Humans and other primates somehow recognize whether objects have been seen in the recent past or not, that is, whether they are familiar, and the individual knows approximately when the object was last seen. This ability seems effortless. It has been hypothesized that rhinal cortex in the temporal lobe (Rh) and orbitofrontal cortex (OFC), and their interaction, are critical for this ability to classify objects as familiar or not. Anatomically orbitofrontal cortex and rhinal cortex are reciprocally connected within the same half of the brain. To test the hypothesis that they must interact for sensing visual object repetition in time, we produced a functional disconnection between these structures by removing the Rh in one hemisphere, and interfering with OFC function in the other hemisphere. The OFC interventions were of two types. In 3 monkeys the targeted OFC was removed. In two monkeys, neurons were silenced reversibly by using introducing a genetic tool into the tissue. This genetic tool, a DREADD (Designer Receptor Activated by Designer Drug), produces a receptor within the neurons that prevents normal neuronal activity when activated by a chemical, clozapine-N-oxide (CNO) given systemically. Three normal monkeys served as control subjects. Visual stimuli were presented one at a time, with a different stimulus presented in each trial. By the end of the testing session each stimulus would have appeared twice. The monkeys had to indicate whether the stimulus displayed was being presented for the first or second time. The interval between stimulus repetitions within a session varied between 0 to 128 stimuli. A stimulus set consisted of 6000 images. No stimulus was reused within a 30 day period. The three control monkeys reliably differentiated between the first and second presentations of stimuli. The performance of the monkeys with crossed Rh-OFC lesions was significantly worse than controls at all retention intervals tested. When the DREADD agent, the hM4di gene, was activated by systemic injection of clozapine-N-oxide (CNO) in the two DREADD treated monkeys, performance on the recognition memory task was mildly impaired compared to sessions without CNO administration. These results using the DREADD are equivocal so far. The possible explanations for the results are that an intact rhinal-orbitofrontal connection may only be necessary during the learning of the serial recognition test used here, and/or the volume of OFC tissue inactivated by the DREADD may have been insufficient to replicate the effect of the permanent removal. Finally the procedure for removing the OFC tissue might have inadvertently damaged fibers from neurons in other areas as they pass the region of the removal, so-called fibers of passage. Visual perceptual generalization is the process through which we assign objects into categories based on some similarity in their appearance. Previously we have demonstrated that rhesus monkeys quickly learn (in less than one testing session) a visual category task with two categories of stimuli, e.g., cats vs dogs. Inferior temporal (IT) cortex is considered a late stage of visual processing in the ventral visual pathway. Monkeys with lesions of IT cortex are impaired in discriminating between pairs of patterns. Single neurons in IT cortex, i.e. area TE, show selectivity for visual stimuli, most notably faces or complex objects. These findings lead to the inference that area TE plays a critical role in generating perceptual categories for faces or other objects. Previously we reported that, despite the importance of TE in visual perception and learning, removal of this cortex caused only a mild disruption in acquisition and retention of perceptual categories. This striking result led us to look elsewhere for candidate areas important for acquisition of perceptual categories, such as the rhinal cortex. Rhinal cortex (Rh) has extensive input from TE and other visual association areas. It is important for stimulus-stimulus and stimulus-reward associations, and is required for generalization across new views and discrimination between ambiguous stimuli. Under these conditions there was no impairment in categorization tasks. To ensure the groups were not using an A-not-A method to discriminate between pairs of categories (e.g. adopting a cat-versus-not cat strategy to discriminate cats from dogs), we introduced a category task that required discrimination among 6 interleaved categories (dogs, cats, cars, trucks, human faces and monkey faces) taken two at a time. This is now a more challenging categorization task, requiring simultaneous stimulus generalization, that is, recognizing the class the stimulus was in, and distinguishing the arbitrary assignment of stimulus classes with each other, that is, the monkey had to recognize both the generalized class, e.g., dog, but also learn that it belonged to the same category as trucks. The stimuli had seldom or never previously been presented in the past. Three control monkeys, three monkeys with bilateral TE ablations, and three with bilateral Rh ablations were tested. All of the monkeys discriminated easily and accurately among categories within the first testing session in which they were presented; thus neither TE nor rhinal cortex lesions alone produce a deficit in the ability to assign stimuli to one of multiple interleaved categories.
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