Kathleen A. Garrison

The Mirror Neuron System: A Neural Substrate for Methods in Stroke Rehabilitation

Mirror neurons found in the premotor and parietal cortex respond not only during action execution, but also during observation of actions being performed by others. Thus, the motor system may be activated without overt movement. Rehabilitation of motor function after stroke is often challenging due to severity of impairment and poor to absent voluntary movement ability. Methods in stroke rehabilitation based on the mirror neuron system—action observation, motor imagery, and imitation—take advantage of this opportunity to rebuild motor function despite impairments, as an alternative or complement to physical therapy. Here the authors review research into each condition of practice, and discuss the relevance of the mirror neuron system to stroke recovery.

Optimizing real time fMRI neurofeedback for therapeutic discovery and development

While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain–behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders.

What about the "Self" is Processed in the Posterior Cingulate Cortex?

In the past decade, neuroimaging research has begun to identify key brain regions involved in self-referential processing, most consistently midline structures such as the posterior cingulate cortex (PCC). The majority of studies have employed cognitive tasks such as judgment about trait adjectives or mind wandering, that have been associated with increased PCC activity. Conversely, tasks that share an element of present-centered attention (being “on task”), ranging from working memory to meditation, have been associated with decreased PCC activity. Given the complexity of cognitive processes that likely contribute to these tasks, the specific contribution of the PCC to self-related processes still remains unknown. Building on this prior literature, recent studies have employed sampling methods that more precisely link subjective experience to brain activity, such as real-time fMRI neurofeedback. This recent work suggests that PCC activity may represent a sub-component cognitive process of self-reference – “getting caught up in” one’s experience. For example, getting caught up in a drug craving or a particular viewpoint. In this paper, we will review evidence across a number of different domains of cognitive neuroscience that converges in activation and deactivation of the PCC including recent neurophenomenological studies of PCC activity using real-time fMRI neurofeedback.

Measurement of Whole-Brain Atrophy in Multiple Sclerosis

Brain atrophy reflects the net result of irreversible and destructive pathological processes in multiple sclerosis (MS). The gross morphological changes can be accurately quantified using standard magnetic resonance imaging (MRI) acquisitions and various image analysis tools. The current methods used to assess whole‐brain atrophy in patients with MS can be classified into 2 groups based on their reliance on segmentation and registration. Segmentation‐based methods employed to measure whole‐brain atrophy in MS include the brain parenchymal fraction, the index of brain atrophy, the whole‐brain ratio, the brain to intracranial capacity ratio, fuzzy connectedness/Udupas method, 3DVIEWNIX, the Alfano method, and SIENAX. Current registration‐based methods used to measure whole‐brain atrophy in MS include the brain boundary shift integral, SIENA, statistical parametric mapping, template‐driven seg mentation, and voxel‐based morphometry. Most of the methods presented here are sensitive to subtle changes in brain structures and have been successfully applied to MS as measures of whole‐brain atrophy. Yet comparative studies of these methods are limited and are complicated by the lack of a gold standard for image acquisition, a segmentation algorithm, an image analysis method, or a reproducibility measure. Overall, the measure of whole‐brain atrophy from MRI contributes to an appreciation of the dynamics of MS pathology and its relationship to the clinical course of MS. Determination of the relative reproducibility, precision, sensitivity, and validity of these methods will promote the use of whole‐brain atrophy measures as components of comprehensive MRI‐based outcome assessment in MS clinical trials.

Real-time fMRI links subjective experience with brain activity during focused attention.

Recent advances in brain imaging have improved the measure of neural processes related to perceptual, cognitive and affective functions, yet the relation between brain activity and subjective experience remains poorly characterized. In part, it is a challenge to obtain reliable accounts of participants experience in such studies. Here we addressed this limitation by utilizing experienced meditators who are expert in introspection. We tested a novel method to link objective and subjective data, using real-time fMRI (rt-fMRI) to provide participants with feedback of their own brain activity during an ongoing task. We provided real-time feedback during a focused attention task from the posterior cingulate cortex, a hub of the default mode network shown to be activated during mind-wandering and deactivated during meditation. In a first experiment, both meditators and non-meditators reported significant correspondence between the feedback graph and their subjective experience of focused attention and mind-wandering. When instructed to volitionally decrease the feedback graph, meditators, but not non-meditators, showed significant deactivation of the posterior cingulate cortex. We were able to replicate these results in a separate group of meditators using a novel step-wise rt-fMRI discovery protocol in which participants were not provided with prior knowledge of the expected relationship between their experience and the feedback graph (i.e., focused attention versus mind-wandering). These findings support the feasibility of using rt-fMRI to link objective measures of brain activity with reports of ongoing subjective experience in cognitive neuroscience research, and demonstrate the generalization of expertise in introspective awareness to novel contexts.

The (in)stability of functional brain network measures across thresholds.

The large-scale organization of the brain has features of complex networks that can be quantified using network measures from graph theory. However, many network measures were designed to be calculated on binary graphs, whereas functional brain organization is typically inferred from a continuous measure of correlations in temporal signal between brain regions. Thresholding is a necessary step to use binary graphs derived from functional connectivity data. However, there is no current consensus on what threshold to use, and network measures and group contrasts may be unstable across thresholds. Nevertheless, whole-brain network analyses are being applied widely with findings typically reported at an arbitrary threshold or range of thresholds. This study sought to evaluate the stability of network measures across thresholds in a large resting state functional connectivity dataset. Network measures were evaluated across absolute (correlation-based) and proportional (sparsity-based) thresholds, and compared between sex and age groups. Overall, network measures were found to be unstable across absolute thresholds. For example, the direction of group differences in a given network measure may change depending on the threshold. Network measures were found to be more stable across proportional thresholds. These results demonstrate that caution should be used when applying thresholds to functional connectivity data and when interpreting results from binary graph models.

Modulating the Motor System by Action Observation After Stroke

Background and Purpose— Much recent interest surrounds the use of action observation, which is observing another individual performing a motor task, in stroke rehabilitation, to promote motor recovery by engaging similar brain regions to action execution. This may be especially useful in individuals with limited mobility. Here, we assess how cortical motor activity during action observation is affected by stroke and by stroke-related motor deficits. Methods— We used functional MRI to compare brain activity during right and left hand action observation in right-handed nondisabled participants and participants who were right-handed before left hemisphere stroke. All participants performed the same actions after their functional MRI. Results— Nondisabled participants show greater bilateral cortical motor activity when observing actions made using the left hand, whereas participants with stroke show greater ipsilesional cortical motor activity when observing actions made using the right (paretic) hand (P<0.05; corrected). For both groups, action processing is modulated by motor capability: cortical motor activity is greater when observing the hand with lower motor scores (P<0.05; corrected). Furthermore, for stroke, the extent of ipsilesional activity correlates with lesion volume (P=0.049), in a pattern that suggests adaptive plasticity. Conclusions— We found that action observation activates specific motor plans in damaged motor circuits after stroke, and this activity is related to motor capability to perform the same actions. Cortical motor activity during action observation may be relevant to motor learning, and to motor relearning in stroke rehabilitation.

The posterior cingulate cortex as a plausible mechanistic target of meditation: findings from neuroimaging

There has been an increased interest in mindfulness and meditation training over the past decade. As evidenced by exponential growth in the number of publications since the beginning of the 21st century, progressively more is becoming known about both the clinical efficacy and underlying neurobiological mechanisms of mindfulness training. This paper briefly highlights psychological models of stress that converge between ancient and modern day (e.g., operant conditioning); identifies key brain regions that, with these models, are biologically plausible targets for mindfulness (e.g., posterior cingulate cortex); and discusses recent and emerging findings from neuroimaging studies of meditation therein, including new advances using real‐time functional magnetic resonance imaging neurofeedback in neurophenomenological studies.

A randomized controlled trial of smartphone-based mindfulness training for smoking cessation: a study protocol

BackgroundTobacco use is responsible for the death of about 1 in 10 individuals worldwide. Mindfulness training has shown preliminary efficacy as a behavioral treatment for smoking cessation. Recent advances in mobile health suggest advantages to smartphone-based smoking cessation treatment including smartphone-based mindfulness training. This study evaluates the efficacy of a smartphone app-based mindfulness training program for improving smoking cessation rates at 6-months follow-up.Methods/DesignA two-group parallel-randomized clinical trial with allocation concealment will be conducted. Group assignment will be concealed from study researchers through to follow-up. The study will be conducted by smartphone and online. Daily smokers who are interested in quitting smoking and own a smartphone (n = 140) will be recruited through study advertisements posted online. After completion of a baseline survey, participants will be allocated randomly to the control or intervention group. Participants in both groups will receive a 22-day smartphone-based treatment program for smoking. Participants in the intervention group will receive mobile mindfulness training plus experience sampling. Participants in the control group will receive experience sampling-only. The primary outcome measure will be one-week point prevalence abstinence from smoking (at 6-months follow-up) assessed using carbon monoxide breath monitoring, which will be validated through smartphone-based video chat.DiscussionThis is the first intervention study to evaluate smartphone-based delivery of mindfulness training for smoking cessation. Such an intervention may provide treatment in-hand, in real-world contexts, to help individuals quit smoking.Trial registrationClinicaltrials.gov NCT02134509. Registered 7 May 2014.

Meditation leads to reduced default mode network activity beyond an active task

Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest, despite other studies having reported differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, in this study we compared meditation to another active cognitive task, both to replicate the findings that meditation is associated with relatively reduced default mode network activity and to extend these findings by testing whether default mode activity was reduced during meditation, beyond the typical reductions observed during effortful tasks. In addition, prior studies had used small groups, whereas in the present study we tested these hypotheses in a larger group. The results indicated that meditation is associated with reduced activations in the default mode network, relative to an active task, for meditators as compared to controls. Regions of the default mode network showing a Group × Task interaction included the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that the suppression of default mode processing may represent a central neural process in long-term meditation, and they suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task.