Recordings In Non-human Primates Research Articles

Proactive and reactive control by the medial frontal cortex

Adaptive behavior requires the ability to flexibly control actions. This can occur either proactively to anticipate task requirements, or reactively in response to sudden changes. Recent work in humans has identified a network of cortical and subcortical brain region that might have an important role in proactive and reactive control. However, due to technical limitations, such as the spatial and temporal resolution of the BOLD signal, human imaging experiments are not able to disambiguate the specific function(s) of these brain regions. These limitations can be overcome through single-unit recordings in non-human primates. In this article, we describe the behavioral and physiological evidence for dual mechanisms of control in response inhibition in the medial frontal cortex of monkeys performing the stop signal or countermanding task.

Decoding Effector-Dependent and Effector-Independent Movement Intentions from Human Parieto-Frontal Brain Activity

Our present understanding of the neural mechanisms and sensorimotor transformations that govern the planning of arm and eye movements predominantly come from invasive parieto-frontal neural recordings in nonhuman primates. While functional MRI (fMRI) has motivated investigations on much of these same issues in humans, the highly distributed and multiplexed organization of parieto-frontal neurons necessarily constrain the types of intention-related signals that can be detected with traditional fMRI analysis techniques. Here we employed multivoxel pattern analysis (MVPA), a multivariate technique sensitive to spatially distributed fMRI patterns, to provide a more detailed understanding of how hand and eye movement plans are coded in human parieto-frontal cortex. Subjects performed an event-related delayed movement task requiring that a reach or saccade be planned and executed toward one of two spatial target positions. We show with MVPA that, even in the absence of signal amplitude differences, the fMRI spatial activity patterns preceding movement onset are predictive of upcoming reaches and saccades and their intended directions. Within certain parieto-frontal regions we show that these predictive activity patterns reflect a similar spatial target representation for the hand and eye. Within some of the same regions, we further demonstrate that these preparatory spatial signals can be discriminated from nonspatial, effector-specific signals. In contrast to the largely graded effector- and direction-related planning responses found with fMRI subtraction methods, these results reveal considerable consensus with the parieto-frontal network organization suggested from primate neurophysiology and specifically show how predictive spatial and nonspatial movement information coexists within single human parieto-frontal areas.

Decoding Action Intentions from Preparatory Brain Activity in Human Parieto-Frontal Networks

How and where in the human brain high-level sensorimotor processes such as intentions and decisions are coded remain important yet essentially unanswered questions. This is in part because, to date, decoding intended actions from brain signals has been primarily constrained to invasive neural recordings in nonhuman primates. Here we demonstrate using functional MRI (fMRI) pattern recognition techniques that we can also decode movement intentions from human brain signals, specifically object-directed grasp and reach movements, moments before their initiation. Subjects performed an event-related delayed movement task toward a single centrally located object (consisting of a small cube attached atop a larger cube). For each trial, after visual presentation of the object, one of three hand movements was instructed: grasp the top cube, grasp the bottom cube, or reach to touch the side of the object (without preshaping the hand). We found that, despite an absence of fMRI signal amplitude differences between the planned movements, the spatial activity patterns in multiple parietal and premotor brain areas accurately predicted upcoming grasp and reach movements. Furthermore, the patterns of activity in a subset of these areas additionally predicted which of the two cubes were to be grasped. These findings offer new insights into the detailed movement information contained in human preparatory brain activity and advance our present understanding of sensorimotor planning processes through a unique description of parieto-frontal regions according to the specific types of hand movements they can predict.

FMRI Adaptation Reveals a Cortical Mechanism for the Coding of Space Near the Hand

Behavioral studies in humans and electrophysiological recordings in nonhuman primates have suggested the existence of a specific representation of the space immediately surrounding the body. In macaques, neurons that have visual receptive fields limited to a region of space close around a body part have been found in premotor and parietal areas. These cells are hypothesized to encode the location of external objects in coordinate systems that are centered on individual body parts. In the present study, we used an fMRI adaptation paradigm on healthy participants to reveal areas in the anterior part of the intraparietal sulcus, the inferior parietal lobe (supramarginal gyrus), and the dorsal and ventral portions of the premotor cortex that exhibit selective BOLD adaptation to an object moving near the right hand. Crucially, these areas did not manifest adaptation if the stimulus was presented in far space (100 cm) or when the hand was retracted from the object. This hand-centered selectivity could not be detected when a traditional fMRI analysis approach was used. These findings are important as they provide the most conclusive neuroimaging evidence to date for a representation of near-personal space in the human brain. They also demonstrate a selective mechanism implemented by human perihand neurons in the premotor and posterior parietal areas and add to earlier findings from humans and nonhuman primates.

Fractionating the Default Mode Network: Distinct Contributions of the Ventral and Dorsal Posterior Cingulate Cortex to Cognitive Control

The posterior cingulate cortex (PCC) is a central part of the default mode network (DMN) and part of the structural core of the brain. Although the PCC often shows consistent deactivation when attention is focused on external events, anatomical studies show that the region is not homogeneous, and electrophysiological recordings in nonhuman primates suggest that it is directly involved in some forms of attention. We report a functional magnetic resonance imaging study of an attentionally demanding task (either a zero- or two-back working memory task). Standard subtraction analysis within the PCC shows a relative deactivation as task difficulty increases. In contrast, a dual-regression functional connectivity analysis reveals a clear dissociation between ventral and dorsal parts of the PCC. As task difficulty increases, the ventral PCC shows reduced integration within the DMN and less anticorrelation with the cognitive control network (CCN) activated by the task. The dorsal PCC shows an opposite pattern, with increased DMN integration and more anticorrelation. At rest, the dorsal PCC also shows functional connectivity with both the DMN and attentional networks. As expected, these results provide evidence that the PCC is involved in supporting internally directed thought, as the region is more highly integrated with the DMN at low task demands. In contrast, the task-dependent increases in connectivity between the dorsal PCC and the CCN are consistent with a role for this region in modulating the dynamic interaction between these two networks controlling the efficient allocation of attention.

Visual Aftereffects for Walking Actions Reveal Underlying Neural Mechanisms for Action Recognition

The results of this study illustrate a new high-level visual aftereffect: Observing actors walking forward, without horizontal translation, makes subsequent actors appear to walk backward, and the opposite effect is obtained after observing backward walking. We used this aftereffect, which cannot be explained by simple low-level adaptation to motion direction, to investigate the properties of neural mechanisms underlying recognition of walking actions. Our results suggest that the perception of walking and the perception of static images of actors in walking postures rely on common brain mechanisms that are primarily object centered, rather than viewer centered, and that are blind to the identity of the actor. These results, obtained with human psychophysical adaptation techniques, support previous evidence accumulated using single-unit recording in nonhuman primates. In addition, these results provide evidence that current models of human action recognition require an object-centered processing stage.

A non-invasive technique to monitor wakefulness during electrophysiologic recording experiments in primates

Although the state of wakefulness has an impact on many physiological parameters, this variable is seldom controlled for in in vivo experiments, because the existing techniques to identify periods of wakefulness are laborious and difficult to implement. We here report on a simple non-invasive technique to achieve this goal, using the analysis of video material, collected along with the electrophysiologic data, to analyze eyelid movements. The technique was applied to recordings in non-human primates, and allowed us to automatically identify periods during which the subject has its eyes open. A comparison with frontal electroencephalographic records confirmed that such periods corresponded to wakefulness.

Uncorrupted recording of neurons during microstimulation in situ : Cleaning out the artifacts

An intractable limitation in electrophysiology has been the corruption of neural recording when electrical stimulation is applied within the same tissue. Because stimulation pulses corrupt the neural recordings with large artifacts, neural activity that falls within the time course of the artifacts are obscured or corrupted. Using an adaptive noise cancellation technique, we have developed a real-time method for recording neural activity during experimental microstimulation without interfering with the spectrum of the neural recording. We have developed the technique during in vivo extracellular recording in non-human primates while using microstimulation to activate or perturb ongoing behaviors. We can accurately recover action potentials during prolonged stimulation, regardless of the size, shape, or timing between action potentials and stimulation artifacts. Signal detection reliability for recovery of action potentials can achieve better than one error in 104. Analytical and preliminary experimental studies demonstrate the utility of the technique for intracellular recording as well. Electronic development supported by Riverbend Instruments, Inc.; JWG is supported by NEI (R01-EY015870, R03_EY016234 ) and NINDS (U54_NS039407).

Multisensory processing and oscillatory activity: analyzing non-linear electrophysiological measures in humans and simians

Stimulus-related oscillations are known to be closely linked to integrative processing in the brain. One research domain within which there has been tremendous interest in oscillatory mechanisms is in the integration of inputs across the widely separated sensory systems. Under the standard approach of assessing multisensory interactions in electrophysiological datasets, the event-related response to a multisensory stimulus is directly compared with the sum of the responses to its unisensory constituents when presented alone. When using methods like wavelet transformation or fast Fourier transformation to derive induced oscillatory signals, however, such linear operations are not appropriate. Here we introduce a simple bootstrapping procedure wherein the linear summation of single unisensory trials forms a distribution against which multisensory trials may be statistically compared, an approach that circumvents the issue of non-linearity when combining unisensory oscillatory responses. To test this approach we applied it to datasets from intracranial recordings in non-human primates and human scalp-recorded EEG, both derived from a simple audio-visual integration paradigm. Significant multisensory interactions were revealed in oscillatory activity centered at 15 and 20 Hz (the so-called beta band). Simulations of different levels of background noise further validated the results obtained by this method. By demonstrating super- and sub-additive effects, our analyses showed that this approach is a valuable metric for studying multisensory interactions reflected in induced oscillatory responses.

Distributed digit somatotopy in primary somatosensory cortex

We obtained high-resolution somatotopic maps of the human digits using 4.0 T functional magnetic resonance imaging (fMRI). In separate experiments, the volar surface of either the right thumb, index, or ring finger was stimulated in a sliding-window fashion in both distal-to-proximal and proximal-to-distal directions using a custom-built pneumatic apparatus. Analysis of the functional images was restricted to Brodmann's areas 3b and 1 and control areas 4 and 3a, as well as a randomized simulation of the functional data in each of these areas. Using in-house algorithms, we detected discrete regions of cortical activation showing phase reversal coinciding with alternation in stimulation direction. Most stimulation-related phase maps of the digits were obtained in areas 3b and 1, rather than areas 3a or 4, despite the somatic input to the latter two areas. The area 3b and 1 representations thus appear to be relatively discrete and somatotopic compared to other somatic processing regions. Our results within areas 3b and 1 confirm the nonlinear mapping of the body surface suggested by recordings in nonhuman primates in terms of phase band topography, scaling, and frequency relative to the actual digit surfaces. The scaling and frequency nonlinearities were more evident within area 3b than area 1, suggesting a functional differentiation of these regions as has previously been observed only in more invasive recordings. Specifically, the area 1 representations were larger overall than those observed in area 3b, and the frequencies of area 3b phase bands and voxels were related disproportionately to thumb and index finger stimulation and to particular areas on the digit surface, suggesting a weighting based in part on receptor distribution.

Size matters: effects of stimulus size, duration and eccentricity on the visual gamma-band response

Objective: The effects of stimulus size, duration and eccentricity on the visual gamma-band response (GBR) in human EEG were investigated and compared to visual evoked potentials (VEPs) in order to differentiate in future (and past) experiments whether changes in GBRs are due to stimulus-related (exogenous) or cognitive effects. Methods: EEG was recorded from 23 subjects while they performed a simple choice reaction time task requiring discrimination of squares and circles. In separate blocks stimulus size, duration, and eccentricity were manipulated. EEG was recorded from 64 electrodes. A wavelet transform based on Morlet wavelets was employed for the analysis of gamma-band activity. Results: Amplitude of the GBR was diminished for small and peripheral stimuli. With short stimulus durations ON and OFF responses of the GBR merged into one peak. In comparison, VEP amplitudes were less susceptible to stimulus features. In contrast to VEP latencies, however, GBR latency did not show a lateralization for eccentric stimuli. Conclusions: In addition to previous experiments which have shown a modulation of the GBR by various cognitive processes, the present results demonstrate the susceptibility of the GBR in human EEG to exogenous factors, as numerous intracortical recordings in non-human primates have shown before. The results suggest that the human GBR resides in early visual areas. Significance: The demonstration of the susceptibility of the GBR to stimulus properties implies that studies aimed at exploring the involvement of the GBR in information processing have to be designed carefully. It also constrains the localization of the human GBR.

A functional neuroimaging study of motivation and executive function

Executive functions, such as working memory, must intersect with functions that determine value for the organism. Functional imaging work in humans and single-unit recordings in non-human primates provide evidence that PFC might integrate motivational context with working memory. With functional magnetic resonance imaging (fMRI), we addressed the question of motivation and working memory, using a trial-related design in an object-working memory task. The design permitted the analysis of BOLD signal at separate stages, corresponding to encoding, maintenance, and retrieval. Subjects were motivated by a financial incentive during the task, such that they could gain a high or a low reward. The two different levels of reward also entailed greater or lesser risk of losing money for incorrect responses. In the high, relative to the low, reward condition, subjects shifted response bias, and showed a trend to greater sensitivity. We found main effects in fMRI BOLD signal for reward, which overlapped with BOLD effects for maintenance of information, in the right superior frontal sulcus and bilateral intraparietal sulcus. We also found an interaction between reward and retrieval from working memory in the right dorsolateral prefrontal cortex. Main effects of load and reward occurred in adjacent regions of the ventrolateral PFC during retrieval. The data demonstrate that when subjects perform a simple working memory task, financial incentives motivate performance and interact with some of the same neural networks that process various stages of working memory. Areas of overlap and interaction may integrate information about value, or they may represent a general effect of motivation increasing neural effort.

MEG correlates of categorical perception of a voice onset time continuum in humans

Event-related magnetic fields (ERFs) were recorded from the left hemisphere in nine normal volunteers in response to four consonant-vowel (CV) syllables varying in voice-onset time (VOT). CVs with VOT values of 0 and +20 ms were perceived as /ga/ and those with VOT values of +40 and +60 ms as /ka/. Results showed: (1) a displacement of the N1m peak equivalent current dipole toward more medial locations; and (2) an abrupt reduction in peak magnetic flux strength, as VOT values increased from +20 to +40 ms. No systematic differences were noted between the 0 and +20 ms stimuli or between the +40 and +60 ms CVs. The findings are in agreement with the results of multiunit invasive recordings in non-human primates regarding the spatial and temporal pattern of neuronal population responses in the human auditory cortex which could serve as neural cues for the perception of voicing contrasts.

The Time Course of Changes during Motor Sequence Learning: A Whole-Brain fMRI Study

There is a discrepancy between the results of imaging studies in which subjects learn motor sequences. Some experiments have shown decreases in the activation of some areas as learning increased, whereas others have reported learning-related increases as learning progressed. We have exploited fMRI to measure changes in blood oxygen level-dependent (BOLD) signal throughout the course of learning. T2*-weighted echo-planar images were acquired over the whole brain for 40 min while the subjects learned a sequence eight moves long by trial and error. The movements were visually paced every 3.2 s and visual feedback was provided to the subjects. A baseline period followed each activation period. The effect due to the experimental conditions was modeled using a square-wave function, time locked to their occurrence. Changes over time in the difference between activation and baseline signal were modeled using a set of polynomial basis functions. This allowed us to take into account linear as well as nonlinear changes over time. Low-frequency changes over time common to both activation and baseline conditions (and thus not learning related) were modeled and removed. Linear and nonlinear changes of BOLD signal over time were found in prefrontal, premotor, and parietal cortex and in neostriatal and cerebellar areas. Single-unit recordings in nonhuman primates during the learning of motor tasks have clearly shown increased activity early in learning, followed by a decrease as learning progressed. Both phenomena can be observed at the population level in the present study.