There is growing evidence that impaired sensory-processing significantly contributes to the cognitive deficits found in schizophrenia. For example, the mismatch negativity (MMN) and P3a event-related potentials (ERPs), neurophysiological indices of sensory and cognitive function, are reduced in schizophrenia patients and may be used as biomarkers of the disease. In agreement with glutamatergic theories of schizophrenia, NMDA antagonists, such as ketamine, elicit many symptoms of schizophrenia when administered to normal subjects, including reductions in the MMN and the P3a. We sought to develop a nonhuman primate (NHP) model of schizophrenia based on NMDA-receptor blockade using subanesthetic administration of ketamine. This provided neurophysiological measures of sensory and cognitive function that were directly comparable to those recorded from humans. We first developed methods that allowed recording of ERPs from humans and rhesus macaques and found homologous MMN and P3a ERPs during an auditory oddball paradigm. We then investigated the effect of ketamine on these ERPs in macaques. As found in humans with schizophrenia, as well as in normal subjects given ketamine, we observed a significant decrease in amplitude of both ERPs. Our findings suggest the potential of a pharmacologically induced model of schizophrenia in NHPs that can pave the way for EEG-guided investigations into cellular mechanisms and therapies. Furthermore, given the established link between these ERPs, the glutamatergic system, and deficits in other neuropsychiatric disorders, our model can be used to investigate a wide range of pathologies.brain | psychiatry | neurology | monkey | medicine S chizophrenia is a multifaceted disorder that may originate from neuronal pathology in multiple brain systems (1). Current theories suggest that some of the sensory and cognitive symptoms of schizophrenia may, at least partially, result from dysfunction of the glutamate neurotransmitter system (2). In support of this theory, it has been found that acute subanesthetic doses of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine induces sensory and cognitive deficits akin to those experienced by schizophrenia patients, as well as decreases of the mismatch negativity (MMN) and P3 event-related potential (ERP) amplitudes (3).The MMN is thought to reflect preattentive detection of a deviant stimulus (4), whereas the P3 is thought to reflect the redirection of attention to that deviant stimulus (5). In an oddball paradigm, responses to deviant (or "oddball") stimuli occurring among a sequence of standard stimuli are measured. The MMN is obtained by subtracting the ERP to the standard stimulus from the ERP to the deviant stimulus, whereas the P3a is typically observed in the ERP to deviants.Schizophrenia patients appear less able to detect and direct attention to novel stimuli than healthy controls (6). Consistent with this behavioral deficit, the amplitudes of both the MMN (7) and the P3 (8) have been found to be reduced in schizophrenia patients, l...

The origin of brain mechanisms that support human language-whether these originated de novo in humans or evolved from a neural substrate that existed in a common ancestor-remains a controversial issue. Although the answer is not provided by the fossil record, it is possible to make inferences by studying living species of nonhuman primates. Here we identified neural systems associated with perceiving species-specific vocalizations in rhesus macaques using H(2)(15)O positron emission tomography (PET). These vocalizations evoke distinct patterns of brain activity in homologs of the human perisylvian language areas. Rather than resulting from differences in elementary acoustic properties, this activity seems to reflect higher order auditory processing. Although parallel evolution within independent primate species is feasible, this finding suggests the possibility that the last common ancestor of macaques and humans, which lived 25-30 million years ago, possessed key neural mechanisms that were plausible candidates for exaptation during the evolution of language.

Non-human primates produce a diverse repertoire of speciesspecific calls and have rich conceptual systems. Some of their calls are designed to convey information about concepts such as predators, food, and social relationships, as well as the affective state of the caller. Little is known about the neural architecture of these calls, and much of what we do know is based on single-cell physiology from anesthetized subjects. By using positron emission tomography in awake rhesus macaques, we found that conspecific vocalizations elicited activity in higher-order visual areas, including regions in the temporal lobe associated with the visual perception of object form (TE͞TEO) and motion (superior temporal sulcus) and storing visual object information into long-term memory (TE), as well as in limbic (the amygdala and hippocampus) and paralimbic regions (ventromedial prefrontal cortex) associated with the interpretation and memory-encoding of highly salient and affective material. This neural circuitry strongly corresponds to the network shown to support representation of conspecifics and affective information in humans. These findings shed light on the evolutionary precursors of conceptual representation in humans, suggesting that monkeys and humans have a common neural substrate for representing object concepts.auditory ͉ brain ͉ evolution ͉ vocalizations ͉ concepts S tudies of the evolution of animal signaling systems reveal specializations of the peripheral and central nervous systems for producing and perceiving signals linked to survival and reproduction. These signals can be represented, both within and between species, in various modalities, including visual, auditory, olfactory, and tactile, and are often designed to convey considerable information about the signaler and its socioecological context. In particular, non-human primates have evolved complex auditory communication systems that can convey information about a variety of objects and events, such as individual identity (1), motivational state (2), reproductive status (3), body size (4), types of food (5), and predators (6). It has been argued that many of these calls are functionally linked to rich conceptual representations (5-8).In humans, evidence from behavioral (9), neuropsychological (10), and functional brain-imaging (11) studies suggests that conceptual representations are directly grounded in perception, action, and emotion. For example, functional brain-imaging studies have shown that tasks probing knowledge of animate things and social interactions activate a well defined network that includes regions in the posterior cortex associated with perceiving their visual form (including the fusiform face area) (12) and biological motion [superior temporal sulcus (STS)] (13), as well as limbic and paralimbic cortical areas involved in perceiving and modulating affect (especially the amygdala and medial prefrontal cortex) (11,14). Neural responses in these regions are elicited by a variety of input modalities, such as visual (12, 15) or auditory (16,...