Functional Neuroimaging Research Research Articles

CE Workshop 07: Cognitive Effects of Cancer and Treatment: “Chemobrain” and Beyond

Abstract & Learning Objectives:Improvements in treatment for non-CNS cancer have greatly improved survivorship, allowing increased attention to cancer- and treatment-related sequelae. Cognitive symptoms (cancer-related cognitive impairment, or CRCI) are reported by a large percentage of cancer survivors, and can have a clinically meaningful impact on educational, vocational, and social functioning, and thus overall quality of life. Better understanding of these concerns is therefore of critical importance, and is needed to guide treatment and potential prevention strategies. Neuropsychological studies over the past 40 years have demonstrated cognitive domains commonly affected in cancer patients treated with chemotherapy, but have also shown cognitive differences in patients not treated with systemic therapy and those receiving other types of treatment (e.g., hormonal therapies) relative to non-cancer control groups. More recently, structural and functional neuroimaging research has added to our understanding of the neural substrate of these cognitive symptoms. This course will describe various neuroimaging modalities used to investigate CRCI, including examination of grey and white matter volume and structural integrity, blood flow, brain activation during cognitive processing and at rest, and structural and functional connectivity. The presentation will also review how neuroimaging findings relate to objective and self-reported cognition and clinical and treatment factors, and discuss potential approaches currently being investigated to treat CRCI. Upon conclusion of this course, learners will be able to:1.Explain commonly affected cognitive domains after non-CNS cancer and treatment2.Discuss structural and functional brain changes related to cancer, chemotherapy, and other treatments3.Describe treatment interventions being investigated to treat cancer- and treatment-related cognitive symptoms.

Resting state network connectivity alterations in HIV: Parallels with aging.

The increasing incidence of age-related comorbidities in people with HIV (PWH) has led to accelerated aging theories. Functional neuroimaging research, including functional connectivity (FC) using resting-state functional magnetic resonance imaging (rs-fMRI), has identified neural aberrations related to HIV infection. Yet little is known about the relationship between aging and resting-state FC in PWH. This study included 86 virally suppressed PWH and 99 demographically matched controls spanning 22-72 years old who underwent rs-fMRI. The independent and interactive effects of HIV and aging on FC were investigated both within- and between-network using a 7-network atlas. The relationship between HIV-related cognitive deficits and FC was also examined. We also conducted network-based statistical analyses using a brain anatomical atlas (n = 512 regions) to ensure similar results across independent approaches. We found independent effects of age and HIV in between-network FC. The age-related increases in FC were widespread, while PWH displayed further increases above and beyond aging, particularly between-network FC of the default-mode and executive control networks. The results were overall similar using the regional approach. Since both HIV infection and aging are associated with independent increases in between-network FC, HIV infection may be associated with a reorganization of the major brain networks and their functional interactions in a manner similar to aging.

Visuo-spatial imagery in dreams of congenitally and early blind: a systematic review.

The presence of visual imagery in dreams of congenitally blind people has long been a matter of substantial controversy. We set to systematically review body of published work on the presence and nature of oneiric visuo-spatial impressions in congenitally and early blind subjects across different areas of research, from experimental psychology, functional neuroimaging, sensory substitution, and sleep research. Relevant studies were identified using the following databases: EMBASE, MEDLINE and PsychINFO. Studies using diverse imaging techniques and sensory substitution devices broadly suggest that the "blind" occipital cortex may be able to integrate non-visual sensory inputs, and thus possibly also generate visuo-spatial impressions. Visual impressions have also been reported by blind subjects who had near-death or out-of-body experiences. Deciphering the mechanistic nature of these visual impression could open new possibility in utilization of neuroplasticity and its potential role for treatment of neurodisability.

Structural differences in the cortex of individuals who experience the autonomous sensory meridian response.

The autonomous sensory meridian response (ASMR) is a multimodal perceptual phenomenon in which specific sensory triggers evoke tingling sensations on the scalp, neck, and shoulders; these sensations are accompanied by a positive and calming affective state. Previous functional neuroimaging research has shown that ASMR experiences involve medial prefrontal and sensorimotor brain areas. The purpose of the current study was to examine whether there are structural differences in the cortex of individuals who experience ASMR. Seventeen individuals with ASMR and 17 matched control participants completed an MPRAGE structural MRI scan. These data were analyzed to determine if group differences were present for measures of cortical thickness, cortical complexity, sulcal depth, and gyrification. ASMR was associated with reduced cortical thickness in a number of regions including the left precuneus, precentral gyrus, and insula, and the right orbitofrontal cortex, superior frontal cortex, and paracentral lobule. Reduced thickness was observed bilaterally in the supramarginal gyrus. Individuals with ASMR also showed less cortical complexity in the pars opercularis and pars triangularis. The differences in cortical thickness and complexity were in brain areas whose functions relate to the ASMR experience. These differences include neural regions related to phonological processing, sensorimotor functions, and attention.

Interpreting mental state decoding with deep learning models.

In mental state decoding, researchers aim to identify the set of mental states (e.g., experiencing happiness or fear) that can be reliably identified from the activity patterns of a brain region (or network). Deep learning (DL) models are highly promising for mental state decoding because of their unmatched ability to learn versatile representations of complex data. However, their widespread application in mental state decoding is hindered by their lack of interpretability, difficulties in applying them to small datasets, and in ensuring their reproducibility and robustness. We recommend approaching these challenges by leveraging recent advances in explainable artificial intelligence (XAI) and transfer learning, and also provide recommendations on how to improve the reproducibility and robustness of DL models in mental state decoding.

Brain system integration and message consistent health behavior change.

Modifiable behaviors, including physical activity and sedentary behavior, are important determinants of health, and messages are important tools for influencing these behaviors. Functional neuroimaging research suggests that activity in regions of the brain's default mode and salience systems are independently associated with attending to health promoting messages. However, it remains unclear how these brain systems interact during exposure to persuasive messages and how this interaction relates to subsequent behavior change. Here, we examine how between-person differences in the relative integration between default mode and salience systems while viewing health messages relates to changes in health behavior. Using wrist-worn accelerometers, we logged physical activity in 150 participants (mean age = 33.17 years, 64% women; 43% Black, 37% white, 7% Asian, 5% Hispanic, and 8% other) continuously for an average of 10 days. Participants then viewed health messages encouraging physical activity while undergoing functional MRI (fMRI) and completed an additional month where physical activity was logged and the health messages were reinforced with daily text reminders. Individuals with higher default mode and salience system integration during health message exposure were more likely to decrease their sedentary behavior and increase light physical activity in the month following fMRI than participants with lower brain integration. Interactions between the salience and default mode systems are associated with message receptivity and subsequent behavior change, highlighting the value of expanding the focus from the role of single brain regions in studying health behavior change to larger-scale connectivity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Enhanced top-down sensorimotor processing in somatic anxiety

Functional neuroimaging research on anxiety has traditionally focused on brain networks associated with the psychological aspects of anxiety. Here, instead, we target the somatic aspects of anxiety. Motivated by the growing appreciation that top-down cortical processing plays a crucial role in perception and action, we used resting-state functional MRI data from the Human Connectome Project and Dynamic Causal Modeling (DCM) to characterize effective connectivity among hierarchically organized regions in the exteroceptive, interoceptive, and motor cortices. In people with high (fear-related) somatic arousal, top-down effective connectivity was enhanced in all three networks: an observation that corroborates well with the phenomenology of anxiety. The anxiety-associated changes in connectivity were sufficiently reliable to predict whether a new participant has mild or severe somatic anxiety. Interestingly, the increase in top-down connections to sensorimotor cortex were not associated with fear affect scores, thus establishing the (relative) dissociation between somatic and cognitive dimensions of anxiety. Overall, enhanced top-down effective connectivity in sensorimotor cortices emerges as a promising and quantifiable candidate marker of trait somatic anxiety.

Altered resting-state functional connectivity of medial frontal cortex in overweight individuals: Link to food-specific intentional inhibition and weight gain

Numerous findings from functional neuroimaging research suggest that overweight may be associated with alterations in reactive inhibition. However, there is a dearth of research investigating the functional connectivity that mediates intentional inhibition in overweight individuals. To explore this issue, 55 overweight and 45 normal-weight adults completed an assessment consisting of a resting-state functional magnetic resonance imaging scan, a behavioural task measuring food-specific intentional inhibition, and a 1-year longitudinal measurement of BMI change. A seed-based approach was employed to examine the group-difference of the resting-state functional connectivity (rsFC) of the medial frontal cortex (MFC) (dorsal fronto-medial cortex [dFMC], pre-supplementary motor area, and premotor cortex) regions involved in intentional inhibition. Compared with normal-weight adults, the overweight individuals exhibited higher rsFC between the MFC seeds and (i) cerebellum, (ii) postcentral gyrus, (iii) middle temporal gyrus, and (iv) posterior cingulate cortex, while lower rsFC strength were observed between MFC seeds and (i) putamen and (ii) insula. The overweight individuals with higher dFMC–cerebellum rsFC strength showed poorer performance in food-specific intentional inhibition and gained more weight a year later than those of normal-weight participants. Results suggested that altered functional connections between MFC and regions associated with reward and maladaptive eating may be key neural mechanisms of food-specific intentional inhibition in overweight status. Therefore, individuals are encouraged to make informed decisions about their health and reduce their consumption of obesogenic foods from the perspective of intentional inhibition.

Mind-wandering: mechanistic insights from lesion, tDCS, and iEEG.

Cognitive neuroscience has witnessed a surge of interest in investigating the neural correlates of the mind when it drifts away from an ongoing task and the external environment. To that end, functional neuroimaging research has consistently implicated the default mode network (DMN) and frontoparietal control network (FPCN) in mind-wandering. Yet, it remains unknown which subregions within these networks are necessary and how they facilitate mind-wandering. In this review, we synthesize evidence from lesion, transcranial direct current stimulation (tDCS), and intracranial electroencephalogram (iEEG) studies demonstrating the causal relevance of brain regions, and providing insights into the neuronal mechanism underlying mind-wandering. We propose that the integration of complementary approaches is the optimal strategy to establish a comprehensive understanding of the neural basis of mind-wandering.

Altered effective connectivity in sensorimotor cortices is a signature of severity and clinical course in depression

Functional neuroimaging research on depression has traditionally targeted neural networks associated with the psychological aspects of depression. In this study, instead, we focus on alterations of sensorimotor function in depression. We used resting-state functional MRI data and dynamic causal modeling (DCM) to assess the hypothesis that depression is associated with aberrant effective connectivity within and between key regions in the sensorimotor hierarchy. Using hierarchical modeling of between-subject effects in DCM with parametric empirical Bayes we first established the architecture of effective connectivity in sensorimotor cortices. We found that in (interoceptive and exteroceptive) sensory cortices across participants, the backward connections are predominantly inhibitory, whereas the forward connections are mainly excitatory in nature. In motor cortices these parities were reversed. With increasing depression severity, these patterns are depreciated in exteroceptive and motor cortices and augmented in the interoceptive cortex, an observation that speaks to depressive symptomatology. We established the robustness of these results in a leave-one-out cross-validation analysis and by reproducing the main results in a follow-up dataset. Interestingly, with (nonpharmacological) treatment, depression-associated changes in backward and forward effective connectivity partially reverted to group mean levels. Overall, altered effective connectivity in sensorimotor cortices emerges as a promising and quantifiable candidate marker of depression severity and treatment response.

Predictive processing models and affective neuroscience

The neural bases of affective experience remain elusive. Early neuroscience models of affect searched for specific brain regions that uniquely carried out the computations that underlie dimensions of valence and arousal. However, a growing body of work has failed to identify these circuits. Research turned to multivariate analyses, but these strategies, too, have made limited progress. Predictive processing models offer exciting new directions to address this problem. Here, we use predictive processing models as a lens to critique prevailing functional neuroimaging research practices in affective neuroscience. Our review highlights how much work relies on rigid assumptions that are inconsistent with a predictive processing approach. We outline the central aspects of a predictive processing model and draw out their implications for research in affective and cognitive neuroscience. Predictive models motivate a reformulation of “reverse inference” in cognitive neuroscience, and placing a greater emphasis on external validity in experimental design.

Methods and Technologies of Internal Speech Recognition by Non-Invasive Neurointerfaces

The brain coordinates the reproduction and understanding of internal speech. The processes of thinking are given in the form of internal speech. The perception of internal speech involves the primary and secondary crust centers of analyzers, which record the corresponding waves, signals and rhythms and qualify them as language. This is achieved in two ways: either use functional neuroimaging and other additional research methods that allow localizing the structures currently functioning, or select patients with damage to certain areas and conduct a detailed neurocognitive study in comparison with healthy people from the control group, determining which functions in this lesion fall out. The principal issue of internal speech research is languages. A more complex question is the study of the connection of thinking, memory with internal speech. Now, especially when neurologists take into account the plasticity of the brain, functional relationships, general principles, pathways of excitation are of greater interest. Technologists of non-invasive neurointerfaces use methods and technologies to localize structures that control the understanding and reproduction of internal speech, the communication between them, the stages of speech signal processing and the role of each structure at these stages. The introduction to the study highlights approaches and methods for identifying various functional speech aspects. The mental lexicon section discloses the semantic component and the syntactic component, as well as the perceived and reproducible forms of words of internal speech. The section holographic human consciousness describes aspects of storing life information. The hologram of consciousness is the main form of storage of information about human life. In the section, holographic fixation of internal speech presents functional magnetic resonance tomography focused on BOLD effect detection, which is today the optimal tool for mapping neuronal activity, more precisely, the functional state of neural networks - the basis for visualizing our holographic images in real time. Using nanoresonators with Fourier transducers, the brain activity of a human internal speech holographic image can fix mental noninvasive neurointerface in language form by mental lexicon.

A comprehensive macaque fMRI pipeline and hierarchical atlas

Functional neuroimaging research in the non-human primate (NHP) has been advancing at a remarkable rate. The increase in available data establishes a need for robust analysis pipelines designed for NHP neuroimaging and accompanying template spaces to standardize the localization of neuroimaging results. Our group recently developed the NIMH Macaque Template (NMT), a high-resolution population average anatomical template and associated neuroimaging resources, providing researchers with a standard space for macaque neuroimaging . Here, we release NMT v2, which includes both symmetric and asymmetric templates in stereotaxic orientation, with improvements in spatial contrast, processing efficiency, and segmentation. We also introduce the Cortical Hierarchy Atlas of the Rhesus Macaque (CHARM), a hierarchical parcellation of the macaque cerebral cortex with varying degrees of detail. These tools have been integrated into the neuroimaging analysis software AFNI to provide a comprehensive and robust pipeline for fMRI processing, visualization and analysis of NHP data. AFNI's new @animal_warper program can be used to efficiently align anatomical scans to the NMT v2 space, and afni_proc.py integrates these results with full fMRI processing using macaque-specific parameters: from motion correction through regression modeling. Taken together, the NMT v2 and AFNI represent an all-in-one package for macaque functional neuroimaging analysis, as demonstrated with available demos for both task and resting state fMRI.

Distinct patterns of resting-state connectivity in U.S. service members with mild traumatic brain injury versus posttraumatic stress disorder

Mild traumatic brain injury (mTBI) is highly prevalent in military populations, with many service members suffering from long-term symptoms. Posttraumatic stress disorder (PTSD) often co-occurs with mTBI and predicts worse clinical outcomes. Functional neuroimaging research suggests there are both overlapping and distinct patterns of resting-state functional connectivity (rsFC) in mTBI versus PTSD. However, few studies have directly compared rsFC of cortical networks in military service members with these two conditions. In the present study, U.S. service members (n = 137; ages 19-59; 120 male) underwent resting-state fMRI scans. Participants were divided into three study groups: mTBI only, PTSD only, and orthopedically injured (OI) controls. Analyses investigated group differences in rsFC for cortical networks: default mode (DMN), frontoparietal (FPN), salience, somatosensory, motor, auditory, and visual. Analyses were family-wise error (FWE) cluster-corrected and Bonferroni-corrected for number of network seeds regions at the whole brain level (pFWE < 0.002). Both mTBI and PTSD groups had reduced rsFC for DMN and FPN regions compared with OI controls. These group differences were largely driven by diminished connectivity in the PTSD group. rsFC with the middle frontal gyrus of the FPN was increased in mTBI, but decreased in PTSD. Overall, these results suggest that PTSD symptoms may have a more consistent signal than mTBI. Our novel findings of opposite patterns of connectivity with lateral prefrontal cortex highlight a potential biomarker that could be used to differentiate between these conditions.

Effects of the dopamine transporter gene on neuroimaging findings in different attention deficit hyperactivity disorder presentations.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a phenotipically and neurobiologically heterogeneous disorder. Deficiencies at different levels in response inhibition, differences in dopamine transporter genotype (DAT1) and various symptomatic presentations contribute to ADHD heterogeneity. Integrating these three aspects into a functional neuroimaging research could help unreval specific neurobiological components of more phenotipically homogeneous groups of patients with ADHD. During the Go-NoGo trial, we investigated the effect of the DAT1 gene using 3T MRI in 72 ADHD cases and 24 (TD) controls that typically developed between the ages 8 and 15years. In the total ADHD group, DAT1 predicted homozygosity for the 10R allele and hypoactivation in the anterior cingulate cortex and paracingulate cortex. There were no significant activation differences between DAT1 10R/10R homozygotes and 9R carriers in TD controls. Subjects with predominantly inattentive ADHD (ADHD-I) presentation with DAT1 10R/10R homozygous reduced neuronal activation during Go trial particularly in the frontal regions and insular cortex, and in the parietal regions during NoGo trial (brain regions reported as part of Default Mode Network- DMN). Additionally, DAT1 10R/10R homozygousness was associated with increased occipital zone activation during only the Go trial in the ADHD combined presentation (ADHD-C) group. Our results point the three main findings: 1) The DAT1 gene is 10R homozygous for differentiated brain activation in ADHD cases but not in the TD controls, supporting the DAT1 gene as a potential marker for ADHD, 2) The relationship between the DAT1 gene and the occipital regions in ADHD-C group which may reflect compensatory mechanisms, 3) The relationship between DAT1 gene and the reduced DMN suppression for 9R carriers probabaly stems from the ADHD-I group.

Face-Selective Units in Human Ventral Temporal Cortex Reactivate during Free Recall

Research in functional neuroimaging has suggested that category-selective regions of visual cortex, including the ventral temporal cortex (VTC), can be reactivated endogenously through imagery and recall. Face representation in the monkey face-patch system has been well studied and is an attractive domain in which to explore these processes in humans. The VTCs of eight human subjects (four female) undergoing invasive monitoring for epilepsy surgery were implanted with microelectrodes. Most (26 of 33) category-selective units showed specificity for face stimuli. Different face exemplars evoked consistent and discriminable responses in the population of units sampled. During free recall, face-selective units preferentially reactivated in the absence of visual stimulation during a 2-second window preceding face recall events. Furthermore, we show that in at least one subject, the identity of the recalled face could be predicted by comparing activity preceding recall events to activity evoked by visual stimulation. We show that face-selective units in the human VTC are reactivated endogenously, and present initial evidence that consistent representations of individual face exemplars are specifically reactivated in this manner.SIGNIFICANCE STATEMENT The role of "top-down" endogenous reactivation of native representations in higher sensory areas is poorly understood in humans. We conducted the first detailed single-unit survey of VTC in human subjects, showing that, similarly to non-human primates, humans encode different faces using different rate codes. Then, we demonstrated that when subjects recalled and imagined a given face, VTC neurons reactivated with the same rate codes as when subjects initially viewed that face. This suggests that the VTC units not only carry durable representations of faces, but that those representations can be endogenously reactivated via "top-down" mechanisms.

Resting State Hypoconnectivity of Reward Networks in Binge Eating Disorder.

The clinical presentation of binge eating disorder (BED) and data emerging from task-based functional neuroimaging research suggests that this disorder may be associated with alterations in reward processing. However, there is a dearth of research investigating the functional organization of brain networks that mediate reward in BED. To address this gap, 27 adults with BED and 21 weight-matched healthy controls (WMC) completed a multimodel assessment consisting of a resting functional magnetic resonance imaging scan, behavioral tasks measuring reward-based decision-making (i.e., delay discounting and reversal learning), and self-report assessing clinical symptoms. A seed-based approach was employed to examine the resting state functional connectivity (rsFC) of the striatum (nucleus accumbens [NAcc] and ventral and dorsal caudate), a collection of regions implicated in reward processing. Compared with WMC, the BED group exhibited lower rsFC of striatal seeds, with frontal regions mediating executive functioning (e.g., superior frontal gyrus [SFG]) and posterior, parietal, and temporal regions implicated in emotional processing. Lower NAcc-SFG rsFC was associated with more difficulties with reversal learning and binge eating frequency in the BED group. Results suggest that hypoconnectivity of striatal networks that integrate self-regulation and reward processing may promote the clinical phenomenology of BED. Interventions for BED may benefit from targeting these circuit-based disturbances.

Multi-contrast anatomical subcortical structures parcellation

The human subcortex is comprised of more than 450 individual nuclei which lie deep in the brain. Due to their small size and close proximity, up until now only 7% have been depicted in standard MRI atlases. Thus, the human subcortex can largely be considered as terra incognita. Here, we present a new open-source parcellation algorithm to automatically map the subcortex. The new algorithm has been tested on 17 prominent subcortical structures based on a large quantitative MRI dataset at 7 Tesla. It has been carefully validated against expert human raters and previous methods, and can easily be extended to other subcortical structures and applied to any quantitative MRI dataset. In sum, we hope this novel parcellation algorithm will facilitate functional and structural neuroimaging research into small subcortical nuclei and help to chart terra incognita.

Causal Evidence for a Double Dissociation between Object- and Scene-Selective Regions of Visual Cortex: A Preregistered TMS Replication Study.

Natural scenes are characterized by individual objects as well as by global scene properties such as spatial layout. Functional neuroimaging research has shown that this distinction between object and scene processing is one of the main organizing principles of human high-level visual cortex. For example, object-selective regions, including the lateral occipital complex (LOC), were shown to represent object content (but not scene layout), while scene-selective regions, including the occipital place area (OPA), were shown to represent scene layout (but not object content). Causal evidence for a double dissociation between LOC and OPA in representing objects and scenes is currently limited, however. One TMS experiment, conducted in a relatively small sample (N = 13), reported an interaction between LOC and OPA stimulation and object and scene recognition performance (Dilks et al., 2013). Here, we present a high-powered preregistered replication of this study (N = 72, including male and female human participants), using group-average fMRI coordinates to target LOC and OPA. Results revealed unambiguous evidence for a double dissociation between LOC and OPA: relative to vertex stimulation, TMS over LOC selectively impaired the recognition of objects, while TMS over OPA selectively impaired the recognition of scenes. Furthermore, we found that these effects were stable over time and consistent across individual objects and scenes. These results show that LOC and OPA can be reliably and selectively targeted with TMS, even when defined based on group-average fMRI coordinates. More generally, they support the distinction between object and scene processing as an organizing principle of human high-level visual cortex.SIGNIFICANCE STATEMENT Our daily-life environments are characterized both by individual objects and by global scene properties. The distinction between object and scene processing features prominently in visual cognitive neuroscience, with fMRI studies showing that this distinction is one of the main organizing principles of human high-level visual cortex. However, causal evidence for the selective involvement of object- and scene-selective regions in processing their preferred category is less conclusive. Here, testing a large sample (N = 72) using an established paradigm and a preregistered protocol, we found that TMS over object-selective cortex (lateral occipital complex) selectively impaired object recognition, while TMS over scene-selective cortex (occipital place area) selectively impaired scene recognition. These results provide strong causal evidence for the distinction between object and scene processing in human visual cortex.

Data Triangulation in Consumer Neuroscience: Integrating Functional Neuroimaging With Meta-Analyses, Psychometrics, and Behavioral Data.

This article reviews a wide range of functional magnetic resonance imaging (fMRI) studies conducted in the field of consumer neuroscience to (1) highlight common interpretative approaches of neuroimaging data (i.e., forward inference and reverse inference), (2) discuss potential interpretative issues associated with these approaches, and (3) provide a framework that employs a multi-method approach aimed to possibly raise the explanatory power and, thus, the validity of functional neuroimaging research in consumer neuroscience. Based on this framework, we argue that the validity of fMRI studies can be improved by the triangulation of (1) careful design of neuroimaging studies and analyses of data, (2) meta-analyses, and (3) the integration of psychometric and behavioral data with neuroimaging data. Guidelines on when and how to employ triangulation methods on neuroimaging data are included. Moreover, we also included discussions on practices and research directions that validate fMRI studies in consumer neuroscience beyond data triangulation.