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Biomedical subjects

Christof Koch

Publications and source records attributed to Christof Koch.

At least 19 recordsLinked to original sources

Comparative cellular analysis of motor cortex in human, marmoset and mouse.

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

Animals↗

Attention and consciousness: two distinct brain processes.

The close relationship between attention and consciousness has led many scholars to conflate these processes. This article summarizes psychophysical evidence, arguing that top-down attention and consciousness are distinct phenomena that need not occur together and that can be manipulated using distinct paradigms. Subjects can become conscious of an isolated object or the gist of a scene despite the near absence of top-down attention; conversely, subjects can attend to perceptually invisible objects. Furthermore, top-down attention and consciousness can have opposing effects. Such dissociations are easier to understand when the different functions of these two processes are considered. Untangling their tight relationship is necessary for the scientific elucidation of consciousness and its material substrate.

Attention↗

A single-neuron correlate of change detection and change blindness in the human medial temporal lobe.

Observers are often unaware of changes in their visual environment when attention is not focused at the location of the change . Because of its rather intriguing nature, this phenomenon, known as change blindness, has been extensively studied with psychophysics as well as with fMRI . However, whether change blindness can be tracked in the activity of single cells is not clear. To explore the neural correlates of change detection and change blindness, we recorded from single neurons in the human medial temporal lobe (MTL) during a change-detection paradigm. The preferred pictures of the visually responsive units elicited significantly higher firing rates on the attended trials when subjects correctly identified a change (change detection) compared to the unattended trials when they missed it (change blindness). On correct trials, the firing activity of individual units allowed us to predict the occurrence of a change, on a trial-by-trial basis, with 67% accuracy. In contrast, this prediction was at chance for incorrect, unattended trials. The firing rates of visually selective MTL cells thus constitute a neural correlate of change detection.

Action Potentials↗

The relation of phase noise and luminance contrast to overt attention in complex visual stimuli.

Models of attention are typically based on difference maps in low-level features but neglect higher order stimulus structure. To what extent does higher order statistics affect human attention in natural stimuli? We recorded eye movements while observers viewed unmodified and modified images of natural scenes. Modifications included contrast modulations (resulting in changes to first- and second-order statistics), as well as the addition of noise to the Fourier phase (resulting in changes to higher order statistics). We have the following findings: (1) Subjects' interpretation of a stimulus as a "natural" depiction of an outdoor scene depends on higher order statistics in a highly nonlinear, categorical fashion. (2) Confirming previous findings, contrast is elevated at fixated locations for a variety of stimulus categories. In addition, we find that the size of this elevation depends on higher order statistics and reduces with increasing phase noise. (3) Global modulations of contrast bias eye position toward high contrasts, consistent with a linear effect of contrast on fixation probability. This bias is independent of phase noise. (4) Small patches of locally decreased contrast repel eye position less than large patches of the same aggregate area, irrespective of phase noise. Our findings provide evidence that deviations from surrounding statistics, rather than contrast per se, underlie the well-established relation of contrast to fixation.

Adult↗

Sparse representation in the human medial temporal lobe.

Recent experiments characterized individual neurons in the human medial temporal lobe with remarkably selective, invariant, and explicit responses to images of famous individuals or landmark buildings. Here, we used a probabilistic analysis to show that these data are consistent with a sparse code in which neurons respond in a selective manner to a small fraction of stimuli.

Models, Neurological↗

Depth of interocular suppression associated with continuous flash suppression, flash suppression, and binocular rivalry.

When conflicting images are presented to the corresponding regions of the two eyes, only one image may be consciously perceived. In binocular rivalry (BR), two images alternate in phenomenal visibility; even a salient image is eventually suppressed by an image of low saliency. Recently, N. Tsuchiya and C. Koch (2005) reported a technique called continuous flash suppression (CFS), extending the suppression duration more than 10-fold. Here, we investigated the depth of this prolonged form of interocular suppression as well as conventional BR and flash suppression (FS) using a probe detection task. Compared to monocular viewing condition, CFS elevated detection thresholds more than 20-fold, whereas BR did so by 3-fold. In subsequent experiments, we dissected CFS into several components. By manipulating the number and timing of flashes with respect to the probe, we found that the stronger suppression in CFS is not due to summation between BR and FS but is caused by the summation of the suppression due to multiple flashes. Our results support the view that CFS is not a stronger version of BR but is due to the accumulated suppressive effects of multiple flashes.

Humans↗

Face identification in the near-absence of focal attention.

In contrast to artificial geometric shapes, natural scenes and face-gender can be processed even when spatial attention is not fully available. In this study, we investigate whether a finer discrimination, at the level of the individual, is possible in the near-absence of focal attention. Using the paradigm, subjects performed face identification on faces of celebrities and relatively unfamiliar individuals, along with a task that is known to engage spatial attention. We find that face-identification performance is only modestly impaired under dual-task conditions. These results suggest that the visual system is well able to make complex judgments of natural stimuli, even when attention is not fully available.

Adult↗

Spike propagation in dendrites with stochastic ion channels.

We investigate the effects of the stochastic nature of ion channels on the faithfulness, precision and reproducibility of electrical signal transmission in weakly active, dendritic membrane under in vitro conditions. The properties of forward and backpropagating action potentials (BPAPs) in the dendritic tree of pyramidal cells are the subject of intense empirical work and theoretical speculation (Larkum et al., 1999; Zhu, 2000; Larkum et al., 2001; Larkum and Zhu, 2002; Schaefer et al., 2003; Williams, 2004; Waters et al., 2005). We numerically simulate the effects of stochastic ion channels on the forward and backward propagation of dendritic spikes in Monte-Carlo simulations on a reconstructed layer 5 pyramidal neuron. We report that in most instances there is little variation in timing or amplitude for a single BPAP, while variable backpropagation can occur for trains of action potentials. Additionally, we find that the generation and forward propagation of dendritic Ca(2+) spikes are susceptible to channel variability. This indicates limitations on computations that depend on the precise timing of Ca(2+) spikes.

Action Potentials↗

On the origin of the extracellular action potential waveform: A modeling study.

Although extracellular unit recording is typically used for the detection of spike occurrences, it also has the theoretical ability to report about what are typically considered intracellular features of the action potential. We address this theoretical ability by developing a model system that captures features of experimentally recorded simultaneous intracellular and extracellular recordings of CA1 pyramidal neurons. We use the line source approximation method of Holt and Koch to model the extracellular action potential (EAP) voltage resulting from the spiking activity of individual neurons. We compare the simultaneous intracellular and extracellular recordings of CA1 pyramidal neurons recorded in vivo with model predictions for the same cells reconstructed and simulated with compartmental models. The model accurately reproduces both the waveform and the amplitude of the EAPs, although it was difficult to achieve simultaneous good matches on both the intracellular and extracellular waveforms. This suggests that accounting for the EAP waveform provides a considerable constraint on the overall model. The developed model explains how and why the waveform varies with electrode position relative to the recorded cell. Interestingly, each cell's dendritic morphology had very little impact on the EAP waveform. The model also demonstrates that the varied composition of ionic currents in different cells is reflected in the features of the EAP.

Action Potentials↗

The continuous wagon wheel illusion is associated with changes in electroencephalogram power at approximately 13 Hz.

Continuously moving objects sometimes appear to spontaneously reverse their motion direction. The mechanisms underlying this bistable phenomenon (the "continuous wagon wheel illusion") are heavily debated, but one interpretation suggests that motion information is perceived in discrete episodes at a rate between 10 and 15 Hz. Here, we asked observers to report the perceived direction of a continuously rotating wheel while 32-channel electroencephalogram (EEG) was recorded. We then separated periods of perceived true from illusory (reversed) motion and compared the EEG power spectrum under these two perceptually distinct yet physically identical conditions. The only reliable difference was observed approximately 13 Hz over centroparietal electrodes, independent of the temporal frequency of the wheel. Thus, it is likely to reflect internal processes rather than purely stimulus-driven activity. EEG power (13 Hz) decreased before the onset of illusory motion and increased before transitions back to real motion. Using this relationship, it was possible to predict above chance, on a trial-by-trial basis, the direction of the upcoming perceptual transition. These data are compatible with the idea that motion perception occurs in snapshots <100 ms in duration.

Adult↗

Modeling attention to salient proto-objects.

Selective visual attention is believed to be responsible for serializing visual information for recognizing one object at a time in a complex scene. But how can we attend to objects before they are recognized? In coherence theory of visual cognition, so-called proto-objects form volatile units of visual information that can be accessed by selective attention and subsequently validated as actual objects. We propose a biologically plausible model of forming and attending to proto-objects in natural scenes. We demonstrate that the suggested model can enable a model of object recognition in cortex to expand from recognizing individual objects in isolation to sequentially recognizing all objects in a more complex scene.

Attention↗

Contingency awareness in human aversive conditioning involves the middle frontal gyrus.

In contrast to the wealth of data describing the neural mechanisms underlying classical conditioning, we know remarkably little about the mechanisms involved in acquisition of explicit contingency awareness. Subjects variably acquire contingency awareness in classical conditioning paradigms, in which they are able to describe the temporal relationship between a conditioned cue and its outcome. Previous studies have implicated the hippocampus and prefrontal cortex in the acquisition of explicit knowledge, although their specific roles remain unclear. We used functional magnetic resonance imaging to track the trial-by-trial acquisition of explicit knowledge in a concurrent trace and delay conditioning paradigm. We show that activity in bilateral middle frontal gyrus and parahippocampal gyrus correlates with the accuracy of explicit contingency awareness on each trial. In contrast, amygdala activation correlates with conditioned responses indexed by skin conductance responses (SCRs). These results demonstrate that brain regions known to be involved in other aspects of learning and memory also play a specific role, reflecting on each trial the acquisition and representation of contingency awareness.

Adult↗

Continuous flash suppression reduces negative afterimages.

Illusions that produce perceptual suppression despite constant retinal input are used to manipulate visual consciousness. Here we report on a powerful variant of existing techniques, continuous flash suppression. Distinct images flashed successively at approximately 10 Hz into one eye reliably suppress an image presented to the other eye. The duration of perceptual suppression is at least ten times greater than that produced by binocular rivalry. Using this tool we show that the strength of the negative afterimage of an adaptor was reduced by half when it was perceptually suppressed by input from the other eye. The more completely the adaptor was suppressed, the more strongly the afterimage intensity was reduced. Paradoxically, trial-to-trial visibility of the adaptor did not correlate with the degree of reduction. Our results imply that formation of afterimages involves neuronal structures that access input from both eyes but that do not correspond directly to the neuronal correlates of perceptual awareness.

Figural Aftereffect↗

What is the function of the claustrum?

The claustrum is a thin, irregular, sheet-like neuronal structure hidden beneath the inner surface of the neocortex in the general region of the insula. Its function is enigmatic. Its anatomy is quite remarkable in that it receives input from almost all regions of cortex and projects back to almost all regions of cortex. We here briefly summarize what is known about the claustrum, speculate on its possible relationship to the processes that give rise to integrated conscious percepts, propose mechanisms that enable information to travel widely within the claustrum and discuss experiments to address these questions.

Basal Ganglia↗

Attention-driven discrete sampling of motion perception.

In movies or on TV, a wheel can seem to rotate backwards, due to the temporal subsampling inherent in the recording process (the wagon wheel illusion). Surprisingly, this effect has also been reported under continuous light, suggesting that our visual system, too, might sample motion in discrete "snapshots." Recently, these results and their interpretation have been challenged. Here, we investigate the continuous wagon wheel illusion as a form of bistable percept. We observe a strong temporal frequency dependence: the illusion is maximal at alternation rates around 10 Hz but shows no spatial frequency dependence. We introduce an objective method, based on unbalanced counterphase gratings, for measuring this phenomenon and demonstrate that the effect critically depends on attention: the continuous wagon wheel illusion was almost abolished in the absence of focused attention. A motion-energy model, coupled with attention-dependent temporal subsampling of the perceptual stream at rates between 10 and 20 Hz, can quantitatively account for the observed data.

Attention↗

Subthreshold voltage noise of rat neocortical pyramidal neurones.

Neurones are noisy elements. Noise arises from both intrinsic and extrinsic sources, and manifests itself as fluctuations in the membrane potential. These fluctuations limit the accuracy of a neurone's output but have also been suggested to play a computational role. We present a detailed study of the amplitude and spectrum of voltage noise recorded at the soma of layer IV-V pyramidal neurones in slices taken from rat neocortex. The dependence of the noise on holding potential, synaptic activity and Na+ conductance is systematically analysed. We demonstrate that voltage noise increases non-linearly as the cell depolarizes (from a standard deviation (s.d.) of 0.19 mV at -75 mV to an s.d. of 0.54 mV at -55 mV). The increase in voltage noise is accompanied by an increase in the cell impedance, due to voltage dependence of Na+ conductance. The impedance increase accounts for the majority (70%) of the voltage noise increase. The increase in voltage noise and impedance is restricted to the low-frequency range (0.2-2 Hz). At the high frequency range (5-100 Hz) the voltage noise is dominated by synaptic activity. In our slice preparation, synaptic noise has little effect on the cell impedance. A minimal model reproduces qualitatively these data. Our results imply that ion channel noise contributes significantly to membrane voltage fluctuations at the subthreshold voltage range, and that Na+ conductance plays a key role in determining the amplitude of this noise by acting as a voltage-dependent amplifier of low-frequency transients.

Animals↗

Face adaptation depends on seeing the face.

Retinal input that is suppressed from visual awareness can nevertheless produce measurable aftereffects, revealing neural processes that do not directly result in a conscious percept. We here report that the face identity-specific aftereffect requires a visible face; it is effectively cancelled by binocular suppression or by inattentional blindness of the inducing face. Conversely, the same suppression does not interfere with the orientation-specific aftereffect. Thus, the competition between incompatible or interfering visual inputs to reach awareness is resolved before those aspects of information that are exploited in face identification are processed. We also found that the face aftereffect remained intact when the visual distracters in the inattention experiment were replaced with auditory distracters. Thus, cross-modal or cognitive interference that does not affect the visibility of the face does not interfere with the face aftereffect. We conclude that adaptation to face identity depends on seeing the face.

Adaptation, Physiological↗