Preprocessing of functional magnetic resonance imaging (fMRI) involves numerous steps to clean and standardize the data before statistical analysis. Generally, researchers create ad hoc preprocessing workflows for each dataset, building upon a large inventory of available tools. The complexity of these workflows has snowballed with rapid advances in acquisition and processing. We introduce fMRIPrep, an analysis-agnostic tool that addresses the challenge of robust and reproducible preprocessing for fMRI data. fMRIPrep automatically adapts a best-in-breed workflow to the idiosyncrasies of virtually any dataset, ensuring high-quality preprocessing without manual intervention. By introducing visual assessment checkpoints into an iterative integration framework for software testing, we show that fMRIPrep robustly produces high-quality results on a diverse fMRI data collection. Additionally, fMRIPrep introduces less uncontrolled spatial smoothness than observed with commonly used preprocessing tools. fMRIPrep equips neuroscientists with an easy-to-use and transparent preprocessing workflow, which can help ensure the validity of inference and the interpretability of results.

/pdf/fmriprep-a-robust-preprocessing-pipeline-for-functional-mri-1slhybkz7w.pdf

fMRIPrep: a robust preprocessing pipeline for functional MRI

Functional magnetic resonance imaging (fMRI) studies investigating the acquisition of sequential motor skills in humans have revealed learning-related functional reorganizations of the cortico-striatal and cortico-cerebellar motor systems accompanied with an initial hippocampal contribution. Yet, the functional significance of these activity-level changes remains ambiguous as they convey the evolution of both sequence-specific knowledge and unspecific task ability. Moreover, these changes do not specifically assess the occurrence of learning-related plasticity. To address these issues, we investigated local circuits tuning to sequence-specific information using multivariate distances between patterns evoked by consolidated or newly acquired motor sequences production. The results reveal that representations in dorsolateral striatum, prefrontal and secondary motor cortices are greater when executing consolidated sequences than untrained ones. By contrast, sequence representations in the hippocampus and dorsomedial striatum becomes less engaged. Our findings show, for the first time in humans, that complementary sequence-specific motor representations evolve distinctively during critical phases of skill acquisition and consolidation.

Consolidation alters motor sequence-specific distributed representations.

Preprocessing of functional MRI (fMRI) involves numerous steps to clean and standardize data before statistical analysis. Generally, researchers create ad hoc preprocessing workflows for each new dataset, building upon a large inventory of tools available for each step. The complexity of these workflows has snowballed with rapid advances in MR data acquisition and image processing techniques. We introduce fMRIPrep, an analysis-agnostic tool that addresses the challenge of robust and reproducible preprocessing for task-based and resting fMRI data. FMRIPrep automatically adapts a best-in-breed workflow to the idiosyncrasies of virtually any dataset, ensuring high-quality preprocessing with no manual intervention. By introducing visual assessment checkpoints into an iterative integration framework for software-testing, we show that fMRIPrep robustly produces high-quality results on a diverse fMRI data collection comprising participants from 54 different studies in the OpenfMRI repository. We review the distinctive features of fMRIPrep in a qualitative comparison to other preprocessing workflows. We demonstrate that fMRIPrep achieves higher spatial accuracy as it introduces less uncontrolled spatial smoothness than one commonly used preprocessing tool. FMRIPrep has the potential to transform fMRI research by equipping neuroscientists with a high-quality, robust, easy-to-use and transparent preprocessing workflow which can help ensure the validity of inference and the interpretability of their results.

/pdf/fmriprep-a-robust-preprocessing-pipeline-for-functional-mri-3hqkp1p52t.pdf

FMRIPrep: a robust preprocessing pipeline for functional MRI

https://www.cell.com/neuron/pdf/S0896-6273(15)00761-8.pdf

The Consolidation and Transformation of Memory

Strategies to therapeutically target the tumor microenvironment (TME) have emerged as a promising approach for cancer treatment in recent years due to the critical roles of the TME in regulating tumor progression and modulating response to standard-of-care therapies Here, we summarize the current knowledge regarding the most advanced TME-directed therapies, which have either been clinically approved or are currently being evaluated in trials, including immunotherapies, antiangiogenic drugs, and treatments directed against cancer-associated fibroblasts and the extracellular matrix We also discuss some of the challenges associated with TME therapies, and future perspectives in this evolving field SIGNIFICANCE: This review provides a comprehensive analysis of the current therapies targeting the TME, combining a discussion of the underlying basic biology with clinical evaluation of different therapeutic approaches, and highlighting the challenges and future perspectives

Therapeutic Targeting of the Tumor Microenvironment

The learning of sequential motor behaviors involves the integration of separate movements into a unified and coordinated sequence of actions through practice. Neuroimaging studies in humans strongly suggest that this form of procedural memory relies on the progressive reorganization of motor-related neural networks over the course of learning. This experience-driven reorganization of internal task representations is also subserved by consolidation processes that require time, and sometimes sleep, to become effective, hence constituting the mechanism by which long-term memory of the skill is achieved. In this review, we present the current understanding of the behavioral determinants, brain functional plasticity and neurophysiological processes related to the formation and long-term retention of motor sequence knowledge. Insights from clinical research and their practical implications, with the development of non-invasive and patient-oriented interventions, are also discussed.

Current issues related to motor sequence learning in humans

FMRI studies investigating the acquisition of sequential motor skills in humans have revealed learning-related functional reorganizations of the cortico-striatal and cortico-cerebellar motor systems in link with the hippocampus. Yet, the functional significance of these activity level changes is not fully understood as they convey the evolution of both sequence-specific knowledge and unspecific task expertise. Moreover, these changes do not specifically assess the occurrence of learning-related plasticity. To address these issues, we investigated local circuits tuning to sequence-specific information using multivariate distances between patterns evoked by consolidated or newly acquired motor sequences production. Results reveal that representations in dorsolateral striatum, prefrontal and secondary motor cortices are greater when executing consolidated sequences than untrained ones. By contrast, sequence representations in the hippocampus and dorsomedial striatum are less engaged. Our findings show, for the first time in humans, that complementary sequence-specific motor representations evolve distinctively during critical phases of skill acquisition and consolidation.

https://www.biorxiv.org/content/biorxiv/early/2018/07/25/376053.full.pdf

Consolidation alters motor sequence-specific distributed representations

It is not clear how the engagement of motor mnemonic processes is expressed in online brain activity. We scanned participants, using fMRI, during the paced performance of a finger-to-thumb opposition sequence FOS, intensively trained a day earlier T-FOS, and a similarly constructed, but novel, untrained FOS U-FOS. Both movement sequences were performed in pairs of blocks separated by a brief rest interval 30 sec. We have recently shown that in the primary motor cortex M1 motor memory was not expressed in the average signal intensity but rather in the across-block signal modulations, that is, when comparing the first to the second performance block across the brief rest interval. Here, using an M1 seed, we show that for the T-FOS, the M1-striatum functional connectivity decreased across blocks; however, for the U-FOS, connectivity within the M1 and between M1 and striatum increased. In addition, in M1, the pattern of within-block signal change, but not signal variability per se, reliably differentiated the two sequences. Only for the U-FOS and only within the first blocks in each pair, the signal significantly decreased. No such modulation was found within the second corresponding blocks following the brief rest interval in either FOS. We propose that a network including M1 and striatum underlies online motor working memory. This network may promote a transient integrated representation of a new movement sequence and readily retrieves a previously established movement sequence representation. Averaging over single events or blocks may not capture the dynamics of motor representations that occur over multiple timescales.

Patterns of modulation in the activity and connectivity of motor cortex during the repeated generation of movement sequences

An almost universally accepted tacit expectation is that learning and memory consolidation processes must be reflected in the average brain activity in brain areas relevant to task performance. Motor cortex (M1) plasticity has been implicated in motor skill acquisition and its consolidation. Nevertheless, no consistent pattern of changes in the average signal, related to motor learning or motor memory consolidation following a single session of training, has emerged from imaging studies. Here we show that the pattern and magnitude of short-term brain activity modulations in response to task repetition, in M1, may provide a robust signature for effective motor memory consolidation processes. We studied participants during the paced performance of a finger-to-thumb opposition sequence (FOS), intensively trained a day earlier, and a similarly constructed untrained FOS. In addition to within-session "on-line" gains, most participants expressed delayed, consolidation-phase gains in the performance of the trained FOS. The execution of the trained FOS induced repetition enhancements in the contralateral M1 and bilaterally in the medial-temporal lobes, offsetting novelty-related repetition suppression effects. Moreover, the M1 modulations were positively correlated with the magnitude of each participant's overnight delayed gains but not with absolute performance levels. Our results suggest that short-term enhancements of brain signals upon task repetition reflect the effectiveness of overnight motor memory consolidation. We propose that procedural memory consolidation processes may affect the excitation—inhibition balance within cortical representations of the trained movements; this new balance is better reflected in repetition effects than in the average level of evoked neural activity.

Ella Gabitov

Papers

Consolidation alters motor sequence-specific distributed representations.

Current issues related to motor sequence learning in humans

Consolidation alters motor sequence-specific distributed representations

Patterns of modulation in the activity and connectivity of motor cortex during the repeated generation of movement sequences

Done that: Short-term repetition related modulations of motor cortex activity as a stable signature for overnight motor memory consolidation