Quantitative susceptibility mapping of basal ganglia iron is associated with cognitive and motor functions that distinguish spinocerebellar ataxia type 6 and type 3.

Background: In spinocerebellar ataxia type 3 (SCA3), volume loss has been reported in the basal ganglia, an iron-rich brain region, but iron content has not been examined. Recent studies have reported that patients with SCA6 have markedly decreased iron content in the cerebellar dentate, coupled with severe volume loss. Changing brain iron levels can disrupt cognitive and motor functions, yet this has not been examined in the SCAs, a disease in which iron-rich regions are affected. Methods: In the present study, we used quantitative susceptibility mapping (QSM) to measure tissue magnetic susceptibility (indicating iron concentration), structural volume, and normalized susceptibility mass (indicating iron content) in the cerebellar dentate and basal ganglia in people with SCA3 (n = 10) and SCA6 (n = 6) and healthy controls (n = 9). Data were acquired using a 7T Philips MRI scanner. Supplemental measures assessed motor, cognitive, and mood domains. Results: Putamen volume was lower in both SCA groups relative to controls, replicating prior findings. Dentate susceptibility mass and volume in SCA6 was lower than in SCA3 or controls, also replicating prior findings. The novel finding was that higher basal ganglia susceptibility mass in SCA6 correlated with lower cognitive performance and greater motor impairment, an association that was not observed in SCA3. Cerebellar dentate susceptibility mass, however, had the opposite relationship with cognition and motor function in SCA6, suggesting that, as dentate iron is depleted, it relocated to the basal ganglia, which contributed to cognitive and motor decline. By contrast, basal ganglia volume loss, rather than iron content, appeared to drive changes in motor function in SCA3. Conclusion: The associations of higher basal ganglia iron with lower motor and cognitive function in SCA6 but not in SCA3 suggest the potential for using brain iron deposition profiles beyond the cerebellar dentate to assess disease states within the cerebellar ataxias. Moreover, the role of the basal ganglia deserves greater attention as a contributor to pathologic and phenotypic changes associated with SCA.

Brain-computer interfaces increase whole-brain signal to noise.

Brain-computer interfaces (BCIs) can convert mental states into signals to drive real-world devices, but it is not known if a given covert task is the same when performed with and without BCI-based control. Using a BCI likely involves additional cognitive processes, such as multitasking, attention, and conflict monitoring. In addition, it is challenging to measure the quality of covert task performance. We used whole-brain classifier-based real-time functional MRI to address these issues, because the method provides both classifier-based maps to examine the neural requirements of BCI and classification accuracy to quantify the quality of task performance. Subjects performed a covert counting task at fast and slow rates to control a visual interface. Compared with the same task when viewing but not controlling the interface, we observed that being in control of a BCI improved task classification of fast and slow counting states. Additional BCI control increased subjects' whole-brain signal-to-noise ratio compared with the absence of control. The neural pattern for control consisted of a positive network comprised of dorsal parietal and frontal regions and the anterior insula of the right hemisphere as well as an expansive negative network of regions. These findings suggest that real-time functional MRI can serve as a platform for exploring information processing and frontoparietal and insula network-based regulation of whole-brain task signal-to-noise ratio.

Investigation of fMRI neurofeedback of differential primary motor cortex activity using kinesthetic motor imagery.

Functional MRI neurofeedback (fMRI NF) is an emerging technique that trains subjects to regulate their brain activity while they manipulate sensory stimulus representations of fMRI signals in "real-time". Here we report an fMRI NF study of brain activity associated with kinesthetic motor imagery (kMI), analyzed using partial least squares (PLS), a multivariate analysis technique. Thirteen healthy young adult subjects performed kMI involving each hand separately, with NF training targeting regions of interest (ROIs) in the left and right primary motor cortex (M1). Throughout, subjects attempted to maximize a laterality index (LI) of brain activity-the difference in activity between the contralateral ROI (relative to the hand involved in kMI) and the ipsilateral M1 ROI-while receiving real-time updates on a visual display. Six of 13 subjects were successful in increasing the LI value, whereas the other 7 were not successful and performed similarly to 5 control subjects who received sham NF training. Ability to suppress activity in the ipsilateral M1 ROI was the primary driver of successful NF performance. Multiple PLS analyses depicted activated networks of brain regions involved with imagery, self-awareness, and feedback processing, and additionally showed that activation of the task positive network was correlated with task performance. These results indicate that fMRI NF of kMI is capable of modulating brain activity in primary motor regions in a subset of the population. In the future, such methods may be useful in the development of NF training methods for enhancing motor rehabilitation following stroke.

Decoding fMRI brain states in real-time.

This article reviews a technological advance that originates from two areas of ongoing neuroimaging innovation-(1) the use of multivariate supervised learning to decode brain states and (2) real-time functional magnetic resonance imaging (rtfMRI). The approach uses multivariate methods to train a model capable of decoding a subject's brain state from fMRI images. The decoded brain states can be used as a control signal for a brain computer interface (BCI) or to provide neurofeedback to the subject. The ability to adapt the stimulus during the fMRI experiment adds a new level of flexibility for task paradigms and has potential applications in a number of areas, including performance enhancement, rehabilitation, and therapy. Multivariate approaches to real-time fMRI are complementary to region-of-interest (ROI)-based methods and provide a principled method for dealing with distributed patterns of brain responses. Specifically, a multivariate approach is advantageous when network activity is expected, when mental strategies could vary from individual to individual, or when one or a few ROIs are not unequivocally the most appropriate for the investigation. Beyond highlighting important developments in rtfMRI and supervised learning, the article discusses important practical issues, including implementation considerations, existing resources, and future challenges and opportunities. Some possible future directions are described, calling for advances arising from increased experimental flexibility, improvements in predictive modeling, better comparisons across rtfMRI and other BCI implementations, and further investigation of the types of feedback and degree to which interface modulation is obtainable for various tasks.

Neurofeedback of two motor functions using supervised learning-based real-time functional magnetic resonance imaging.

This study examines the effects of neurofeedback provided by support vector machine (SVM) classification-based real-time functional magnetic resonance imaging (rt-fMRI) during two types of motor tasks. This approach also enables the examination of the neural regions associated with predicting mental states in different domains of motor control, which is critical to further our understanding of normal and impaired function. Healthy volunteers (n = 13) performed both a simple button tapping task, and a covert rate-of-speech counting task. The average prediction accuracy was approximately 95% for the button tapping task and 86% for the speech task. However, subsequent offline analysis revealed that classification of the initial runs was significantly lower - 75% (p<0.001) for button and 72% (p<0.005) for speech. To explore this effect, a group analysis was performed using the spatial maps derived from the SVM models, which showed significant differences between the two fMRI runs. One possible explanation for the difference in spatial patterns and the asymmetry in the prediction accuracies is that when subjects are actively engaged in the task (i.e. when they are trying to control a computer interface), they are generating stronger BOLD responses in terms of both intensity and spatial extent.

Real-time fMRI using brain-state classification.

We have implemented a real-time functional magnetic resonance imaging system based on multivariate classification. This approach is distinctly different from spatially localized real-time implementations, since it does not require prior assumptions about functional localization and individual performance strategies, and has the ability to provide feedback based on intuitive translations of brain state rather than localized fluctuations. Thus this approach provides the capability for a new class of experimental designs in which real-time feedback control of the stimulus is possible-rather than using a fixed paradigm, experiments can adaptively evolve as subjects receive brain-state feedback. In this report, we describe our implementation and characterize its performance capabilities. We observed approximately 80% classification accuracy using whole brain, block-design, motor data. Within both left and right motor task conditions, important differences exist between the initial transient period produced by task switching (changing between rapid left or right index finger button presses) and the subsequent stable period during sustained activity. Further analysis revealed that very high accuracy is achievable during stable task periods, and that the responsiveness of the classifier to changes in task condition can be much faster than signal time-to-peak rates. Finally, we demonstrate the versatility of this implementation with respect to behavioral task, suggesting that our results are applicable across a spectrum of cognitive domains. Beyond basic research, this technology can complement electroencephalography-based brain computer interface research, and has potential applications in the areas of biofeedback rehabilitation, lie detection, learning studies, virtual reality-based training, and enhanced conscious awareness.