Gregor Rainer

Selective representation of relevant information by neurons in the primate prefrontal cortex

The severe limitation of the capacity of working memory, the ability to store temporarily and manipulate information, necessitates mechanisms that restrict access to it. Here we report tests to discover whether the activity of neurons in the prefrontal (PF)cortex, the putative neural correlate of working memory, might reflect these mechanisms and preferentially represent behaviourally relevant information. Monkeys performed a ‘delayed-matching-to-sample’ task with an array of three objects. Only one of the objects in the array was relevant for task performance and the monkeys needed to find that object (the target) and remember its location. For many PF neurons, activity to physically identical arrays varied with the target location; the location of the non-target objects had little or no influence on activity. Information about the target location was present in activity as early as 140 ms after array onset. Also, information about which object was the target was reflected in the sustained activity of many PF neurons. These results suggest that the prefrontal cortex is involved in selecting and maintaining behaviourally relevant information.

Phase Locking of Single Neuron Activity to Theta Oscillations during Working Memory in Monkey Extrastriate Visual Cortex

Working memory has been linked to elevated single neuron discharge in monkeys and to oscillatory changes in the human EEG, but the relation between these effects has remained largely unexplored. We addressed this question by measuring local field potentials and single unit activity simultaneously from multiple electrodes placed in extrastriate visual cortex while monkeys were performing a working memory task. We describe a significant enhancement in theta band energy during the delay period. Theta oscillations had a systematic effect on single neuron activity, with neurons emitting more action potentials near their preferred angle of each theta cycle. Sample-selective delay activity was enhanced if only action potentials emitted near the preferred theta angle were considered. Our results suggest that extrastriate visual cortex is involved in short-term maintenance of information and that theta oscillations provide a mechanism for structuring the recurrent interaction between neurons in different brain regions that underlie working memory.

The zebrafish heart regenerates after cryoinjury-induced myocardial infarction

BackgroundIn humans, myocardial infarction is characterized by irreversible loss of heart tissue, which becomes replaced with a fibrous scar. By contrast, teleost fish and urodele amphibians are capable of heart regeneration after a partial amputation. However, due to the lack of a suitable infarct model, it is not known how these animals respond to myocardial infarction.ResultsHere, we have established a heart infarct model in zebrafish using cryoinjury. In contrast to the common method of partial resection, cryoinjury results in massive cell death within 20% of the ventricular wall, similar to that observed in mammalian infarcts. As in mammals, the initial stages of the injury response include thrombosis, accumulation of fibroblasts and collagen deposition. However, at later stages, cardiac cells can enter the cell cycle and invade the infarct area in zebrafish. In the subsequent two months, fibrotic scar tissue is progressively eliminated by cell apoptosis and becomes replaced with a new myocardium, resulting in scarless regeneration. We show that tissue remodeling at the myocardial-infarct border zone is associated with accumulation of Vimentin-positive fibroblasts and with expression of an extracellular matrix protein Tenascin-C. Electrocardiogram analysis demonstrated that the reconstitution of the cardiac muscle leads to the restoration of the heart function.ConclusionsWe developed a new cryoinjury model to induce myocardial infarction in zebrafish. Although the initial stages following cryoinjury resemble typical healing in mammals, the zebrafish heart is capable of structural and functional regeneration. Understanding the key healing processes after myocardial infarction in zebrafish may result in identification of the barriers to efficient cardiac regeneration in mammals.

Cholinergic Control of Visual Categorization in Macaques

Acetylcholine (ACh) is a neurotransmitter acting via muscarinic and nicotinic receptors that is implicated in several cognitive functions and impairments, such as Alzheimer’s disease. It is believed to especially affect the acquisition of new information, which is particularly important when behavior needs to be adapted to new situations and to novel sensory events. Categorization, the process of assigning stimuli to a category, is a cognitive function that also involves information acquisition. The role of ACh on categorization has not been previously studied. We have examined the effects of scopolamine, an antagonist of muscarinic ACh receptors, on visual categorization in macaque monkeys using familiar and novel stimuli. When the peripheral effects of scopolamine on the parasympathetic nervous system were controlled for, categorization performance was disrupted following systemic injections of scopolamine. This impairment was observed only when the stimuli that needed to be categorized had not been seen before. In other words, the monkeys were not impaired by the central action of scopolamine in categorizing a set of familiar stimuli (stimuli which they had categorized successfully in previous sessions). Categorization performance also deteriorated as the stimulus became less salient by an increase in the level of visual noise. However, scopolamine did not cause additional performance disruptions for difficult categorization judgments at lower coherence levels. Scopolamine, therefore, specifically affects the assignment of new exemplars to established cognitive categories, presumably by impairing the processing of novel information. Since we did not find an effect of scopolamine in the categorization of familiar stimuli, scopolamine had no significant central action on other cognitive functions such as perception, attention, memory, or executive control within the context of our categorization task.

The effect of a serotonin-induced dissociation between spiking and perisynaptic activity on BOLD functional MRI

The relationship of the blood oxygen-level-dependent (BOLD) signal to its underlying neuronal activity is still poorly understood. Combined physiology and functional MRI experiments suggested that local field potential (LFP) is a better predictor of the BOLD signal than multiunit activity (MUA). To further explore this relationship, we simultaneously recorded BOLD and electrophysiological activity while inducing a dissociation of MUA from LFP activity with injections of the neuromodulator BP554 into the primary visual cortex of anesthetized monkeys. BP554 is a 5-HT1A agonist acting primarily on the membrane of efferent neurons by potassium-induced hyperpolarization. Its infusion in visual cortex reliably reduced MUA without affecting either LFP or BOLD activity. This finding suggests that the efferents of a neuronal network pose relatively little metabolic burden compared with the overall presynaptic and postsynaptic processing of incoming afferents. We discuss implications of this finding for the interpretation of BOLD activity.

Nonmonotonic noise tuning of BOLD fMRI signal to natural images in the visual cortex of the anesthetized monkey

BACKGROUND The perceptual ability of humans and monkeys to identify objects in the presence of noise varies systematically and monotonically as a function of how much noise is introduced to the visual display. That is, it becomes more and more difficult to identify an object with increasing noise. Here we examine whether the blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) signal in anesthetized monkeys also shows such monotonic tuning. We employed parametric stimulus sets containing natural images and noise patterns matched for spatial frequency and intensity as well as intermediate images generated by interpolation between natural images and noise patterns. Anesthetized monkeys provide us with the unique opportunity to examine visual processing largely in the absence of top-down cognitive modulations and can thus provide an important baseline against which work with awake monkeys and humans can be compared. RESULTS We measured BOLD activity in occipital visual cortical areas as natural images and noise patterns, as well as intermediate interpolated patterns at three interpolation levels (25%, 50%, and 75%) were presented to anesthetized monkeys in a block paradigm. We observed reliable visual activity in occipital visual areas including V1, V2, V3, V3A, and V4 as well as the fundus and anterior bank of the superior temporal sulcus (STS). Natural images consistently elicited higher BOLD levels than noise patterns. For intermediate images, however, we did not observe monotonic tuning. Instead, we observed a characteristic V-shaped noise-tuning function in primary and extrastriate visual areas. BOLD signals initially decreased as noise was added to the stimulus but then increased again as the pure noise pattern was approached. We present a simple model based on the number of activated neurons and the strength of activation per neuron that can account for these results. CONCLUSIONS We show that, for our parametric stimulus set, BOLD activity varied nonmonotonically as a function of how much noise was added to the visual stimuli, unlike the perceptual ability of humans and monkeys to identify such stimuli. This raises important caveats for interpreting fMRI data and demonstrates the importance of assessing not only which neural populations are activated by contrasting conditions during an fMRI study, but also the strength of this activation. This becomes particularly important when using the BOLD signal to make inferences about the relationship between neural activity and behavior.

Timecourse of object-related neural activity in the primate prefrontal cortex during a short-term memory task

We studied the timecourse of neural activity in the primate (Macacca mulatta) prefrontal (PF) cortex during an object delayed‐matching‐to‐sample (DMS) task. To assess the effects of experience on this timecourse, we conducted the task using both novel and highly familiar objects. In addition, noise patterns containing no task‐relevant information were used as samples on some trials. Comparison of average PF ensemble activity relative to baseline activity generated by objects and noise patterns revealed three distinct activity periods. (i) Sample onset elicited a transient sensory visual response. In this sensory period, novel objects elicited stronger average ensemble activity than both familiar objects and noise patterns. (ii) An intermediate period of elevated activity followed, which began before sample offset, and continued well into the delay period. In the intermediate period, activity was elevated for noise patterns and novel objects, but near baseline for familiar objects. (iii) Finally, after average ensemble activity reached baseline activity at the end of the intermediate period, a reactivation period occurred late in the delay. Experience had little effect during reactivation, where activity was elevated for both novel and familiar objects compared to noise patterns. We show that the ensemble average resembles the activity timecourse of many single prefrontal neurons. These results suggest that PF delay activity does not merely maintain recent sensory input, but is subject to more complex experience‐dependent dynamics. This has implications for how delay activity is generated and maintained.

Object features used by humans and monkeys to identify rotated shapes

Humans and rhesus monkeys can identify shapes that have been rotated in the picture plane. Recognition of rotated shapes can be as efficient as recognition of upright shapes. Here we investigate whether subjects showing view-invariant performance use the same object features to identify upright and rotated versions of a shape. We find marked differences between humans and monkeys. While humans tend to use the same features independent of shape orientation, monkeys use unique features for each orientation. Humans are able to generalize to a greater degree across orientation changes than rhesus monkey observers, who tend to relearn separate problems at each orientation rather than flexibly apply previously learned knowledge to novel problems.

Temporal kernel CCA and its application in multimodal neuronal data analysis

Data recorded from multiple sources sometimes exhibit non-instantaneous couplings. For simple data sets, cross-correlograms may reveal the coupling dynamics. But when dealing with high-dimensional multivariate data there is no such measure as the cross-correlogram. We propose a simple algorithm based on Kernel Canonical Correlation Analysis (kCCA) that computes a multivariate temporal filter which links one data modality to another one. The filters can be used to compute a multivariate extension of the cross-correlogram, the canonical correlogram, between data sources that have different dimensionalities and temporal resolutions. The canonical correlogram reflects the coupling dynamics between the two sources. The temporal filter reveals which features in the data give rise to these couplings and when they do so. We present results from simulations and neuroscientific experiments showing that tkCCA yields easily interpretable temporal filters and correlograms. In the experiments, we simultaneously performed electrode recordings and functional magnetic resonance imaging (fMRI) in primary visual cortex of the non-human primate. While electrode recordings reflect brain activity directly, fMRI provides only an indirect view of neural activity via the Blood Oxygen Level Dependent (BOLD) response. Thus it is crucial for our understanding and the interpretation of fMRI signals in general to relate them to direct measures of neural activity acquired with electrodes. The results computed by tkCCA confirm recent models of the hemodynamic response to neural activity and allow for a more detailed analysis of neurovascular coupling dynamics.

Dissociation Between Local Field Potentials and Spiking Activity in Macaque Inferior Temporal Cortex Reveals Diagnosticity-Based Encoding of Complex Objects

Neurons in the inferior temporal (IT) cortex respond selectively to complex objects, and maintain their selectivity despite partial occlusion. However, relatively little is known about how the occlusion of different shape parts influences responses in the IT cortex. Here, we determine experimentally which parts of complex objects monkeys are relying on in a discrimination task. We then study the effect of occlusion of parts with different behavioral relevance on neural responses in the IT cortex at the level of spiking activity and local field potentials (LFPs). For both spiking activity and LFPs, we found that the diagnostic object parts, which were important for behavioral judgments, were preferentially represented in the IT cortex. Our data show that the effects of diagnosticity grew systematically stronger along a posterior–anterior axis for LFPs, but were evenly distributed for single units, suggesting that diagnosticity is first encoded in the posterior IT cortex. Our findings highlight the power of combined analysis of field potentials and spiking activity for mapping structure to computational function in the brain.