Methodological challenges and solutions in auditory functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) studies involve substantial acoustic noise. This review covers the difficulties posed by such noise for auditory neuroscience, as well as a number of possible solutions that have emerged. Acoustic noise can affect the processing of auditory stimuli by making them inaudible or unintelligible, and can result in reduced sensitivity to auditory activation in auditory cortex. Equally importantly, acoustic noise may also lead to increased listening effort, meaning that even when auditory stimuli are perceived, neural processing may differ from when the same stimuli are presented in quiet. These and other challenges have motivated a number of approaches for collecting auditory fMRI data. Although using a continuous echoplanar imaging (EPI) sequence provides high quality imaging data, these data may also be contaminated by background acoustic noise. Traditional sparse imaging has the advantage of avoiding acoustic noise during stimulus presentation, but at a cost of reduced temporal resolution. Recently, three classes of techniques have been developed to circumvent these limitations. The first is Interleaved Silent Steady State (ISSS) imaging, a variation of sparse imaging that involves collecting multiple volumes following a silent period while maintaining steady-state longitudinal magnetization. The second involves active noise control to limit the impact of acoustic scanner noise. Finally, novel MRI sequences that reduce the amount of acoustic noise produced during fMRI make the use of continuous scanning a more practical option. Together these advances provide unprecedented opportunities for researchers to collect high-quality data of hemodynamic responses to auditory stimuli using fMRI

Adjusting for global effects in voxel-based morphometry: Gray matter decline in normal aging

AbstractResults from studies that have examined age-related changes in gray matter based on structural MRI scans have not always been consistent. Reasons for this variability likely include small or unevenly-distributed samples, different methods for tissue class segmentation and spatial normalization, and the use of different statistical models. Particularly relevant to the latter is the method of adjusting for global (total) gray matter when making inferences about regionally-specific changes. In the current study, we use voxel-based morphometry (VBM) to explore the impact of these methodological choices in assessing age-related changes in gray matter volume in a sample of 420 adults evenly distributed between the ages of 18–77years. At a broad level, we replicate previous findings, showing age-related gray matter decline in nearly all parts of the brain, with particularly rapid decline in inferior regions of frontal cortex (e.g., insula and left inferior frontal gyrus) and the central sulcus. Segmentation was improved by increasing the number of tissue classes and using less age-biased templates, and registration was improved by using a diffeomorphic flow-based algorithm (DARTEL) rather than a “constrained warp” approach. Importantly, different approaches to adjusting for global effects – not adjusting, Local Covariation, Global Scaling, and Local Scaling – significantly affected regionally-specific estimates of age-related decline, as demonstrated by ranking age effects across anatomical ROIs. Split-half cross-validation showed that, on average, Local Covariation explained a greater proportion of age-related variance across these ROIs than did Global Scaling. Nonetheless, the appropriate choice for global adjustment depends on one's assumptions and specific research questions. More generally, these results emphasize the importance of being explicit about the assumptions underlying key methodological choices made in VBM analyses and the inferences that follow

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

Converging evidence for the neuroanatomic basis of combinatorial semantics in the angular gyrus

Human thought and language rely on the brain's 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

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