Michael F. Bonner

Reversal of the concreteness effect in semantic dementia

Patients with semantic dementia (SD) have a striking impairment in semantic memory, but the basis for this deficit is unclear. We examined semantic memory for concrete and abstract verbs with a two-alternative, forced-choice measure of lexical semantic associative knowledge. Patients with SD had significantly greater difficulty with concrete verbs (z = –3.33) than with abstract verbs (z = –2.05), a “reversal of the concreteness effect” that was present in a majority of individual patients. The subgroup of SD patients with imaging had significant cortical thinning in the anterior and inferolateral portions of the temporal lobes. These areas of visual association cortex may be important for storing and processing visual features for word meaning. Moreover, poor performance with concrete relative to abstract verbs correlated with cortical thinning of the right anterior temporal lobe in SD, suggesting that this region may contribute to storing and processing visual semantic features. These observations raise the possibility that degraded visual feature knowledge contributes in part to the impaired comprehension of concrete words in SD.

Heteromodal conceptual processing in the angular gyrus.

Concepts bind together the features commonly associated with objects and events to form networks in long-term semantic memory. These conceptual networks are the basis of human knowledge and underlie perception, imagination, and the ability to communicate about experiences and the contents of the environment. Although it is often assumed that this distributed semantic information is integrated in higher-level heteromodal association cortices, open questions remain about the role and anatomic basis of heteromodal representations in semantic memory. Here we used combined neuroimaging evidence from functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to characterize the cortical networks underlying concept representation. Using a lexical decision task, we examined the processing of concepts in four semantic categories that varied on their sensory-motor feature associations (sight, sound, manipulation, and abstract). We found that the angular gyrus was activated across all categories regardless of their modality-specific feature associations, consistent with a heteromodal account for the angular gyrus. Exploratory analyses suggested that categories with weighted sensory-motor features additionally recruited modality-specific association cortices. Furthermore, DTI tractography identified white matter tracts connecting these regions of modality-specific functional activation with the angular gyrus. These findings are consistent with a distributed semantic network that includes a heteromodal, integrative component in the angular gyrus in combination with sensory-motor feature representations in modality-specific association cortices.

Converging Evidence for the Neuroanatomic Basis of Combinatorial Semantics in the Angular Gyrus

Human thought and language rely on the brains ability to combine conceptual information. This fundamental process supports the construction of complex concepts from basic constituents. For example, both “jacket” and “plaid” can be represented as individual concepts, but they can also be integrated to form the more complex representation “plaid jacket.” Although this process is central to the expression and comprehension of language, little is known about its neural basis. Here we present evidence for a neuroanatomic model of conceptual combination from three experiments. We predicted that the highly integrative region of heteromodal association cortex in the angular gyrus would be critical for conceptual combination, given its anatomic connectivity and its strong association with semantic memory in functional neuroimaging studies. Consistent with this hypothesis, we found that the process of combining concepts to form meaningful representations specifically modulates neural activity in the angular gyrus of healthy adults, independent of the modality of the semantic content integrated. We also found that individual differences in the structure of the angular gyrus in healthy adults are related to variability in behavioral performance on the conceptual combination task. Finally, in a group of patients with neurodegenerative disease, we found that the degree of atrophy in the angular gyrus is specifically related to impaired performance on combinatorial processing. These converging anatomic findings are consistent with a critical role for the angular gyrus in conceptual combination.

HP1 Proteins Are Essential for a Dynamic Nuclear Response That Rescues the Function of Perturbed Heterochromatin in Primary Human Cells

ABSTRACT Cellular information is encoded genetically in the DNA nucleotide sequence and epigenetically by the “histone code,” DNA methylation, and higher-order packaging of DNA into chromatin. Cells possess intricate mechanisms to sense and repair damage to DNA and the genetic code. However, nothing is known of the mechanisms, if any, that repair and/or compensate for damage to epigenetically encoded information, predicted to result from perturbation of DNA and histone modifications or other changes in chromatin structure. Here we show that primary human cells respond to a variety of small molecules that perturb DNA and histone modifications by recruiting HP1 proteins to sites of altered pericentromeric heterochromatin. This response is essential to maintain the HP1-binding kinetochore protein hMis12 at kinetochores and to suppress catastrophic mitotic defects. Recruitment of HP1 proteins to pericentromeres depends on histone H3.3 variant deposition, mediated by the HIRA histone chaperone. These data indicate that defects in pericentromeric epigenetic heterochromatin modifications initiate a dynamic HP1-dependent response that rescues pericentromeric heterochromatin function and is essential for viable progression through mitosis.

Where is the anterior temporal lobe and what does it do

The anterior temporal lobe (ATL) is thought to be critical for semantic memory–our knowledge of objects, people, words, and facts. However, there is substantial disagreement over the precise role of the ATL in semantic memory, and there is considerable variability in the anatomic findings that

Gray Matter Density of Auditory Association Cortex Relates to Knowledge of Sound Concepts in Primary Progressive Aphasia

Long-term memory integrates the multimodal information acquired through perception into unified concepts, supporting object recognition, thought, and language. While some theories of human cognition have considered concepts to be abstract symbols, recent functional neuroimaging evidence has supported an alternative theory: that concepts are multimodal representations associated with the sensory and motor systems through which they are acquired. However, few studies have examined the effects of cortical lesions on the sensory and motor associations of concepts. We tested the hypothesis that individuals with disease in auditory association cortex would have difficulty processing concepts with strong sound associations (e.g., thunder). Human participants with the logopenic variant of primary progressive aphasia (lvPPA) performed a recognition task on words with strong associations in three modalities: Sound, Sight, and Manipulation. LvPPA participants had selective difficulty on Sound words relative to other modalities. Structural MRI analysis in lvPPA revealed gray matter atrophy in auditory association cortex, as defined functionally in a separate BOLD fMRI study of healthy adults. Moreover, lvPPA showed reduced gray matter density in the region of auditory association cortex that healthy participants activated when processing the same Sound words in a separate BOLD fMRI experiment. Finally, reduced gray matter density in this region in lvPPA directly correlated with impaired performance on Sound words. These findings support the hypothesis that conceptual memories are represented in the sensory and motor association cortices through which they are acquired.

Preserved Musical Semantic Memory in Semantic Dementia

OBJECTIVE To understand the scope of semantic impairment in semantic dementia. DESIGN Case study. SETTING Academic medical center. PATIENT A man with semantic dementia, as demonstrated by clinical, neuropsychological, and imaging studies. MAIN OUTCOME MEASURES Music performance and magnetic resonance imaging results. RESULTS Despite profoundly impaired semantic memory for words and objects due to left temporal lobe atrophy, this semiprofessional musician was creative and expressive in demonstrating preserved musical knowledge. CONCLUSION Long-term representations of words and objects in semantic memory may be dissociated from meaningful knowledge in other domains, such as music.

Causal Evidence for a Mechanism of Semantic Integration in the Angular Gyrus as Revealed by High-Definition Transcranial Direct Current Stimulation

A defining aspect of human cognition is the ability to integrate conceptual information into complex semantic combinations. For example, we can comprehend “plaid” and “jacket” as individual concepts, but we can also effortlessly combine these concepts to form the semantic representation of “plaid jacket.” Many neuroanatomic models of semantic memory propose that heteromodal cortical hubs integrate distributed semantic features into coherent representations. However, little work has specifically examined these proposed integrative mechanisms and the causal role of these regions in semantic integration. Here, we test the hypothesis that the angular gyrus (AG) is critical for integrating semantic information by applying high-definition transcranial direct current stimulation (tDCS) to an fMRI-guided region-of-interest in the left AG. We found that anodal stimulation to the left AG modulated semantic integration but had no effect on a letter-string control task. Specifically, anodal stimulation to the left AG resulted in faster comprehension of semantically meaningful combinations like “tiny radish” relative to non-meaningful combinations, such as “fast blueberry,” when compared to the effects observed during sham stimulation and stimulation to a right-hemisphere control brain region. Moreover, the size of the effect from brain stimulation correlated with the degree of semantic coherence between the word pairs. These findings demonstrate that the left AG plays a causal role in the integration of lexical-semantic information, and that high-definition tDCS to an associative cortical hub can selectively modulate integrative processes in semantic memory. SIGNIFICANCE STATEMENT A major goal of neuroscience is to understand the neural basis of behaviors that are fundamental to human intelligence. One essential behavior is the ability to integrate conceptual knowledge from semantic memory, allowing us to construct an almost unlimited number of complex concepts from a limited set of basic constituents (e.g., “leaf” and “wet” can be combined into the more complex representation “wet leaf”). Here, we present a novel approach to studying integrative processes in semantic memory by applying focal brain stimulation to a heteromodal cortical hub implicated in semantic processing. Our findings demonstrate a causal role of the left angular gyrus in lexical-semantic integration and provide motivation for novel therapeutic applications in patients with lexical-semantic deficits.

Coding of navigational affordances in the human visual system

Significance As we move about the world, we use vision to determine where we can go in our local environment and where our path is blocked. Despite the ubiquity of this problem, little is known about how it is solved by the brain. Here we show that a specific region in the human visual system, known as the occipital place area, automatically encodes the structure of navigable space in visual scenes, thus providing evidence for a bottom-up visual mechanism for perceiving potential paths for movement in one’s immediate surroundings. These findings are consistent with classic theoretical work predicting that sensory systems are optimized for processing environmental features that afford ecologically relevant behaviors, including the fundamental behavior of navigation. A central component of spatial navigation is determining where one can and cannot go in the immediate environment. We used fMRI to test the hypothesis that the human visual system solves this problem by automatically identifying the navigational affordances of the local scene. Multivoxel pattern analyses showed that a scene-selective region of dorsal occipitoparietal cortex, known as the occipital place area, represents pathways for movement in scenes in a manner that is tolerant to variability in other visual features. These effects were found in two experiments: One using tightly controlled artificial environments as stimuli, the other using a diverse set of complex, natural scenes. A reconstruction analysis demonstrated that the population codes of the occipital place area could be used to predict the affordances of novel scenes. Taken together, these results reveal a previously unknown mechanism for perceiving the affordance structure of navigable space.

Semantics of the visual environment encoded in parahippocampal cortex

Semantic representations capture the statistics of experience and store this information in memory. A fundamental component of this memory system is knowledge of the visual environment, including knowledge of objects and their associations. Visual semantic information underlies a range of behaviors, from perceptual categorization to cognitive processes such as language and reasoning. Here we examine the neuroanatomic system that encodes visual semantics. Across three experiments, we found converging evidence indicating that knowledge of verbally mediated visual concepts relies on information encoded in a region of the ventral-medial temporal lobe centered on parahippocampal cortex. In an fMRI study, this region was strongly engaged by the processing of concepts relying on visual knowledge but not by concepts relying on other sensory modalities. In a study of patients with the semantic variant of primary progressive aphasia (semantic dementia), atrophy that encompassed this region was associated with a specific impairment in verbally mediated visual semantic knowledge. Finally, in a structural study of healthy adults from the fMRI experiment, gray matter density in this region related to individual variability in the processing of visual concepts. The anatomic location of these findings aligns with recent work linking the ventral-medial temporal lobe with high-level visual representation, contextual associations, and reasoning through imagination. Together, this work suggests a critical role for parahippocampal cortex in linking the visual environment with knowledge systems in the human brain.