Brain state monitoring for the future prediction of migraine attacks.

BACKGROUND: Migraine attacks are unpredictable, precluding preemptive interventions and leading to lack of control over individuals' lives. Although there are neurophysiological changes 24-48 hours before migraine attacks, so far, they have not been used in patients' management. This study evaluates the applicability and the ability to identify pre-attack changes of daily "at home" electroencephalography obtained with a portable system for migraine patients. METHODS: Patients with episodic migraine fulfilling ICHD-3 beta criteria used a mobile system composed of a wireless EEG device (BrainStation®, Neuroverse®, Inc., USA) and mobile application (BrainVitalsM®, Neuroverse®, Inc., USA) to self-record their neural activity daily at home while resting and while performing an attention task, over the course of 2 weeks. Standard EEG spectral analysis and event-related brain potentials (ERP) methods were used and recordings were grouped by time from migraine attacks (i.e. "Interictal day", "24 h Before Migraine", "Migraine day" and "Post Migraine"). RESULTS: Twenty-four patients (22 women) recorded an average of 13.3 ± 1.9 days and had 2 ± 0.9 attacks. Twenty-four hours before attack onset, there was a statistically significant modulation of relative power in the delta (decrease) and beta (increase) frequency bands, at rest, and a significant reduction of the amplitude and inter-trial coherence measures of an attention event-related brain potential (P300). CONCLUSIONS: This proof-of-concept study shows that brain state monitoring, utilising an easy-to-use wearable EEG system to track neural modulations at home, can identify physiological changes preceding a migraine attack enabling valuable pre-symptom prediction and subsequent early intervention.

Nonhuman primate model of schizophrenia using a noninvasive EEG method.

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.

Vervet monkeys and humans show brain asymmetries for processing conspecific vocalizations, but with opposite patterns of laterality.

A robust finding in the human neurosciences is the observation of a left hemisphere specialization for processing spoken language. Previous studies suggest that this auditory specialization and brain asymmetry derive from a primate ancestor. Most of these studies focus on the genus Macaca and all demonstrate a left hemisphere bias. Due to the narrow taxonomic scope, however, we lack a sense of the distribution of this asymmetry among primates. Further, although the left hemisphere bias appears mediated by conspecific calls, other possibilities exist including familiarity, emotional relevance and more general acoustic properties of the signal. To broaden the taxonomic scope and test the specificity of the apparent hemisphere bias, we conducted an experiment on vervets (Cercopithecus aethiops)-a different genus of old world monkeys and implemented the relevant acoustic controls. Using the same head orienting procedure tested with macaques, results show a strong left ear/right hemisphere bias for conspecific vocalizations (both familiar and unfamiliar), but no asymmetry for other primate vocalizations or non-biological sounds. These results suggest that although auditory asymmetries for processing species-specific vocalizations are a common feature of the primate brain, the direction of this asymmetry may be relatively plastic. This finding raises significant questions for how ontogenetic and evolutionary forces have impacted on primate brain evolution.

Species-specific calls activate homologs of Broca's and Wernicke's areas in the macaque.

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.

Using PET H2O15 brain imaging to study the functional-anatomical correlates of non-human primate communication.

In this article, we describe methods for using oxygen-15 water (H2O15) positron emission tomography (PET) to explore the functional neuroanatomy of cognition in awake, non-human primates. The discussion is based on a recent study designed to identify regions in the monkey brain associated with perceiving auditory stimuli, and species-specific calls, in particular [Gil-da-Costa et al., Proc. Natl. Acad. Sci. USA 101 (2004) 17516-17521]. Details are provided concerning critical aspects of the experimental paradigm, including pre-scanning habituation sessions to acclimate the animals to the PET scanner environment, and details of a pilot study to determine the auditory stimulus parameters necessary to produce robust activity in brain regions known to process auditory information (belt and parabelt regions of monkey auditory cortex). Methods for acquiring and analyzing PET data to identify significant regions of brain activity in single animals are also presented.

Toward an evolutionary perspective on conceptual representation: species-specific calls activate visual and affective processing systems in the macaque.

Non-human primates produce a diverse repertoire of species-specific 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 (TE/TEO) 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.

Rapid acquisition of an alarm response by a neotropical primate to a newly introduced avian predator.

Predation is an important selective pressure in natural ecosystems. Among non-human primates, relatively little is known about how predators hunt primate prey and how primates acquire adaptive responses to counteract predation. In this study we took advantage of the recent reintroduction of radio-tagged harpy eagles (Harpia harpyja) to Barro Colorado Island (BCI), Panama to explore how mantled howler monkeys (Alouatta palliata), one of their primary prey, acquire anti-predator defences. Based on the observation that harpies follow their prey prior to attack, and often call during this pursuit period, we broadcast harpy eagle calls to howlers on BCI as well as to a nearby control population with no harpy predation. Although harpies have been extinct from this area for 50-100 years, results indicate that BCI howlers rapidly acquired an adaptive anti-predator response to harpy calls, while showing no response to other avian vocalizations; howlers maintained this response several months after the removal of the eagles. These results not only show that non-human primates can rapidly acquire an alarm response to a newly introduced predator, but that they can detect and identify predators on the basis of acoustic cues alone. These findings have significant implications both for the role of learning mechanisms in the evolution of prey defence and for conservation strategies, suggesting that the use of 'probing' approaches, such as auditory playbacks, may highly enhance an a priori assessment of the impact of species reintroduction.