Publications

Abstract

The social significance of recognizing the person who talks to us is obvious, but the neural mechanisms that mediate talker identification are unclear. Regions along the bilateral superior temporal sulcus (STS) and the inferior frontal cortex (IFC) of the human brain are selective for voices, and they are sensitive to rapid voice changes. Although it has been proposed that voice recognition is supported by prototype-centered voice representations, the involvement of these category-selective cortical regions in the neural coding of such "mean voices" has not previously been demonstrated. Using fMRI in combination with a voice identity learning paradigm, we show that voice-selective regions are involved in the mean-based coding of voice identities. Voice typicality is encoded on a supra-individual level in the right STS along a stimulus-dependent, identity-independent (i.e., voice-acoustic) dimension, and on an intra-individual level in the right IFC along a stimulus-independent, identity-dependent (i.e., voice identity) dimension. Voice recognition therefore entails at least two anatomically separable stages, each characterized by neural mechanisms that reference the central tendencies of voice categories.

Abstract

In spoken language, pitch accent can mark certain information as focus, whereby more attentional resources are allocated to the focused information. Using functional magnetic resonance imaging, this study examined whether pitch accent, used for marking focus, recruited general attention networks during sentence comprehension. In a language task, we independently manipulated the prosody and semantic/pragmatic congruence of sentences. We found that semantic/pragmatic processing affected bilateral inferior and middle frontal gyrus. The prosody manipulation showed bilateral involvement of the superior/inferior parietal cortex, superior and middle temporal cortex, as well as inferior, middle, and posterior parts of the frontal cortex. We compared these regions with attention networks localized in an auditory spatial attention task. Both tasks activated bilateral superior/inferior parietal cortex, superior temporal cortex, and left precentral cortex. Furthermore, an interaction between prosody and congruence was observed in bilateral inferior parietal regions: for incongruent sentences, but not for congruent ones, there was a larger activation if the incongruent word carried a pitch accent, than if it did not. The common activations between the language task and the spatial attention task demonstrate that pitch accent activates a domain general attention network, which is sensitive to semantic/pragmatic aspects of language. Therefore, attention and language comprehension are highly interactive.

Abstract

Grammar acquisition is a high level cognitive function that requires the extraction of complex rules. While it has been proposed that offline time might benefit this type of rule extraction, this remains to be tested. Here, we addressed this question using an artificial grammar learning paradigm. During a short-term memory cover task, eighty-one human participants were exposed to letter sequences generated according to an unknown artificial grammar. Following a time delay of 15 min, 12 h (wake or sleep) or 24 h, participants classified novel test sequences as Grammatical or Non-Grammatical. Previous behavioral and functional neuroimaging work has shown that classification can be guided by two distinct underlying processes: (1) the holistic abstraction of the underlying grammar rules and (2) the detection of sequence chunks that appear at varying frequencies during exposure. Here, we show that classification performance improved after sleep. Moreover, this improvement was due to an enhancement of rule abstraction, while the effect of chunk frequency was unaltered by sleep. These findings suggest that sleep plays a critical role in extracting complex structure from separate but related items during integrative memory processing. Our findings stress the importance of alternating periods of learning with sleep in settings in which complex information must be acquired.

Abstract

Behavioral syntactic priming effects during sentence comprehension are typically observed only if both the syntactic structure and lexical head are repeated. In contrast, during production syntactic priming occurs with structure repetition alone, but the effect is boosted by repetition of the lexical head. We used fMRI to investigate the neuronal correlates of syntactic priming and lexical boost effects during sentence production and comprehension. The critical measure was the magnitude of fMRI adaptation to repetition of sentences in active or passive voice, with or without verb repetition. In conditions with repeated verbs, we observed adaptation to structure repetition in the left IFG and MTG, for active and passive voice. However, in the absence of repeated verbs, adaptation occurred only for passive sentences. None of the fMRI adaptation effects yielded differential effects for production versus comprehension, suggesting that sentence comprehension and production are subserved by the same neuronal infrastructure for syntactic processing.

Abstract

Repetition suppression in fMRI studies is generally thought to underlie behavioural facilitation effects (i.e., priming) and it is often used to identify the neuronal representations associated with a stimulus. However, this pays little heed to the large number of repetition enhancement effects observed under similar conditions. In this review, we identify several cognitive variables biasing repetition effects in the BOLD response towards enhancement instead of suppression. These variables are stimulus recognition, learning, attention, expectation and explicit memory. We also evaluate which models can account for these repetition effects and come to the conclusion that there is no one single model that is able to embrace all repetition enhancement effects. Accumulation, novel network formation as well as predictive coding models can all explain subsets of repetition enhancement effects.

Abstract

Participants were unknowingly exposed to complex regularities in a working memory task. The existence of implicit knowledge was subsequently inferred from a preference for stimuli with similar grammatical regularities. Several affective traits have been shown to influence
AGL performance positively, many of which are related to a tendency for automatic responding. We therefore tested whether the mindfulness trait predicted a reduction of grammatically congruent preferences, and used emotional primes to explore the influence of affect. Mindfulness was shown to correlate negatively with grammatically congruent responses. Negative primes were shown to result in faster and more negative evaluations.
We conclude that grammatically congruent preference ratings rely on habitual responses, and that our findings provide empirical evidence for the non-reactive disposition of the mindfulness trait.

Abstract

Several studies have reported an association between dyslexia and implicit learning deficits. It has been suggested that the weakness in implicit learning observed in dyslexic individuals may be related to sequential processing and implicit sequence learning. In the present article, we review the current literature on implicit learning and dyslexia. We describe a novel, forced-choice structural "mere exposure" artificial grammar learning paradigm and characterize this paradigm in normal readers in relation to the standard grammaticality classification paradigm. We argue that preference classification is a more optimal measure of the outcome of implicit acquisition since in the preference version participants are kept completely unaware of the underlying generative mechanism, while in the grammaticality version, the subjects have, at least in principle, been informed about the existence of an underlying complex set of rules at the point of classification (but not during acquisition). On the basis of the "mere exposure effect," we tested the prediction that the development of preference will correlate with the grammaticality status of the classification items. In addition, we examined the effects of grammaticality (grammatical/nongrammatical) and associative chunk strength (ACS; high/low) on the classification tasks (preference/grammaticality). Using a balanced ACS design in which the factors of grammaticality (grammatical/nongrammatical) and ACS (high/low) were independently controlled in a 2 × 2 factorial design, we confirmed our predictions. We discuss the suitability of this task for further investigation of the implicit learning characteristics in dyslexia.

Abstract

Human implicit learning can be investigated with implicit artificial grammar learning, a paradigm that has been proposed as a simple model for aspects of natural language acquisition. In the present study we compared the typical yes–no grammaticality classification, with yes–no preference classification. In the case of preference instruction no reference to the underlying generative mechanism (i.e., grammar) is needed and the subjects are therefore completely uninformed about an underlying structure in the acquisition material. In experiment 1, subjects engaged in a short-term memory task using only grammatical strings without performance feedback for 5 days. As a result of the 5 acquisition days, classification performance was independent of instruction type and both the preference and the grammaticality group acquired relevant knowledge of the underlying generative mechanism to a similar degree. Changing the grammatical stings to random strings in the acquisition material (experiment 2) resulted in classification being driven by local substring familiarity. Contrasting repeated vs. non-repeated preference classification (experiment 3) showed that the effect of local substring familiarity decreases with repeated classification. This was not the case for repeated grammaticality classifications. We conclude that classification performance is largely independent of instruction type and that forced-choice preference classification is equivalent to the typical grammaticality classification.

Abstract

Cognitive neuroscience approaches the brain as a cognitive system: a system that functionally is conceptualized in terms of information processing. We outline some aspects of this concept and consider a physical system to be an information processing device when a subclass of its physical states can be viewed as representational/cognitive and transitions between these can be conceptualized as a process operating on these states by implementing operations on the corresponding representational structures. We identify a generic and fundamental problem in cognition: sequentially organized structured processing. Structured sequence processing provides the brain, in an essential sense, with its processing logic. In an approach addressing this problem, we illustrate how to integrate levels of analysis within a framework of adaptive dynamical systems. We note that the dynamical system framework lends itself to a description of asynchronous event-driven devices, which is likely to be important in cognition because the brain appears to be an asynchronous processing system. We use the human language faculty and natural language processing as a concrete example through out.

Abstract

Remembering complex, multidimensional information typically requires strategic memory retrieval, during which information is structured, for instance by spatial- or temporal associations. Although brain regions involved in strategic memory retrieval in general have been identified, differences in retrieval operations related to distinct retrieval strategies are not well-understood. Thus, our aim was to identify brain regions whose activity is differentially involved in spatial-associative and temporal-associative retrieval. First, we showed that our behavioral paradigm probing memory for a set of object-location associations promoted the use of a spatial-associative structure following an encoding condition that provided multiple associations to neighboring objects (spatial-associative condition) and the use of a temporal- associative structure following another study condition that provided predominantly temporal associations between sequentially presented items (temporal-associative condition). Next, we used an adapted version of this paradigm for functional MRI, where we contrasted brain activity related to the recall of object-location associations that were either encoded in the spatial- or the temporal-associative condition. In addition to brain regions generally involved in recall, we found that activity in higher-order visual regions, including the fusiform gyrus, the lingual gyrus, and the cuneus, was relatively enhanced when subjects used a spatial-associative structure for retrieval. In contrast, activity in the globus pallidus and the thalamus was relatively enhanced when subjects used a temporal-associative structure for retrieval. In conclusion, we provide evidence for differential involvement of these brain regions related to different types of strategic memory retrieval and the neural structures described play a role in either spatial-associative or temporal-associative memory retrieval.

Abstract

We used simultaneously recorded EEG and fMRI to investigate in which areas the BOLD signal correlates with frontal theta power changes, while subjects were quietly lying resting in the scanner with their eyes open. To obtain a reliable estimate of frontal theta power we applied ICA on band-pass filtered (2–9 Hz) EEG data. For each subject we selected the component that best matched the mid-frontal scalp topography associated with the frontal theta rhythm. We applied a time-frequency analysis on this component and used the time course of the frequency bin with the highest overall power to form a regressor that modeled spontaneous fluctuations in frontal theta power. No significant positive BOLD correlations with this regressor were observed. Extensive negative correlations were observed in the areas that together form the default mode network. We conclude that frontal theta activity can be seen as an EEG index of default mode network activity.

Abstract

We investigated how the hippocampus and its adjacent mediotemporal structures contribute to contextual and noncontextual declarative memory retrieval by manipulating the amount of contextual information across two levels of the same contextual dimension in a source memory task. A first analysis identified medial temporal lobe (MTL) substructures mediating either contextual or noncontextual retrieval. A linearly weighted analysis elucidated which MTL substructures show a gradually increasing neural activity, depending on the amount of contextual information retrieved. A hippocampal engagement was found during both levels of source memory but not during item memory retrieval. The anterior MTL including the perirhinal cortex was only engaged during item memory retrieval by an activity decrease. Only the posterior parahippocampal cortex showed an activation increasing with the amount of contextual information retrieved. If one assumes a roughly linear relationship between the blood-oxygenation level-dependent (BOLD) signal and the associated cognitive process, our results suggest that the posterior parahippocampal cortex is involved in contextual retrieval on the basis of memory strength while the hippocampus processes representations of item-context binding. The anterior MTL including perirhinal cortex seems to be particularly engaged in familiarity-based item recognition. If one assumes departure from linearity, however, our results can also be explained by one-dimensional modulation of memory strength.

Abstract

The human capacity to implicitly acquire knowledge of structured sequences has recently been investigated in artificial grammar learning using functional magnetic resonance imaging. It was found that the left inferior frontal cortex (IFC; Brodmann's area (BA) 44/45) was related to classification performance. The objective of this study was to investigate whether the IFC (BA 44/45) is causally related to classification of artificial syntactic structures by means of an off-line repetitive transcranial magnetic stimulation (rTMS) paradigm. We manipulated the stimulus material in a 2 × 2 factorial design with grammaticality status and local substring familiarity as factors. The participants showed a reliable effect of grammaticality on classification of novel items after 5days of exposure to grammatical exemplars without performance feedback in an implicit acquisition task. The results show that rTMS of BA 44/45 improves syntactic classification performance by increasing the rejection rate of non-grammatical items and by shortening reaction times of correct rejections specifically after left-sided stimulation. A similar pattern of results is observed in FMRI experiments on artificial syntactic classification. These results suggest that activity in the inferior frontal region is causally related to artificial syntax processing.

Abstract

The acute neural effects of progesterone are mediated by its neuroactive metabolites allopregnanolone and pregnanolone. These neurosteroids potentiate the inhibitory actions of c-aminobutyric acid (GABA). Progesterone is known to produce anxiolytic effects in animals, but recent animal studies suggest that pregnanolone increases anxiety after a period of low allopregnanolone concentration. This effect is potentially mediated by the amygdala and related to the negative mood symptoms in humans that are observed during increased allopregnanolone levels. Therefore, we investigated with functional magnetic resonance imaging (MRI) whether a single progesterone administration to healthy young women in their follicular phase modulates the amygdala response to salient, biologically relevant stimuli. The progesterone administration increased the plasma concentrations of progesterone and allopregnanolone to levels that are reached during the luteal phase and early pregnancy. The imaging results show that progesterone selectively increased amygdala reactivity. Furthermore, functional connectivity analyses indicate that progesterone modulated functional coupling of the amygdala with distant brain regions. These results reveal a neural mechanism by which progesterone may mediate adverse effects on anxiety and mood.

Abstract

Knowing what is going to happen next, that is, the capacity to predict upcoming events, modulates the extent to which aversive stimuli induce stress and anxiety. We explored this issue by manipulating the temporal predictability of aversive events by means of a visual cue, which was either correlated or uncorrelated with pain stimuli (electric shocks). Subjects reported lower levels of anxiety, negative valence and pain intensity when shocks were predictable. In addition to attenuate focus on danger, predictability allows for correct temporal estimation of, and selective attention to, the sensory input. With functional magnetic resonance imaging, we found that predictability was related to enhanced activity in relevant sensory-discriminative processing areas, such as the primary and secondary sensory cortex and posterior insula. In contrast, the unpredictable more aversive context was correlated to brain activity in the anterior insula and the orbitofrontal cortex, areas associated with affective pain processing. This context also prompted increased activity in the posterior parietal cortex and lateral prefrontal cortex that we attribute to enhanced alertness and sustained attention during unpredictability.

Abstract

The human brain supports acquisition mechanisms that extract structural regularities implicitly from experience without the induction of an explicit model. It has been argued that the capacity to generalize to new input is based on the acquisition of abstract representations, which reflect underlying structural regularities in the input ensemble. In this study, we explored the outcome of this acquisition mechanism, and to this end, we investigated the neural correlates of artificial syntactic classification using event-related functional magnetic resonance imaging. The participants engaged once a day during an 8-day period in a short-term memory acquisition task in which consonant-strings generated from an artificial grammar were presented in a sequential fashion without performance feedback. They performed reliably above chance on the grammaticality classification tasks on days 1 and 8 which correlated with a corticostriatal processing network, including frontal, cingulate, inferior parietal, and middle occipital/occipitotemporal regions as well as the caudate nucleus. Part of the left inferior frontal region (BA 45) was specifically related to syntactic violations and showed no sensitivity to local substring familiarity. In addition, the head of the caudate nucleus correlated positively with syntactic correctness on day 8 but not day 1, suggesting that this region contributes to an increase in cognitive processing fluency.

Abstract

There is evidence for cognitive as well as neural plasticity across the adult life span, although aging is associated with certain constraints on plasticity. In the current paper, we argue that the age-related reduction in cognitive plasticity may be due to (a) deficits in general processing resources, and (b) failure to engage in task-relevant cognitive operations. Memory-training research suggests that age-related processing deficits (e.g., executive functions, speed) hinder older adults from utilizing mnemonic techniques as efficiently as the young, and that this age difference is reflected by diminished frontal activity during mnemonic use. Additional constraints on memory plasticity in old age are related to difficulties that are specific to the task, such as creating visual images, as well as in binding together the information to be remembered. These deficiencies are paralleled by reduced activity in occipito-parietal and medial–temporal regions, respectively. Future attempts to optimize intervention-related gains in old age should consider targeting both general processing and task-specific origins of age-associated reductions in cognitive plasticity.

Abstract

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE {varepsilon}4 carriers (age range: 49–74 years; 19 females), of which 10 were homozygous for the {varepsilon}4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE {varepsilon}4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE {varepsilon}4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.

Abstract

Literacy and education represent essential aspects of contemporary society and subserve important aspects of socialization and cultural transmission. The study of illiterate subjects represents one approach to investigate the interactions between neurobiological and cultural factors in cognitive development, individual learning, and their influence on the functional organization of the brain. In this chapter we review some recent cognitive, neuroanatomic, and functional neuroimaging results indicating that formal education influences important aspects of the human brain. Taken together this provides strong support for the idea that the brain is modulated by literacy and formal education, which in turn change the brains capacity to interact with its environment, including the individual's contemporary culture. In other words, the individual is able to participate in, interact with, and actively contribute to the process of cultural transmission in new ways through acquired cognitive skills.

Abstract

The irrelevant speech effect illustrates that sounds that are irrelevant to a visually presented short-term memory task still interfere with neuronal function. In the present study we explore the functional and effective connectivity of such interference. The functional connectivity analysis suggested an interaction between the level of irrelevant speech and the correlation between in particular the left superior temporal region, associated with verbal working memory, and the left medial temporal lobe. Based on this psycho-physiological interaction, and to broaden the understanding of this result, we performed a network analysis, using a simple network model for verbal working memory, to analyze its interaction with the medial temporal lobe memory system. The results showed dissociations in terms of network interactions between frontal as well as parietal and temporal areas in relation to the medial temporal lobe. The results of the present study suggest that a transition from phonological loop processing towards an engagement of episodic processing might take place during the processing of interfering irrelevant sounds. We speculate that, in response to the irrelevant sounds, this reflects a dynamic shift in processing as suggested by a closer interaction between a verbal working memory system and the medial temporal lobe memory system.

Abstract

Doubts have been cast on the strict dissociation between short- and long-term memory systems. Specifically, several neuroimaging studies have shown that the medial temporal lobe, a region almost invariably associated with long-term memory, is involved in active short-term memory maintenance. Furthermore, a recent study in hippocampally lesioned patients has shown that the hippocampus is critically involved in associating objects and their locations, even when the delay period lasts only 8 s. However, the critical feature that causes the medial temporal lobe, and in particular the hippocampus, to participate in active maintenance is still unknown. This study was designed in order to explore hippocampal involvement in active maintenance of spatial and non-spatial associations. Eighteen participants performed a delayed-match-to-sample task in which they had to maintain either object–location associations, color–number association, single colors, or single locations. Whole-brain activity was measured using event-related functional magnetic resonance imaging and analyzed using a random effects model. Right lateralized hippocampal activity was evident when participants had to maintain object–location associations, but not when they had to maintain object–color associations or single items. The present results suggest a hippocampal involvement in active maintenance when feature combinations that include spatial information have to be maintained online.

Abstract

Previous work has shown that illiterate subjects are better at naming two-dimensional representations of real objects when presented as colored photos as compared to black and white drawings. This raises the question if color or textural details selectively improve object recognition and naming in illiterate compared to literate subjects. In this study, we investigated whether the surface texture and/or color of objects is used to access stored object knowledge in illiterate subjects. A group of illiterate subjects and a matched literate control group were compared on an immediate object naming task with four conditions: color and black and white (i.e., grey-scaled) photos, as well as color and black and white (i.e., grey-scaled) drawings of common everyday objects. The results show that illiterate subjects perform significantly better when the stimuli are colored and this effect is independent of the photographic detail. In addition, there were significant differences between the literacy groups in the black and white condition for both drawings and photos. These results suggest that color object information contributes to object recognition. This effect was particularly prominent in the illiterate group

Abstract

Retrieval of recently acquired declarative memories depends on
the hippocampus, but with time, retrieval is increasingly sustainable
by neocortical representations alone. This process has been
conceptualized as system-level consolidation. Using functional
magnetic resonance imaging, we assessed over the course of three
months how consolidation affects the neural correlates of memory
retrieval. The duration of slow-wave sleep during a nap/rest
period after the initial study session and before the first scan
session on day 1 correlated positively with recognition memory
performance for items studied before the nap and negatively with
hippocampal activity associated with correct confident recognition.
Over the course of the entire study, hippocampal activity for
correct confident recognition continued to decrease, whereas activity
in a ventral medial prefrontal region increased. These findings,
together with data obtained in rodents, may prompt a
revision of classical consolidation theory, incorporating a transfer
of putative linking nodes from hippocampal to prelimbic prefrontal
areas.