Articles

by Olga Dal Monte, Cheng C. J. Chu, Nicholas A. Fagan and Steve W. C. Chang in Nature Neuroscience

A study published in Nature Neuroscience finds that highly specialized coordination between the amygdala and medial prefrontal cortex in the brain promotes prosocial, compared to antisocial, decisions

Social behaviors recruit multiple cognitive operations that require interactions between cortical and subcortical brain regions. Interareal synchrony may facilitate such interactions between cortical and subcortical neural populations. However, it remains unknown how neurons from different nodes in the social brain network interact during social decision-making. Here the authors investigated oscillatory neuronal interactions between the basolateral amygdala and the rostral anterior cingulate gyrus of the medial prefrontal cortex while monkeys expressed context-dependent positive or negative other-regarding preference (ORP), whereby decisions affected the reward received by another monkey. Synchronization between the two nodes was enhanced for a positive ORP but suppressed for a negative ORP. These interactions occurred in beta and gamma frequency bands depending on the area contributing the spikes, exhibited a specific directionality of information flow associated with a positive ORP and could be used to decode social decisions. These findings suggest that specialized coordination in the medial prefrontal–amyg-dala network underlies social-decision preferences.

by Evelina Sjöstedt, Wen Zhong, Linn Fagerberg, Max Karlsson, Nicholas Mitsios, Csaba Adori, Per Oksvold, Fredrik Edfors, Agnieszka Limiszewska, Feria Hikmet, Jinrong Huang, Yutao Du, Lin Lin at al. in Science

An international team of scientists has launched a comprehensive overview of all proteins expressed in the brain, published in Science

The diverse physiology of the brain is reflected in its complex organization at regional, cellular, and subcellular levels. Sjöstedt et al. combined data — both newly acquired and from other large-scale brain mapping projects — from transcriptomics, single-cell genomics, in situ hybridization, and antibody-based protein profiling to map the molecular profiles in human, pig, and mouse brain. The analysis is consistent with a conserved basic brain architecture during mammalian evolution, but it does show differences in regional gene expression profiles.

Genome-wide transcriptomics analysis of anatomically dissected regions in mammalian brains uncovers regional and species-specific expression.

Multiple regions of the human, pig, and mouse brain were dissected and analyzed. A uniform manifold approximation and projection (UMAP) analysis (middle) shows the global expression patterns of 1710 samples in the human brain, with the cerebellum as the outlier. The HPA Brain Atlas (right) shows the expression of individual genes, for example, synaptosomal-associated protein 25 (SNAP25), in the different brain regions in the three mammalian species.

Alexantrou Serb, Andrea Corna, Richard George, Ali Khiat, Federico Rocchi, Marco Reato, Marta Maschietto, Christian Mayr, Giacomo Indiveri, Stefano Vassanelli & Themistoklis Prodromakis in Nature Scientific Reports

Research on novel nanoelectronics devices has enabled brain neurons and artificial neurons to communicate with each other

Brain function relies on circuits of spiking neurons with synapses playing the key role of merging transmission with memory storage and processing. Electronics has made important advances to emulate neurons and synapses and brain-computer interfacing concepts that interlink brain and brain-inspired devices are beginning to materialise. The authors report on memristive links between brain and silicon spiking neurons that emulate transmission and plasticity properties of real synapses. A memristor paired with a metal-thin film titanium oxide microelectrode connects a silicon neuron to a neuron of the rat hippocampus. Memristive plasticity accounts for modulation of connection strength, while transmission is mediated by weighted stimuli through the thin film oxide leading to responses that resemble excitatory postsynaptic potentials. The reverse brain-to-silicon link is established through a microelectrode-memristor pair. On these bases, they demonstrate a three-neuron brain-silicon network where memristive synapses undergo long-term potentiation or depression driven by neuronal firing rates.

by Emily Cowan, Anli Liu, Simon Henin, Sanjeev Kothare, Orrin Devinsky and Lila Davachi in Journal of Neuroscience

Sleep spindles affect the way memories are represented after sleep and may be a physiological mechanism supporting integration of memories via hippocampal-cortical connectivity, according to new JNeurosci research

How new experiences are transformed into long-term memories remains a fundamental question for neuroscience research. Theories suggest that memories are stabilized as they are reorganized in the brain, a process thought to be supported by sleep oscillations, particularly sleep spindles. Although sleep spindles have been associated with benefits in memory retention, it is not well understood how spindles modify neural memory traces. This study found that spindles during overnight sleep correlate with changes in neural memory traces, including enhanced functional connectivity in distinct hippocampal–cortical networks and increased pattern similarity among memories in the cortex. The results provide critical evidence that spindles during overnight sleep may act as a physiological mechanism for the restructuring of neural memory traces.

by Ella Bar, Anat Arzi, Ofer Perl, Ethan Livne, Noam Sobel, Yadin Dudai, Yuval Nir

A new study suggests that the process in the brain that uses smell can strengthen memories stored in one side of the brain

Memory consolidation can be promoted via Targeted Memory Reactivation (TMR) that re-presents training cues or context during sleep. Whether TMR acts locally or globally on cortical sleep oscillations remains unknown. The authors exploit the unique functional neuroanatomy of olfaction with its ipsilateral stimulus processing to perform local TMR in one brain hemisphere. Participants learned associations between words and locations in left or right visual fields with contextual odor throughout. During post-learning naps, odors were presented to one nostril throughout NREM sleep. We found improved memory for specific words processed in the cued hemisphere (ipsilateral to stimulated nostril). Unilateral odor cues locally modulated slow wave activity (SWA) such that regional SWA increase in the cued hemisphere negatively correlated with select memories for cued words. Moreover, local TMR improved slow wave-spindle coupling specifically in the cued hemisphere. Thus, TMR in human sleep transcends global action by selectively promoting specific memories associated with local sleep oscillations.

by Alex P. Vaz, John H. Wittig Jr., Sara K. Inati, Kareem A. Zaghloul in Science

Our brains use distinct firing patterns to store and replay memories

Animal studies suggest that sequence replay of neuronal activity may underlie memory retrieval and consolidation. However, there is no direct evidence that the replay of spiking activity sequences is important for these processes in the human brain. Vaz et al. simultaneously recorded single-unit spikes, local field potential, and intracranial electroencephalography signals in the brain while participants performed a memory task. Sharp wave ripple oscillations in the temporal lobe cortex reflected bursts of neural spiking, and these bursts of spikes organized into sequences during memory formation. These sequences were replayed during successful memory retrieval. The extent of sequence replay during correct recall was related to the extent to which cortical spiking activity was coupled with ripples in the medial temporal lobe.

by Stefano Espinoza, Ilya Sukhanov, Evgeniya V. Efimova, Alena Kozlova, Kristina A. Antonova, Placido Illiano, Damiana Leo, Natalia Merkulyeva, Daria Kalinina. et al.

Researchers discover a role in the emotional brain for neurotransmitter

Trace amine-associated receptors (TAARs) are a class of G-protein-coupled receptors found in mammals. While TAAR1 is expressed in several brain regions, all the other TAARs have been described mainly in the olfactory epithelium and the glomerular layer of the olfactory bulb and are believed to serve as a new class of olfactory receptors sensing innate odors. However, there is evidence that TAAR5 could play a role also in the central nervous system. In this study, the authors characterized a mouse line lacking TAAR5 (TAAR5 knockout, TAAR5-KO) expressing beta-galactosidase mapping TAAR5 expression. They found that TAAR5 is expressed not only in the glomerular layer in the olfactory bulb but also in deeper layers projecting to the limbic brain olfactory circuitry with prominent expression in numerous limbic brain regions, such as the anterior olfactory nucleus, the olfactory tubercle, the orbitofrontal cortex (OFC), the amygdala, the hippocampus, the piriform cortex, the entorhinal cortex, the nucleus accumbens, and the thalamic and hypothalamic nuclei. TAAR5-KO mice did not show gross developmental abnormalities but demonstrated less anxiety- and depressive-like behavior in several behavioral tests. TAAR5-KO mice also showed significant decreases in the tissue levels of serotonin and its metabolite in several brain areas and were more sensitive to the hypothermic action of serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propilamino)tetralin (8-OH-DPAT). These observations indicate that TAAR5 is not just innate odor-sensing olfactory receptor but also serves to provide olfactory input into limbic brain areas to regulate emotional behaviors likely via modulation of the serotonin system. Thus, anxiolytic and/or antidepressant action of future TAAR5 antagonists could be predicted. In general, “olfactory” TAAR-mediated brain circuitry may represent a previously unappreciated neurotransmitter system involved in the transmission of innate odors into emotional behavioral responses.

by Christopher S. Morrow, Tiaira J. Porter, Nan Xu, Zachary P. Arndt, Kayla Ako-Asare, Helen J. Heo, Elizabeth A.N.Thompson, Darcie L.Moore

Scientists have revealed how a cellular filament helps neural stem cells clear damaged and clumped proteins, an important step in producing new neurons

Maintaining a healthy proteome throughout life is critical for proper somatic stem cell function, but the complexities of the stem cell response to increases in damaged or aggregated proteins remain unclear. The authors demonstrate that adult neural stem cells (NSCs) utilize aggresomes to recover from disrupted proteostasis and describe a novel function for the intermediate filament vimentin in proteostasis as a spatial coordinator of proteasomes to the aggresome. In the absence of vimentin, NSCs have a reduced capacity to exit quiescence, a time when NSCs are required to clear a wave of aggregated proteins, and demonstrate an early age-dependent decline in proliferation and neurogenesis. Taken together, these data reveal a significant role of vimentin and aggresomes in the regulation of proteostasis during quiescent NSC activation.

by Siugzdaite R., Bathelt J., Holmes J., Astle D.E.

Different learning difficulties do not correspond to specific regions of the brain, as previously thought, say researchers at the University of Cambridge

Childhood learning difficulties and developmental disorders are common, but progress toward understanding their underlying brain mechanisms has been slow. Structural neuroimaging, cognitive, and learning data were collected from 479 children (299 boys, ranging in age from 62 to 223 months), 337 of whom had been referred to the study on the basis of learning-related cognitive problems. Machine learning identified different cognitive profiles within the sample, and hold-out cross-validation showed that these profiles were significantly associated with children’s learning ability. The same machine learning approach was applied to cortical morphology data to identify different brain profiles. Hold-out cross-validation demonstrated that these were significantly associated with children’s cognitive profiles. Crucially, these mappings were not one-to-one. The same neural profile could be associated with different cognitive impairments across different children. One possibility is that the organization of some children’s brains is less susceptible to local deficits. This was tested by using diffusion-weighted imaging (DWI) to construct whole-brain white-matter connectomes. A simulated attack on each child’s connectome revealed that some brain networks were strongly organized around highly connected hubs. Children with these networks had only selective cognitive impairments or no cognitive impairments at all. By contrast, the same attacks had a significantly different impact on some children’s networks, because their brain efficiency was less critically dependent on hubs. These children had the most widespread and severe cognitive impairments. On this basis, the authors propose a new framework in which the nature and mechanisms of brain-to-cognition relationships are moderated by the organizational context of the overall network.

by Julen Hernandez-Lallement, Augustine Triumph Attah, Efe Soyman, Cindy M. Pinhal, Valeria Gazzola, Christian Keysers in Current Biology

Rats avoid to hurt other rats: findings shed light on human empathy disorders

Empathy, the ability to share another individual’s emotional state and/or experience, has been suggested to be a source of prosocial motivation by attributing negative value to actions that harm others. The neural underpinnings and evolution of such harm aversion remain poorly understood. The authors characterize an animal model of harm aversion in which a rat can choose between two levers providing equal amounts of food but one additionally delivering a footshock to a neighboring rat. They find that independently of sex and familiarity, rats reduce their usage of the preferred lever when it causes harm to a conspecific, displaying an individually varying degree of harm aversion. Prior experience with pain increases this effect. In additional experiments, they show that rats reduce the usage of the harm-inducing lever when it delivers twice, but not thrice, the number of pellets than the no-harm lever, setting boundaries on the magnitude of harm aversion. Finally, they show that pharmacological deactivation of the anterior cingulate cortex, a region the authors have shown to be essential for emotional contagion, reduces harm aversion while leaving behavioral flexibility unaffected. This model of harm aversion might help shed light onto the neural basis of psychiatric disorders characterized by reduced harm aversion, including psychopathy and conduct disorders with reduced empathy, and provides an assay for the development of pharmacological treatments of such disorders.

Check out the video abstract here.

by Yohsuke R. Miyamoto, Shengxin Wang & Maurice A. Smith in Nature Neuroscience

Implicit learning increases the fidelity of performance during motor learning by acting to adaptively clean up the noise resulting from low-fidelity explicit strategy

Sports are replete with strategies, yet coaching lore often emphasizes ‘quieting the mind’, ‘trusting the body’ and ‘avoiding overthinking’ in referring to the importance of relying less on high-level explicit strategies in favor of low-level implicit motor learning. The authors investigated the interactions between explicit strategy and implicit motor adaptation by designing a sensorimotor learning paradigm that drives adaptive changes in some dimensions but not others. They find that strategy and implicit adaptation synergize in driven dimensions, but effectively cancel each other in undriven dimensions. Independent analyses — based on time lags, the correlational structure in the data and computational modeling — demonstrate that this cancellation occurs because implicit adaptation effectively compensates for noise in explicit strategy rather than the converse, acting to clean up the motor noise resulting from low-fidelity explicit strategy during motor learning. These results provide new insight into why implicit learning increasingly takes over from explicit strategy as skill learning proceeds.

Also, check out the News & Views, Aiming for stable control

by Xiang Zhou, Shalaka Wahane, Marie-Sophie Friedl, Michael Kluge, Caroline C. Friedel, Kleopatra Avrampou, Venetia Zachariou, Lei Guo, Bin Zhang, Xijing He, Roland H. Friedel & Hongyan Zou in Nature Neuroscience

Researchers identify protein critical for wound healing after spinal cord injury

Tissue repair after spinal cord injury requires the mobilization of immune and glial cells to form a protective barrier that seals the wound and facilitates debris clearing, inflammatory containment and matrix compaction. This process involves corralling, wherein phagocytic immune cells become confined to the necrotic core, which is surrounded by an astrocytic border. Here we elucidate a temporally distinct gene signature in injury-activated microglia and macrophages (IAMs) that engages axon guidance pathways. Plexin-B2 is upregulated in IAMs and is required for motor sensory recovery after spinal cord injury. Plexin-B2 deletion in myeloid cells impairs corralling, leading to diffuse tissue damage, inflammatory spillover and hampered axon regeneration. Corralling begins early and requires Plexin-B2 in both microglia and macrophages. Mechanistically, Plexin-B2 promotes microglia motility, steers IAMs away from colliding cells and facilitates matrix compaction. The data therefore establish Plexin-B2 as an important link that integrates biochemical cues and physical interactions of IAMs with the injury microenvironment during wound healing.

by Chloé Berland, Enrica Montalban, Elodie Perrin, Mathieu Di Miceli, Yuko Nakamura, Maud Martinat, Mary Sullivan, et al.

Researchers have uncovered how fatty nutrients act on the brain in the reward circuit, providing insight into the connection between food and eating disorders

Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote reward dysfunctions, compulsive feeding, and weight gain. Yet the mechanisms by which nutrients influence the MCL circuitry remain elusive. The authors show that nutritional triglycerides (TGs), a conserved post-prandial metabolic signature among mammals, can be metabolized within the MCL system and modulate DA-associated behaviors by gating the activity of dopamine receptor subtype 2 (DRD2)-expressing neurons through a mechanism that involves the action of the lipoprotein lipase (LPL). Further, they show that in humans, post-prandial TG excursions modulate brain responses to food cues in individuals carrying a genetic risk for reduced DRD2 signaling. Collectively, these findings unveil a novel mechanism by which dietary TGs directly alter signaling in the reward circuit to regulate behavior, thereby providing a new mechanistic basis by which energy-rich diets may lead to (mal)adaptations in DA signaling that underlie reward deficit and compulsive behavior.

by Sufyan Ashhad and Jack L. Feldman in Neuron

Disordered neurons make every breath we take unique

The authors assessed the mechanism of mammalian breathing rhythmogenesis in the preBötzinger complex (preBötC) in vitro, where experimental tests remain inconsistent with hypotheses of canonical rhythmogenic cellular or synaptic mechanisms, i.e., pacemaker neurons or inhibition. Under rhythmic conditions, in each cycle, an inspiratory burst emerges as (presumptive) preBötC rhythmogenic neurons transition from aperiodic uncorrelated population spike activity to become increasingly synchronized during preinspiration (for ∼50–500 ms), which can trigger inspiratory bursts that propagate to motoneurons. In nonrhythmic conditions, antagonizing GABAA receptors can initiate this synchronization while inducing a higher conductance state in nonrhythmogenic preBötC output neurons. The analyses uncover salient features of preBötC network dynamics where inspiratory bursts arise when and only when the preBötC rhythmogenic subpopulation strongly synchronizes to drive output neurons. Furthermore, downstream propagation of preBötC network activity, ultimately to motoneurons, is dependent on the strength of input synchrony onto preBötC output neurons exemplifying synchronous propagation of network activity.

by Abhishek Parija, Joseph V. Handy, Justin L. Andrews, Jinpeng Wu, Linda Wangoh, Sujay Singh, Chris Jozwiak, Aaron Bostwick, Eli Rotenberg, Wanli Yang, Sirine C. Fakra, Mohammed Al-Hashimi, et al.

Chameleon-like material could enable brain-like computing

Silicon circuitry has dominated the semiconductor industry for decades but is constrained in its power efficiency by the Fermi-Dirac distribution of electron energies. Electron-correlated transition metal oxides exhibiting metal-to-insulator transitions (MITs) are excellent candidates for energy-efficient computation, which can further emulate the spiking behavior of biological neural circuitry. Researchers demonstrate that β′-CuxV2O5 exhibits a pronounced nonlinear response to applied temperature, voltage, and current, and the response can be modulated as a function of Cu stoichiometry. They show that polaron oscillation, coupled to the real-space shuttling of Cu ions across two adjacent sites, underpins the MIT of this material. These results reveal the interplay between crystal structure distortions and electron correlation in underpinning the metal-insulator transition of a strongly correlated system. The utilization of coupled cation diffusion and polaron oscillation further demonstrates a means of using ionic vectors to obtain highly nonlinear conductance switching as required for neuromorphic computing.

by Julia V. Sopova, Elena I. Koshel, Tatiana A. Belashova, Sergey P. Zadorsky, Alexandra V. Sergeeva, Vera A. Siniukova, Alexandr A. Shenfeld, Maria E. Velizhanina, Kirill V. Volkov, Anton A. Nizhnikov, Daniel V. Kachkin, Elena R. Gaginskaya & Alexey P. Galkin in Nature

Researchers at the Department of Genetics and Biotechnology of St Petersburg University have discovered a functioning amyloid in a healthy brain

Amyloids are β-sheets-rich protein fibrils that cause neurodegenerative and other incurable human diseases affecting millions of people worldwide. However, a number of proteins is functional in the amyloid state in various organisms from bacteria to humans. Using an original proteomic approach, the authors identified a set of proteins forming amyloid-like aggregates in the brain of young healthy rats. One of them is the FXR1 protein, which is known to regulate memory and emotions. They showed that FXR1 clearly colocalizes in cortical neurons with amyloid-specific dyes Congo-Red, Thioflavines S and T. FXR1 extracted from brain by immunoprecipitation shows yellow-green birefringence after staining with Congo red. This protein forms in brain detergent-resistant amyloid oligomers and insoluble aggregates. RNA molecules that are colocalized with FXR1 in cortical neurons are insensitive to treatment with RNase A. All these data suggest that FXR1 functions in rat brain in amyloid form. The N-terminal amyloid-forming fragment of FXR1 is highly conserved across mammals. They assume that the FXR1 protein may be presented in amyloid form in brain of different species of mammals, including humans.

by D. A. Martins, N. Mazibuko, F. Zelaya, S. Vasilakopoulou, J. Loveridge, A. Oates, S. Maltezos, M. Mehta, S. Wastling, M. Howard, G. McAlonan, D. Murphy, S. C. R. Williams, A. Fotopoulou, U. Schuschnig & Y. Paloyelis in Nature

New research has given insight into how oxytocin could be administered in a more targeted and effective way to help treat social problems occurring in a range of psychiatric disorders

Could nose-to-brain pathways mediate the effects of peptides such as oxytocin (OT) on brain physiology when delivered intranasally? The authors address this question by contrasting two methods of intranasal administration (a standard nasal spray, and a nebulizer expected to improve OT deposition in nasal areas putatively involved in direct nose-to-brain transport) to intravenous administration in terms of effects on regional cerebral blood flow during two hours post-dosing. They demonstrate that OT-induced decreases in amygdala perfusion, a key hub of the OT central circuitry, are explained entirely by OT increases in systemic circulation following both intranasal and intravenous OT administration. Yet they also provide robust evidence confirming the validity of the intranasal route to target specific brain regions. Their work has important translational implications and demonstrates the need to carefully consider the method of administration in the efforts to engage specific central oxytocinergic targets for the treatment of neuropsychiatric disorders.

by Xiaochun Han, Michele J Gelfand, Bing Wu, Ting Zhang, Wenxin Li, Tianyu Gao, Chenyu Pang, Taoyu Wu, Yuqing Zhou, Shuai Zhou, et al.

Researchers discover that oxytocin is responsible for revenge

Revenge during intergroup conflict is a human universal, but its neurobiological underpinnings remain unclear. We address this by integrating functional MRI and measurements of endogenous oxytocin in participants who view an ingroup and an outgroup member’s suffering that is caused mutually (Revenge group) or by a computer (Control group). We show that intergroup conflict encountered by the Revenge group is associated with an increased level of oxytocin in saliva compared to that in the Control group. Furthermore, the medial prefrontal activity in response to ingroup pain in the Revenge group but not in the Control group mediates the association between endogenous oxytocin and the propensity to give painful electric shocks to outgroup members, regardless of whether they were directly involved in the conflict. Our findings highlight an important neurobiological correlate of revenge propensity, which may be implicated in conflict contagion across individuals in the context of intergroup conflict.

Experimental procedure and behavioral results.

(A) Experimental procedure. Phase 1 assigned four participants and two confederates into two groups who played a game to create group affiliation. In Phase two, the experimenter (in a grey T-shirt) introduced a participant (in a red T-shirt facing the experimenter) to witness a conflict between an ingroup member and an outgroup member (both played by the confederates) who played a competitive game. During fMRI scanning (Phase 3), the participant witnessed ingroup and outgroup members who were directly involved or uninvolved in conflict. Saliva was collected at three points in time. (B) Trial structure during fMRI scanning. An ID-photo of Involved_Ingroup or Involved_Outgroup target indicated the loser of the game and the participant had to judge his group identity. A yellow circle or lightning symbol then indicated a non-painful or painful shock. After a fixation, a photo of the loser’s face with a painful or neutral expression was displayed to indicate that he was experiencing a painful or non-painful shock. When ID-photos of uninvolved targets were presented, the participant also judged their group identities and passively viewed a following photo of the target with neutral or painful expression.

by View ORCID ProfileFrederik S. Kamps, Cassandra L. Hendrix, Patricia A. Brennan, and Daniel D. Dilks

New research suggests that at as young as six days old, a baby’s brain appears hardwired for the specialized tasks of seeing faces and places

It is well established that the adult brain contains a mosaic of domain-specific networks. But how do these domain-specific networks develop? The authors tested the hypothesis that the brain comes prewired with connections that precede the development of domain-specific function. Using resting-state fMRI in the youngest sample of newborn humans tested to date, they indeed found that cortical networks that will later develop strong face selectivity (including the “proto” occipital face area and fusiform face area) and scene selectivity (including the “proto” parahippocampal place area and retrosplenial complex) by adulthood, already show domain-specific patterns of functional connectivity as early as 27 d of age (beginning as early as 6 d of age). Furthermore, they asked how these networks are functionally connected to early visual cortex and found that the proto face network shows biased functional connectivity with foveal V1, while the proto scene network shows biased functional connectivity with peripheral V1. Given that faces are almost always experienced at the fovea, while scenes always extend across the entire periphery, these differential inputs may serve to facilitate domain-specific processing in each network after that function develops, or even guide the development of domain-specific function in each network in the first place. Taken together, these findings reveal domain-specific and eccentricity-biased connectivity in the earliest days of life, placing new constraints on our understanding of the origins of domain-specific cortical networks.

by Adam C. G. Crego, Fabián Štoček, Alec G. Marchuk, James E. Carmichael, Matthijs A. A. van der Meer and Kyle S. Smith in Journal of Neuroscience

A new study demonstrates how habits can be controlled depending on how active a specific region of the brain, the dorsolateral striatum, is

Despite clear evidence linking the basal ganglia to the control of outcome insensitivity (i.e., habit) and behavioral vigor (i.e., its behavioral speed/fluidity), it remains unclear whether or how these functions relate to one another. Here, using male Long–Evans rats in response-based and cue-based maze-running tasks, the authors demonstrate that phasic dorsolateral striatum (DLS) activity occurring at the onset of a learned behavior regulates how vigorous and habitual it is. In a response-based task, brief optogenetic excitation at the onset of runs decreased run duration and the occurrence of deliberative behaviors, whereas midrun stimulation carried little effect. Outcome devaluation showed these runs to be habitual. DLS inhibition at run start did not produce robust effects on behavior until after outcome devaluation. At that time, when the DLS was plausibly most critically required for performance (i.e., habitual), inhibition reduced performance vigor measures and caused a dramatic loss of habitual responding (i.e., animals quit the task). In a second cue-based “beacon” task requiring behavior initiation at the start of the run and again in the middle of the run, DLS excitation at both time points could improve the vigor of runs. Postdevaluation testing showed behavior on the beacon task to be habitual as well. This pattern of results suggests that one role for phasic DLS activity at behavior initiation is to promote the execution of the behavior in a vigorous and habitual fashion by a diverse set of measures.

The research expands the literature twofold. First, they find that features of a habitual behavior that are typically studied separately (i.e., maze response performance, deliberation movements, running vigor, and outcome insensitivity) are quite closely linked together. Second, efforts have been made to understand “what” the dorsolateral striatum (DLS) does for habitual behavior, and the research provides a key set of results showing “when” it is important (i.e., at behavior initiation). By showing such dramatic control over habits by DLS activity in a phasic time window, plausible real-world applications could involve more informed DLS perturbations to curb intractably problematic habits.

by Qian Chen, Christopher A. Deister, Xian Gao, Baolin Guo, Taylor Lynn-Jones, Naiyan Chen, Michael F. Wells, Runpeng Liu, Michael J. Goard, Jordane Dimidschstein, Shijing Feng, Yiwu Shi, Weiping Liao, Zhonghua Lu, Gord Fishell, Christopher I. Moore & Guoping Feng in Nature Neuroscience

A new study may explain why people with autism are often highly sensitive to light and noise

Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B−/− mouse model of ASD. Male and female Shank3B−/− mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task. In vivo population calcium imaging in vibrissa primary somatosensory cortex (vS1) revealed increased spontaneous and stimulus-evoked firing in pyramidal neurons but reduced activity in interneurons. Preferential deletion of Shank3 in vS1 inhibitory interneurons led to pyramidal neuron hyperactivity and increased stimulus sensitivity in the vibrissa motion detection task. These findings provide evidence that cortical GABAergic interneuron dysfunction plays a key role in sensory hyper-reactivity in a Shank3 mouse model of ASD and identify a potential cellular target for exploring therapeutic interventions.

by Philippe Albouy, Lucas Benjamin, Benjamin Morillon, Robert J. Zatorre in Science

A capella shows how the brain processes speech and music

To what extent does the perception of speech and music depend on different mechanisms in the human brain? What is the anatomical basis underlying this specialization? Albouy et al. created a corpus of a cappella songs that contain both speech (semantic) and music (melodic) information and degraded each stimulus selectively in either the temporal or spectral domain. Degradation of temporal information impaired speech recognition but not melody recognition, whereas degradation of spectral information impaired melody recognition but not speech recognition. Brain scanning revealed a right-left asymmetry for speech and music. Classification of speech content occurred exclusively in the left auditory cortex, whereas classification of melodic content occurred only in the right auditory cortex.

by Narayan Sankaran, Thomas A. Carlson and William Forde Thompson in Journal of Neuroscience

In tonal music, continuous acoustic waveforms are mapped onto discrete, hierarchically arranged, internal representations of pitch. To examine the neural dynamics underlying this transformation, researchers presented listeners with tones embedded within a Western tonal context while recording their cortical activity using magnetoencephalography

Machine learning classifiers were then trained to decode different tones from their underlying neural activation patterns at each peristimulus time sample, providing a dynamic measure of their dissimilarity in cortex. Comparing the time-varying dissimilarity between tones with the predictions of acoustic and perceptual models, they observed a temporal evolution in the brain’s representational structure. Whereas initial dissimilarities mirrored their fundamental-frequency separation, dissimilarities beyond 200 ms reflected the perceptual status of each tone within the tonal hierarchy of Western music. These effects occurred regardless of stimulus regularities within the context or whether listeners were engaged in a task requiring explicit pitch analysis. Lastly, patterns of cortical activity that discriminated between tones became increasingly stable in time as the information coded by those patterns transitioned from low-to-high level properties. Current results reveal the dynamics with which the complex perceptual structure of Western tonal music emerges in cortex at the timescale of an individual tone.

by Rebecca Sims, Matthew Hill & Julie Williams in Nature Neuroscience

A review on a multiplex model of the genetics of Alzheimer’s disease

Genes play a strong role in Alzheimer’s disease (AD), with late-onset AD showing heritability of 58–79% and early-onset AD showing over 90%. Genetic association provides a robust platform to build our understanding of the etiology of this complex disease. Over 50 loci are now implicated for AD, suggesting that AD is a disease of multiple components, as supported by pathway analyses (immunity, endocytosis, cholesterol transport, ubiquitination, amyloid-β and tau processing). Over 50% of late-onset AD heritability has been captured, allowing researchers to calculate the accumulation of AD genetic risk through polygenic risk scores. A polygenic risk score predicts disease with up to 90% accuracy and is an exciting tool in our research armory that could allow selection of those with high polygenic risk scores for clinical trials and precision medicine. It could also allow cellular modelling of the combined risk. Here the authors propose the multiplex model as a new perspective from which to understand AD. The multiplex model reflects the combination of some, or all, of these model components (genetic and environmental), in a tissue-specific manner, to trigger or sustain a disease cascade, which ultimately results in the cell and synaptic loss observed in AD.

Elisabeth H. Thijssen, Renaud La Joie, Amy Wolf, Amelia Strom, Ping Wang, Leonardo Iaccarino, Viktoriya Bourakova, Yann Cobigo, Hilary Heuer, Salvatore Spina, Lawren VandeVrede, Xiyun Chai, Nicholas K. Proctor et al. in Nature

Researchers report an advance in the development of a blood test that could help detect pathological Alzheimer’s disease in people who are showing signs of dementia

With the potential development of new disease-modifying Alzheimer’s disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment. A blood-based test for AD would be a less invasive and less expensive screening tool than the currently approved cerebrospinal fluid or amyloid β positron emission tomography (PET) diagnostic tests. Researchers examined whether plasma tau phosphorylated at residue 181 (pTau181) could differentiate between clinically diagnosed or autopsy-confirmed AD and frontotemporal lobar degeneration. Plasma pTau181 concentrations were increased by 3.5-fold in AD compared to controls and differentiated AD from both clinically diagnosed (receiver operating characteristic area under the curve of 0.894) and autopsy-confirmed frontotemporal lobar degeneration (area under the curve of 0.878). Plasma pTau181 identified individuals who were amyloid β-PET-positive regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by 18F-flortaucipir PET. Plasma pTau181 may be useful to screen for tau pathology associated with AD.

by Ji Hyun Kim, Ickhee Kim, Young-Joon Seol, In Kap Ko, James J. Yoo, Anthony Atala & Sang Jin Lee in Nature Communications

Scientists have developed a tissue engineering technique for skeletal muscles which better integrates neural cells into the bioprinted tissues

A bioengineered skeletal muscle construct that mimics structural and functional characteristics of native skeletal muscle is a promising therapeutic option to treat extensive muscle defect injuries. The authors previously showed that bioprinted human skeletal muscle constructs were able to form multi-layered bundles with aligned myofibers. In this study, they investigate the effects of neural cell integration into the bioprinted skeletal muscle construct to accelerate functional muscle regeneration in vivo. Neural input into this bioprinted skeletal muscle construct shows the improvement of myofiber formation, long-term survival, and neuromuscular junction formation in vitro. More importantly, the bioprinted constructs with neural cell integration facilitate rapid innervation and mature into organized muscle tissue that restores normal muscle weight and function in a rodent model of muscle defect injury. These results suggest that the 3D bioprinted human neural-skeletal muscle constructs can be rapidly integrated with the host neural network, resulting in accelerated muscle function restoration.

by Joana R. A. Loureiro Amber Leaver Megha Vasavada Ashish K. Sahib Antoni Kubicki Shantanu Joshi Roger P. Woods Benjamin Wade Eliza Congdon Randall Espinoza Katherine L. Narr in Wiley Online Library

Electroconvulsive therapy (ECT) and ketamine treatment both induce rapidly acting antidepressant effects in patients with major depressive disorder unresponsive to standard treatments, yet their specific impact on emotion processing is unknown. Here, we examined the neural underpinnings of emotion processing within and across patients (N = 44) receiving either ECT (N = 17, mean age: 36.8, 11.0 SD) or repeated subanesthetic (0.5 mg/kg) intravenous ketamine therapy (N = 27, mean age: 37.3, 10.8 SD) using a naturalistic study design. MRI and clinical data were collected before (TP1) and after treatment (TP2); healthy controls (N = 31, mean age: 34.5, 13.5 SD) completed one MRI session (TP1). An fMRI face‐matching task probed negative‐ and positive‐valence systems. Whole‐brain analysis, comparing neurofunctional changes within and across treatment groups, targeted brain regions involved in emotional facial processing, and included regions‐of‐interest analysis of amygdala responsivity. Main findings revealed a decrease in amygdalar reactivity after both ECT and ketamine for positive and negative emotional face processing (p < .05 family wise‐error (FWE) corrected). Subthreshold changes were observed between treatments within the dorsolateral prefrontal cortex and insula (p < .005, uncorrected). BOLD change for positive faces in the inferior parietal cortex significantly correlated with overall symptom improvement, and BOLD change in frontal regions correlated with anxiety for negative faces, and anhedonia for positive faces (p < .05 FWE corrected). Both serial ketamine and ECT treatment modulate amygdala response, while more subtle treatment‐specific changes occur in the larger functional network. Findings point to both common and differential mechanistic upstream systems‐level effects relating to fast‐acting antidepressant response, and symptoms of anxiety and anhedonia, for the processing of emotionally valenced stimuli.

The long read from The Guardian Why your brain is not a computer

For decades it has been the dominant metaphor in neuroscience. But could this idea have been leading us astray all along? By Matthew Cobb

Researchers explore how certain scents often elicit specific emotions and memories in people, and how marking companies are manipulating the link for branding.