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Using fMRI, we investigated how right temporal lobe gliomas affecting the posterior superior temporal sulcus alter neural processing observed during speech perception and production tasks. Behavioural language testing showed that three pre-operative neurosurgical patients with grade 2, grade 3 or grade 4 tumours had the same pattern of mild language impairment in the domains of object naming and written word comprehension. When matching heard words for semantic relatedness (a speech perception task), these patients showed under-activation in the tumour infiltrated right superior temporal lobe compared to 61 neurotypical participants and 16 patients with tumours that preserved the right postero-superior temporal lobe, with enhanced activation within the (tumour-free) contralateral left superior temporal lobe. In contrast, when correctly naming objects (a speech production task), the patients with right postero-superior temporal lobe tumours showed higher activation than both control groups in the same right postero-superior temporal lobe region that was under-activated during auditory semantic matching. The task dependent pattern of under-activation during the auditory speech task and over-activation during object naming was also observed in eight stroke patients with right hemisphere infarcts that affected the right postero-superior temporal lobe compared to eight stroke patients with right hemisphere infarcts that spared it. These task-specific and site-specific cross-pathology effects highlight the importance of the right temporal lobe for language processing and motivate further study of how right temporal lobe tumours affect language performance and neural reorganisation. These findings may have important implications for surgical management of these patients, as knowledge of the regions showing functional reorganisation may help to avoid their inadvertent damage during neurosurgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yamamoto, Sanjuán, Pope, Parker Jones, Hope, Prejawa, Oberhuber, Mancini, Ekert, Garjardo-Vidal, Creasey, Yousry, Green and Price.)

Background: Pre- and intra-operative language mapping in neurosurgery patients frequently involves an object naming task. The choice of the optimal object naming paradigm remains challenging due to lack of normative data and standardization in mapping practices. The aim of this study was to identify object naming paradigms that robustly and consistently activate classical language regions and could therefore be used to improve the sensitivity of language mapping in brain tumor and epilepsy patients. Methods: Functional magnetic resonance imaging (fMRI) data from two independent groups of healthy controls (total = 79) were used to generate threshold-weighted voxel-based consistency maps. This novel approach allowed us to compare inter-subject consistency of activation for naming single objects in the visual and auditory modality and naming two objects in a phrase or a sentence. Results: We found that the consistency of activation in language regions was greater for naming two objects per picture than one object per picture, even when controlling for the number of names produced in 5 s. Conclusion: More consistent activation in language areas for naming two objects compared to one object suggests that two-object naming tasks may be more suitable for delimiting language eloquent regions with pre- and intra-operative language testing. More broadly, we propose that the functional specificity of brain mapping paradigms for a whole range of different linguistic and non-linguistic functions could be enhanced by referring to databased models of inter-subject consistency and variability in typical and atypical brain responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ekert, Kirkman, Seghier, Green and Price.)

Emotions are by nature embodied, as the brain has evolved to quickly assess the emotional significance of stimuli and output signals to the body's viscera and periphery to aid adaptive responses. Emotions involve both implicit bodily and explicit narrative processes, and patients may experience transdiagnostic distress when bodily signals are not attended to and holistically integrated with explicit narratives about experience. Similarly, therapists may be trained in more implicit body-based approaches (i.e., massage/bodywork, physical and occupational therapy, and nursing/medicine) or more explicit narrative-based approaches (i.e., psychotherapy), and may lack training in skills that integrate both levels of emotion processing to aid healing and growth. To address these gaps, we propose a framework where the bridge between implicit bodily sensations and explicit narratives lies in cultivating mindful awareness of bodily sensations associated with emotions. This process brings subjective awareness to notice inner body experience (or interoceptive awareness) that is often outside of conscious awareness, so that it may be understood and re-integrated in more adaptive ways, which we call somatic reappraisal. Using clinical theory and example vignettes, we present mindful interoceptive awareness for adaptive emotion processing as a framework to cultivate and enhance somatic reappraisal. Mindful interoceptive awareness brings more focused and sustained attention to inner body experience; likewise, internal sensations associated with emotions become more granular, vivid, and can shift in ways that facilitate somatic reappraisal. Learning to sustain interoceptive awareness when engaged with mindfulness qualities of nonjudgment and compassion promotes an experience where new associations between emotions, meanings, and memories can be made that generate insights that are holistic and integrative. A clinical vignette is used in this paper to provide examples of this approach in psychotherapy. An example script for use in mindfulness groups is included, and resources are suggested for clinicians to gain more experience. Mindful interoceptive awareness for adaptive emotion processing is a clinical process that can be learned and applied by a range of clinicians to treat mental and physical health conditions that may benefit greater embodied awareness., Competing Interests: CP serves as the director of the Center for Mindful Body Awareness, a 501c3 organization that provides educational trainings in the mindful awareness in body-oriented therapy (MABT) approach to therapists/practitioners in the community, at academic institutions, and in clinical settings. The Center also develops, implements, and evaluates programs involving the practice of interoceptive awareness practice in collaboration with community or academic clinical settings. There are no other disclosures reported. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Price and Weng.)

Functional imaging studies of neurologically intact adults have demonstrated that the right posterior cerebellum is activated during verb generation, semantic processing, sentence processing, and verbal fluency. Studies of patients with cerebellar damage converge to show that the cerebellum supports sentence processing and verbal fluency. However, to date there are no patient studies that investigated the specific importance of the right posterior cerebellum in language processing, because: (i) case studies presented patients with lesions affecting the anterior cerebellum (with or without damage to the posterior cerebellum), and (ii) group studies combined patients with lesions to different cerebellar regions, without specifically reporting the effects of right posterior cerebellar damage. Here we investigated whether damage to the right posterior cerebellum is critical for sentence processing and verbal fluency in four patients with focal stroke damage to different parts of the right posterior cerebellum (all involving Crus II, and lobules VII and VIII). We examined detailed lesion location by going beyond common anatomical definitions of cerebellar anatomy (i.e., according to lobules or vascular territory), and employed a recently proposed functional parcellation of the cerebellum. All four patients experienced language difficulties that persisted for at least a month after stroke but three performed in the normal range within a year. In contrast, one patient with more damage to lobule IX than the other patients had profound long-lasting impairments in the comprehension and repetition of sentences, and the production of spoken sentences during picture description. Spoken and written word comprehension and visual recognition memory were also impaired, however, verbal fluency was within the normal range, together with object naming, visual perception and verbal short-term memory. This is the first study to show that focal damage to the right posterior cerebellum leads to language difficulties after stroke; and that processing impairments persisted in the case with most damage to lobule IX. We discuss these results in relation to current theories of cerebellar contribution to language processing. Overall, our study highlights the need for longitudinal studies of language function in patients with focal damage to different cerebellar regions, with functional imaging to understand the mechanisms that support recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Geva, Schneider, Roberts, Green and Price.)

Emotion regulation involves a coherent relationship with the self, specifically effective communication between body, mind, and feelings. Effective emotion regulation involves the ability to accurately detect and evaluate cues related to physiological reactions to stressful events, accompanied by appropriate regulation strategies that temper and influence the emotional response. There is compelling evidence demonstrating links between poor or disrupted awareness of sensory information, or interoceptive awareness, and difficulties with emotion regulation. This paper presents a framework, based on psychological and neurobiological research, for understanding how interoceptive awareness facilitates regulation and an integrated sense of self, and thus contributes to health and well-being. A mind-body therapeutic approach called mindful awareness in body-oriented therapy (MABT), uniquely designed to teach fundamental skills of interoceptive awareness, is described. MABT develops the distinct interoceptive awareness capacities of identifying, accessing, and appraising internal bodily signals that are identified in physiological models as the critical components of interoception for emotion regulation. The explanatory model is that the development of these key interoceptive capacities improves sensory (physical and emotional) awareness, reduces distress, and improves regulation. Strategies for teaching and learning interoceptive awareness are not well-developed in mindfulness or psychotherapeutic approaches, particularly important for people who may have difficulty attending to interoceptive awareness due to stress, chronic pain or trauma. To address this issue, MABT provides an individualized protocol for scaffolding interoceptive awareness through a combination of psychoeducation and somatic approaches explicitly addressing difficulties with interoceptive processing. Clinical vignettes are included to provide exemplars of this approach and to highlight key components of the therapeutic process. Results from research are also included to highlight the acceptability, safety, health outcomes, and possible mechanisms underlying the MABT approach.

Interoception can be broadly defined as the sense of signals originating within the body. As such, interoception is critical for our sense of embodiment, motivation, and well-being. And yet, despite its importance, interoception remains poorly understood within modern science. This paper reviews interdisciplinary perspectives on interoception, with the goal of presenting a unified perspective from diverse fields such as neuroscience, clinical practice, and contemplative studies. It is hoped that this integrative effort will advance our understanding of how interoception determines well-being, and identify the central challenges to such understanding. To this end, we introduce an expanded taxonomy of interoceptive processes, arguing that many of these processes can be understood through an emerging predictive coding model for mind-body integration. The model, which describes the tension between expected and felt body sensation, parallels contemplative theories, and implicates interoception in a variety of affective and psychosomatic disorders. We conclude that maladaptive construal of bodily sensations may lie at the heart of many contemporary maladies, and that contemplative practices may attenuate these interpretative biases, restoring a person's sense of presence and agency in the world.

This fMRI study used a single, multi-factorial, within-subjects design to dissociate multiple linguistic and non-linguistic processing areas that are all involved in repeating back heard words. The study compared: (1) auditory to visual inputs; (2) phonological to non-phonological inputs; (3) semantic to non-semantic inputs; and (4) speech production to finger-press responses. The stimuli included words (semantic and phonological inputs), pseudowords (phonological input), pictures and sounds of animals or objects (semantic input), and colored patterns and hums (non-semantic and non-phonological). The speech production tasks involved auditory repetition, reading, and naming while the finger press tasks involved one-back matching. The results from the main effects and interactions were compared to predictions from a previously reported functional anatomical model of language based on a meta-analysis of many different neuroimaging experiments. Although many findings from the current experiment replicated many of those predicted, our within-subject design also revealed novel results by providing sufficient anatomical precision to dissect several different regions within the anterior insula, pars orbitalis, anterior cingulate, SMA, and cerebellum. For example, we found one part of the pars orbitalis was involved in phonological processing and another in semantic processing. We also dissociated four different types of phonological effects in the left superior temporal sulcus (STS), left putamen, left ventral premotor cortex, and left pars orbitalis. Our findings challenge some of the commonly-held opinions on the functional anatomy of language, and resolve some previously conflicting findings about specific brain regions-and our experimental design reveals details of the word repetition process that are not well captured by current models.

The aim of this paper was to investigate the neurological underpinnings of auditory-to-motor translation during auditory repetition of unfamiliar pseudowords. We tested two different hypotheses. First we used functional magnetic resonance imaging in 25 healthy subjects to determine whether a functionally defined area in the left temporo-parietal junction (TPJ), referred to as Sylvian-parietal-temporal region (Spt), reflected the demands on auditory-to-motor integration during the repetition of pseudowords relative to a semantically mediated nonverbal sound-naming task. The experiment also allowed us to test alternative accounts of Spt function, namely that Spt is involved in subvocal articulation or auditory processing that can be driven either bottom-up or top-down. The results did not provide convincing evidence that activation increased in either Spt or any other cortical area when non-semantic auditory inputs were being translated into motor outputs. Instead, the results were most consistent with Spt responding to bottom up or top down auditory processing, independent of the demands on auditory-to-motor integration. Second, we investigated the lesion sites in eight patients who had selective difficulties repeating heard words but with preserved word comprehension, picture naming and verbal fluency (i.e., conduction aphasia). All eight patients had white-matter tract damage in the vicinity of the arcuate fasciculus and only one of the eight patients had additional damage to the Spt region, defined functionally in our fMRI data. Our results are therefore most consistent with the neurological tradition that emphasizes the importance of the arcuate fasciculus in the non-semantic integration of auditory and motor speech processing.

Brain tumors can have different shapes or locations, making their identification very challenging. In functional MRI, it is not unusual that patients have only one anatomical image due to time and financial constraints. Here, we provide a modified automatic lesion identification (ALI) procedure which enables brain tumor identification from single MR images. Our method rests on (A) a modified segmentation-normalization procedure with an explicit "extra prior" for the tumor and (B) an outlier detection procedure for abnormal voxel (i.e., tumor) classification. To minimize tissue misclassification, the segmentation-normalization procedure requires prior information of the tumor location and extent. We therefore propose that ALI is run iteratively so that the output of Step B is used as a patient-specific prior in Step A. We test this procedure on real T1-weighted images from 18 patients, and the results were validated in comparison to two independent observers' manual tracings. The automated procedure identified the tumors successfully with an excellent agreement with the manual segmentation (area under the ROC curve = 0.97 ± 0.03). The proposed procedure increases the flexibility and robustness of the ALI tool and will be particularly useful for lesion-behavior mapping studies, or when lesion identification and/or spatial normalization are problematic.

Previous studies have investigated orthographic-to-phonological mapping during reading by comparing brain activation for (1) reading words to object naming, or (2) reading pseudowords (e.g., "phume") to words (e.g., "plume"). Here we combined both approaches to provide new insights into the underlying neural mechanisms. In fMRI data from 25 healthy adult readers, we first identified activation that was greater for reading words and pseudowords relative to picture and color naming. The most significant effect was observed in the left putamen, extending to both anterior and posterior borders. Second, consistent with previous studies, we show that both the anterior and posterior putamen are involved in articulating speech with greater activation during our overt speech production tasks (reading, repetition, object naming, and color naming) than silent one-back-matching on the same stimuli. Third, we compared putamen activation for words versus pseudowords during overt reading and auditory repetition. This revealed that the anterior putamen was most activated by reading pseudowords, whereas the posterior putamen was most activated by words irrespective of whether the task was reading words or auditory word repetition. The pseudoword effect in the anterior putamen is consistent with prior studies that associated this region with the initiation of novel sequences of movements. In contrast, the heightened word response in the posterior putamen is consistent with other studies that associated this region with "memory guided movement." Our results illustrate how the functional dissociation between the anterior and posterior putamen supports sublexical and lexical processing during reading.

This fMRI study investigated the functional heterogeneity of the core nodes of the default mode network (DMN) during language processing. The core nodes of the DMN were defined as task-induced deactivations over multiple tasks in 94 healthy subjects. We used a factorial design that manipulated different tasks (semantic matching or speech production) and stimuli (familiar words and objects or unfamiliar stimuli), alternating with periods of fixation/rest. Our findings revealed several consistent effects in the DMN, namely less deactivations in the left inferior parietal lobule during semantic than perceptual matching in parallel with greater deactivations during semantic matching in anterior subdivisions of the posterior cingulate cortex (PCC) and the ventromedial prefrontal cortex (MPFC). This suggests that, when the brain is engaged in effortful semantic tasks, a part of the DMN in the left angular gyrus was less deactivated as five other nodes of the DMN were more deactivated. These five DMN areas, where deactivation was greater for semantic than perceptual matching, were further differentiated because deactivation was greater in (i) posterior ventral MPFC for speech production relative to semantic matching, (ii) posterior precuneus and PCC for perceptual processing relative to speech production, and (iii) right inferior parietal cortex for pictures of objects relative to written words during both naming and semantic decisions. Our results thus highlight that task difficulty alone cannot fully explain the functional variability in task-induced deactivations. Together these results emphasize that core nodes within the DMN are functionally heterogeneous and differentially sensitive to the type of language processing.

Speech production involves the generation of an auditory signal from the articulators and vocal tract. When the intended auditory signal does not match the produced sounds, subsequent articulatory commands can be adjusted to reduce the difference between the intended and produced sounds. This requires an internal model of the intended speech output that can be compared to the produced speech. The aim of this functional imaging study was to identify brain activation related to the internal model of speech production after activation related to vocalization, auditory feedback, and movement in the articulators had been controlled. There were four conditions: silent articulation of speech, non-speech mouth movements, finger tapping, and visual fixation. In the speech conditions, participants produced the mouth movements associated with the words "one" and "three." We eliminated auditory feedback from the spoken output by instructing participants to articulate these words without producing any sound. The non-speech mouth movement conditions involved lip pursing and tongue protrusions to control for movement in the articulators. The main difference between our speech and non-speech mouth movement conditions is that prior experience producing speech sounds leads to the automatic and covert generation of auditory and phonological associations that may play a role in predicting auditory feedback. We found that, relative to non-speech mouth movements, silent speech activated Broca's area in the left dorsal pars opercularis and Wernicke's area in the left posterior superior temporal sulcus. We discuss these results in the context of a generative model of speech production and propose that Broca's and Wernicke's areas may be involved in predicting the speech output that follows articulation. These predictions could provide a mechanism by which rapid movement of the articulators is precisely matched to the intended speech outputs during future articulations.

How numerical representation is encoded in the adult human brain is important for a basic understanding of human brain organization, its typical and atypical development, its evolutionary precursors, cognitive architectures, education, and rehabilitation. Previous studies have shown that numerical processing activates the same intraparietal regions irrespective of the presentation format (e.g., symbolic digits or non-symbolic dot arrays). This has led to claims that there is a single format-independent, numerical representation. In the current study we used a functional magnetic resonance adaptation paradigm, and effective connectivity analysis to re-examine whether numerical processing in the intraparietal sulci is dependent or independent on the format of the stimuli. We obtained two novel results. First, the whole brain analysis revealed that format change (e.g., from dots to digits), in the absence of a change in magnitude, activated the same intraparietal regions as magnitude change, but to a greater degree. Second, using dynamic causal modeling as a tool to disentangle neuronal specialization across regions that are commonly activated, we found that the connectivity between the left and right intraparietal sulci is format-dependent. Together, this line of results supports the idea that numerical representation is subserved by multiple mechanisms within the same parietal regions.

Functional imaging studies of brain damaged patients offer a unique opportunity to understand how sensorimotor and cognitive tasks can be carried out when parts of the neural system that support normal performance are no longer available. In addition to knowing which regions a patient activates, we also need to know how these regions interact with one another, and how these inter-regional interactions deviate from normal. Dynamic causal modeling (DCM) offers the opportunity to assess task-dependent interactions within a set of regions. Here we review its use in patients when the question of interest concerns the characterization of abnormal connectivity for a given pathology. We describe the currently available implementations of DCM for fMRI responses, varying from the deterministic bilinear models with one-state equation to the stochastic non-linear models with two-state equations. We also highlight the importance of the new Bayesian model selection and averaging tools that allow different plausible models to be compared at the single subject and group level. These procedures allow inferences to be made at different levels of model selection, from features (model families) to connectivity parameters. Following a critical review of previous DCM studies that investigated abnormal connectivity we propose a systematic procedure that will ensure more flexibility and efficiency when using DCM in patients. Finally, some practical and methodological issues crucial for interpreting or generalizing DCM findings in patients are discussed.