M Augath

Neurophysiological investigation of the basis of the fMRI signal

Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trial-by-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.

Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1

Most functional brain imaging studies use task-induced hemodynamic responses to infer underlying changes in neuronal activity. In addition to increases in cerebral blood flow and blood oxygenation level–dependent (BOLD) signals, sustained negative responses are pervasive in functional imaging. The origin of negative responses and their relationship to neural activity remain poorly understood. Through simultaneous functional magnetic resonance imaging and electrophysiological recording, we demonstrate a negative BOLD response (NBR) beyond the stimulated regions of visual cortex, associated with local decreases in neuronal activity below spontaneous activity, detected 7.15 ± 3.14 mm away from the closest positively responding region in V1. Trial-by-trial amplitude fluctuations revealed tight coupling between the NBR and neuronal activity decreases. The NBR was associated with comparable decreases in local field potentials and multiunit activity. Our findings indicate that a significant component of the NBR originates in neuronal activity decreases.

Integration of touch and sound in auditory cortex

To form a coherent percept of the environment, our brain combines information from different senses. Such multisensory integration occurs in higher association cortices; but supposedly, it also occurs in early sensory areas. Confirming the latter hypothesis, we unequivocally demonstrate supra-additive integration of touch and sound stimulation at the second stage of the auditory cortex. Using high-resolution fMRI of the macaque monkey, we quantified the integration of auditory broad-band noise and tactile stimulation of hand and foot in anaesthetized animals. Integration was found posterior to and along the lateral side of the primary auditory cortex in the caudal auditory belt. Integration was stronger for temporally coincident stimuli and obeyed the principle of inverse effectiveness: greater enhancement for less effective stimuli. These findings demonstrates that multisensory integration occurs early and close to primary sensory areas and--because it occurs in anaesthetized animals--suggests that this integration is mediated by preattentive bottom-up mechanisms.

Integration of local features into global shapes: monkey and human FMRI studies

The integration of local image features into global shapes was investigated in monkeys and humans using fMRI. An adaptation paradigm was used, in which stimulus selectivity was deduced by changes in the course of adaptation of a pattern of randomly oriented elements. Accordingly, we observed stronger activity when orientation changes in the adapting stimulus resulted in a collinear contour than a different random pattern. This selectivity to collinear contours was observed not only in higher visual areas that are implicated in shape processing, but also in early visual areas where selectivity depended on the receptive field size. These findings suggest that unified shape perception in both monkeys and humans involves multiple visual areas that may integrate local elements to global shapes at different spatial scales.

Magnetic Resonance Imaging of Neuronal Connections in the Macaque Monkey

Recently, an MRI-detectable, neuronal tract-tracing method in living animals was introduced that exploits the anterograde transport of manganese (Mn2+). We present the results of experiments simultaneously tracing manganese chloride and wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) to evaluate the specificity of the former by tracing the neuronal connections of the basal ganglia of the monkey. Mn2+ and WGA-HRP yielded remarkably similar and highly specific projection patterns. By showing the sequential transport of Mn2+ from striatum to pallidum-substantia nigra and then to thalamus, we demonstrated MRI visualization of transport across at least one synapse in the CNS of the primate. Transsynaptic tract tracing in living primates will allow chronic studies of development and plasticity and provide valuable anatomical information for fMRI and electrophysiological experiments in primates.

Functional Imaging Reveals Visual Modulation of Specific Fields in Auditory Cortex

Merging the information from different senses is essential for successful interaction with real-life situations. Indeed, sensory integration can reduce perceptual ambiguity, speed reactions, or change the qualitative sensory experience. It is widely held that integration occurs at later processing stages and mostly in higher association cortices; however, recent studies suggest that sensory convergence can occur in primary sensory cortex. A good model for early convergence proved to be the auditory cortex, which can be modulated by visual and tactile stimulation; however, given the large number and small size of auditory fields, neither human imaging nor microelectrode recordings have systematically identified which fields are susceptible to multisensory influences. To reconcile findings from human imaging with anatomical knowledge from nonhuman primates, we exploited high-resolution imaging (functional magnetic resonance imaging) of the macaque monkey to study the modulation of auditory processing by visual stimulation. Using a functional parcellation of auditory cortex, we localized modulations to individual fields. Our results demonstrate that both primary (core) and nonprimary (belt) auditory fields can be activated by the mere presentation of visual scenes. Audiovisual convergence was restricted to caudal fields [prominently the core field (primary auditory cortex) and belt fields (caudomedial field, caudolateral field, and mediomedial field)] and continued in the auditory parabelt and the superior temporal sulcus. The same fields exhibited enhancement of auditory activation by visual stimulation and showed stronger enhancement for less effective stimuli, two characteristics of sensory integration. Together, these findings reveal multisensory modulation of auditory processing prominently in caudal fields but also at the lowest stages of auditory cortical processing.

The effects of electrical microstimulation on cortical signal propagation

Electrical stimulation has been used in animals and humans to study potential causal links between neural activity and specific cognitive functions. Recently, it has found increasing use in electrotherapy and neural prostheses. However, the manner in which electrical stimulation–elicited signals propagate in brain tissues remains unclear. We used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in the lateral geniculate nucleus (LGN) increased the fMRI signal in the regions of primary visual cortex (V1) that received input from that site, but suppressed it in the retinotopically matched regions of extrastriate cortex. Consistent with previous observations, intracranial recordings indicated that a short excitatory response occurring immediately after a stimulation pulse was followed by a long-lasting inhibition. Following microinjections of GABA antagonists in V1, LGN stimulation induced positive fMRI signals in all of the cortical areas. Taken together, our findings suggest that electrical stimulation disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated.

Functional imaging reveals numerous fields in the monkey auditory cortex.

Anatomical studies propose that the primate auditory cortex contains more fields than have actually been functionally confirmed or described. Spatially resolved functional magnetic resonance imaging (fMRI) with carefully designed acoustical stimulation could be ideally suited to extend our understanding of the processing within these fields. However, after numerous experiments in humans, many auditory fields remain poorly characterized. Imaging the macaque monkey is of particular interest as these species have a richer set of anatomical and neurophysiological data to clarify the source of the imaged activity. We functionally mapped the auditory cortex of behaving and of anesthetized macaque monkeys with high resolution fMRI. By optimizing our imaging and stimulation procedures, we obtained robust activity throughout auditory cortex using tonal and band-passed noise sounds. Then, by varying the frequency content of the sounds, spatially specific activity patterns were observed over this region. As a result, the activity patterns could be assigned to many auditory cortical fields, including those whose functional properties were previously undescribed. The results provide an extensive functional tessellation of the macaque auditory cortex and suggest that 11 fields contain neurons tuned for the frequency of sounds. This study provides functional support for a model where three fields in primary auditory cortex are surrounded by eight neighboring “belt” fields in non-primary auditory cortex. The findings can now guide neurophysiological recordings in the monkey to expand our understanding of the processing within these fields. Additionally, this work will improve fMRI investigations of the human auditory cortex.

Mapping Cortical Activity Elicited with Electrical Microstimulation Using fMRI in the Macaque

Over the last two centuries, electrical microstimulation has been used to demonstrate causal links between neural activity and specific behaviors and cognitive functions. However, to establish these links it is imperative to characterize the cortical activity patterns that are elicited by stimulation locally around the electrode and in other functionally connected areas. We have developed a technique to record brain activity using the blood oxygen level dependent (BOLD) signal while applying electrical microstimulation to the primate brain. We find that the spread of activity around the electrode tip in macaque area V1 was larger than expected from calculations based on passive spread of current and therefore may reflect functional spread by way of horizontal connections. Consistent with this functional transynaptic spread we also obtained activation in expected projection sites in extrastriate visual areas, demonstrating the utility of our technique in uncovering in vivo functional connectivity maps.

Lack of long-term cortical reorganization after macaque retinal lesions

Several aspects of cortical organization are thought to remain plastic into adulthood, allowing cortical sensorimotor maps to be modified continuously by experience. This dynamic nature of cortical circuitry is important for learning, as well as for repair after injury to the nervous system. Electrophysiology studies suggest that adult macaque primary visual cortex (V1) undergoes large-scale reorganization within a few months after retinal lesioning, but this issue has not been conclusively settled. Here we applied the technique of functional magnetic resonance imaging (fMRI) to detect changes in the cortical topography of macaque area V1 after binocular retinal lesions. fMRI allows non-invasive, in vivo, long-term monitoring of cortical activity with a wide field of view, sampling signals from multiple neurons per unit cortical area. We show that, in contrast with previous studies, adult macaque V1 does not approach normal responsivity during 7.5 months of follow-up after retinal lesions, and its topography does not change. Electrophysiology experiments corroborated the fMRI results. This indicates that adult macaque V1 has limited potential for reorganization in the months following retinal injury.