Dominik R. Bach

Processing of Temporal Unpredictability in Human and Animal Amygdala

The amygdala has been studied extensively for its critical role in associative fear conditioning in animals and humans. Noxious stimuli, such as those used for fear conditioning, are most effective in eliciting behavioral responses and amygdala activation when experienced in an unpredictable manner. Here, we show, using a translational approach in mice and humans, that unpredictability per se without interaction with motivational information is sufficient to induce sustained neural activity in the amygdala and to elicit anxiety-like behavior. Exposing mice to mere temporal unpredictability within a time series of neutral sound pulses in an otherwise neutral sensory environment increased expression of the immediate-early gene c-fos and prevented rapid habituation of single neuron activity in the basolateral amygdala. At the behavioral level, unpredictable, but not predictable, auditory stimulation induced avoidance and anxiety-like behavior. In humans, functional magnetic resonance imaging revealed that temporal unpredictably causes sustained neural activity in amygdala and anxiety-like behavior as quantified by enhanced attention toward emotional faces. Our findings show that unpredictability per se is an important feature of the sensory environment influencing habituation of neuronal activity in amygdala and emotional behavior and indicate that regulation of amygdala habituation represents an evolutionary-conserved mechanism for adapting behavior in anticipation of temporally unpredictable events.

How the Opinion of Others Affects Our Valuation of Objects

Summary The opinions of others can easily affect how much we value things. We investigated what happens in our brain when we agree with others about the value of an object and whether or not there is evidence, at the neural level, for social conformity through which we change object valuation. Using functional magnetic resonance imaging we independently modeled (1) learning reviewer opinions about a piece of music, (2) reward value while receiving a token for that music, and (3) their interaction in 28 healthy adults. We show that agreement with two “expert” reviewers on music choice produces activity in a region of ventral striatum that also responds when receiving a valued object. It is known that the magnitude of activity in the ventral striatum reflects the value of reward-predicting stimuli [1–8]. We show that social influence on the value of an object is associated with the magnitude of the ventral striatum response to receiving it. This finding provides clear evidence that social influence mediates very basic value signals in known reinforcement learning circuitry [9–12]. Influence at such a low level could contribute to rapid learning and the swift spread of values throughout a population.

Knowing how much you don't know: a neural organization of uncertainty estimates

How we estimate uncertainty is important in decision neuroscience and has wide-ranging implications in basic and clinical neuroscience, from computational models of optimality to ideas on psychopathological disorders including anxiety, depression and schizophrenia. Empirical research in neuroscience, which has been based on divergent theoretical assumptions, has focused on the fundamental question of how uncertainty is encoded in the brain and how it influences behaviour. Here, we integrate several theoretical concepts about uncertainty into a decision-making framework. We conclude that the currently available evidence indicates that distinct neural encoding (including summary statistic-type representations) of uncertainty occurs in distinct neural systems.

The effect of appraisal level on processing of emotional prosody in meaningless speech

In visual perception of emotional stimuli, low- and high-level appraisal processes have been found to engage different neural structures. Beyond emotional facial expression, emotional prosody is an important auditory cue for social interaction. Neuroimaging studies have proposed a network for emotional prosody processing that involves a right temporal input region and explicit evaluation in bilateral prefrontal areas. However, the comparison of different appraisal levels has so far relied upon using linguistic instructions during low-level processing, which might confound effects of processing level and linguistic task. In order to circumvent this problem, we examined processing of emotional prosody in meaningless speech during gender labelling (implicit, low-level appraisal) and emotion labelling (explicit, high-level appraisal). While bilateral amygdala, left superior temporal sulcus and right parietal areas showed stronger blood oxygen level-dependent (BOLD) responses during implicit processing, areas with stronger BOLD responses during explicit processing included the left inferior frontal gyrus, bilateral parietal, anterior cingulate and supplemental motor cortex. Emotional versus neutral prosody evoked BOLD responses in right superior temporal gyrus, bilateral anterior cingulate, left inferior frontal gyrus, insula and bilateral putamen. Basal ganglia and right anterior cingulate responses to emotional versus neutral prosody were particularly pronounced during explicit processing. These results are in line with an amygdala-prefrontal-cingulate network controlling different appraisal levels, and suggest a specific role of the left inferior frontal gyrus in explicit evaluation of emotional prosody. In addition to brain areas commonly related to prosody processing, our results suggest specific functions of anterior cingulate and basal ganglia in detecting emotional prosody, particularly when explicit identification is necessary.

Deep and superficial amygdala nuclei projections revealed in vivo by probabilistic tractography.

Despite a homogenous macroscopic appearance on magnetic resonance images, subregions of the amygdala express distinct functional profiles as well as corresponding differences in connectivity. In particular, histological analysis shows stronger connections for superficial (i.e., centromedial and cortical), compared with deep (i.e., basolateral and other), amygdala nuclei to lateral orbitofrontal cortex and stronger connections of deep compared with superficial, nuclei to polymodal areas in the temporal pole. Here, we use diffusion weighted imaging with probabilistic tractography to investigate these connections in humans. We use a data-driven approach to segment the amygdala into two subregions using k-means clustering. The identified subregions are spatially contiguous and their location corresponds to deep and superficial nuclear groups. Quantification of the connection strength between these amygdala clusters and individual target regions corresponds to qualitative histological findings in non-human primates, indicating such findings can be extrapolated to humans. We propose that connectivity profiles provide a potentially powerful approach for in vivo amygdala parcellation and can serve as a guide in studies that exploit functional and anatomical neuroimaging.

Time-series analysis for rapid event-related skin conductance responses

Event-related skin conductance responses (SCRs) are traditionally analysed by comparing the amplitude of individual peaks against a pre-stimulus baseline. Many experimental manipulations in cognitive neuroscience dictate paradigms with short inter trial intervals, precluding accurate baseline estimation for SCR measurements. Here, we present a novel and general approach to SCR analysis, derived from methods used in neuroimaging that estimate responses using a linear convolution model. In effect, the method obviates peak-scoring and makes use of the full SCR. We demonstrate, across three experiments, that the method has face validity in analysing reactions to a loud white noise and emotional pictures, can be generalised to paradigms where the shape of the response function is unknown and can account for parametric trial-by-trial effects. We suggest our approach provides greater flexibility in analysing SCRs than existing methods.

Cholinergic Enhancement of Visual Attention and Neural Oscillations in the Human Brain

Summary Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations [1–6]. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing [7–9]. The cholinergic system is linked to attentional function in vivo [10–13], whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations [14–16]. This has led to theoretical proposals [17–19] that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex [20, 21].

Neural Activity Associated with the Passive Prediction of Ambiguity and Risk for Aversive Events

In economic decision making, outcomes are described in terms of risk (uncertain outcomes with certain probabilities) and ambiguity (uncertain outcomes with uncertain probabilities). Humans are more averse to ambiguity than to risk, with a distinct neural system suggested as mediating this effect. However, there has been no clear disambiguation of activity related to decisions themselves from perceptual processing of ambiguity. In a functional magnetic resonance imaging (fMRI) experiment, we contrasted ambiguity, defined as a lack of information about outcome probabilities, to risk, where outcome probabilities are known, or ignorance, where outcomes are completely unknown and unknowable. We modified previously learned pavlovian CS+ stimuli such that they became an ambiguous cue and contrasted evoked brain activity both with an unmodified predictive CS+ (risky cue), and a cue that conveyed no information about outcome probabilities (ignorance cue). Compared with risk, ambiguous cues elicited activity in posterior inferior frontal gyrus and posterior parietal cortex during outcome anticipation. Furthermore, a similar set of regions was activated when ambiguous cues were compared with ignorance cues. Thus, regions previously shown to be engaged by decisions about ambiguous rewarding outcomes are also engaged by ambiguous outcome prediction in the context of aversive outcomes. Moreover, activation in these regions was seen even when no actual decision is made. Our findings suggest that these regions subserve a general function of contextual analysis when search for hidden information during outcome anticipation is both necessary and meaningful.

Modelling event-related skin conductance responses

Analytic tools for psychophysiological signals often make implicit assumptions that are unspecified. In developing a mathematical framework for analysis of skin conductance responses [SCRs], we formalise our assumptions by positing that SCRs can be regarded as the output of a linear time-invariant filter. Here, we provide an empirical test of these assumptions. Our findings indicate that a large component of the variance in SCRs can be explained by one response function per individual. We note that baseline variance (i.e. variance in the absence of evoked responses) is higher than variance that could not be explained by a linear time-invariant model of evoked responses. Furthermore, there was no evidence for nonlinear interactions among evoked responses that depended on their temporal overlap. We develop a canonical response function and show that it can be used for signals from different recording sites. We discuss the implications of these observations for model-based analysis of SCRs.

Looming sounds as warning signals: The function of motion cues

Sounds with increasing intensity can act as intrinsic warning cues by signalling that the sound source is approaching. However, intensity change is not always the dominant motion cue to a moving sound, and the effects of simple rising intensity sounds versus sounds with full three dimensional motion cues have not yet been directly compared. Here, we examined skin conductance responses, phasic alertness, and perceptual and explicit emotional ratings in response to approaching and receding sounds characterised either by full motion cues or by intensity change only. We found a stronger approach/recede effect in sounds with full motion cues for skin conductance response amplitude, suggesting sustained mobilisation of resources due to their greater saliency. Otherwise, the approach/recede effect was comparable in sounds with and without full motion cues. Overall, approaching sounds elicited greater skin conductance responses and phasic alertness, and loudness change was estimated higher. Also, they were rated as more unpleasant, potent, arousing and intense, and the probability of such sounds to signal a salient event or threat was rated higher. Several of these effects were modulated by sex. In summary, this study supports the suggestion that intensity change is the dominant motion cue mediating the effects of approaching sound sources, thus clarifying the interpretation of previous studies using such stimuli. Explicit emotional appraisal of such sounds shows a strong directional asymmetry and thus may reflect their implicit warning properties.