Pierre Pouget

Influence of history on saccade countermanding performance in humans and macaque monkeys

The stop-signal or countermanding task probes the ability to control action by requiring subjects to withhold a planned movement in response to an infrequent stop signal which they do with variable success depending on the delay of the stop signal. We investigated whether performance of humans and macaque monkeys in a saccade countermanding task was influenced by stimulus and performance history. In spite of idiosyncrasies across subjects several trends were evident in both humans and monkeys. Response time decreased after successive trials with no stop signal. Response time increased after successive trials with a stop signal. However, post-error slowing was not observed. Increased response time was observed mainly or only after cancelled (signal inhibit) trials and not after noncancelled (signal respond) trials. These global trends were based on rapid adjustments of response time in response to momentary fluctuations in the fraction of stop signal trials. The effects of trial sequence on the probability of responding were weaker and more idiosyncratic across subjects when stop signal fraction was fixed. However, both response time and probability of responding were influenced strongly by variations in the fraction of stop signal trials. These results indicate that the race model of countermanding performance requires extension to account for these sequential dependencies and provide a basis for physiological studies of executive control of countermanding saccade performance.

REVIEW OF SIGNAL DISTORTION THROUGH METAL MICROELECTRODE RECORDING CIRCUITS AND FILTERS

Interest in local field potentials (LFPs) and action potential shape has increased markedly. The present work describes distortions of these signals that occur for two reasons. First, the microelectrode recording circuit operates as a voltage divider producing frequency-dependent attenuation and phase shifts when electrode impedance is not negligible relative to amplifier input impedance. Because of the much higher electrode impedance at low frequencies, this occurred over frequency ranges of LFPs measured by neurophysiologists for one head-stage tested. Second, frequency-dependent phase shifts are induced by subsequent filters. Thus, we report these effects and the resulting amplitude envelope delays and distortion of waveforms recorded through a commercial data acquisition system and a range of tungsten microelectrodes. These distortions can be corrected, but must be accounted for when interpreting field potential and spike shape data.

Low-intensity focused ultrasound modulates monkey visuomotor behavior.

In vivo feasibility of using low-intensity focused ultrasound (FUS) to transiently modulate the function of regional brain tissue has been recently tested in anesthetized lagomorphs [1] and rodents [2-4]. Hypothetically, ultrasonic stimulation of the brain possesses several advantages [5]: it does not necessitate surgery or genetic alteration but could ultimately confer spatial resolutions superior to other noninvasive methods. Here, we gauged the ability of noninvasive FUS to causally modulate high-level cognitive behavior. Therefore, we examined how FUS might interfere with prefrontal activity in two awake macaque rhesus monkeys that had been trained to perform an antisaccade (AS) task. We show that ultrasound significantly modulated AS latencies. Such effects proved to be dependent on FUS hemifield of stimulation (relative latency increases most for ipsilateral AS). These results are interpreted in terms of a modulation of saccade inhibition to the contralateral visual field due to the disruption of processing across the frontal eye fields. Our study demonstrates for the first time the feasibility of using FUS stimulation to causally modulate behavior in the awake nonhuman primate brain. This result supports the use of this approach to study brain function. Neurostimulation with ultrasound could be used for exploratory and therapeutic purposes noninvasively, with potentially unprecedented spatial resolution.

Neural Basis of Adaptive Response Time Adjustment during Saccade Countermanding

Humans and macaque monkeys adjust their response time adaptively in stop-signal (countermanding) tasks, responding slower after stop-signal trials than after control trials with no stop signal. We investigated the neural mechanism underlying this adaptive response time adjustment in macaque monkeys performing a saccade countermanding task. Earlier research showed that movements are initiated when the random accumulation of presaccadic movement-related activity reaches a fixed threshold. We found that a systematic delay in response time after stop-signal trials was accomplished not through a change of threshold, baseline, or accumulation rate, but instead through a change in the time when activity first began to accumulate. The neurons underlying movement initiation have been identified with stochastic accumulator models of response time performance. Therefore, this new result provides surprising new insights into the neural instantiation of stochastic accumulator models and the mechanisms through which executive control can be exerted.

Visual and Motor Connectivity and the Distribution of Calcium-Binding Proteins in Macaque Frontal Eye Field: Implications for Saccade Target Selection

The frontal eye field (FEF) contributes to directing visual attention and saccadic eye movement through intrinsic processing, interactions with extrastriate visual cortical areas (e.g., V4), and projections to subcortical structures (e.g., superior colliculus, SC). Several models have been proposed to describe the relationship between the allocation of visual attention and the production of saccades. We obtained anatomical information that might provide useful constraints on these models by evaluating two characteristics of FEF. First, we investigated the laminar distribution of efferent connections from FEF to visual areas V4 + TEO and to SC. Second, we examined the laminar distribution of different populations of GABAergic neurons in FEF. We found that the neurons in FEF that project to V4 + TEO are located predominantly in the supragranular layers, colocalized with the highest density of calbindin- and calretinin-immunoreactive inhibitory interneurons. In contrast, the cell bodies of neurons that project to SC are found only in layer 5 of FEF, colocalized primarily with parvalbumin inhibitory interneurons. None of the neurons in layer 5 that project to V4 + TEO also project to SC. These results provide useful constraints for cognitive models of visual attention and saccade production by indicating that different populations of neurons project to extrastriate visual cortical areas and to SC. This finding also suggests that FEF neurons projecting to visual cortex and SC are embedded in different patterns of intracortical circuitry.

An internationally standardised antisaccade protocol

Detailed measurements of saccadic latency--the time taken to make an eye movement to a suddenly-presented visual target--have proved a valuable source of detailed and quantitative information in a wide range of neurological conditions, as well as shedding light on the mechanisms of decision, currently of intense interest to cognitive neuroscientists. However, there is no doubt that more complex oculomotor tasks, and in particular the antisaccade task in which a participant must make a saccade in the opposite direction to the target, are potentially more sensitive indicators of neurological dysfunction, particularly in neurodegenerative conditions. But two obstacles currently hinder their widespread adoption for this purpose. First, that much of the potential information from antisaccade experiments, notably about latency distribution and amplitude, is typically thrown away. Second, that there is no standardised protocol for carrying out antisaccade experiments, so that results from one laboratory cannot easily be compared with those from another. This paper, the outcome of a recent international meeting of oculomotor scientists and clinicians with an unusually wide experience of such measurements, sets out a proposed protocol for clinical antisaccade trials: its adoption will greatly enhance the clinical and scientific benefits of making these kinds of measurements.

Widespread spatial integration in primary somatosensory cortex

Tactile discrimination depends on integration of information from the discrete receptive fields (RFs) of peripheral sensory afferents. Because this information is processed over a hierarchy of subcortical nuclei and cortical areas, the integration likely occurs at multiple levels. The current study presents results indicating that neurons across most of the extent of the hand representation in monkey primary somatosensory cortex (area 3b) interact, even when these neurons have separate RFs. We obtained simultaneous recordings by using a 100-electrode array implanted in the hand representation of primary somatosensory cortex of two anesthetized owl monkeys. During a series of 0.5-s skin indentations with single or dual probes, the distance between electrodes from which neurons with synchronized spike times were recorded exceeded 2 mm. The results provide evidence that stimuli on different parts of the hand influence the degree of synchronous firing among a large population of neurons. Because spike synchrony potentiates the activation of commonly targeted neurons, synchronous neural activity in primary somatosensory cortex can contribute to discrimination of complex tactile stimuli.

Do Electrode Properties Create a Problem in Interpreting Local Field Potential Recordings

Local field potential (LFP) recordings within the brain have become an important tool used by neuroscientists to make inferences about the activity of a population of cells near an electrode. Each passing year analysis of LFPs in neuroscience seems to bring important new insights on the possible workings of networks in the brain to produce behavior (Buschman and Miller 2007; Canolty et al. 2006; Gregoriou et al. 2009; Liu and Newsome 2006; Lubenov and Siapas 2009; Pesaran et al. 2008; Womelsdorf et al. 2006). Indeed LFPs have become a near-ubiquitous tool in neurophysiology seemingly in use anywhere extracellular spikes are also recorded.

Functional Distinction Between Visuomovement and Movement Neurons in Macaque Frontal Eye Field During Saccade Countermanding

In the previous studies on the neural control of saccade initiation using the countermanding paradigm, movement and visuomovement neurons in the frontal eye field were grouped as movement-related neurons. The activity of both types of neurons was modulated when a saccade was inhibited in response to a stop signal, and this modulation occurred early enough to contribute to the control of the saccade initiation. We now report a functional difference between these two classes of neurons when saccades are produced. Movement neurons exhibited a progressive accumulation of discharge rate following target presentation that triggered a saccade when it reached a threshold. When saccades were inhibited with lower probability in response to a stop signal appearing at longer delays, this accumulating activity was interrupted at levels progressively closer to the threshold. In contrast, visuomovement neurons exhibited a maintained elevated discharge rate following target presentation that was followed by a further enhancement immediately before the saccade initiation. When saccades were inhibited in response to a stop signal, the late enhancement was absent and the maintained activity decayed regardless of stop-signal delay. These results demonstrate that the activity of movement neurons realizes the progressive commitment to the saccade initiation modeled by the activation of the go unit in computational models of countermanding performance. The lack of correspondence of the activity of visuomovement neurons with any elements of these models indicates that visuomovement neurons perform a function other than the saccade preparation such as a corollary discharge to update visual processing.

Performance Monitoring Local Field Potentials in the Medial Frontal Cortex of Primates: Supplementary Eye Field

We describe intracranial local field potentials (LFPs) recorded in the supplementary eye field (SEF) of macaque monkeys performing a saccade countermanding task. The most prominent feature at 90% of the sites was a negative-going polarization evoked by a contralateral visual target. At roughly 50% of sites a negative-going polarization was observed preceding saccades, but in stop signal trials this polarization was not modulated in a manner sufficient to control saccade initiation. When saccades were canceled in stop signal trials, LFP modulation increased with the inferred magnitude of response conflict derived from the coactivation of gaze-shifting and gaze-holding neurons. At 30% of sites, a pronounced negative-going polarization occurred after errors. This negative polarity did not appear in unrewarded correct trials. Variations of response time with trial history were not related to any features of the LFP. The results provide new evidence that error-related and conflict-related but not feedback-related signals are conveyed by the LFP in the macaque SEF and are important for identifying the generator of the error-related negativity.