Spreading and synchronization of intrinsic signals in visual cortex of macaque monkey evoked by a localized visual stimulus

Spatio-temporal maps of the occipital cortex of macaque monkeys were analyzed using optical imaging of intrinsic signals. The images obtained during localized visual stimulation (IS) were compared with the images obtained on presentation of a blank screen (IB). We first investigated spontaneous variations of the intrinsic signals by analyzing the 100 IBs for each of the three cortical areas. Slow periodical activation was observed in alternation over the cortical areas. Cross-correlation analysis indicated that synchronization of spontaneous activation only took place within each cortical area, but not between them. When a small, drifting grating (2degreesX2degrees) was presented on the fovea. a dark spot appeared in the optical image at the cortical representation of this retinal location. It spread bilaterally along the border between V1 and V2, continuing as a number of parallel dark bands covering a large area of the lateral surface of V1. Cross-correlation analysis showed that during visual stimulation the intrinsic signals over all of the three cortical areas were synchronized, with in-phase activation of V1 and V2 and anti-phase activation of V4 and V1/V2. The significance of these extensive synergistic and antagonistic interactions between different cortical areas is discussed. (C) 2003 Elsevier B.V. All rights reserved.

A study of pyramidal cell structure in the cingulate cortex of the macaque monkey with comparative notes on inferotemporal and primary visual cortex

Recent studies have revealed a marked degree of variation in the pyramidal cell phenotype in visual, somatosensory, motor and prefrontal cortical areas in the brain of different primates, which are believed to subserve specialized cortical function. In the present study we carried out comparisons of dendritic structure of layer III pyramidal cells in the anterior and posterior cingulate cortex and compared their structure with those sampled from inferotemporal cortex (IT) and the primary visual area (V1) in macaque monkeys. Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors was determined, and somal areas measured. We found that pyramidal cells in anterior cingulate cortex were more branched and more spinous than those in posterior cingulate cortex, and cells in both anterior and posterior cingulate were considerably larger, more branched, and more spinous than those in area V1. These data show that pyramidal cell structure differs between posterior dysgranular and anterior granular cingulate cortex, and that pyramidal neurons in cingulate cortex have different structure to those in many other cortical areas. These results provide further evidence for a parallel between structural and functional specialization in cortex.

Visual thalamocortical projections in the flying fox: Parallel pathways to striate and extrastriate areas

We studied thalamic projections to the visual cortex in flying foxes, animals that share neural features believed to resemble those present in the brains of early primates. Neurones labeled by injections of fluorescent tracers in striate and extrastriate cortices were charted relative to the architectural boundaries of thalamic nuclei. Three main findings are reported: First, there are parallel lateral geniculate nucleus (LGN) projections to striate and extrastriate cortices. Second, the pulvinar complex is expansive, and contains multiple subdivisions. Third, across the visual thalamus, the location of cells labeled after visual cortex injections changes systematically, with caudal visual areas receiving their strongest projections from the most lateral thalamic nuclei, and rostral areas receiving strong projections from medial nuclei. We identified three architectural layers in the LGN, and three subdivisions of the pulvinar complex. The outer LGN layer contained the largest cells, and had strong projections to the areas V1, V2 and V3. Neurones in the intermediate LGN layer were intermediate in size, and projected to V1 and, less densely, to V2. The layer nearest to the origin of the optic radiation contained the smallest cells, and projected not only to V1, V2 and V3, but also, weakly, to the occipitotemporal area (OT, which is similar to primate middle temporal area) and the occipitoparietal area (OP, a third tier area located near the dorsal midline). V1, V2 and V3 received strong projections from the lateral and intermediate subdivisions of the pulvinar complex, while OP and OT received their main thalamic input from the intermediate and medial subdivisions of the pulvinar complex. These results suggest parallels with the carnivore visual system, and indicate that the restriction of the projections of the large- and intermediatesized LGN layers to V1, observed in present-day primates, evolved from a more generalized mammalian condition. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.

Detection of fruit and the selection of primate visual pigments for color vision

Primates have X chromosome genes for cone photopigments with sensitivity maxima from 535 to 562 nm. Old World monkeys and apes (catarrhines) and the New World ( platyrrhine) genus Alouatta have separate genes for 535-nm ( medium wavelength; M) and 562-nm ( long wavelength; L) pigments. These pigments, together with a 425-nm ( short wavelength) pigment, permit trichromatic color vision. Other platyrrhines and prosimians have a single X chromosome gene but often with alleles for two or three M/L photopigments. Consequently, heterozygote females are trichromats, but males and homozygote females are dichromats. The criteria that affect the evolution of M/L alleles and maintain genetic polymorphism remain a puzzle, but selection for finding food may be important. We compare different types of color vision for detecting more than 100 plant species consumed by tamarins ( Saguinus spp.) in Peru. There is evidence that both frequency-dependent selection on homozygotes and heterozygote advantage favor M/L polymorphism and that trichromatic color vision is most advantageous in dim light. Also, whereas the 562-nm allele is present in all species, the occurrence of 535- to 556-nm alleles varies between species. This variation probably arises because trichromatic color vision favors widely separated pigments and equal frequencies of 535/543- and 562-nm alleles, whereas in dichromats, long-wavelength pigment alleles are fitter.

Pyramidal cell specialization in the occipitotemporal cortex of the vervet monkey

Pyramidal cells were injected intracellularly in fixed, flat-mounted cortical slices taken from the first and fourth visual areas (VI and V4, respectively) and cytoarchitectonic areas TEO and TE of two age and gender-matched vervet monkeys and the size, branching complexity and spine density of their basal dendritic trees determined. In both animals, we found marked differences in the pyramidal cell phenotype between cortical areas. More specifically, a consistent trend for larger, more branched and more spinous pyramidal cells with progression through VI, V4, TEO and TE was observed. These findings support earlier reports of interareal specialization in pyramidal cell structure in occipitotemporal visual areas in the macaque monkey. (c) 2005 Lippincott Williams & Wilkins.

Pyramidal neurons of granular prefrontal cortex of the galago: Complexity in evolution of the psychic cell in primates

Typically, cognitive abilities of humans have been attributed to their greatly expanded cortical mantle, granular prefrontal cortex (gPFC) in particular. Recently we have demonstrated systematic differences in microstructure of gPFC in different species. Specifically, pyramidal cells in adult human gPFC are considerably more spinous than those in the gPFC of the macaque monkey, which are more spinous than those in the gPFC of marmoset and owl monkeys. As most cortical dendritic spines receive at least one excitatory input, pyramidal cells in these different species putatively receive different numbers of inputs. These differences in the gPFC pyramidal cell phenotype may be of fundamental importance in determining the functional characteristics of prefrontal circuitry and hence the cognitive styles of the different species. However, it remains unknown as to why the gPFC pyramidal cell phenotype differs between species. Differences could be attributed to, among other things, brain size, relative size of gPFC, or the lineage to which the species belong. Here we investigated pyramidal cells in the dorsolateral gPFC of the prosimian galago to extend the basis for comparison. We found these cells to be less spinous than those in human, macaque, and marmoset. (c) 2005 Wiley-Liss, Inc.

Resolving the organization of the New World monkey third visual complex: The dorsal extrastriate cortex of the marmoset (Callithrix jacchus)

We tested current hypotheses on the functional organization of the third visual complex, a particularly controversial region of the primate extrastriate cortex. In anatomical experiments, injections of retrograde tracers were placed in the dorsal cortex immediately rostral to the second visual area (V2) of New World monkeys (Callithrix jacchus), revealing the topography of interconnections between the third tier cortex and the primary visual area (V1). The data indicate the presence of a dorsomedial area (DM), which represents the entire upper and lower quadrants of the visual field, and which receives strong, topographically organized projections from the superficial layers of V1. The visuotopic organization and boundaries of DM were confirmed by electrophysiological recordings in the same animals and by architectural characteristics which were distinct from those found in ventral extrastriate cortex rostral to V2. There was no electrophysiological or histological evidence for a transitional area between V2 and DM. In particular, the central representation of the upper quadrant in DM was directly adjacent to the representation of the horizontal meridian that marks the rostral border of V2. The present results argue in favor of the hypothesis that the third visual complex in New World monkeys contains different areas in its dorsal and ventral components: area DM, near the dorsal midline, and a homolog of area 19 of other mammals, located more lateral and ventrally. The characteristics of DM suggest that it may correspond to visual area 6 (V6) of Old World monkeys. (C) 2005 Wiley-Liss, Inc.

Pyramidal cell specialization in the occipitotemporal cortex of the Chacma baboon (Papio ursinus)

Pyramidal cell structure varies systematically in occipitotemporal visual areas in monkeys. The dendritic trees of pyramidal cells, on average, become larger, more branched and more spinous with progression from the primary visual area (V1) to the second visual area (V2), the fourth (V4, or dorsolateral DL visual area) and inferotemporal (IT) cortex. Presently available data reveal that the extent of this increase in complexity parallels the expansion of occipitotemporal cortex. Here we extend the basis for comparison by studying pyramidal cell structure in occipitotemporal cortical areas in the chacma baboon. We found a systematic increase in the size of and branching complexity in the basal dendritic trees, as well as a progressive increase in the spine density along the basal dendrites of layer III pyramidal cells through V1, V2 and V4. These data suggest that the trend for more complex pyramidal cells with anterior progression through occipitotemporal visual areas is not a feature restricted to monkeys and prosimians, but is a widespread feature of occipitotemporal cortex in primates.

Brain maps, great and small: lessons from comparative studies of primate visual cortical organization

In this paper, we review evidence from comparative studies of primate cortical organization, highlighting recent findings and hypotheses that may help us to understand the rules governing evolutionary changes of the cortical map and the process of formation of areas during development. We argue that clear unequivocal views of cortical areas and their homologies are more likely to emerge for 'core' fields, including the primary sensory areas, which are specified early in development by precise molecular identification steps. In primates, the middle temporal area is probably one of these primordial cortical fields. Areas that form at progressively later stages of development correspond to progressively more recent evolutionary events, their development being less firmly anchored in molecular specification. The certainty with which areal boundaries can be delimited, and likely homologies can be assigned, becomes increasingly blurred in parallel with this evolutionary/developmental sequence. For example, while current concepts for the definition of cortical areas have been vindicated in allowing a clarification of the organization of the New World monkey 'third tier' visual cortex (the third and dorsomedial areas, V3 and DM), our analyses suggest that more flexible mapping criteria may be needed to unravel the organization of higher-order visual association and polysensory areas.

West Nile and St. Louis encephalitis virus antibody seroconversion, prevalence, and persistence in naturally infected pig-tailed macaques (Macaca nemestrina)

Pig-tailed macaques (Macaca nemestrina) naturally infected with West Nile virus were monitored from 1999 to 2005 to determine virus-specific antibody seroconversion, prevalence, and persistence. Antibodies persisted for up to 36 months, as detected by epitope-blocking enzyme-linked immunosorbent and hemagglutination inhibition assays. Exposure to cocirculating St. Louis encephalitis virus was evaluated by Western blotting and immunofluorescence assays.

Disturbing visual working memory:electrophysiological evidence for a role of the prefrontal cortex in recovery from interference

Single cell recordings in monkeys support the notion that the lateral prefrontal cortex (PFC) controls reactivation of visual working memory representations when rehearsal is disrupted. In contrast, recent fMRI findings yielded a double dissociation for PFC and the medial temporal lobe (MTL) in a letter working memory task. PFC was engaged in interference protection during reactivation while MTL was prominently involved in the retrieval of the letter representations. We present event-related potential data (ERP) that support PFC involvement in the top-down control of reactivation during a visual working memory task with endogenously triggered recovery after visual interference. A differentiating view is proposed for the role of PFC in working memory with respect to endogenous/exogenous control and to stimulus type. General implications for binding and retention mechanisms are discussed.

Mirror self-recognition in a gorilla (gorilla gorilla gorilla)

Psychologists have studied self-recognition in human infants as an indication of self-knowledge (Amsterdam, 1972) and the development of abstract thought processes. Gallup (1970) modified the mark test used in human infant work to examine if nonhuman primates showed similar evidence of mirror self-recognition. Chimpanzees (Pan troglodytes) and orangutans (Pongo pygmnaeus) pass the mirror self-recognition test with limited mirror training or exposure. Other species of primates, such as gorillas and monkeys, have not passed the mirror test, despite extensive mirror exposure and training (Gallup, 1979). This project examined a gorilla (G. gorilla gorilla) named Otto in the traditional mark test. Using the modified mark-test, there were more incidents of touching the marked area while Otto was in front of the mirror than when he was not in front of the mirror. These results indicated that Otto was able to show some evidence of selfawareness.

O papel dos quintais urbanos na segurança alimentar, bem estar e conservação da biodiversidade

Residential homegardens have environmental and social roles in the urban environment. These green spaces can potentially minimize the impacts caused by the growth of cities, being an alternative to connect fragmented areas or offer refuge to wildlife and therefore support the conservation of biodiversity. In addition, the homegardens demonstrate a leading role in increasing human well-being by promoting socialization opportunities, contact with nature, local culture as well as improvements in food security for the urban families. Nevertheless, it is still unclear what specific characteristics of homegardens can act effectively in the conservation of the biodiversity, as well as in the construction of food security and well being of the homegardeners and their families. The first chapter of this thesis analyzed the diversity of plant species (native and exotic) and assessed the contribution of different types of urban gardens (ornamental and forest gardens alike) in the presence of wildlife such as birds, monkeys and lizards. In the second chapter we evaluated the contribution of those gardens to the welfare and food security of their owners. In order to do this, 41 gardens were visited in Pium, a southern coastal town in the northeastern Brazil, which also happens to be in a periurban region undergoing rapid urban expansion and pressure from the real estate market. We surveyed the planned biodiversity and fauna associated with homegardens. The data related to food security and welfare were sampled through interviews with the person in charge of taking care of the gardens. These interviews covered issues on the supply of food from the garden and absence of chemical products, as well as aspects of the GNH indicator (Gross National Happiness). The results showed that these homegardens generally contribute little to the maintenance of native plant species (native species = 29/ total = 187). From its main features, the gardens were classified as ornamental, forest gardens and forest farms. These groups had a different effect on the presence of the animals studied and the last two contained most of the sampled native species. The diversity of plants and trees was a good predictor of the presence of birds and monkeys. Thus, the contribution of yards for the conservation of biodiversity depends on the type of garden: some even can have negative effects on conservation. These results can direct new approaches to detailed understanding of gardens and also of public policies applied to urban planning. The results of the second chapter showed that the two types of forest gardens contributed to household food security, for providing food and medicinal herbs, which mostly did not have pesticides and chemical 12 fertilizers. But the three groups of gardens are important components for the well being of their stakeholders. Gardens help promote the transmission of knowledge on agriculture, socialization, contact with nature and bring up feelings related to peace and harmony. Thus, forest gardens can be considered important means to get through public projects and policies designed to encourage biodiversity and promote food security and well-being in urban areas

Non-auditory Influences on the Auditory Periphery

Once thought to be predominantly the domain of cortex, multisensory integration has now been found at numerous sub-cortical locations in the auditory pathway. Prominent ascending and descending connection within the pathway suggest that the system may utilize non-auditory activity to help filter incoming sounds as they first enter the ear. Active mechanisms in the periphery, particularly the outer hair cells (OHCs) of the cochlea and middle ear muscles (MEMs), are capable of modulating the sensitivity of other peripheral mechanisms involved in the transduction of sound into the system. Through indirect mechanical coupling of the OHCs and MEMs to the eardrum, motion of these mechanisms can be recorded as acoustic signals in the ear canal. Here, we utilize this recording technique to describe three different experiments that demonstrate novel multisensory interactions occurring at the level of the eardrum. 1) In the first experiment, measurements in humans and monkeys performing a saccadic eye movement task to visual targets indicate that the eardrum oscillates in conjunction with eye movements. The amplitude and phase of the eardrum movement, which we dub the Oscillatory Saccadic Eardrum Associated Response or OSEAR, depended on the direction and horizontal amplitude of the saccade and occurred in the absence of any externally delivered sounds. 2) For the second experiment, we use an audiovisual cueing task to demonstrate a dynamic change to pressure levels in the ear when a sound is expected versus when one is not. Specifically, we observe a drop in frequency power and variability from 0.1 to 4kHz around the time when the sound is expected to occur in contract to a slight increase in power at both lower and higher frequencies. 3) For the third experiment, we show that seeing a speaker say a syllable that is incongruent with the accompanying audio can alter the response patterns of the auditory periphery, particularly during the most relevant moments in the speech stream. These visually influenced changes may contribute to the altered percept of the speech sound. Collectively, we presume that these findings represent the combined effect of OHCs and MEMs acting in tandem in response to various non-auditory signals in order to manipulate the receptive properties of the auditory system. These influences may have a profound, and previously unrecognized, impact on how the auditory system processes sounds from initial sensory transduction all the way to perception and behavior. Moreover, we demonstrate that the entire auditory system is, fundamentally, a multisensory system.

Stimulus Integration and Parsing in the Primate Auditory Midbrain

Integrating information from multiple sources is a crucial function of the brain. Examples of such integration include multiple stimuli of different modalties, such as visual and auditory, multiple stimuli of the same modality, such as auditory and auditory, and integrating stimuli from the sensory organs (i.e. ears) with stimuli delivered from brain-machine interfaces.

The overall aim of this body of work is to empirically examine stimulus integration in these three domains to inform our broader understanding of how and when the brain combines information from multiple sources.

First, I examine visually-guided auditory, a problem with implications for the general problem in learning of how the brain determines what lesson to learn (and what lessons not to learn). For example, sound localization is a behavior that is partially learned with the aid of vision. This process requires correctly matching a visual location to that of a sound. This is an intrinsically circular problem when sound location is itself uncertain and the visual scene is rife with possible visual matches. Here, we develop a simple paradigm using visual guidance of sound localization to gain insight into how the brain confronts this type of circularity. We tested two competing hypotheses. 1: The brain guides sound location learning based on the synchrony or simultaneity of auditory-visual stimuli, potentially involving a Hebbian associative mechanism. 2: The brain uses a ‘guess and check’ heuristic in which visual feedback that is obtained after an eye movement to a sound alters future performance, perhaps by recruiting the brain’s reward-related circuitry. We assessed the effects of exposure to visual stimuli spatially mismatched from sounds on performance of an interleaved auditory-only saccade task. We found that when humans and monkeys were provided the visual stimulus asynchronously with the sound but as feedback to an auditory-guided saccade, they shifted their subsequent auditory-only performance toward the direction of the visual cue by 1.3-1.7 degrees, or 22-28% of the original 6 degree visual-auditory mismatch. In contrast when the visual stimulus was presented synchronously with the sound but extinguished too quickly to provide this feedback, there was little change in subsequent auditory-only performance. Our results suggest that the outcome of our own actions is vital to localizing sounds correctly. Contrary to previous expectations, visual calibration of auditory space does not appear to require visual-auditory associations based on synchrony/simultaneity.

My next line of research examines how electrical stimulation of the inferior colliculus influences perception of sounds in a nonhuman primate. The central nucleus of the inferior colliculus is the major ascending relay of auditory information before it reaches the forebrain, and thus an ideal target for understanding low-level information processing prior to the forebrain, as almost all auditory signals pass through the central nucleus of the inferior colliculus before reaching the forebrain. Thus, the inferior colliculus is the ideal structure to examine to understand the format of the inputs into the forebrain and, by extension, the processing of auditory scenes that occurs in the brainstem. Therefore, the inferior colliculus was an attractive target for understanding stimulus integration in the ascending auditory pathway.

Moreover, understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5-80 µA, 100-300 Hz, n=172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals’ judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site in comparison to the reference frequency employed in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site’s response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated and provide a greater range of evoked percepts.

My next line of research employs a frequency-tagging approach to examine the extent to which multiple sound sources are combined (or segregated) in the nonhuman primate inferior colliculus. In the single-sound case, most inferior colliculus neurons respond and entrain to sounds in a very broad region of space, and many are entirely spatially insensitive, so it is unknown how the neurons will respond to a situation with more than one sound. I use multiple AM stimuli of different frequencies, which the inferior colliculus represents using a spike timing code. This allows me to measure spike timing in the inferior colliculus to determine which sound source is responsible for neural activity in an auditory scene containing multiple sounds. Using this approach, I find that the same neurons that are tuned to broad regions of space in the single sound condition become dramatically more selective in the dual sound condition, preferentially entraining spikes to stimuli from a smaller region of space. I will examine the possibility that there may be a conceptual linkage between this finding and the finding of receptive field shifts in the visual system.

In chapter 5, I will comment on these findings more generally, compare them to existing theoretical models, and discuss what these results tell us about processing in the central nervous system in a multi-stimulus situation. My results suggest that the brain is flexible in its processing and can adapt its integration schema to fit the available cues and the demands of the task.