Boosting the effect of reward on cognitive control using TMS over the left IFJ.

Although an enhancing effect of reward on cognitive performance has been observed consistently, its neural underpinnings remain elusive. Recent evidence suggests that the inferior frontal junction (IFJ) may be a key player underlying such an enhancement by integrating motivational processes and cognitive control. However, its exact role and in particular a potential causality of IFJ activation is still unclear. In the present study, we therefore investigated the causal contributions of the left IFJ in motivated task switching by temporarily disrupting its activity using continuous theta burst stimulation (cTBS, Exp.1) or 1 Hz repetitive transcranial magnetic stimulation (rTMS, Exp.2). After TMS application over the left IFJ or a control site (vertex), participants performed a switch task in which numbers had to be judged by magnitude or parity. Different amounts of monetary rewards (high vs low) were used to manipulate the participants' motivational states. We measured reaction times and error rates. Irrespective of TMS stimulation, participants exhibited slower responses following task switches compared to task repeats. This effect was reduced in high reward trials. Importantly, we found that disrupting the IFJ improved participants' behavioral performance in the high reward condition. For high reward trials exclusively, error rates decreased when the IFJ was modulated with cTBS or 1 Hz rTMS but not after vertex stimulation. Our results suggest that the left IFJ is causally related to the increase in cognitive performance through reward.

Event-related potentials and neural oscillations dissociate levels of cognitive control.

Recent models of human behavior suggest a hierarchical organization of cognitive control processes. These models assume that different sub-goals of cognitive control processes are nested in each other, such that higher-level sub-goals can only be accomplished when lower-level sub-goals have been realized. While the neuroanatomical localization of this organizational principle has already been successfully tested, the exact temporal nature remains to be explored. The present study applied event-related potentials (ERPs) and investigated neural oscillations during performance of three different nested cognitive control tasks. Results demonstrated a parametric modulation of the P300 component as well as beta-band (13-25Hz) oscillations as a function of different levels of cognitive control. Moreover, conditions requiring flexible updating of information exhibited similar alpha-band (8-13Hz) oscillations, which differed from the condition without flexible updating (low-level). These results suggest dissociable mechanisms of flexible information updating and complexity of cognitive control processes indexed by different oscillatory effects.

Influence of motivation on control hierarchy in the human frontal cortex.

The frontal cortex mediates cognitive control and motivation to shape human behavior. It is generally observed that medial frontal areas are involved in motivational aspects of behavior, whereas lateral frontal regions are involved in cognitive control. Recent models of cognitive control suggest a rostro-caudal gradient in lateral frontal regions, such that progressively more rostral (anterior) regions process more complex aspects of cognitive control. How motivation influences such a control hierarchy is still under debate. Although some researchers argue that both systems work in parallel, others argue in favor of an interaction between motivation and cognitive control. In the latter case it is yet unclear how motivation would affect the different levels of the control hierarchy. This was investigated in the present functional MRI study applying different levels of cognitive control under different motivational states (low vs high reward anticipation). Three levels of cognitive control were tested by varying rule complexity: stimulus-response mapping (low-level), flexible task updating (mid-level), and sustained cue-task associations (high-level). We found an interaction between levels of cognitive control and motivation in medial and lateral frontal subregions. Specifically, flexible updating (mid-level of control) showed the strongest beneficial effect of reward and only this level exhibited functional coupling between dopamine-rich midbrain regions and the lateral frontal cortex. These findings suggest that motivation differentially affects the levels of a control hierarchy, influencing recruitment of frontal cortical control regions depending on specific task demands.

The Rostro-Caudal Axis of Frontal Cortex Is Sensitive to the Domain of Stimulus Information.

Evidence suggests that lateral frontal cortex implements cognitive control processing along its rostro-caudal axis, yet other evidence supports a dorsal-ventral functional organization for processes engaged by different stimulus domains (e.g., spatial vs. nonspatial). This functional magnetic resonance imaging study investigated whether separable dorsolateral and ventrolateral rostro-caudal gradients exist in humans, while participants performed tasks requiring cognitive control at 3 levels of abstraction with language or spatial stimuli. Abstraction was manipulated by using 3 different task sets that varied in relational complexity. Relational complexity refers to the process of manipulating the relationship between task components (e.g., to associate a particular cue with a task) and drawing inferences about that relationship. Tasks using different stimulus domains engaged distinct posterior regions, but within the lateral frontal cortex, we found evidence for a single rostro-caudal gradient that was organized according to the level of abstraction and was independent of processing of the stimulus domain. However, a pattern of dorsal/ventral segregation of processing engaged by domain-specific information was evident in each separable frontal region only within the most rostral region recruited by task demands. These results suggest that increasingly abstract information is represented in the frontal cortex along distinct rostro-caudal gradients that also segregate along a dorsal-ventral axis dependent on task demands.

Brain signature of working memory for sentence structure: enriched encoding and facilitated maintenance.

Sentences are easier to memorize than ungrammatical word strings, a phenomenon known as the sentence superiority effect. Yet, it is unclear how higher-order linguistic information facilitates verbal working memory and how this is implemented in the neural system. The goal of the current fMRI study was to specify the brain mechanisms underlying the sentence superiority effect during encoding and during maintenance in working memory by manipulating syntactic structure and working memory load. The encoding of sentence material, as compared with the encoding of ungrammatical word strings, recruited not only inferior frontal (BA 47) and anterior temporal language-related areas but also the medial-temporal lobe, which is not classically reported for language tasks. During maintenance, it was sentence structure as contrasted with ungrammatical word strings that led to activation decrease in Broca's area, SMA, and parietal regions. Furthermore, in Broca's area, an interaction effect revealed a load effect for ungrammatical word strings but not for sentences. The sentence superiority effect, thus, is neurally reflected in a twofold pattern, consisting of increased activation in classical language as well as memory areas during the encoding phase and decreased maintenance-related activation. This pattern reflects how chunking, based on sentential syntactic and semantic information, alleviates rehearsal demands and thus leads to improved working memory performance.

Predicting vocal emotion expressions from the human brain.

Speech is an important carrier of emotional information. However, little is known about how different vocal emotion expressions are recognized in a receiver's brain. We used multivariate pattern analysis of functional magnetic resonance imaging data to investigate to which degree distinct vocal emotion expressions are represented in the receiver's local brain activity patterns. Specific vocal emotion expressions are encoded in a right fronto-operculo-temporal network involving temporal regions known to subserve suprasegmental acoustic processes and a fronto-opercular region known to support emotional evaluation, and, moreover, in left temporo-cerebellar regions covering sequential processes. The right inferior frontal region, in particular, was found to differentiate distinct emotional expressions. The present analysis reveals vocal emotion to be encoded in a shared cortical network reflected by distinct brain activity patterns. These results shed new light on theoretical and empirical controversies about the perception of distinct vocal emotion expressions at the level of large-scale human brain signals.

Levels of integration in cognitive control and sequence processing in the prefrontal cortex.

Cognitive control is necessary to flexibly act in changing environments. Sequence processing is needed in language comprehension to build the syntactic structure in sentences. Functional imaging studies suggest that sequence processing engages the left ventrolateral prefrontal cortex (PFC). In contrast, cognitive control processes additionally recruit bilateral rostral lateral PFC regions. The present study aimed to investigate these two types of processes in one experimental paradigm. Sequence processing was manipulated using two different sequencing rules varying in complexity. Cognitive control was varied with different cue-sets that determined the choice of a sequencing rule. Univariate analyses revealed distinct PFC regions for the two types of processing (i.e. sequence processing: left ventrolateral PFC and cognitive control processing: bilateral dorsolateral and rostral PFC). Moreover, in a common brain network (including left lateral PFC and intraparietal sulcus) no interaction between sequence and cognitive control processing was observed. In contrast, a multivariate pattern analysis revealed an interaction of sequence and cognitive control processing, such that voxels in left lateral PFC and parietal cortex showed different tuning functions for tasks involving different sequencing and cognitive control demands. These results suggest that the difference between the process of rule selection (i.e. cognitive control) and the process of rule-based sequencing (i.e. sequence processing) find their neuronal underpinnings in distinct activation patterns in lateral PFC. Moreover, the combination of rule selection and rule sequencing can shape the response of neurons in lateral PFC and parietal cortex.

A rostro-caudal gradient of structured sequence processing in the left inferior frontal gyrus.

In this paper, we present two novel perspectives on the function of the left inferior frontal gyrus (LIFG). First, a structured sequence processing perspective facilitates the search for functional segregation within the LIFG and provides a way to express common aspects across cognitive domains including language, music and action. Converging evidence from functional magnetic resonance imaging and transcranial magnetic stimulation studies suggests that the LIFG is engaged in sequential processing in artificial grammar learning, independently of particular stimulus features of the elements (whether letters, syllables or shapes are used to build up sequences). The LIFG has been repeatedly linked to processing of artificial grammars across all different grammars tested, whether they include non-adjacent dependencies or mere adjacent dependencies. Second, we apply the sequence processing perspective to understand how the functional segregation of semantics, syntax and phonology in the LIFG can be integrated in the general organization of the lateral prefrontal cortex (PFC). Recently, it was proposed that the functional organization of the lateral PFC follows a rostro-caudal gradient, such that more abstract processing in cognitive control is subserved by more rostral regions of the lateral PFC. We explore the literature from the viewpoint that functional segregation within the LIFG can be embedded in a general rostro-caudal abstraction gradient in the lateral PFC. If the lateral PFC follows a rostro-caudal abstraction gradient, then this predicts that the LIFG follows the same principles, but this prediction has not yet been tested or explored in the LIFG literature. Integration might provide further insights into the functional architecture of the LIFG and the lateral PFC.

An approach to separating the levels of hierarchical structure building in language and mathematics.

We aimed to dissociate two levels of hierarchical structure building in language and mathematics, namely 'first-level' (the build-up of hierarchical structure with externally given elements) and 'second-level' (the build-up of hierarchical structure with internally represented elements produced by first-level processes). Using functional magnetic resonance imaging, we investigated these processes in three domains: sentence comprehension, arithmetic calculation (using Reverse Polish notation, which gives two operands followed by an operator) and a working memory control task. All tasks required the build-up of hierarchical structures at the first- and second-level, resulting in a similar computational hierarchy across language and mathematics, as well as in a working memory control task. Using a novel method that estimates the difference in the integration cost for conditions of different trial durations, we found an anterior-to-posterior functional organization in the prefrontal cortex, according to the level of hierarchy. Common to all domains, the ventral premotor cortex (PMv) supports first-level hierarchy building, while the dorsal pars opercularis (POd) subserves second-level hierarchy building, with lower activation for language compared with the other two tasks. These results suggest that the POd and the PMv support domain-general mechanisms for hierarchical structure building, with the POd being uniquely efficient for language.

Perisylvian Functional Connectivity during Processing of Sentential Negation.

Every language has the means to reverse the truth value of a sentence by using specific linguistic markers of negation. In the present study we investigated the neural processing costs afforded by the construction of meaning in German sentences containing negation in different clause types. We studied negations within and across clause boundaries as well as single and double negations. Participants read German sentences comprising of affirmations, single negations in the main or in the subordinate clause, or double negations. As a result, we found a network including the left inferior frontal gyrus (pars triangularis, BA 45), and the left inferior parietal gyrus (BA 40) to be activated whenever negations in the main clause had to be processed. Additionally, we found increased functional coupling between the left pars triangularis (BA 45), left pars opercularis (BA 44), left SMA (BA 6), and left superior temporal gyrus (BA 42) during the processing of main clause negations. The study shows that in order to process negations that require semantic integration across clause boundaries left BA 45 interplays with other areas that have been related to language processing and/or the processing of cognitive demands and logical/conditional reasoning. Thus, the results indicate that the left perisylvian language network synchronizes in order to resolve negations, in particular, whenever requirements on meaning integration are enhanced.

Learnability of embedded syntactic structures depends on prosodic cues.

The ability to process center-embedded structures has been claimed to represent a core function of the language faculty. Recently, several studies have investigated the learning of center-embedded dependencies in artificial grammar settings. Yet some of the results seem to question the learnability of these structures in artificial grammar tasks. Here, we tested under which exposure conditions learning of center-embedded structures in an artificial grammar is possible. We used naturally spoken syllable sequences and varied the presence of prosodic cues. The results suggest that mere distributional information does not suffice for successful learning. Prosodic cues marking the boundaries of the major relevant units, however, can lead to learning success. Thus, our data are consistent with the hypothesis that center-embedded syntactic structures can be learned in artificial grammar tasks if language-like acoustic cues are provided.

Neural circuits of hierarchical visuo-spatial sequence processing.

Sequence processing has been investigated in a number of studies using serial reaction time tasks or simple artificial grammar tasks. Little, however, is known about higher-order sequence processing entailing the hierarchical organization of events. Here, we manipulated the regularities within sequentially occurring, non-linguistic visual symbols by applying two types of prediction rules. In one rule (the adjacent dependency rule), the sequences consisted of alternating items from two different categories. In the second rule (the hierarchical dependency rule), a hierarchical structure was generated using the same set of item types. Thus, predictions about non-adjacent elements were required for the latter rule. Functional Magnetic Resonance Imaging (fMRI) was used to investigate the neural correlates of the application of the two prediction rules. We found that the hierarchical dependency rule correlated with activity in the pre-supplementary motor area, and the head of the caudate nucleus. In addition, in a hypothesis-driven ROI analysis in Broca's area (BA 44), we found a significantly higher hemodynamic response to the hierarchical dependency rule than to the adjacent dependency rule. These results suggest that this neural network supports hierarchical sequencing, possibly contributing to the integration of sequential elements into higher-order structural events. Importantly, the findings suggest that Broca's area is also engaged in hierarchical sequencing in domains other than language.

Segregating the core computational faculty of human language from working memory.

In contrast to simple structures in animal vocal behavior, hierarchical structures such as center-embedded sentences manifest the core computational faculty of human language. Previous artificial grammar learning studies found that the left pars opercularis (LPO) subserves the processing of hierarchical structures. However, it is not clear whether this area is activated by the structural complexity per se or by the increased memory load entailed in processing hierarchical structures. To dissociate the effect of structural complexity from the effect of memory cost, we conducted a functional magnetic resonance imaging study of German sentence processing with a 2-way factorial design tapping structural complexity (with/without hierarchical structure, i.e., center-embedding of clauses) and working memory load (long/short distance between syntactically dependent elements; i.e., subject nouns and their respective verbs). Functional imaging data revealed that the processes for structure and memory operate separately but co-operatively in the left inferior frontal gyrus; activities in the LPO increased as a function of structural complexity, whereas activities in the left inferior frontal sulcus (LIFS) were modulated by the distance over which the syntactic information had to be transferred. Diffusion tensor imaging showed that these 2 regions were interconnected through white matter fibers. Moreover, functional coupling between the 2 regions was found to increase during the processing of complex, hierarchically structured sentences. These results suggest a neuroanatomical segregation of syntax-related aspects represented in the LPO from memory-related aspects reflected in the LIFS, which are, however, highly interconnected functionally and anatomically.

The role of the posterior superior temporal cortex in sentence comprehension.

The study investigates to what extent the posterior superior temporal cortex is involved in processing complex sentences. Using functional MRI, we show that hierarchically structured sentences activate the superior temporal cortex bilaterally to greater extent than sentences with a linear structure. The activation in the left hemisphere comprises the superior temporal gyrus and sulcus, whereas the activation in the right hemisphere is confined to the superior temporal sulcus. As earlier studies using similar syntactic structures in semantic-free grammars did not show activation in the superior temporal cortex but instead only in the prefrontal cortex, we conclude that the role of the posterior superior temporal cortex is to integrate lexical-semantic and syntactic information during sentence comprehension.

Hierarchical artificial grammar processing engages Broca's area.

The present fMRI study investigates the neural basis of hierarchical processing using two types of artificial grammars: one governed by rules of adjacent dependencies and the other by rules of hierarchical dependencies. The adjacent dependency sequences followed the rule (AB)(n), at which simple transitions between two types of syllable categories were generated (e.g. A(1)B(1)A(2)B(2)). The hierarchical syllable sequences followed the rule A(n)B(n), generating a center-embedded structure (e.g. A(2)A(1)B(1)B(2)) the learning of which required the processing of hierarchical dependencies. When comparing the processing of hierarchical dependencies to adjacent dependencies, significantly higher activations were observed in Broca's area and the adjacent rim of the ventral premotor cortex (BA 44/6) in addition to some several other cortical and sub-cortical regions. These results indicate that Broca's area is part of a neural circuit that is responsible for the processing of hierarchical structures in an artificial grammar.

An fMRI study of canonical and noncanonical word order in German.

Understanding a complex sentence requires the processing of information at different (e.g., phonological, semantic, and syntactic) levels, the intermediate storage of this information and the unification of this information to compute the meaning of the sentence information. The present investigation homed in on two aspects of sentence processing: working memory and reanalysis. Event-related functional MRI was used in 12 healthy native speakers of German, while they read sentences. Half of the sentences had unambiguous initial noun-phrases (masculine nominative, masculine accusative) and thus signaled subject-first (canonical) or object-first (noncanonical) sentences. Noncanonical unambiguous sentences were supposed to entail greater demand on working memory, because of their more complex syntactic structure. The other half of the sentences had case-ambiguous initial noun-phrases (feminine gender). Only the second unambiguous noun-phrase (eighth position in the sentences) revealed, whether a canonical or noncanonical word order was present. Based on previous data it was hypothesized that ambiguous noncanonical sentences required a recomputation of the sentence, as subjects would initially commit to a subject first reading. In the respective contrasts two main areas of brain activation were observed. Unambiguous noncanonical sentences elicited more activation in left inferior frontal cortex relative unambiguous canonical sentences. This was interpreted in conjunction with the greater demands on working memory in the former condition. For noncanonical ambiguous relative to canonical ambiguous sentences, an activation of the left supramarginal gyrus was revealed, which was interpreted as a reflection of the reanalysis-requirements induced by this condition.

Hierarchical and linear sequence processing: an electrophysiological exploration of two different grammar types.

The present study investigated the processing of two types of artificial grammars by means of event-related brain potentials. Two categories of meaningless CV syllables were applied in each grammar type. The two grammars differed with regard to the type of the underlying rule. The finite-state grammar (FSG) followed the rule (AB)n, thereby generating local transitions between As and Bs (e.g., n=2, ABAB). The phrase structure grammar (PSG) followed the rule AnBn, thereby generating center-embedded structures in which the first A and the last B embed the middle elements (e.g., n=2, [A[AB]B]). Two sequence lengths (n=2, n=4) were used. Violations of the structures were introduced at different positions of the syllable sequences. Early violations were situated at the beginning of a sequence, and late violations were placed at the end of a sequence. A posteriorly distributed early negativity elicited by violations was present only in FSG. This effect was interpreted as the possible reflection of a violated local expectancy. Moreover, both grammar-type violations elicited a late positivity. This positivity varied as a function of the violation position in PSG, but not in FSG. These findings suggest that the late positivity could reflect difficulty of integration in PSG sequences.

Neural circuits subserving the retrieval of stems and grammatical features in regular and irregular verbs.

Many languages, including English and Spanish, feature regular (dance --> danced) and irregular (catch --> caught) inflectional systems. According to psycholinguistic theories, regular and irregular inflections are instantiated either by a single or by two specialized mechanisms. Those theories differ in their assumptions concerning the underlying information necessary for the processing of regular verbs. Whereas single mechanism accounts have stated an increased involvement of phonological processing for regular verbs, dual accounts emphasize the prominence of grammatical information. Using event-related functional magnetic resonance imaging, we sought to delineate the brain areas involved in the generation of complex verb forms in Spanish. This language has the advantage of isolating specific differences in the regular-irregular contrasts in terms of the number of stems associated with a verb while controlling for compositionality (regular and irregular verbs apply suffixes to be inflected). The present study showed that areas related to grammatical processing are active for both types of verbs (left opercular inferior frontal gyrus). In addition, major differences between regular and irregular verbs were also observed. Several areas of the prefrontal cortex were selectively active for irregular production, presumably reflecting their role in lexical retrieval (bilateral inferior frontal area and dorsolateral prefrontal cortex). Regular verbs, however, showed increased activation in areas related to grammatical processing (anterior superior temporal gyrus/insular cortex) and in the left hippocampus, the latter possibly related to a greater implication of the phonological loop necessary for the reutilization of the same stem shared across all forms in regular verbs.

The brain differentiates human and non-human grammars: functional localization and structural connectivity.

The human language faculty has been claimed to be grounded in the ability to process hierarchically structured sequences. This human ability goes beyond the capacity to process sequences with simple transitional probabilities of adjacent elements observable in non-human primates. Here we show that the processing of these two sequence types is supported by different areas in the human brain. Processing of local transitions is subserved by the left frontal operculum, a region that is phylogenetically older than Broca's area, which specifically holds responsible the computation of hierarchical dependencies. Tractography data revealing differential structural connectivity signatures for these two brain areas provide additional evidence for a segregation of two areas in the left inferior frontal cortex.