For more than a century, speech repetition has been used as an assay for gauging the integrity of the auditory-motor pathway in aphasia, thought classically to involve a linkage between Wernicke's area and Broca's area via the arcuate fasciculus. During the last decade, evidence primarily from functional imaging in healthy individuals has refined this picture both computationally and anatomically, suggesting the existence of a cortical hub located at the parietal-temporal boundary (area Spt) that functions to integrate auditory and motor speech networks for both repetition and spontaneous speech production. While functional imaging research can pinpoint the regions activated in repetition/auditory-motor integration, lesion-based studies are needed to infer causal involvement. Previous lesion studies of repetition have yielded mixed results with respect to Spt's critical involvement in speech repetition. The present study used voxel-based lesion symptom mapping (VLSM) to investigate the neuroanatomy of repetition of both real words and non-words in a sample of 47 patients with focal left hemisphere brain damage. VLSMs identified a large voxel cluster spanning gray and white matter in the left temporal-parietal junction, including area Spt, where damage was significantly related to poor non-word repetition. Repetition of real words implicated a very similar dorsal network including area Spt. Cortical regions including Spt were implicated in repetition performance even when white matter damage was factored out. In addition, removing variance associated with speech perception abilities did not alter the overall lesion pattern for either task. Together with past functional imaging work, our results suggest that area Spt is integral in both word and non-word repetition, that its contribution is above and beyond that made by white matter pathways, and is not driven by perceptual processes alone. These findings are highly consistent with the claim that Spt is an area of sensory-motor translation in speech processing.

Background

Drug dependent individuals often make drug-taking decisions when they do not feel well. Yet, few studies have examined the influence of an aversive state on decision-making related neural processing.

Methods

We investigate brain activation to decision-making during an aversive interoceptive challenge in methamphetamine users using functional magnetic resonance imaging (fMRI). Recently abstinent inpatients with methamphetamine use disorder (METH; n=20) and healthy comparison subjects (CTL; n=22) performed a two-choice prediction task at three fixed error rates (ER; 20%=reward, 50%=uncertainty, 80%=punishment) while anticipating and experiencing episodes of inspiratory breathing load during fMRI.

Results

METH exhibited higher trait anxiety in conjunction with lower anterior insula (AI) and inferior frontal gyrus (IFG) activation than CTL across trials. METH also showed lower posterior insula (PI) and anterior cingulate cortex (ACC) activation than CTL during breathing load independent of ER. For the crucial ER by interoception interaction, METH displayed lower ACC activation to punishment/loss than CTL during breathing load. Within METH, lower trait anxiety was linked to AI/IFG attenuation across trials.

Conclusions

AI/IFG attenuations in METH are suggestive of an executive functioning deficit, particularly in users with low anxiety, reflecting reduced resources allocated to choice selection. In contrast, PI/ACC reductions in METH appear specific to impairments in registering and evaluating interoceptive experiences. Taken together, inadequate activation of brain areas that are important for regulating when one does not feel well may be the neural basis for poor decision-making by METH.

Interoception refers to the process by which the nervous system senses, interprets, and integrates signals originating from within the body, providing a moment-by-moment mapping of the body's internal landscape across conscious and unconscious levels. Interoceptive signaling has been considered a component process of reflexes, urges, feelings, drives, adaptive responses, and cognitive and emotional experiences, highlighting its contributions to the maintenance of homeostatic functioning, body regulation, and survival. Dysfunction of interoception is increasingly recognized as an important component of different mental health conditions, including anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders. However, a number of conceptual and methodological challenges have made it difficult for interoceptive constructs to be broadly applied in mental health research and treatment settings. In November 2016, the Laureate Institute for Brain Research organized the first Interoception Summit, a gathering of interoception experts from around the world, with the goal of accelerating progress in understanding the role of interoception in mental health. The discussions at the meeting were organized around four themes: interoceptive assessment, interoceptive integration, interoceptive psychopathology, and the generation of a roadmap that could serve as a guide for future endeavors. This review article presents an overview of the emerging consensus generated by the meeting.