Andrew H. Bell

Object Representations in the Temporal Cortex of Monkeys and Humans as Revealed by Functional Magnetic Resonance Imaging

Increasing evidence suggests that the neural processes associated with identifying everyday stimuli include the classification of those stimuli into a limited number of semantic categories. How the neural representations of these stimuli are organized in the temporal lobe remains under debate. Here we used functional magnetic resonance imaging (fMRI) to identify correlates for three current hypotheses concerning object representations in the inferior temporal (IT) cortex of monkeys and humans: representations based on animacy, semantic categories, or visual features. Subjects were presented with blocked images of faces, body parts (animate stimuli), objects, and places (inanimate stimuli), and multiple overlapping contrasts were used to identify the voxels most selective for each category. Stimulus representations appeared to segregate according to semantic relationships. Discrete regions selective for animate and inanimate stimuli were found in both species. These regions could be further subdivided into regions selective for individual categories. Notably, face-selective regions were contiguous with body-part-selective regions, and object-selective regions were contiguous with place-selective regions. When category-selective regions in monkeys were tested with blocks of single exemplars, individual voxels showed preferences for visually dissimilar exemplars from the same category and voxels with similar preferences tended to cluster together. Our results provide some novel observations with respect to how stimulus representations are organized in IT cortex. In addition, they further support the idea that representations of complex stimuli in IT cortex are organized into multiple hierarchical tiers, encompassing both semantic and physical properties.

Stimulus intensity modifies saccadic reaction time and visual response latency in the superior colliculus

Performance in a reaction time task can be strongly influenced by the physical properties of the stimuli used (e.g., position and intensity). The reduction in reaction time observed with higher-intensity visual stimuli has been suggested to arise from reduced processing time along the visual pathway. If this hypothesis is correct, activity should be registered in neurons sooner for higher-intensity stimuli. We evaluated this hypothesis by measuring the onset of neural activity in the intermediate layers of the superior colliculus while monkeys generated saccades to high or low-intensity visual stimuli. When stimulus intensity was high, the response onset latency was significantly reduced compared to low-intensity stimuli. As a result, the minimum time for visually triggered saccades was reduced, accounting for the shorter saccadic reaction times (SRTs) observed following high-intensity stimuli. Our results establish a link between changes in neural activity related to stimulus intensity and changes to SRTs, which supports the hypothesis that shorter SRTs with higher-intensity stimuli are due to reduced processing time.

Comparative effects of cyclo-oxygenase and nitric oxide synthase inhibition on the development and reversal of spinal opioid tolerance.

This study examined the effects of the COX inhibitors, ketorolac and ibuprofen, and the NOS inhibitor L‐NAME for their potential to both inhibit the development and reverse tolerance to the antinociceptive action of morphine. Repeated administration of intrathecal morphine (15 μg), once daily, resulted in a progressive decline of antinociceptive effect and an increase in the ED50 value in the tailflick and paw pressure tests. Co‐administration of ketorolac (30 and 45 μg) or S(+) ibuprofen (10 μg) with morphine (15 μg) prevented the decline of antinociceptive effect and increase in ED50 value. Similar treatment with L‐NAME (100 μg) exerted weaker effects. Administration of S(+) but not R(−) ibuprofen (10 mg kg−1) had similar effects on systemic administration of morphine (15 mg kg−1). Intrathecal or systemic administration of the COX or NOS inhibitors did not alter the baseline responses in either tests. Acute keterolac or S(+) ibuprofen also did not potentiate the acute actions of spinal or systemic morphine, but chronic intrathecal administration of these agents increased the potency of acute morphine. In animals already tolerant to intrathecal morphine, subsequent administration of ketorolac (30 μg) with morphine (15 μg) partially restored the antinociceptive effect and ED50 value of acute morphine, reflecting the reversal of tolerance. Intrathecal L‐NAME (100 μg) exerted a weaker effect. These data suggest that spinal COX activity, and to a lesser extent NOS activity, contributes to the development and expression of opioid tolerance. Inhibition of COX may represent a useful approach for the prevention as well as reversal of opioid tolerance.

Relationship between functional magnetic resonance imaging-identified regions and neuronal category selectivity.

Functional magnetic resonance imaging (fMRI) has been used extensively to identify regions in the inferior temporal (IT) cortex that are selective for categories of visual stimuli. However, comparatively little is known about the neuronal responses relative to these fMRI-defined regions. Here, we compared in nonhuman primates the distribution and response properties of IT neurons recorded within versus outside fMRI regions selective for four different visual categories: faces, body parts, objects, and places. Although individual neurons that preferred each of the four categories were found throughout the sampled regions, they were most concentrated within the corresponding fMRI region, decreasing significantly within 1–4 mm from the edge of these regions. Furthermore, the correspondence between fMRI and neuronal distributions was specific to neurons that increased their firing rates in response to the visual stimuli but not to neurons suppressed by visual stimuli, suggesting that the processes associated with inhibiting neuronal activity did not contribute strongly to the fMRI signal in this experiment.

Perception of emotional expressions is independent of face selectivity in monkey inferior temporal cortex

The ability to perceive and differentiate facial expressions is vital for social communication. Numerous functional MRI (fMRI) studies in humans have shown enhanced responses to faces with different emotional valence, in both the amygdala and the visual cortex. However, relatively few studies have examined how valence influences neural responses in monkeys, thereby limiting the ability to draw comparisons across species and thus understand the underlying neural mechanisms. Here we tested the effects of macaque facial expressions on neural activation within these two regions using fMRI in three awake, behaving monkeys. Monkeys maintained central fixation while blocks of different monkey facial expressions were presented. Four different facial expressions were tested: (i) neutral, (ii) aggressive (open-mouthed threat), (iii) fearful (fear grin), and (iv) submissive (lip smack). Our results confirmed that both the amygdala and the inferior temporal cortex in monkeys are modulated by facial expressions. As in human fMRI, fearful expressions evoked the greatest response in monkeys—even though fearful expressions are physically dissimilar in humans and macaques. Furthermore, we found that valence effects were not uniformly distributed over the inferior temporal cortex. Surprisingly, these valence maps were independent of two related functional maps: (i) the map of “face-selective” regions (faces versus non-face objects) and (ii) the map of “face-responsive” regions (faces versus scrambled images). Thus, the neural mechanisms underlying face perception and valence perception appear to be distinct.

A neural circuit covarying with social hierarchy in macaques.

A neural circuit that covaries with social hierarchy A neuroimaging study reveals that individual variation in brain circuits in structures below the cerebral cortex of macaques is associated with experience at different ends of the social hierarchy.

Amygdala lesions disrupt modulation of functional MRI activity evoked by facial expression in the monkey inferior temporal cortex

Significance Successful social interaction depends on the ability to recognize others, evaluate their mental states (e.g. intentions, desires, and beliefs), and “read” their emotional states. Here, we show that, in monkeys, damage to the amygdala, a brain structure that is central to the expression of emotion, significantly disrupts the processing of emotional facial expression in high-level visual cortical areas involved in face recognition. These findings suggest that the projections of the amygdala to visual cortical areas likely enhance the sensory processing of biologically important signals, including those related to potential environmental threats and social contexts. We previously showed that facial expressions modulate functional MRI activity in the face-processing regions of the macaque monkey’s amygdala and inferior temporal (IT) cortex. Specifically, we showed that faces expressing emotion yield greater activation than neutral faces; we term this difference the “valence effect.” We hypothesized that amygdala lesions would disrupt the valence effect by eliminating the modulatory feedback from the amygdala to the IT cortex. We compared the valence effects within the IT cortex in monkeys with excitotoxic amygdala lesions (n = 3) with those in intact control animals (n = 3) using contrast agent-based functional MRI at 3 T. Images of four distinct monkey facial expressions—neutral, aggressive (open mouth threat), fearful (fear grin), and appeasing (lip smack)—were presented to the subjects in a blocked design. Our results showed that in monkeys with amygdala lesions the valence effects were strongly disrupted within the IT cortex, whereas face responsivity (neutral faces > scrambled faces) and face selectivity (neutral faces > non-face objects) were unaffected. Furthermore, sparing of the anterior amygdala led to intact valence effects in the anterior IT cortex (which included the anterior face-selective regions), whereas sparing of the posterior amygdala led to intact valence effects in the posterior IT cortex (which included the posterior face-selective regions). Overall, our data demonstrate that the feedback projections from the amygdala to the IT cortex mediate the valence effect found there. Moreover, these modulatory effects are consistent with an anterior-to-posterior gradient of projections, as suggested by classical tracer studies.

Engagement of visual fixation suppresses sensory responsiveness and multisensory integration in the primate superior colliculus

Neurons in the intermediate and deep layers of the superior colliculus (SC) often exhibit sensory‐related activity in addition to discharging for saccadic eye movements. These two patterns of activity can combine so that modifications of the sensory response can lead to changes in orienting behaviour. Can behavioural factors, however, influence sensory activity? In this study of rhesus monkeys, we isolate one behavioural factor, the state of visual fixation, and examine its influences on sensory processing and multisensory integration in the primate SC. Two interleaved fixation conditions were used: a FIX condition requiring exogenous fixation of a visible fixation point; and a FIX‐BLINK condition, requiring endogenous fixation in the absence of a visible fixation point. Neurons of the SC were influenced by fixation state, exhibiting both lower levels of sensory activity and reduced multisensory interactions when fixation was exogenously engaged on a visible fixation point. These results are consistent with active visual fixation suppressing responses to extraneous stimuli, and thus demonstrate that sensory processing and multisensory responses in the SC are not dependent solely on the physical properties of the sensory environment, but are also dynamically influenced by the behavioural state of the animal.

Contrasting Roles for Orbitofrontal Cortex and Amygdala in Credit Assignment and Learning in Macaques

Summary Recent studies have challenged the view that orbitofrontal cortex (OFC) and amygdala mediate flexible reward-guided behavior. We trained macaques to perform an object discrimination reversal task during fMRI sessions and identified a lateral OFC (lOFC) region in which activity predicted adaptive win-stay/lose-shift behavior. Amygdala and lOFC activity was more strongly coupled on lose-shift trials. However, lOFC-amygdala coupling was also modulated by the relevance of reward information in a manner consistent with a role in establishing how credit for reward should be assigned. Day-to-day fluctuations in signals and signal coupling were correlated with day-to-day fluctuation in performance. A second experiment confirmed the existence of signals for adaptive stay/shift behavior in lOFC and reflecting irrelevant reward in the amygdala in a probabilistic learning task. Our data demonstrate that OFC and amygdala each make unique contributions to flexible behavior and credit assignment.

Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography

It has been suggested that some cortically blind patients can process the emotional valence of visual stimuli via a fast, subcortical pathway from the superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide in vivo evidence for connectivity between the SC and the amygdala via the pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor imaging tractography revealed a streamlined path that passes dorsolaterally through the pulvinar before arcing rostrally to traverse above the temporal horn of the lateral ventricle and connect to the lateral amygdala. To obviate artifactual connectivity with crossing fibers of the stria terminalis, the stria was also dissected. The putative streamline between the SC and amygdala traverses above the temporal horn dorsal to the stria terminalis and is positioned medial to it in humans and lateral to it in monkeys. The topography of the streamline was examined in relation to lesion anatomy in five patients who had previously participated in behavioral experiments studying the processing of emotionally valenced visual stimuli. The pulvinar lesion interrupted the streamline in two patients who had exhibited contralesional processing deficits and spared the streamline in three patients who had no deficit. Although not definitive, this evidence supports the existence of a subcortical pathway linking the SC with the amygdala in primates. It also provides a necessary bridge between behavioral data obtained in future studies of neurological patients, and any forthcoming evidence from more invasive techniques, such as anatomical tracing studies and electrophysiological investigations only possible in nonhuman species.