Voxel selection in fMRI data analysis based on sparse representation

Multivariate pattern analysis approaches toward detection of brain regions from fMRI data have been gaining attention recently. In this study, we introduce an iterative sparse-representation-based algorithm for detection of voxels in functional MRI (fMRI) data with task relevant information. In each iteration of the algorithm, a linear programming problem is solved and a sparse weight vector is subsequently obtained. The final weight vector is the mean of those obtained in all iterations. The characteristics of our algorithm are as follows: 1) the weight vector (output) is sparse; 2) the magnitude of each entry of the weight vector represents the significance of its corresponding variable or feature in a classification or regression problem; and 3) due to the convergence of this algorithm, a stable weight vector is obtained. To demonstrate the validity of our algorithm and illustrate its application, we apply the algorithm to the Pittsburgh Brain Activity Interpretation Competition 2007 functional fMRI dataset for selecting the voxels, which are the most relevant to the tasks of the subjects. Based on this dataset, the aforementioned characteristics of our algorithm are analyzed, and a comparison between our method with the univariate general-linear-model-based statistical parametric mapping is performed. Using our method, a combination of voxels are selected based on the principle of effective/sparse representation of a task. Data analysis results in this paper show that this combination of voxels is suitable for decoding tasks and demonstrate the effectiveness of our method

Optogenetic dissection of neural circuits underlying emotional valence and motivated behaviors

The neural circuits underlying emotional valence and motivated behaviors are several synapses away from both defined sensory inputs and quantifiable motor outputs. Electrophysiology has provided us with a suitable means for observing neural activity during behavior, but methods for controlling activity for the purpose of studying motivated behaviors have been inadequate: electrical stimulation lacks cellular specificity and pharmacological manipulation lacks temporal resolution. The recent emergence of optogenetic tools provides a new means for establishing causal relationships between neural activity and behavior. Optogenetics, the use of genetically-encodable light-activated proteins, permits the modulation of specific neural circuit elements with millisecond precision. The ability to control individual cell types, and even projections between distal regions, allows us to investigate functional connectivity in a causal manner. The greatest consequence of controlling neural activity with finer precision has been the characterization of individual neural circuits within anatomical brain regions as defined functional units. Within the mesolimbic dopamine system, optogenetics has helped separate subsets of dopamine neurons with distinct functions for reward, aversion and salience processing, elucidated GABA neuronal effects on behavior, and characterized connectivity with forebrain and cortical structures. Within the striatum, optogenetics has confirmed the opposing relationship between direct and indirect pathway medium spiny neurons (MSNs), in addition to characterizing the inhibition of MSNs by cholinergic interneurons. Within the hypothalamus, optogenetics has helped overcome the heterogeneity in neuronal cell-type and revealed distinct circuits mediating aggression and feeding. Within the amygdala, optogenetics has allowed the study of intra-amygdala microcircuitry as well as interconnections with distal regions involved in fear and anxiety. In this review, we will present the body of optogenetic studies that has significantly enhanced our understanding of emotional valence and motivated behaviors.Picower Institute for Learning and Memory (Innovation Fund)Whitehall Foundation (2012-08-45)Wade AwardPicower Neurological Disorder Research FundNational Science Foundation (U.S.). Graduate Research Fellowship ProgramIntegrative Neuronal Systems Center (Grant 6926328)Brain and Cognitive Sciences Special Award (1497200)Marcus Fellowship to Honor Norman B. Leventhal (3891441

Organization of Valence-Encoding and Projection-Defined Neurons in the Basolateral Amygdala

The basolateral amygdala (BLA) mediates associative learning for both fear and reward. Accumulating evidence supports the notion that different BLA projections distinctly alter motivated behavior, including projections to the nucleus accumbens (NAc), medial aspect of the central amygdala (CeM), and ventral hippocampus (vHPC). Although there is consensus regarding the existence of distinct subsets of BLA neurons encoding positive or negative valence, controversy remains regarding the anatomical arrangement of these populations. First, we map the location of more than 1,000 neurons distributed across the BLA and recorded during a Pavlovian discrimination task. Next, we determine the location of projection-defined neurons labeled with retrograde tracers and use CLARITY to reveal the axonal path in 3-dimensional space. Finally, we examine the local influence of each projection-defined populations within the BLA. Understanding the functional and topographical organization of circuits underlying valence assignment could reveal fundamental principles about emotional processing. Basolateral amygdala (BLA) neurons distinctly encode cues predicting rewards or punishments, but how does form give rise to function? Beyeler et al. overlay anatomical projection target, location of neurons in a 3D map, and encoding properties during cue discrimination. The influence on local networks differs across projection-defined BLA populations. Keywords: reward; aversion; topography; tracing; connectivity; network; channelrhodopsin; phototagging; photoexcitation; photoinhitionNational Institute of Mental Health (U.S.) (Grant R01-MH102441)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Award DP2-DK-102256

Divergent Routing of Positive and Negative Information from the Amygdala during Memory Retrieval

Although the basolateral amygdala (BLA) is known to play a critical role in the formation of memories of both positive and negative valence, the coding and routing of valence-related information is poorly understood. Here, we recorded BLA neurons during the retrieval of associative memories and used optogenetic-mediated phototagging to identify populations of neurons that synapse in the nucleus accumbens (NAc), the central amygdala (CeA), or ventral hippocampus (vHPC). We found that despite heterogeneous neural responses within each population, the proportions of BLA-NAc neurons excited by reward predictive cues and of BLA-CeA neurons excited by aversion predictive cues were higher than within the entire BLA. Although the BLA-vHPC projection is known to drive behaviors of innate negative valence, these neurons did not preferentially code for learned negative valence. Together, these findings suggest that valence encoding in the BLA is at least partially mediated via divergent activity of anatomically defined neural populations.National Institute of Mental Health (U.S.) (Grant R01-MH102441-01)National Institutes of Health (U.S.) (Grant DP2-DK-102256-01

Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment

Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock- and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLA→PL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA→PL circuit is critical in governing the selection of behavioral responses in the face of competing signals.National Institutes of Health (U.S.) (Award 1R25-MH092912-01)National Institute of Mental Health (U.S.) (Grant R01- MH102441-01)National Institutes of Health (U.S.) (Award DP2- DK-102256-01

Nature

The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different basolateral amygdala (BLA) projections are potentiated following reward or punishment learning1–7. However, we do not yet understand how valence specific information is routed to the BLA neurons with the appropriate downstream projections. Nor do we understand how to reconcile the subsecond timescales of synaptic plasticity8–11 with the longer timescales separating the predictive cues from their outcomes. Here, we demonstrate that neurotensin (NT) neurons in the paraventricular nucleus of the thalamus (PVT) projecting to the BLA (PVT-BLA:NT) mediate valence assignment by exerting concentration-dependent modulation in BLA during associative learning. We found that optogenetic activation of the PVT-BLA:NT projection promotes reward learning, while PVT-BLA projection-specific Nt gene knockout augments punishment learning. Using genetically encoded calcium and NT sensors, we further revealed that both calcium dynamics within the PVT-BLA:NT projection and NT concentrations in the BLA are enhanced after reward learning and reduced after punishment learning. Finally, we showed that CRISPR-mediated knockout of the Nt gene in the PVT-BLA pathway blunts BLA neural dynamics and attenuates the preference to active behavioral strategies to reward and punishment predictive cues. Taken together, we have identified NT as a neuropeptide that signals valence in the BLA, and showed that NT is a critical neuromodulator that orchestrates positive and negative valence assignment in amygdala neurons by extending valence-specific plasticity to behaviorally-relevant timescales

BLA circuits for differentiating positive and negative associations

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2016.Cataloged from PDF version of thesis.Includes bibliographical references (pages 201-215).The ability to differentiate between rewarding and threatening stimuli, and engaging the appropriate behavioral response is critical for survival. The Basolateral Amygdala (BLA) is an almond shaped structure in the brain where rewarding and fearful associations are encoded by different populations of neurons. However, identifying features of these populations have remained an enigma. My thesis work shows that populations of BLA neurons that differ in their long range anatomical connectivity play opposing roles in the acquisition of positive and negative associations, and dissects a mechanism by which these associations are encoded in the BLA. We show that BLA neurons projecting to the nucleus accumbens (NAc) and BLA neurons projecting to the centromedial nucleus of the amygdala (CeM) undergo opposing changes at their input synapses after rewarding and fearful associations. We then establish the in vivo ramifications of these opposing changes in synaptic strength in response to rewarding and fearful associations by assaying neural activity from BLA neurons and identifying the NAc and CeM projectors. Finally, in order to compare and contrast the role of BLA neural populations in encoding positive and negative associations, we propose a model that parametrizes neural responses to positive and negative cues from large scale electrophysiological recordings. My thesis work identifies functional roles of specific circuit components based on their long range anatomical connectivity, identifies differentially expressed receptors within these circuit components and provides a mechanistic explanation, on synaptic, cellular, circuit and molecular levels, for how positive and negative associations can be formed within, and diverge from the BLA.by Praneeth Namburi.Ph. D

Respiratory Inductance Plethysmography to Assess Fatigability during Repetitive Work

This work was supported by Project OPERATOR (NORTE01-0247-FEDER-045910), cofinanced by the ERDF—European Regional Development Fund through the North Portugal Regional Operational Program and Lisbon Regional Operational Program and by the Portuguese Foundation for Science and Technology, under the MIT Portugal Program (2019 Open Call for Flagship projects). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Cumulative fatigue during repetitive work is associated with occupational risk and productivity reduction. Usually, subjective measures or muscle activity are used for a cumulative evaluation; however, Industry 4.0 wearables allow overcoming the challenges observed in those methods. Thus, the aim of this study is to analyze alterations in respiratory inductance plethysmography (RIP) to measure the asynchrony between thorax and abdomen walls during repetitive work and its relationship with local fatigue. A total of 22 healthy participants (age: 27.0 ± 8.3 yrs; height: 1.72 ± 0.09 m; mass: 63.4 ± 12.9 kg) were recruited to perform a task that includes grabbing, moving, and placing a box in an upper and lower shelf. This task was repeated for 10 min in three trials with a fatigue protocol between them. Significant main effects were found from Baseline trial to the Fatigue trials (p < 0.001) for both RIP correlation and phase synchrony. Similar results were found for the activation amplitude of agonist muscle (p < 0.001), and to the muscle acting mainly as a joint stabilizer (p < 0.001). The latter showed a significant effect in predicting both RIP correlation and phase synchronization. Both RIP correlation and phase synchronization can be used for an overall fatigue assessment during repetitive work.publishersversionpublishe

Dopamine enhances signal-to-noise ratio in cortical-brainstem encoding of aversive stimuli

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