Bärbel Herrnberger

The Sound of Concepts: Four Markers for a Link between Auditory and Conceptual Brain Systems

Traditionally, concepts are conceived as abstract mental entities distinct from perceptual or motor brain systems. However, recent results let assume modality-specific representations of concepts. The ultimate test for grounding concepts in perception requires the fulfillment of the following four markers: conceptual processing during (1) an implicit task should activate (2) a perceptual region (3) rapidly and (4) selectively. Here, we show using functional magnetic resonance imaging and recordings of event-related potentials, that acoustic conceptual features recruit auditory brain areas even when implicitly presented through visual words. Fulfilling the four markers, the findings of our study unequivocally link the auditory and conceptual brain systems: recognition of words denoting objects, for which acoustic features are highly relevant (e.g.,“telephone”), ignited cell assemblies in posterior superior and middle temporal gyri (pSTG/MTG) within 150 ms that were also activated by sound perception. Importantly, activity within a cluster of pSTG/MTG increased selectively as a function of acoustic, but not of visual and action-related feature relevance. The implicitness of the conceptual task, the selective modulation of left pSTG/MTG activity by acoustic feature relevance, the early onset of this activity at 150 ms and its anatomical overlap with perceptual sound processing are four markers for a modality-specific representation of auditory conceptual features in left pSTG/MTG. Our results therefore provide the first direct evidence for a link between perceptual and conceptual acoustic processing. They demonstrate that access to concepts involves a partial reinstatement of brain activity during the perception of objects.

Conceptual flexibility in the human brain: Dynamic recruitment of semantic maps from visual, motor, and motion-related areas

Traditionally, concepts are assumed to be situational invariant mental knowledge entities (conceptual stability), which are represented in a unitary brain system distinct from sensory and motor areas (amodality). However, accumulating evidence suggests that concepts are embodied in perception and action in that their conceptual features are stored within modality-specific semantic maps in the sensory and motor cortex. Nonetheless, the first traditional assumption of conceptual stability largely remains unquestioned. Here, we tested the notion of flexible concepts using functional magnetic resonance imaging and event-related potentials (ERPs) during the verification of two attribute types (visual, action-related) for words denoting artifactual and natural objects. Functional imaging predominantly revealed crossover interactions between category and attribute type in visual, motor, and motion-related brain areas, indicating that access to conceptual knowledge is strongly modulated by attribute type: Activity in these areas was highest when nondominant conceptual attributes had to be verified. ERPs indicated that these category-attribute interactions emerged as early as 116 msec after stimulus onset, suggesting that they reflect rapid access to conceptual features rather than postconceptual processing. Our results suggest that concepts are situational-dependent mental entities. They are composed of semantic features which are flexibly recruited from distributed, yet localized, semantic maps in modality-specific brain regions depending on contextual constraints.

A Neural Signature of Anorexia Nervosa in the Ventral Striatal Reward System

OBJECTIVE Animal studies assessing mechanisms of self-starvation under conditions of stress and diet suggest a pivotal role for the mesolimbic reward system in the maintenance of core symptoms in anorexia nervosa, which is corroborated by initial empirical evidence in human studies. The authors examined activity in the ventral striatal system in response to disease-specific stimuli in women with acute anorexia nervosa. METHOD Participants were 14 women with acute anorexia nervosa and 14 matched healthy comparison women who underwent functional magnetic resonance imaging (fMRI) during evaluation of visual stimuli depicting a female body with underweight, normal weight, and overweight canonical whole-body features according to standardized body mass indices. Participants were required to process each stimulus in a self-referring way. Ratings for each weight category were used as the control task. RESULTS Behaviorally, women with anorexia nervosa provided significantly higher positive ratings in response to underweight stimuli than in response to normal-weight stimuli, while healthy comparison women showed greater preference for normal-weight stimuli relative to underweight stimuli. Functionally, ventral striatal activity demonstrated a highly significant group-by-stimulus interaction for underweight and normal-weight stimuli. In women with anorexia nervosa, activation was higher during processing of underweight stimuli compared with normal-weight stimuli. The reverse pattern was observed in healthy comparison women. CONCLUSIONS These findings are consistent with predictions in animal studies of the pivotal role of the human reward system in anorexia nervosa and thus support theories of starvation dependence in maintenance of the disorder.

Anisotropy in the visual cortex investigated by neuronavigated transcranial magnetic stimulation

Responses to transcranial magnetic stimulation (TMS) of the motor cortex depend on the direction of the induced current with an optimum perpendicular to the orientation of the precentral gyrus. Little is known about anisotropy in other cortical regions. We measured phosphene thresholds in the visual cortex using a frameless neuronavigation system. Comparing horizontal and vertical current orientation as well as monophasic and biphasic pulses in 7 subjects, we found lower thresholds with biphasic pulses and a tendency for lower thresholds with horizontal currents. When varying current directions in steps of 45 degrees centered on a hot spot over the occipital cortex, in 10 out of 12 measurements optimal current orientation ran perpendicular to the underlying gyrus (mean deviation 14.6 degrees). Optimal current orientation was determined as the orientation of the second eigenvector from the covariance matrix of the stimulation sites that had been shifted along the respective current direction by the amount of the measured threshold. Individual cortical architecture was obtained by segmentation of a 3d anatomical MR scan, with large interindividual differences among the orientations of the stimulated gyrus. As with the motor system, the optimum threshold with biphasic pulses was flipped about 180 degrees compared to the optimum with monophasic pulses (p<.02) throughout subjects, suggesting both similar anisotropic properties of networks in the visual and motor cortices and the existence of anisotropic behaviour in any cortical region. As a consequence, optimal TMS application should always take into account the individual orientation of the gyrus to be stimulated.

Neuroplasticity of semantic representations for musical instruments in professional musicians

Professional musicians constitute a model par excellence for understanding experience-dependent plasticity in the human brain, particularly in the auditory domain. Their intensive sensorimotor experience with musical instruments has been shown to entail plastic brain alterations in cortical perceptual and motor maps. It remains an important question whether this neuroplasticity might extend beyond basic perceptual and motor functions and even shape higher-level conceptualizations by which we conceive our physical and social world. Here we show using functional magnetic resonance imaging (fMRI) that conceptual processing of visually presented musical instruments activates auditory association cortex encompassing right posterior superior temporal gyrus, as well as adjacent areas in the superior temporal sulcus and the upper part of middle temporal gyrus (pSTG/MTG) only in musicians, but not in musical laypersons. These areas in and adjacent to auditory association cortex were not only recruited by conceptual processing of musical instruments during visual object recognition, but also by auditory perception of real sounds. Hence, the unique intensive experience of musicians with musical instruments establishes a link between auditory perceptual and conceptual brain systems. Experience-driven neuroplasticity in musicians is thus not confined to alterations of perceptual and motor maps, but even leads to the establishment of higher-level semantic representations for musical instruments in and adjacent to auditory association cortex. These findings highlight the eminent importance of sensory and motor experience for acquiring rich concepts.

Continuous theta-burst stimulation over the dorsal premotor cortex interferes with associative learning during object lifting.

When lifting objects of different mass, humans scale grip force according to the expected mass. In this context, humans are able to associate a sensory cue, such as a colour, to a particular mass of an object and link this association to the grip forces necessary for lifting. Here, we study the role of the dorsal premotor cortex (PMd) in setting-up an association between a colour cue and a particular mass to be lifted. Healthy right-handed subjects used a precision grip between the index finger and thumb to lift two different masses. Colour cues provided information about which of the two masses subjects would have to lift. Subjects first performed a series of lifts with the right hand to establish a stable association between a colour cue and a mass, followed by 20sec of continuous high frequency repetitive trancranial magnetic stimulation using a recently developed protocol (continuous theta-burst stimulation, cTBS) over (i) the left primary motor cortex, (ii) the left PMd and (iii) the left occipital cortex to be commenced by another series of lifts with either the right or left hand. cTBS over the PMd, but not over the primary motor cortex or O1, disrupted the predictive scaling of isometric finger forces based on colour cues, irrespective of whether the right or left hand performed the lifts after the stimulation. Our data highlight the role of the PMd to generalize and maintain associative memory processes relevant for predictive control of grip forces during object manipulation.

Speaking in Multiple Languages: Neural Correlates of Language Proficiency in Multilingual Word Production.

The human brain has the fascinating ability to represent and to process several languages. Although the first and further languages activate partially different brain networks, the linguistic factors underlying these differences in language processing have to be further specified. We investigated the neural correlates of language proficiency in a homogeneous sample of multilingual native Ladin speakers from a mountain valley in South Tyrol, Italy, who speak Italian as second language at a high level, and English at an intermediate level. In a constrained word production task under functional magnetic resonance imaging (fMRI), participants had to name pictures of objects in Ladin, Italian and English in separate blocks. Overall, multilingual word production activated a common set of brain areas dedicated to known subcomponents of picture naming. In comparison to English, the fluently spoken languages Ladin and Italian were associated with enhanced right prefrontal activity. In addition, the MR signal in right prefrontal cortex correlated with naming accuracy as a measure of language proficiency. Our results demonstrate the significance of right prefrontal areas for language proficiency. Based on the role of these areas for cognitive control, our findings suggest that right prefrontal cortex supports language proficiency by effectively supervising word retrieval.

Xenon-induced changes in CNS sensitization to pain.

Electrophysiological investigations of the spinal cord in animals have shown that pain sensitizes the central nervous system via glutamate receptor dependent long-term potentiation (LTP) related to an enhancement of pain perception. To expand these findings, we used functional magnetic resonance (fMRI), blood oxygen level dependent (BOLD) and perfusion imaging in combination with repeated electrical stimulation in humans. Specifically we monitored modulation of somatosensory processing during inhibition of excitatory transmission by ocular application of the glutamate receptor antagonist xenon. BOLD responses upon secondary stimulation increased in mid insular and in primary/secondary sensory cortices under placebo and decreased under xenon treatments. Xenon-induced decreases in regional perfusion were confined to stimulation responsive brain regions and correlated with time courses of xenon concentrations in the cranial blood. Moreover, effects of xenon on behavioral, fMRI and perfusion data scaled with stimulus intensity. The dependence of pain sensitization on sufficient pre-activation reflects a multistage process which is characteristic for glutamate receptor related processes of LTP. This study demonstrates how LTP related processes known from the cellular level can be investigated at the brain systems level.

Mechanisms underlying flexible adaptation of cognitive control: Behavioral and neuroimaging evidence in a flanker task

Cognitive control can be adapted flexibly according to the conflict level in a given situation. In the Eriksen flanker task, interference evoked by flankers is larger in conditions with a higher, rather than a lower proportion of compatible trials. Such compatibility ratio effects also occur for stimuli presented at two spatial locations suggesting that different cognitive control settings can be simultaneously maintained. However, the conditions and the neural correlates of this flexible adaptation of cognitive control are only poorly understood. In the present study, we further elucidated the mechanisms underlying the simultaneous maintenance of two cognitive control settings. In behavioral experiments, stimuli were presented centrally above and below fixation and hence processed by both hemispheres or lateralized to stimulate hemispheres differentially. The different compatibility ratio at two stimulus locations had a differential influence on the flanker effect in both experiments. In an fMRI experiment, blocks with an identical compatibility ratio at two central spatial locations elicited stronger activity in a network of prefrontal and parietal brain areas, which are known to be involved in conflict resolution and cognitive control, as compared with blocks with a different compatibility ratio at the same spatial locations. This demonstrates that the simultaneous maintenance of two conflicting control settings vs. one single setting does not recruit additional neural circuits suggesting the involvement of one single cognitive control system. Instead a crosstalk between multiple control settings renders adaptation of cognitive control more efficient when only one uniform rather than two different control settings has to be simultaneously maintained.

From uncertainty to reward: BOLD characteristics differentiate signaling pathways

BackgroundReward value and uncertainty are represented by dopamine neurons in monkeys by distinct phasic and tonic firing rates. Knowledge about the underlying differential dopaminergic pathways is crucial for a better understanding of dopamine-related processes. Using functional magnetic resonance blood-oxygen level dependent (BOLD) imaging we analyzed brain activation in 15 healthy, male subjects performing a gambling task, upon expectation of potential monetary rewards at different reward values and levels of uncertainty.ResultsConsistent with previous studies, ventral striatal activation was related to both reward magnitudes and values. Activation in medial and lateral orbitofrontal brain areas was best predicted by reward uncertainty. Moreover, late BOLD responses relative to trial onset were due to expectation of different reward values and likely to represent phasic dopaminergic signaling. Early BOLD responses were due to different levels of reward uncertainty and likely to represent tonic dopaminergic signals.ConclusionsWe conclude that differential dopaminergic signaling as revealed in animal studies is not only represented locally by involvement of distinct brain regions but also by distinct BOLD signal characteristics.