Mindfulness-based real-time fMRI neurofeedback: a randomized controlled trial to optimize dosing for depressed adolescents.

BACKGROUND: Adolescence is characterized by a heightened vulnerability for Major Depressive Disorder (MDD) onset, and currently, treatments are only effective for roughly half of adolescents with MDD. Accordingly, novel interventions are urgently needed. This study aims to establish mindfulness-based real-time fMRI neurofeedback (mbNF) as a non-invasive approach to downregulate the default mode network (DMN) in order to decrease ruminatory processes and depressive symptoms. METHODS: Adolescents (N = 90) with a current diagnosis of MDD ages 13-18-years-old will be randomized in a parallel group, two-arm, superiority trial to receive either 15 or 30 min of mbNF with a 1:1 allocation ratio. Real-time neurofeedback based on activation of the frontoparietal network (FPN) relative to the DMN will be displayed to participants via the movement of a ball on a computer screen while participants practice mindfulness in the scanner. We hypothesize that within-DMN (medial prefrontal cortex [mPFC] with posterior cingulate cortex [PCC]) functional connectivity will be reduced following mbNF (Aim 1: Target Engagement). Additionally, we hypothesize that participants in the 30-min mbNF condition will show greater reductions in within-DMN functional connectivity (Aim 2: Dosing Impact on Target Engagement). Aim 1 will analyze data from all participants as a single-group, and Aim 2 will leverage the randomized assignment to analyze data as a parallel-group trial. Secondary analyses will probe changes in depressive symptoms and rumination. DISCUSSION: Results of this study will determine whether mbNF reduces functional connectivity within the DMN among adolescents with MDD, and critically, will identify the optimal dosing with respect to DMN modulation as well as reduction in depressive symptoms and rumination. TRIAL REGISTRATION: This study has been registered with clinicaltrials.gov, most recently updated on July 6, 2023 (trial identifier: NCT05617495).

Hybrid active and passive local shimming (HAPLS) for two-region MRI.

PURPOSE: An MRI scanner is equipped with global shim systems for shimming one region of interest (ROI) only. However, it often fails to reach state-of-the-art when shimming two isolated regions of interest simultaneously, even though the two-area shimming can be essential in scan scenarios, such as bilateral breasts or dyadic brains. To address these challenges, a hybrid active and passive local shimming technique is proposed to simultaneously shim two isolated region-of-interest areas within the whole FOV. METHODS: A local passive shimming system is constructed by optimized bilateral ferromagnetic chip arrays to compensate for the magnet's significant high-order B0 inhomogeneities at the boundary of the manufacturer's specified homogeneous volume, thus locally improving the available FOV. The local active shimming consists of 40-channel DC loops powered by 64-channel current amplifiers. With the optimized current distribution, active shimming can correct the residual low-order B0 inhomogeneities and subject-specific field inhomogeneities. In addition, active shimming is used to homogenize the center frequencies of the two regions. RESULTS: With the implementation of the hybrid active and passive local shimming, the 95% peak-to-peak was reduced from 1.92 to 1.12 ppm by 41.7%, and RMS decreased from 0.473 to 0.255 ppm by 46.1% in a two-phantom experiment. The volume ratio containing MR voxels within a 0.5-ppm frequency span increased from 64.3% to 81.3% by 26.3%. CONCLUSION: The proposed hybrid active and passive local shimming technique uses both passive and active local shimming, and it can efficiently shim two areas simultaneously, which is an unmet need for a commercial MRI scanner.

Dual logic and cerebral coordinates for reciprocal interaction in eye contact.

In order to scientifically study the human brain's response to face-to-face social interaction, the scientific method itself needs to be reconsidered so that both quantitative observation and symbolic reasoning can be adapted to the situation where the observer is also observed. In light of the recent development of dyadic fMRI which can directly observe dyadic brain interacting in one MRI scanner, this paper aims to establish a new form of logic, dual logic, which provides a theoretical platform for deductive reasoning in a complementary dual system with emergence mechanism. Applying the dual logic in the dfMRI experimental design and data analysis, the exogenous and endogenous dual systems in the BOLD responses can be identified; the non-reciprocal responses in the dual system can be suppressed; a cerebral coordinate for reciprocal interaction can be generated. Elucidated by dual logic deductions, the cerebral coordinate for reciprocal interaction suggests: the exogenous and endogenous systems consist of the empathy network and the mentalization network respectively; the default-mode network emerges from the resting state to activation in the endogenous system during reciprocal interaction; the cingulate plays an essential role in the emergence from the exogenous system to the endogenous system. Overall, the dual logic deductions are supported by the dfMRI experimental results and are consistent with current literature. Both the theoretical framework and experimental method set the stage to formally apply the scientific method in studying complex social interaction.

Closed-loop training of attention with real-time brain imaging.

Lapses of attention can have negative consequences, including accidents and lost productivity. Here we used closed-loop neurofeedback to improve sustained attention abilities and reduce the frequency of lapses. During a sustained attention task, the focus of attention was monitored in real time with multivariate pattern analysis of whole-brain neuroimaging data. When indicators of an attentional lapse were detected in the brain, we gave human participants feedback by making the task more difficult. Behavioral performance improved after one training session, relative to control participants who received feedback from other participants' brains. This improvement was largest when feedback carried information from a frontoparietal attention network. A neural consequence of training was that the basal ganglia and ventral temporal cortex came to represent attentional states more distinctively. These findings suggest that attentional failures do not reflect an upper limit on cognitive potential and that attention can be trained with appropriate feedback about neural signals.

Emergence of the default-mode network from resting-state to activation-state in reciprocal social interaction via eye contact.

The default-mode network has been identified as a resting state BOLD response that is often associated with self-referential or sensory task-passive processes. Many recent studies reveal that this vaguely defined network often plays an essential role in many pervasive mental diseases. By taking advantage of the recent development of dyadic fMRI, this study presents the initial experimental evidence that the default-mode network emerges from resting-state to activation-state in social interaction during live eye contact. Moreover, by comparing the BOLD responses between dyadic fMRI and monadic fMRI, it suggests that live eye contact excites empathy networks in the exogenous system which further activates the default mode network in endogenous system; whereas seeing eyes in face pictures activates completely different brain responses in which the default-mode network remains in resting-state.

Dual logic and dual neural basis for reciprocal social interaction in eye contact.

Dyadic brain interactions during eye contact engage multiple processes and recruit multiple networks. To fully characterize these concurrent activities, it's essential to establish the neural basis for reciprocal social interaction. So far most approaches in this pursuit suffered from the limitations in either insufficient dyadic test instruments or entwined reciprocal and non-reciprocal cerebral responses. To address these two challenges, this study not only employed a dual-head coil to directly acquire dyadic fMRI data, but also developed a dual logic to deductively untwine the reciprocal social interactive state and non-reciprocal affective state in cerebral responses. As results, a data-driven neural basis for visual reciprocal interaction is derived, which mainly consists of imitation-empathy network and mentalizing network to facilitate the exogenous and endogenous dual processes. Applications of the neural basis in extracting dyadic network synchronizations are exemplified. In addition, the dual logic formulated emergence of the endogenous process and predicted the default-mode network.

Decoupled circular-polarized dual-head volume coil pair for studying two interacting human brains with dyadic fMRI.

A major function of the human brain is to mediate interactions with other people. Until recently, studying social interactions as they occur within the brain was not possible due to the lack of measurable methods to observe two interacting minds simultaneously. We have developed a novel MRI dual-head volume coil pair that can scan two subjects' brains simultaneously while the subjects are socially interacting in one MRI scanner. The feasibility of using this coil for dyadic functional MRI (fMRI) study has been successfully demonstrated for the first time. Meanwhile, an innovative robust scheme for decoupling two circular-polarized coils (not surface coils) is introduced in theory and validated in practice in the coil technology development.

A decoupled circular-polarized volume head coil pair for studying two interacting human brains with MRI.

One of the major functions of the human brain is to mediate interactions with other people. Until recently, studying brain social interactions has not been possible due to the lack of measurable methods to observe two interacting minds simultaneously. We have developed a novel dual-head MRI coil that can scan two subjects' brains simultaneously while the subjects are socially interacting in one MRI scanner. Meanwhile, a novel scheme for decoupling two quadrature coils (not surface coils) is introduced and validated.

Perspectives on body MR imaging at ultrahigh field.

As investigators consider approaching the challenge of MR imaging at field strengths above 3T, do they follow the same paradigm, and continue to work around the same problems they have encountered thus far at 3T, or do they explore other ways of answering the clinical questions more effectively and more comprehensively? The most immediate problems of imaging at ultrahigh field strength are not unfamiliar, as many of them are still pressing issues at 3T: radiofrequency coils, B1 homogeneity, specific absorption rate, safety, B0 field homogeneity, alterations in tissue contrast, and chemical shift. In this article, these issues are briefly reviewed in terms of how they may affect image quality at field strengths beyond 3T. The authors propose various approaches to overcoming the challenges, and discuss potential applications of ultrahigh field MR imaging as it applies to specific abdominal, pelvic, peripheral vascular, and breast imaging protocols.

On the noise correlation matrix for multiple radio frequency coils.

Noise correlation between multiple receiver coils is discussed using principles of statistical physics. Using the general fluctuation-dissipation theorem we derive the prototypic correlation formula originally determined by Redpath (Magn Res Med 1992;24:85-89), which states that correlation of current spectral noise depends on the real part of the inverse impedance matrix at a given frequency. A distinct correlation formula is also derived using the canonical partition function, which states that correlation of total current noise over the entire frequency spectrum depends on the inverse inductance matrix. The Kramers-Kronig relation is used to equate the inverse inductance matrix to the spectral integral of the inverse impedance matrix, implying that the total noise is equal to the summation of the spectral noise over the entire frequency spectrum. Previous conflicting arguments on noise correlation may be reconciled by differentiating between spectral and total noise correlation. These theoretical derivations are verified experimentally using two-coil arrays.

A transmit/receive volume strip array and its mode mixing theory in MRI.

MRI is increasingly moving towards higher magnetic field, prompting the need for multi-port transmit/receive RF coil arrays to overcome high-frequency limitations such as penetration depth and dielectric resonance effects. In this work, an arbitrary n-element transmit/receive volume strip array (VSA) and an associated mixing mode theory are described to understand the behavior of a multiple-port cyclic symmetrical VSA in both the physical port space and the complementary mode space; the relations between the two spaces are explicitly formulated. The advantage of mode-space analysis is that an arbitrary n x n impedance matrix which describes any VSA in port space can be diagonalized to a diagonal n x n matrix; thus an analytical solution of Kirchhoff's laws for the VSA becomes manageable when n is large. Based on such an analytical solution, we can (a) generate excitation profile of any desired mixed mode during transmission by manipulating external power sources without the need of physically tuning VSA to the mixed mode; (b) identify the sensitivity profiles of the complementary mode distributions during reception, which were unknown in quadrature and decoupled coils. Many predictions are rigidly verified by extensive test measurements from network analyzer and by MR imaging experiments.

Diffusional kurtosis imaging in the lung using hyperpolarized 3He.

Diseases of the small airspaces represent an increasingly important health problem. Asthma is primarily a disease of airway dysfunction, while chronic obstructive pulmonary disease (COPD) is associated with abnormalities in both the small airways and the alveoli. Conventional diffusion magnetic resonance imaging (MRI) of hyperpolarized noble gases, because of the short T(2)* of the gas, is only capable of monitoring diffusion over short times and hence only short distances. Diffusion imaging is therefore only sensitive to changes in small structures of the lung (primarily the alveoli), and will not adequately interrogate diffusion along the longitudinal axes of bronchi and bronchioles. In this communication we present a new method, termed diffusional kurtosis imaging (DKI), that is particularly sensitive to diffusion over longer distances. DKI may therefore be more sensitive to abnormalities in the bronchioles and bronchi than conventional diffusion imaging. Preliminary DKI measurements on healthy human subjects and one patient with symptoms suggestive of small airway disease are presented. Although the apparent diffusion coefficient (ADC) in the patient was similar to that in the normal controls, diffusional kurtosis was markedly reduced. This suggests that DKI measurements may be useful for assessing diseases of the small airways.

Advantages of parallel imaging in conjunction with hyperpolarized helium--a new approach to MRI of the lung.

Hyperpolarized helium (3He) gas MRI has the potential to assess pulmonary function. The non-equilibrium state of hyperpolarized 3He results in the continual depletion of the signal level over the course of excitations. Under non-equilibrium conditions the relationship between the signal-to-noise ratio (SNR) and the number of excitations significantly deviates from that established in the equilibrium state. In many circumstances the SNR increases or remains the same when the number of data acquisitions decreases. This provides a unique opportunity for performing parallel MRI in such a way that both the temporal and spatial resolution will increase without the conventional decrease in the SNR. In this study an analytical relationship between the SNR and the number of excitations for any flip angle was developed. Second, the point-spread function (PSF) was utilized to quantitatively demonstrate the unconventional SNR behavior for parallel imaging in hyperpolarized gas MRI. Third, a 24-channel (24ch) receive and two-channel (2ch) transmit phased-array system was developed to experimentally prove the theoretical predictions with 3He MRI. The in vivo experimental results prove that significant temporal resolution can be gained without the usual SNR loss in an equilibrium system, and that the entire lung can be scanned within one breath-hold (approximately 13 s) by applying parallel imaging to 3D data acquisition.

Lumped-element planar strip array (LPSA) for parallel MRI.

The recently introduced planar strip array (PSA) can significantly reduce scan times in parallel MRI by enabling the utilization of a large number of RF strip detectors that are inherently decoupled, and are tuned by adjusting the strip length to integer multiples of a quarter-wavelength (lambda/4) in the presence of a ground plane and dielectric substrate. In addition, the more explicit spatial information embedded in the phase of the signals from the strip array is advantageous (compared to loop arrays) for limiting aliasing artifacts in parallel MRI. However, losses in the detector as its natural resonance frequency approaches the Larmor frequency (where the wavelength is long at 1.5 T) may limit the signal-to-noise ratio (SNR) of the PSA. Moreover, the PSA's inherent lambda/4 structure severely limits our ability to adjust detector geometry to optimize the performance for a specific organ system, as is done with loop coils. In this study we replaced the dielectric substrate with discrete capacitors, which resulted in both SNR improvement and a tunable lumped-element PSA (LPSA) whose dimensions can be optimized within broad constraints, for a given region of interest (ROI) and MRI frequency. A detailed theoretical analysis of the LPSA is presented, including its equivalent circuit, electromagnetic fields, SNR, and g-factor maps for parallel MRI. Two different decoupling schemes for the LPSA are described. A four-element LPSA prototype was built to test the theory with quantitative measurements on images obtained with parallel and conventional acquisition schemes.

Coupling and decoupling theory and its application to the MRI phased array.

In classical MRI phased-array design, optimal coil overlapping is used to minimize coupling between nearest-neighbor coils, and low input impedance preamplifiers are used to isolate the relatively weak coupling between non-nearest neighbors. However, to make the complex sensitivities of phased-array coils sufficiently distinct in parallel spatially-encoded MRI, it is desirable to have no overlapping between coils. Also, if phased arrays are used as transmit coils in MRI, one can no longer rely on the low input impedance of the preamplifiers for decoupling. Here a coupling and decoupling theory is introduced to provide a better understanding of the relations between coupled and uncoupled signals in the MRI phased array, and to offer a new method for decoupling phased-array coils without overlapping the nearest coil pairs. The new decoupling method is based on the assumption that any n-element phased array can be decoupled by a 2n-port interface system between phased array and preamplifiers. The detailed analysis and the experimental results show that a four-port interface can be used to decouple a two-element phased array. Furthermore, the four-port interfaces can serve as building blocks to construct a 2n-port decoupling interface. This new method allows one to place the coil elements anywhere that could optimize parallel spatial encoding without concern for coupling between the coils. The method can also be used for phased-array transmit coils.

Four-angle saturation transfer (FAST) method for measuring creatine kinase reaction rates in vivo.

A new fast method of measuring kinetic reaction rates for two-site chemical exchange is described. The method employs saturation transfer magnetic resonance spectroscopy (MRS) and acquisition of only four spectra under partially saturated, high signal-to-noise ratio (SNR) conditions. In two acquisitions one of the exchanging species is saturated; the other two employ a control saturation. Each pair of acquisitions is applied with two different flip angles, and the equilibrium magnetization, relaxation times, and reaction rates are calculated therefrom. This four-angle saturation transfer (FAST) method is validated theoretically using the Bloch equations modified for two-state chemical exchange. Potential errors in the rate measurements due to the effects of exchange are evaluated for creatine kinase (CK) metabolism modeled for skeletal and heart muscle, and are found to be < 5% for forward CK flux rates of 0.05 < or = k(f) < or = 1.0 s(-1), and up to a 90% depletion of phosphocreatine (PCr). The effect of too much or too little saturating irradiation on FAST appears to be comparable to that of the conventional saturation transfer method, although the relative performance deteriorates when spillover irradiation cuts the PCr signal by 50% or more. "FASTer" and " FASTest" protocols are introduced for dynamic CK studies wherein [PCr] and/or k(f) changes. These protocols permit the omission of one or two of the four acquisitions in repeat experiments, and the missing information is recreated from initial data via a new iterative algorithm. The FAST method is validated empirically in phosphorus ((31)P) MRS studies of human calf muscle at 1.5 T. FAST measurements of 10 normal volunteers yielded the same CK reaction rates measured by the conventional method (0.29 +/- 0.06 s(-1)) in the same subjects, but an average of seven times faster. Application of the FASTer algorithm to these data correctly restored missing information within seven iterations. Finally, the FAST method was combined with 1D spatially localized (31)P MRS in a study of six volunteers, yielding the same k(f) values independent of depth, in total acquisition times of 17-39 min. These timesaving FAST methods are enabling because they permit localized measurements of metabolic flux, which were previously impractical due to intolerably long scan times.