Task-dependent functional and effective connectivity during conceptual processing

Conceptual knowledge is central to cognition. Previous neuroimaging research indicates that conceptual processing involves both modality-specific perceptual-motor areas and multimodal convergence zones. For example, our previous functional magnetic resonance imaging (fMRI) study revealed that both modality-specific and multimodal regions respond to sound and action features of concepts in a task-dependent fashion (Kuhnke P, Kiefer M, Hartwigsen G. 2020b. Task-dependent recruitment of modality-specific and multimodal regions during conceptual processing. Cereb Cortex. 30:3938-3959.). However, it remains unknown whether and how modality-specific and multimodal areas interact during conceptual tasks. Here, we asked 1) whether multimodal and modality-specific areas are functionally coupled during conceptual processing, 2) whether their coupling depends on the task, 3) whether information flows top-down, bottom-up or both, and 4) whether their coupling is behaviorally relevant. We combined psychophysiological interaction analyses with dynamic causal modeling on the fMRI data of our previous study. We found that functional coupling between multimodal and modality-specific areas strongly depended on the task, involved both top-down and bottom-up information flow, and predicted conceptually guided behavior. Notably, we also found coupling between different modality-specific areas and between different multimodal areas. These results suggest that functional coupling in the conceptual system is extensive, reciprocal, task-dependent, and behaviorally relevant. We propose a new model of the conceptual system that incorporates task-dependent functional interactions between modality-specific and multimodal areas

Task-dependent recruitment of modality-specific and multimodal regions during conceptual processing

Conceptual knowledge is central to cognitive abilities such as word comprehension. Previous neuroimaging evidence indicates that concepts are at least partly composed of perceptual and motor features that are represented in the same modality-specific brain regions involved in actual perception and action. However, it is unclear to what extent the retrieval of perceptual-motor features and the resulting engagement of modality-specific regions depend on the concurrent task. To address this issue, we measured brain activity in 40 young and healthy participants using fMRI, while they performed three different tasks—lexical decision, sound judgment, and action judgment—on words that independently varied in their association with sounds and actions. We found neural activation for sound or action features of concepts selectively when they were task-relevant in auditory or motor-related brain regions, respectively, as well as in higher-level, multimodal regions which were recruited during both sound and action feature retrieval. For the first time, we show that not only modality-specific perceptual-motor areas, but also multimodal regions are engaged in conceptual processing in a flexible, task-dependent fashion, responding selectively to task-relevant conceptual features

Task-dependent recruitment of modality-specific and multimodal regions during conceptual processing

Conceptual knowledge is central to cognitive abilities such as word comprehension. Previous neuroimaging evidence indicates that concepts are at least partly composed of perceptual and motor features that are represented in the same modality-specific brain regions involved in actual perception and action. However, it is unclear to what extent the retrieval of perceptual-motor features and the resulting engagement of modality-specific regions depend on the concurrent task. To address this issue, we measured brain activity in 40 young and healthy participants using fMRI, while they performed three different tasks—lexical decision, sound judgment, and action judgment—on words that independently varied in their association with sounds and actions. We found neural activation for sound or action features of concepts selectively when they were task-relevant in auditory or motor-related brain regions, respectively, as well as in higher-level, multimodal regions which were recruited during both sound and action feature retrieval. For the first time, we show that not only modality-specific perceptual-motor areas, but also multimodal regions are engaged in conceptual processing in a flexible, task-dependent fashion, responding selectively to task-relevant conceptual features

Left posterior inferior frontal gyrus is causally involved in complex sentence comprehension

INTRODUCTION Storage and reordering of words are two core processes required for successful sentence comprehension. Storage is necessary whenever the verb and its arguments (i.e., subject and object) are separated over a long distance, while reordering is necessary whenever the argument order is atypical (e.g., object-first order in German, where subject-first order is typical). Previous neuroimaging work (Meyer et al., 2012) has associated storage with the left planum temporale (PT), and reordering with the left posterior inferior frontal gyrus (pIFG). However, it is unclear whether left PT and pIFG are indeed causally relevant for storage and reordering, respectively. Here, we tested the necessity of the PT and pIFG for storage and reordering using repetitive transcranial magnetic stimulation (rTMS). METHODS We applied either effective online rTMS (5 pulses at 10 Hz) over PT or pIFG, or sham rTMS, while subjects listened to sentences that independently manipulated storage demands (short vs. long argument–verb distance) and reordering demands (subject– vs. object-first argument order). We employed behavioral modeling, using a drift diffusion model, to assess rTMS-induced disruption of sentence comprehension. RESULTS We found that rTMS over pIFG, but not PT, selectively impaired reordering during the processing of sentences with a long argument–verb distance. Specifically, relative to sham rTMS, rTMS over pIFG significantly increased the performance decline for object– vs. subject-first long-distance sentences (t23 = 2.86; p = 0.009). This effect was anatomically specific as the same comparison for PT stimulation was far from significant (t23 = −0.11; p = 0.9), and a direct across-sites comparison showed that the pIFG effect was significantly stronger (t23 = −2.62; p = 0.015). CONCLUSION Our results provide the first causal evidence that the left pIFG supports the reordering of arguments in long-distance sentences. We thereby substantially extend previous neuroimaging studies that showed a correlation between pIFG activation and reordering demands. Together with previous evidence (Lauro et al., 2010), our findings indicate that the left pIFG crucially supports the comprehension of syntactically complex sentences. These results might extend to other domains, such as music (Maess et al., 2001) and action (Clerget et al., 2009), indicating a domain-general role of left pIFG in the processing of hierarchically-structured sequences

Meta-analytic evidence for a novel hierarchical model of conceptual processing

Conceptual knowledge plays a pivotal role in human cognition. Grounded cognition theories propose that concepts consist of perceptual-motor features represented in modality-specific perceptual-motor cortices. However, it is unclear whether conceptual processing consistently engages modality-specific areas. Here, we performed an activation likelihood estimation (ALE) meta-analysis across 212 neuroimaging experiments on conceptual processing related to 7 perceptual-motor modalities (action, sound, visual shape, motion, color, olfaction-gustation, and emotion). We found that conceptual processing consistently engages brain regions also activated during real perceptual-motor experience of the same modalities. In addition, we identified multimodal convergence zones that are recruited for multiple modalities. In particular, the left inferior parietal lobe (IPL) and posterior middle temporal gyrus (pMTG) are engaged for three modalities: action, motion, and sound. These “trimodal” regions are surrounded by “bimodal” regions engaged for two modalities. Our findings support a novel model of the conceptual system, according to which conceptual processing relies on a hierarchical neural architecture from modality-specific to multimodal areas up to an amodal hub

Adaptive plasticity in the healthy reading network investigated through combined neurostimulation and neuroimaging

The reading network in the human brain comprises several regions, including the left inferior frontal cortex (IFC), ventral occipito-temporal cortex (vOTC) and dorsal temporo-parietal cortex (TPC). The left TPC is crucial for phonological decoding, i.e., for learning and retaining sound-letter mappings. Here, we tested the causal contribution of this area for reading with repetitive transcranial magnetic stimulation (rTMS) and explored the response of the reading network using functional magnetic resonance imaging (fMRI). 28 healthy adult readers overtly read simple and complex words and pseudowords during fMRI after effective or sham TMS over the left TPC. Behaviorally, effective stimulation slowed pseudoword reading. A multivariate pattern analysis showed a shift in activity patterns in the left IFC for pseudoword reading after effective relative to sham TMS. Furthermore, active TMS led to increased effective connectivity from the left vOTC to the left TPC, specifically for pseudoword processing. The observed changes in task-related activity and connectivity suggest compensatory reorganization in the reading network following TMS-induced disruption of the left TPC. Our findings provide first evidence for a causal role of the left TPC for overt pseudoword reading and emphasize the relevance of functional interactions in the healthy reading network for successful pseudoword processing

The role of the angular gyrus in semantic cognition: A synthesis of five functional neuroimaging studies

Semantic knowledge is central to human cognition. The angular gyrus (AG) is widely considered a key brain region for semantic cognition. However, the role of the AG in semantic processing is controversial. Key controversies concern response polarity (activation vs. deactivation) and its relation to task difficulty, lateralization (left vs. right AG), and functional-anatomical subdivision (PGa vs. PGp subregions). Here, we combined the fMRI data of five studies on semantic processing (n = 172) and analyzed the response profiles from the same anatomical regions-of-interest for left and right PGa and PGp. We found that the AG was consistently deactivated during non-semantic conditions, whereas response polarity during semantic conditions was inconsistent. However, the AG consistently showed relative response differences between semantic and non-semantic conditions, and between different semantic conditions. A combined analysis across all studies revealed that AG responses could be best explained by separable effects of task difficulty and semantic processing demand. Task difficulty effects were stronger in PGa than PGp, regardless of hemisphere. Semantic effects were stronger in left than right AG, regardless of subregion. These results suggest that the AG is engaged in both domain-general task-difficulty-related processes and domain-specific semantic processes. In semantic processing, we propose that left AG acts as a "multimodal convergence zone" that binds different semantic features associated with the same concept, enabling efficient access to task-relevant features

Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes

ABCB6, a member of the adenosine triphosphate–binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting that only three ABC transporters should be classified as mitochondrial proteins. Taken together, our results challenge the current paradigm linking the expression and function of ABCB6 to mitochondria