Bilateral lesions in a specific subregion of posterior insular cortex impair conditioned taste aversion expression in rats

The gustatory cortex (GC) is widely regarded for its integral role in the acquisition and retention of conditioned taste aversions (CTAs) in rodents, but large lesions in this area do not always result in CTA impairment. Recently, using a new lesion mapping system, we found that severe CTA expression deficits were associated with damage to a critical zone that included the posterior half of GC in addition to the insular cortex (IC) that is just dorsal and caudal to this region (visceral cortex). Lesions in anterior GC were without effect. Here, neurotoxic bilateral lesions were placed in the anterior half of this critical damage zone, at the confluence of the posterior GC and the anterior visceral cortex (termed IC₂), the posterior half of this critical damage zone that contains just VC (termed IC₃), or both of these subregions (IC₂ + IC₃). Then, pre‐ and postsurgically acquired CTAs (to 0.1 M NaCl and 0.1 M sucrose, respectively) were assessed postsurgically in 15‐minute one‐bottle and 96‐hour two‐bottle tests. Li‐injected rats with histologically confirmed bilateral lesions in IC₂ exhibited the most severe CTA deficits, whereas those with bilateral lesions in IC₃ were relatively normal, exhibiting transient disruptions in the one‐bottle sessions. Groupwise lesion maps showed that CTA‐impaired rats had more extensive damage to IC₂ than did unimpaired rats. Some individual differences in CTA expression among rats with similar lesion profiles were observed, suggesting idiosyncrasies in the topographic representation of information in the IC. Nevertheless, this study implicates IC₂ as the critical zone of the IC for normal CTA expression. J. Comp. Neurol. 524:54–73, 2016. © 2015 Wiley Periodicals, Inc.     

Effects of insular cortex lesions on conditioned taste aversion and latent inhibition in the rat

The present study tested the hypothesis that lesions of the insular cortex of the rat retard the acquisition of conditioned taste aversions (CTAs) because of an impairment in the detection of the novelty of taste stimuli. Demonstrating the expected latent inhibition effect, nonlesioned control subjects acquired CTAs more rapidly when the conditioned stimulus (0.15% sodium saccharin) was novel rather than familiar (achieved by pre-exposure to the to-be-conditioned taste cue). However, rats with insular cortex lesions acquired taste aversions at the same slow rate regardless of whether the saccharin was novel or familiar. The pattern of behavioural deficits obtained cannot be interpreted as disruptions of taste detection or stimulus intensity, but is consistent with the view that insular cortex lesions disrupt taste neophobia, a dysfunction that consequently retards CTA acquisition because of a latent inhibition-like effect.     

Restoration of quinine‐stimulated fos‐immunoreactive neurons in the central nucleus of the amygdala and gustatory cortex following reinnervation or cross‐reinnervation of the lingual taste nerves in rats

Remarkably, when lingual gustatory nerves are surgically rerouted to inappropriate taste fields in the tongue, some taste functions recover. We previously demonstrated that quinine‐stimulated oromotor rejection reflexes and neural activity (assessed by Fos immunoreactivity) in subregions of hindbrain gustatory nuclei were restored if the posterior tongue, which contains receptor cells that respond strongly to bitter compounds, was cross‐reinnervated by the chorda tympani nerve. Such functional recovery was not seen if instead, the anterior tongue, where receptor cells are less responsive to bitter compounds, was cross‐reinnervated by the glossopharyngeal nerve, even though this nerve typically responds robustly to bitter substances. Thus, recovery depended more on the taste field being reinnervated than on the nerve itself. Here, the distribution of quinine‐stimulated Fos‐immunoreactive neurons in two taste‐associated forebrain areas was examined in these same rats. In the central nucleus of the amygdala (CeA), a rostrocaudal gradient characterized the normal quinine‐stimulated Fos response, with the greatest number of labeled cells situated rostrally. Quinine‐stimulated neurons were found throughout the gustatory cortex, but a “hot spot” was observed in its anterior–posterior center in subregions approximating the dysgranular/agranular layers. Fos neurons here and in the rostral CeA were highly correlated with quinine‐elicited gapes. Denervation of the posterior tongue eliminated, and its reinnervation by either nerve restored, numbers of quinine‐stimulated labeled cells in the rostralmost CeA and in the subregion approximating the dysgranular gustatory cortex. These results underscore the remarkable plasticity of the gustatory system and also help clarify the functional anatomy of neural circuits activated by bitter taste stimulation. J. Comp. Neurol. 522:2498–2517, 2014. © 2014 Wiley Periodicals, Inc.     

Long-term potentiation in the insular cortex enhances conditioned taste aversion retention

Long-lasting changes in synaptic strength, such as long-term potentiation (LTP), are thought to underlie memory formation. Recent studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and retention of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce LTP in the IC of adult rats in vivo, as well as, that blockade of N-methyl-D-aspartate (NMDA) receptors disrupts CTA and IC-LTP induction in vivo. Here, we present experimental data showing that induction of LTP in the Bla-IC projection previous to CTA training enhances the retention of this task. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying neocortical LTP may contribute to memory related functions performed by the IC.     

Gustatory cortex in the rat. I. Physiological properties and cytoarchitecture

The precise cytoarchitectural localization of taste-elicited cortical responses in the rat was studied using a combination of anatomical and physiological techniques. Multi-unit responses to tongue tactile, thermal and gustatory stimuli were recorded along 97 electrode penetrations positioned parallel to the lateral convexity of the brain and marking lesions were placed at the sites of transitions in these functional properties. Lesions made at sites that received different sensory inputs were consistently located within different cytoarchitectural subdivisions. In this manner, taste cortex in the rat was localized to the agranular insular cytoarchitectural region, in contrast to its traditional assignation to granular insular cortex. Instead, tongue temperature was found to be represented in the cortical area previously termed gustatory, i.e., in ventral granular cortex where layer IV attenuates.     

Real time fMRI feedback of the anterior cingulate and posterior insular cortex in the processing of pain

Self‐regulation of brain activation using real‐time functional magnetic resonance imaging has been used to train subjects to modulate activation in various brain areas and has been associated with behavioral changes such as altered pain perception. The aim of this study was to assess the comparability of upregulation versus downregulation of activation in the rostral anterior cingulate cortex (rACC) and left posterior insula (pInsL) and its effect on pain intensity and unpleasantness. In a first study, we trained 10 healthy subjects to separately upregulate and downregulate the blood oxygenation level‐dependent response in the rACC or pInsL (six trials on 4 days) in response to painful electrical stimulation. The participants learned to significantly downregulate activation in pInsL and rACC and upregulate pInsL but not rACC. Success in the modulation of one region and direction of the modulation was not significantly correlated with success in another condition, indicating that the ability to control pain‐related brain activation is site‐specific. Less covariation between the areas in response to the nociceptive stimulus was positively correlated with learning success. Upregulation or downregulation of either region was unrelated to pain intensity or unpleasantness; however, our subjects did not learn rACC upregulation, which might be important for pain control. A significant increase in pain unpleasantness was found during upregulation of pInsL when covariation with the rACC was low. These initial results suggest that the state of the network involved in the processing of pain needs to be considered in the modulation of pain‐evoked activation and its behavioral effects. Hum Brain Mapp 35:5784–5798, 2014. © 2014 Wiley Periodicals, Inc.     

Distinct fine‐scale fMRI activation patterns of contra‐ and ipsilateral somatosensory areas 3b and 1 in humans

Inter‐areal and ipsilateral cortical responses to tactile stimulation have not been well described in human S1 cortex. By taking advantage of the high signal‐to‐noise ratio at 7 T, we quantified blood oxygenation level dependent (BOLD) response patterns and time courses to tactile stimuli on individual distal finger pads at a fine spatial scale, and examined whether there are inter‐areal (area 3b versus area 1) and interhemispheric response differences to unilateral tactile stimulation in healthy human subjects. We found that 2‐Hz tactile stimulation of individual fingertips evoked detectable BOLD signal changes in both contralateral and ipsilateral area 3b and area 1. Contralateral digit activations were organized in an orderly somatotopic manner, and BOLD responses in area 3b were more digit selective than those in area 1. However, the area of cortex that was responsive to stimulation of a single digit (stimulus–response field) was similar across areas. In the ipsilateral hemisphere, response magnitudes in both areas 3b and 1 were significantly weaker than those of the contralateral hemisphere. Digit activations exhibited no clear somatotopic organizational pattern in either area 3b or area 1, yet digit selectivity was retained in area 1 but not in area 3b. The observation of distinct digit‐selective responses of contralateral area 3b versus area 1 supports a higher order function of contralateral area 1 in spatial integration. In contrast, ipsilateral cortices may play a less discriminative role in the perception of unilateral tactile sensation in humans. Hum Brain Mapp 35:4841–4857, 2014. © 2014 Wiley Periodicals, Inc.     

The NMDA receptor antagonist CPP impairs conditioned taste aversion and insular cortex long-term potentiation in vivo.

It has been proposed that long-term potentiation (LTP) a form of activity-dependent modification of synaptic efficacy, may be a synaptic mechanism for certain types of learning. Recent studies on the insular cortex (IC) a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce an N-methyl- -aspartate (NMDA) dependent LTP in the IC of adult rats in vivo. Here we present experimental data showing that intracortical administration of the NMDA receptor competitive antagonist CPP (-3(-2 carboxipiperazin-4-yl)-propyl-1-phosphonic acid) disrupts the acquisition of conditioned taste aversion, as well as, the IC-LTP induction in vivo. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying NMDA dependent neocortical LTP, constitute a possible mechanism for the learning related functions performed by the IC.     

Self-determined,but not non-self-determined,motivation predicts activations in the anterior insular cortex: an fMRI study of personal agency

Neuroscientific studies on agency focus rather exclusively on the notion of who initiates and regulates actions, not on the notion of why the person does. The present study focused on the latter to investigate two different reasons underlying personal agency. Using event-related functional magnetic resonance imaging, we scanned 16 healthy human subjects while they imagined the enactment of volitional, agentic behavior on the same task but either for a self-determined and intrinsically motivated reason or for a non-self-determined and extrinsically motivated reason. Results showed that the anterior insular cortex (AIC), known to be related to the sense of agency, was more activated during self-determined behavior while the angular gyrus, known to be related to the sense of loss of agency, was more activated during non-self-determined behavior. Furthermore, AIC activities during self-determined behavior correlated highly with participants’ self-reported intrinsic satisfactions. We conclude that self-determined behavior is more agentic than is non-self-determined behavior and that personal agency arises only during self-determined, intrinsically motivated action.     

Judging roughness by sight—A 7‐tesla fMRI study on responsivity of the primary somatosensory cortex during observed touch of self and others

Observing another person being touched activates our own somatosensory system. Whether the primary somatosensory cortex (S1) is also activated during the observation of passive touch, and which subregions of S1 are responsible for self‐ and other‐related observed touch is currently unclear. In our study, we first aimed to clarify whether observing passive touch without any action component can robustly increase activity in S1. Secondly, we investigated whether S1 activity only increases when touch of others is observed, or also when touch of one's own body is observed. We were particularly interested in which subregions of S1 are responsible for either process. We used functional magnetic resonance imaging at 7 Tesla to measure S1 activity changes when participants observed videos of their own or another's hand in either egocentric or allocentric perspective being touched by different pieces of sandpaper. Participants were required to judge the roughness of the different sandpaper surfaces. Our results clearly show that S1 activity does increase in response to observing passive touch, and that activity changes are localized in posterior but not in anterior parts of S1. Importantly, activity increases in S1 were particularly related to observing another person being touched. Self‐related observed touch, in contrast, caused no significant activity changes within S1. We therefore assume that posterior but not anterior S1 is part of a system for sharing tactile experiences with others. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Orbitofrontal and insular cortex: Neural responses to cocaine‐associated cues and cocaine self‐administration

Based on neuro‐imaging studies in cocaine‐addicted humans, it is hypothesized that increases in neural activity within several regions of the prefrontal cortex contribute to cue‐induced cocaine seeking and cocaine‐induced compulsive drug self‐administration. However, electrophysiological tests of these hypotheses are lacking. In the present study, animals were trained to self‐administer cocaine (0.75 mg/kg) for 14 days. On the 14th day, we conducted electrophysiological recordings of lateral orbitofrontal (LO) and ventral anterior insula (AIV) neurons. A subset of the combined population of recorded neurons showed a change in firing rate in association with one or more of the following discrete events: (1) presentation of a discriminative stimulus that signaled the onset of the self‐administration session, (2) occurrence of the first cocaine‐directed operant response, (3) occurrence of a cocaine‐reinforced press, and (4) presentation of cues normally paired with delivery of the cocaine reinforcer. The majority of the stimulus‐ and response‐related changes in firing involved a brief increase in firing during the stimulus and response event, respectively. In addition to these event‐specific responses, approximately half of the recorded neurons exhibited a sustained change in average firing (i.e., discharges per 30‐s bin) during the cocaine self‐administration session, relative to average firing during a presession, drug‐free period (referred to as session changes). The prevalence of session‐increases and decreases were not significantly different. These and other findings are discussed in relation to hypotheses about cue‐evoked and cocaine‐maintained cocaine‐directed behavior. Synapse 64:1–13, 2010. © 2009 Wiley‐Liss, Inc.     

Electrophysiological and behavioural characterization of gustatory responses to antennal 'bitter' taste in honeybees

We combined behavioural and electrophysiological experiments to study whether bitter taste is perceived at the antennal level in honeybees, Apis mellifera. Our behavioural studies showed that neither quinine nor salicin delivered at one antenna at different concentrations induced a retraction of the proboscis once it was extended in response to 1 M sucrose solution delivered to the opposite antenna. Bees that extended massively their proboscis to 1 M sucrose responded only partially when stimulated with a mixture of 1 M sucrose and 100 mM quinine. The mixture of 1 m sucrose and 100 mM salicin had no such suppressive effect. No behavioural suppression was found for mixtures of salt solution and either bitter substance. Electrophysiological recordings of taste sensillae at the antennal tip revealed sensillae that responded specifically either to sucrose or salt solutions, but none responded to the bitter substances quinine and salicin at the different concentrations tested. The electrophysiological responses of sensillae to 15 mM sucrose solution were inhibited by a mixture of 15 mM sucrose and 0.1 mM quinine, but not by a mixture of 15 mM sucrose and 0.1 mM salicin. The responses of sensillae to 50 mM NaCl were reduced by a mixture of 50 mm NaCl and 1 mM quinine but not by a mixture of 50 mM NaCl and 1 mM salicin. We concluded that no receptor cells for the bitter substances tested, exist at the level of the antennal tip of the honeybee and that antennal bitter taste is not represented as a separate perceptual quality.     

Relation between palm and finger cortical representations in primary somatosensory cortex: A 7T fMRI study

Many studies focused on the cortical representations of fingers, while the palm is relatively neglected despite its importance for hand function. Here, we investigated palm representation (PR) and its relationship with finger representations (FRs) in primary somatosensory cortex (S1). Few studies in humans suggested that PR is located medially with respect to FRs in S1, yet to date, no study directly quantified the somatotopic organization of PR and the five FRs. Importantly, the link between the somatotopic organization of PR and FRs and their activation properties remains largely unexplored. Using 7T fMRI, we mapped PR and the five FRs at the single subject level. First, we analyzed the cortical distance between PR and FRs to determine their somatotopic organization. Results show that PR was located medially with respect to D5. Second, we tested whether the observed cortical distances would predict the relationship between PR and FRs activations. Using three complementary measures (cross‐activations, pattern similarity and resting‐state connectivity), we show that the relationship between PR and FRs activations were not determined by their somatotopic organization, that is, there was no gradient moving from D5 to D1, except for resting‐state connectivity, which was predicted by the somatotopy. Instead, we show that the representational geometry of PR and FRs activations reflected the physical structure of the hand. Collectively, our findings suggest that the spatial proximity between topographically organized neuronal populations do not necessarily predicts their functional properties, rather the structure of the sensory space (e.g., the hand shape) better describes the observed results.     

Gustatory pathway in humans: A review of models of taste perception and their potential lateralization

The focus of this review is to interpret recent advances in human gustatory pathways with respect to the laterality of gustatory responses. Psychophysical, neuroimaging, and clinical anatomical studies published in peer reviewed scientific journals were examined. From the anatomical and neuroimaging studies a total of six models are outlined and discussed in the light of some recent psychophysical and clinical results. In the specific of the salt condition and right preferred hand the outcomes have revealed a predominant left ipsilateral pathway with evidences of ipsilateral projection from the left primary gustatory cortex (PGC) to the orbitofrontal cortex, while a bilateral projection from the right oral cavity to the left and right insula seems to be more consistent. Also, the right side predominance of the chemosensory perception is objected. Additionally, the gustatory response appears to be dependent on the taste quality, supporting the idea of a chemotopical organization of the PGC as well as the Labelled-Line Model theory of peripheral taste quality encoding. However, where the fibers branch along the ascending pathway is not unequivocally established. Interestingly, factors like handedness appear to be remarkable when studying the lateralization of brain functions. Finally we suggest that further studies must include handedness and taste quality as distinctive factors that can help to interpret the results in a unique way.     

fMRI与DTI联合应用在神经导航下切除运动区附近病变

目的 探讨fMRI与DTI联合应用在大脑皮层运动区附近病变手术中的价值.方法 对18例大脑皮层运动区附近病变的患者,采用组块设计,利用血氧水平依赖性功能磁共振成像(BOLD-fMRI)获得运动区皮层激活,利用磁共振弥散张量成像技术(DTI)获得白质纤维束走行,应用神经导航系统进行影像融合后,术中定位皮层运动区与锥体束,经神经电生理检查验证后,避开功能区在显微镜下切除病变.结果 fMRI确定的功能区与术中电生理检查结果基本一致.12例病变全切,6例大部切除.术后肢体肌力好转或无变化14例,3例出现一过性加重,1例遗留永久性功能损害.结论 在神经导航辅助下fMRI与DTI联合应用可以准确定位大脑皮层运动区和锥体束,提高病变切除程度,减少术后运动功能障碍.     

Corticocortical projections to representations of the teeth,tongue, and face in somatosensory area 3b of macaques

We placed injections of anatomical tracers into representations of the tongue, teeth, and face in the primary somatosensory cortex (area 3b) of macaque monkeys. Our injections revealed strong projections to representations of the tongue and teeth from other parts of the oral cavity responsive region in 3b. The 3b face also provided input to the representations of the intraoral structures. The primary representation of the face showed a pattern of intrinsic connections similar to that of the mouth. The area 3b hand representation provided little to no input to either the mouth or the face representations. The mouth and face representations of area 3b received projections from the presumptive oral cavity and face regions of other somatosensory areas in the anterior parietal cortex and the lateral sulcus, including areas 3a, 1, 2, the second somatosensory area (S2), the parietal ventral area (PV), and cortex that may include the parietal rostral (PR) and ventral somatosensory (VS) areas. Additional inputs came from primary motor (M1) and ventral premotor (PMv) areas. This areal pattern of projections is similar to the well‐studied pattern revealed by tracer injections in regions of 3b representing the hand. The tongue representation appeared to be unique in area 3b in that it also received inputs from areas in the anterior upper bank of the lateral sulcus and anterior insula that may include the primary gustatory area (area G) and other cortical taste‐processing areas, as well as a region of lateral prefrontal cortex (LPFC) lining the principal sulcus. J. Comp. Neurol. 522:546–572, 2014. © 2013 Wiley Periodicals, Inc.     

The representation of oral fat texture in the human somatosensory cortex

How fat is sensed in the mouth and represented in the brain is important in relation to the pleasantness of food, appetite control, and the design of foods that reproduce the mouthfeel of fat yet have low energy content. We show that the human somatosensory cortex (SSC) is involved in oral fat processing via functional coupling to the orbitofrontal cortex (OFC), where the pleasantness of fat texture is represented. Using functional MRI, we found that activity in SSC was more strongly correlated with the OFC during the consumption of a high fat food with a pleasant (vanilla) flavor compared to a low fat food with the same flavor. This effect was not found in control analyses using high fat foods with a less pleasant flavor or pleasant‐flavored low fat foods. SSC activity correlated with subjective ratings of fattiness, but not of texture pleasantness or flavor pleasantness, indicating a representation that is not involved in hedonic processing per se. Across subjects, the magnitude of OFC‐SSC coupling explained inter‐individual variation in texture pleasantness evaluations. These findings extend known SSC functions to a specific role in the processing of pleasant‐flavored oral fat, and identify a neural mechanism potentially important in appetite, overeating, and obesity. Hum Brain Mapp 35:2521–2530, 2014. © 2013 Wiley Periodicals, Inc .     

In vivo correlates of thermoregulatory defense in humans: Temporal course of sub‐cortical and cortical responses assessed with fMRI

Extensive studies in rodents have established the role of neural pathways that are activated during thermoregulation. However, few studies have been conducted in humans to assess the complex, hierarchically organized thermoregulatory network in the CNS that maintains thermal homeostasis, especially as it pertains to cold exposure. To study the human thermoregulatory network during whole body cold exposure, we have used functional MRI to characterize changes in the BOLD signal within the constituents of the thermoregulatory network in 20 young adult controls during non‐noxious cooling and rewarming of the skin by a water‐perfused body suit. Our results indicate significant decreases of BOLD signal during innocuous whole body cooling stimuli in the midbrain, the right anterior insula, the right anterior cingulate, and the right inferior parietal lobe. Whereas brain activation in these areas decreased during cold exposure, brain activation increased significantly in the bilateral orbitofrontal cortex during this period. The BOLD signal time series derived from significant activation sites in the orbitofrontal cortex showed opposed phase to those observed in the other brain regions, suggesting complementary processing mechanisms during mild hypothermia. The significance of our findings lies in the recognition that whole body cooling evokes a response in a hierarchically organized thermoregulatory network that distinguishes between cold and warm stimuli. This network seems to generate a highly resolved interoceptive representation of the body's condition that provides input to the orbitofrontal cortex, where higher‐order integration takes place and invests internal states with emotional significance that motivate behavior. Hum Brain Mapp 37:3188–3202, 2016. © 2016 Wiley Periodicals, Inc .     

Characterization, distribution and lateralization of baroreceptor-related neurons in the rat insular cortex

The insular cortex contains a site of cardiovascular representation. Stimulation experiments suggest a discrete localization within the rostral posterior insula. In 34 urethane-anesthetized male Sprague-Dawley rats, we investigated whether cells responsive to baroreceptor stimulation with phenylephrine and sodium nitroprusside were selectively clustered within the insula compared with the surrounding frontoparietal cortex, the extent of distribution of these responsive cells within the insula, and whether there was any lateralization of response. In addition, we characterized the cells as SE (sympathoexcitatory), SI (sympathoinhibitory) or null cells using the criteria of Barman. Of the 128 insular cells investigated with extracellular recording techniques, 70% responded to baroreceptor manipulations compared to 32% of the 57 cells investigated outside the insula (P<0.0001). The majority of the responsive cells were SE units and were distributed widely throughout the insular cortex including anterior areas not previously thought to be involved in cardiovascular control. Within the rostral posterior insula from which cardiovascular effects are mainly obtained in stimulation experiments, lateralization was identified, with significantly more cells responding to blood pressure changes being found within the right posterior insula than the left (P<0.003). These data confirm the importance of the right posterior insula in the rat as a site of cardiovascular representation; identify a more extensive distribution of cells responsive to blood pressure changes within the insula than previous studies and imply more widespread convergence of visceral afferent information within the insula.     

Linearity of the fMRI response in category‐selective regions of human visual cortex

The goal of this study was to determine the linearity of the blood oxygen level‐dependent (BOLD) response, as measured by functional magnetic resonance imaging (fMRI), in category‐selective regions of human visual cortex. We defined regions of the temporal lobe that were selective to faces (fusiform face area, FFA) and places (parahippocampal place area, PPA). We then determined the linearity of the BOLD response in these regions to their preferred and nonpreferred stimuli. First, we tested the principle of scaling. As we increased the visibility of the stimulus, there was a corresponding linear increase in the fMRI signal in the FFA and PPA to their preferred stimulus (face and place, respectively). In contrast, responses in the FFA and PPA to the nonpreferred stimulus did not conform to the principle of scaling. Next, we asked whether the fMRI response in these regions of visual cortex conformed to the principle of additivity. To assess this, we determined whether the response to a long stimulus block could be predicted by adding the response to multiple shorter duration blocks. Although the fMRI response in the FFA and PPA was generally linear to the preferred stimulus, a more nonlinear response was apparent to the nonpreferred stimulus. In conclusion, the linearity of the BOLD response in the human ventral visual pathway varied across cortical region and stimulus category. This suggests that measures of linearity may provide a useful indication of neural selectivity in the brain. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.