoun processing in German sentences about persons or things. German allows for separating both processes experimentally. Overall, syntactic processing activated areas adjacent to Broca's area (BA 44), whereas processing of the biological sex, in addition, involved the supramarginal gyrus (BA 39). A previously reported event-related potential study using identical material suggests that syntactic and semantic information is integrated 400-700 ms after target onset, visible in both cases as a P600 but with different effect sizes. The fMRI and ERP results illuminate that pronoun processing involves a highly dynamic spatiotemporal integration of syntactic and biological information depending on the type of the antecedent and whether or not a violation is involved. The results are discussed in the context of cognitive models of pronoun processing.

If attending to a target in a rapid stream of visual stimuli within the next 400 ms or so, a second target in the stream is frequently not detected by an observer. This so-called attentional blink can provide a comparison of neural signals elicited by identical stimuli that, in one condition, reach conscious awareness and, in the other, fail to be selected for awareness. In the present study, using event-related functional magnetic resonance imaging (fMRI), differences of neural activation were studied in an attentional blink experiment in order to identify brain regions putatively involved in controlling the access of information to consciousness. Subjects viewed a rapid stream of black letters in which the second target (T2) was either presented within or outside the attentional blink period, or not at all. We observed an increase in activation for detected as compared to missed T2 presented during the attentional blink in frontal and parietal cortices. In contrast, in occipitotemporal regions activation was increased for missed as compared to detected T2. Furthermore, in several frontal and parietal areas, missed targets were associated with increased activity if compared to the condition in which no second target was presented. Finally, a selective decrease in activation for detected T2 presented during the attentional blink was observed in areas associated with emotional and predominantly automatic processing. While activations in occipitotemporal regions might mainly reflect duration of attentive search, the frontoparietal areas seem to be involved in a highly distributed network controlling visual awareness.

In normal vision, shifts of attention and gaze are tightly coupled. Here we ask if this coupling affects performance also when central vision is not available. To this aim, we trained normal-sighted participants to perform a visual search task while vision was restricted to a gaze-contingent viewing window ("forced field location") either in the left, right, upper, or lower visual field. Gaze direction was manipulated within a continuous visual search task that required leftward, rightward, upward, or downward eye movements. We found no general performance advantage for a particular part of the visual field or for a specific gaze direction. Rather, performance depended on the coordination of visual attention and eye movements, with impaired performance when sustained attention and gaze have to be moved in opposite directions. Our results suggest that during early stages of central visual field loss, the optimal location for the substitution of foveal vision does not depend on the particular retinal location alone, as has previously been thought, but also on the gaze direction required by the task the patient wishes to perform.

Moving dots can evoke a percept of the spatial structure of a three-dimensional object in the absence of other visual cues. This phenomenon, called structure from motion (SFM), suggests that the motion flowfield represented in the dorsal stream can form the basis of object recognition performed in the ventral stream. SFM processing is likely to contribute to object perception whenever there is relative motion between the observer and the object viewed. Here we investigate the motion flowfield component of object recognition with functional magnetic resonance imaging. Our SFM stimuli encoded face surfaces and random three-dimensional control shapes with matched curvature properties. We used two different types of an SFM stimulus with the dots either fixed to the surface of the object or moving on it. Despite the radically different encoding of surface structure in the two types of SFM, both elicited strong surface percepts and involved the same network of cortical regions. From early visual areas, this network extends dorsally into the human motion complex and parietal regions and ventrally into object-related cortex. The SFM stimuli elicited a face-selective response in the fusiform face area. The human motion complex appears to have a central role in SFM object recognition, not merely representing the motion flowfield but also the surface structure of the motion-defined object. The motion complex and a region in the intraparietal sulcus reflected the motion state of the SFM-implicit object, responding more strongly when the implicit object was in motion than when it was stationary.

SummaryDistinct regions within the ventral visual pathway show neural specialization for nonliving and living stimuli (e.g., tools, houses versus animals, faces). The causes of these category preferences are widely debated. Using functional magnetic resonance imaging, we find that the same regions of the ventral stream that show category preferences for nonliving stimuli and animals in sighted adults show the same category preferences in adults who are blind since birth. Both blind and sighted participants had larger blood oxygen-level dependent (BOLD) responses in the medial fusiform gyrus for nonliving stimuli compared to animal stimuli and differential BOLD responses in lateral occipital cortex for animal stimuli compared to nonliving stimuli. These findings demonstrate that the medial-to-lateral bias by conceptual domain in the ventral visual pathway does not require visual experience in order to develop and suggest the operation of innately determined domain-specific constraints on the organization of object knowledge.