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The last few decades have seen major advances in neurobiology and uncovered novel genetic and cellular substrates involved in the control of physiological set points. In this Review, I discuss the limitations in the definition of homeostatic set points established by Walter B Canon and highlight evidence that two other physiological systems, namely rheostasis and allostasis provide distinct inputs to independently modify set-point levels. Using data collected over the past decade, the hypothalamic and genetic basis of regulated changes in set-point values by rheostatic mechanisms are described. Then, the role of higher-order brain regions, such as hippocampal circuits, for experience-dependent, allostatic induced changes in set-points are outlined. I propose that these systems provide a hierarchical organization of physiological stability that exists to maintain set-point values. The hierarchical organization of physiology has direct implications for basic and medical research, and clinical practice. • Multiple physiological systems exhibit variation beyond homeostatic control. • Regulated, rheostatic changes in physiological set-point enhance fitness. • A three-level hierarchical organization of physiological stability is proposed. • Homeostasis, rheostasis and allostasis have distinct genes, cells, and systems. • Computational modelling supports a multi-tiered level of physiological control. [ABSTRACT FROM AUTHOR]

• The mice displayed region-dependent parenchymal and vascular amyloid depositions. • CAA in the brain of TgCRND8 mice is Type 2 CAA. • Injection of Aβ seeds shifted Aβ pathology from parenchymal plaques to CAA. • Injection of Aβ seeds induced CAA in thalamus of mouse brain. • Injection of Aβ seeds reduced neuroinflammation associated with Aβ pathology. Beta amyloid (Aβ) is a key component of parenchymal Aβ plaques and vascular Aβ fibrils, which lead to cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD). Recent studies have revealed that Aβ contained in the cerebrospinal fluid (CSF) can re-enter into brain through paravascular spaces. However, whether Aβ in CSF may act as a constant source of pathogenic Aβ in AD is still unclear. This study aimed to examine whether Aβ pathology could be worsened when CSF Aβ level was enhanced by intra-cisternal infusion of aged brain extract containing abundant Aβ in TgCRND8 host mice. TgCRND8 mouse is an AD animal model which develops predominant parenchymal Aβ plaques in the brain at as early as 3 months of age. Here, we showed that single intracisternal injection of Aβ seeds into TgCRND8 mice before the presence of Aβ pathology induced robust prion-like propagation of CAA within 90 days. The induced CAA is mainly distributed in the cerebral cortex, hippocampus and thalamus of TgCRND8 mice. Surprisingly, despite the robust increase in CAA levels, the TgCRND8 mice had a marked decrease in parenchymal Aβ plaques and the plaques related neuroinflammation in the brains compared with the control mice. These results amply indicate that Aβ in CSF may act as a source of Aβ contributing to the growth of vascular Aβ deposits in CAA. Our findings provide experimental evidence to unravel the mechanisms of CAA formation and the potential of targeting CSF Aβ for CAA. [ABSTRACT FROM AUTHOR]

It has been proposed that accurate motor control relies on Bayesian inference that integrates sensory input with prior contextual knowledge (Bays and Wolpert, 2007; Körding and Wolpert, 2004; Wolpert et al., 1995). Recent evidence has suggested that modulations in beta power (∼12–30 Hz) measured over sensorimotor cortices using electroencephalography (EEG) may represent parameters of Bayesian inference. While the well characterised post-movement beta synchronisation has been shown to correlate with prediction error (H. Tan, Jenkinson, & Brown, 2014; Huiling Tan, Wade, & Brown, 2016), recent evidence suggests that beta power may also represent uncertainty measures (Tan et al., 2016; Tzagarakis et al., 2015). The current study aimed to measure the neurophysiological correlates of uncertainty mediating Bayesian updating during a visuomotor adaptation paradigm in healthy human participants. In particular, sensory uncertainty was directly modulated to measure its effect on sensorimotor beta power. Participant's behaviour was modelled using the Hierarchical Gaussian Filter (HGF) in order to extract the latent variables involved in learning actions required by the task and correlate these with the measured EEG. We found that sensorimotor beta power correlated with inverse uncertainty afforded to sensory prediction errors both prior to and following a movement. This suggests that sensorimotor beta oscillations may more readily represent relative uncertainty within the sensorimotor system rather than error. Neurophysiological models describing the generation of beta oscillations offer a potential mechanism by which this neural signature may encode latent uncertainty parameters. This is essential for understanding how the brain controls behaviour. [ABSTRACT FROM AUTHOR]

Acute stress triggers a broad psychophysiological response that is adaptive if rapidly activated and terminated. While the brain controls the stress response, it is strongly affected by it. Previous research of stress effects on brain activation and connectivity has mainly focused on pre-defined brain regions or networks, potentially missing changes in the rest of the brain. We here investigated how both stress reactivity and stress recovery are reflected in whole-brain network topology and how changes in functional connectivity relate to other stress measures. Healthy young males (n = 67) completed the Trier Social Stress Test or a control task. From 60 min before until 105 min after stress onset, blocks of resting-state fMRI were acquired. Subjective, autonomic, and endocrine measures of the stress response were assessed throughout the experiment. Whole-brain network topology was quantified using Eigenvector centrality (EC) mapping, which detects central hubs of a network. Stress influenced subjective affect, autonomic activity, and endocrine measures. EC differences between groups as well as before and after stress exposure were found in the thalamus, due to widespread connectivity changes in the brain. Stress-driven EC increases in the thalamus were significantly correlated with subjective stress ratings and showed non-significant trends for a correlation with heart rate variability and saliva cortisol. Furthermore, increases in thalamic EC and in saliva cortisol persisted until 105 min after stress onset. We conclude that thalamic areas are central for information processing after stress exposure and may provide an interface for the stress response in the rest of the body and in the mind. • Whole-brain network topology in response to stress was investigated. • Acute stress increases thalamic Eigenvector centrality (EC). • EC changes were related to subjective and bodily stress markers. • EC changes did not recover within 105 min after stress onset. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are believed to play an important role in the proinflammatory form of neuroinflammation. Therefore, the availability of a radiotracer labeled with a positron-emitting radionuclide that can measure levels of ROS in tissue could provide a valuable method for imaging neuroinflammation in vivo with the functional imaging technique positron emission tomography (PET). We previously reported the synthesis and in vivo evaluation of [18F]ROStrace, a radiotracer for imaging ROS in vivo with PET, in an LPS model of neuroinflammation. In the current study, we conducted additional validation studies aimed at determining the cellular localization of this radiotracer in the same model. Our results indicate that [18F]ROStrace is primarily localized in microglia/macrophages and neurons in LPS-treated animals, and provide further support in the use of this radiotracer as a PET-based probe for imaging the proinflammatory form of neuroinflammation. • [18F]ROStrace shows a higher uptake in LPS-treated mouse brain relative to controls. • The regional uptake of [18F]ROStrace matches that of DHE, a fluorescent probe for imaging superoxide levels in tissues. • There is a good correlation between ROStrace in activated microglia/macrophages and neurons in the LPS-treatment model of neuroinflammation. [ABSTRACT FROM AUTHOR]

• With interest involved, self-disadvantageous inequity in preschoolers rose with age. • The improvement of inhibitory control explained this developmental trajectory. • Better theory of mind was associated with self-disadvantaging tendency. The purpose of this study was to investigate the relationship between preschoolers' cognitive abilities and their fairness-related allocation behaviors in a dilemma of equity–efficiency conflict. In Experiment 1, 4- to 6-year-olds (N = 99) decided how to allocate five reward bells. In the first-party condition, preschoolers were asked to choose among giving more to self (self-advantageous inequity), wasting one bell (equity), or giving more to other (self-disadvantageous inequity); in the third-party condition, they chose either to allocate the extra bell to one of two equally deserving recipients or to waste it. Results showed that, compared with the pattern of decision in the third-party condition, preschoolers in the first-party condition were more likely to give the extra bell to other (self-disadvantaging behaviors) and that age, inhibitory control (IC), and theory of mind were positively correlated with their self-disadvantaging choices, but only IC mediated the relationship between age and self-disadvantaging behaviors. Experiment 2 (N = 41) showed that IC still predicted preschoolers' self-disadvantaging behaviors when they could choose only between equity and disadvantageous inequity. These results suggested that IC played a critical role in the implementation of self-disadvantaging behaviors when this required the control over selfishness and envy. [ABSTRACT FROM AUTHOR]

miR-137 is a highly conserved microRNA (miRNA) that is associated with the control of brain function and the etiology of psychiatric disorders including schizophrenia and bipolar disorder. The Caenorhabditis elegans genome encodes a single miR-137 ortholog called mir-234 , the function of which is unknown. Here we show that mir-234 is expressed in a subset of sensory, motor and interneurons in C. elegans. Using a mir-234 deletion strain, we systematically examined the development and function of these neurons in addition to global C. elegans behaviors. We were however unable to detect phenotypes associated with loss of mir-234 , possibly due to genetic redundancy. To circumvent this issue, we overexpressed mir-234 in mir-234 -expressing neurons to uncover possible phenotypes. We found that mir-234 -overexpression endows resistance to the acetylcholinesterase inhibitor aldicarb, suggesting modification of neuromuscular junction (NMJ) function. Further analysis revealed that mir-234 controls neuropeptide levels, therefore positing a cause of NMJ dysfunction. Together, our data suggest that mir-234 functions to control the expression of target genes that are important for neuropeptide maturation and/or transport in C. elegans. The miR-137 family of miRNAs is linked to the control of brain function in humans. Defective regulation of miR-137 is associated with psychiatric disorders that include schizophrenia and bipolar disorder. Previous studies have revealed that miR-137 is required for the development of dendrites and for controlling the release of fast-acting neurotransmitters. Here, we analyzed the function a miR-137 family member (called mir-234) in the nematode animal model using anatomical, behavioral, electrophysiological and neuropeptide analysis. We reveal for the first time that mir-234/miR-137 is required for the release of slow-acting neuropeptides, which may also be of relevance for controlling human brain function. • mir-234 is expressed in a subset of neurons in Caenorhabditis elegans. • mir-234 loss-of-function does not result in detectable behavioral deficits. • Overexpression mir-234 causes an uncoordinated phenotype. • Neuropeptide release is perturbed when mir-234 is overexpressed. [ABSTRACT FROM AUTHOR]

Abstract Daily life is filled with sequences of multiple tasks, each with their own relevant perceptual input. Working memory needs to dissociate representations that drive attention towards currently relevant information from prospective representations that are needed for future tasks, but that until then should be prevented from guiding attention. Yet, little is known about how the brain initiates and controls such sequential prioritization of selection. In the current study we recorded EEG while subjects remembered a color as the target template for one of two sequential search tasks, thus making it either currently relevant (when it was the target for the first search) or prospectively relevant (when it was the target for the second search) prior to the task sequence. Using time-frequency specific linear classifiers, we were able to predict the priority status (current versus prospective) of the memory representation from multivariate patterns of delta (2–4 Hz) and non-lateralized alpha power (8–14 Hz) during both delay periods. The delta band was only transiently involved when initializing the priority status at the start of the first delay, or when switching priority during the second delay, which we interpret as reflecting the momentary top-down control over prioritization. In contrast, alpha power decoding was based on a more stable pattern of activity that generalized across time both within and between delay periods, which we interpret as reflecting a difference in the prioritized memory representations themselves. Taken together, we reveal the involvement of a complex, distributed and dynamic spatiotemporal landscape of frequency-specific oscillatory activity in controlling prioritization of information within working memory. Highlights • MVPA of EEG oscillatory signals dissociates current from future perceptual tasks • Current versus future status can be decoded during the delay prior to the tasks • Status decoding is reflected specifically in oscillatory delta and alpha band activity • Spatial pattern of activity underlying status decoding is complex and distributed • MVPA more sensitive than univariate measures to study higher order brain states [ABSTRACT FROM AUTHOR]

• Higher thought control ability was associated with more negative left amygdala-left frontal pole functional connectivity and less positive left amygdala-left inferior temporal gyrus functional connectivity. • Higher thought control ability was negatively associated with more negative left hippocampus-left inferior frontal gyrus functional connectivity. • Left amygdala-left frontal pole and left amygdala-left inferior temporal gyrus connectivity mediated the influence of thought control ability on trait anxiety. Thought control ability (TCA) refers to the ability to exclude unwanted thoughts. There has been consistent evidence on the protective effect of TCA on anxiety, that higher TCA is associated with lower anxiety. However, the underlying neural mechanism remains unclear. In this study, with a large sample (N = 495), we investigated how seed-based resting-state functional connectivity (RSFC) mediates the relationship between TCA and anxiety. Our behaviour results replicated previous findings that TCA is negatively associated with trait anxiety after controlling for gender, age, and depression. More importantly, the RSFC results revealed that TCA is negatively associated with the left amygdala - left frontal pole (LA-LFP), left amygdala - left inferior temporal gyrus (LA-LITG), and left hippocampus - left inferior frontal gyrus (LH-LIFG) connectivity. In addition, a mediation analysis demonstrated that the LA-LFP and LA-LITG connectivity in particular mediated the influence of TCA on trait anxiety. Overall, our study extends previous research by revealing the neural bases underlying the protective effect of TCA on anxiety and pinpointing specific mediating RSFC pathways. Future studies could explore whether targeted TCA training (behavioural or neural) can help alleviate anxiety. [ABSTRACT FROM AUTHOR]

Proactive brain control optimizes upcoming actions and inhibits unwanted responses. In the present event-related potential (ERP) study, participants freely decided in advance whether to respond or not to an upcoming stimulus, then prepared or not the action according to their decision; finally, a stimulus was delivered, and subjects had to respond (or not). During the decision-making stage, a prefrontal negativity raised bilaterally in case no-response was decided, reflecting the first brain signal of proactive inhibition. Simultaneously, slow activity raised over premotor cortices independently from the decision taken, and then raised during the preparation phase only in the case of response decision (as a sort of accelerator). When the decision was not to respond, the prefrontal activity remained sustained (as a sort of brake) and showed a right-lateralized distribution during the preparation phase. Overall, we described the time-course of a proactive accelerating-braking system regulating self-control of actions. [ABSTRACT FROM AUTHOR]

The 'dependency inducing practices', sometimes called 'brainwashing', that are commonly alleged to occur in deviant "religious" groups such as a cult movements or new religious movements are not well understood and have promoted considerable debate. There is a general agreement that many of these groups are controlled environments in which conformity to behavioural, emotive, cognitive and social expectations as determined by leadership is expected and enforced; however, whether conformity is the result of normal processes of socialisation or deviant practices such as brainwashing that cause harm continues to be disputed. To gain an increased understanding of the conformity and commitment inducing practices that occur in 'cult movements', the accounts of group life of 23 former members of 11 different groups were analysed. A conceptualisation of 'brainwashing' as on a continuum of social influence is proposed, and some legal implications are discussed. [ABSTRACT FROM AUTHOR]

Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating consequences for the paralyzed individual, and great economic consequences for society. Functional electrical stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their autonomy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the paralyzed muscles to contract. Existing clinical systems require the stimulation to be preprogrammed, with the patient typically using residual voluntary movement of another body part to trigger and control the patterned stimulation. The rapid development of neural interfacing in the past decade offers the promise of dramatically improved control for these patients, potentially allowing continuous control of FES through signals recorded from motor cortex, as the patient attempts to control the paralyzed body part. While application of these ‘brain–machine interfaces’ (BMIs) has undergone dramatic development for control of computer cursors and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals. [ABSTRACT FROM AUTHOR]

• Functional connectome uniqueness in adolescents was examined using a temporally rich (up to 9 time points) and a well-controlled (fixed 4 months interval) longitudinal study. • A unique functional connectome exists at 12 years old. • The cingulo-opercular network (a long-acting 'brain control network' configuring information processing) demonstrated marginal uniqueness. • Uniqueness indices of the cingulo-opercular network were significantly and negatively associated with the subsequent psychological distress. Each human brain has a unique functional synchronisation pattern (functional connectome) analogous to a fingerprint that underpins brain functions and related behaviours. Here we examine functional connectome (whole-brain and 13 networks) maturation by measuring its uniqueness in adolescents who underwent brain scans longitudinally from 12 years of age every four months. The uniqueness of a functional connectome is defined as its ratio of self-similarity (from the same subject at a different time point) to the maximal similarity-to-others (from a given subject and any others at a different time point). We found that the unique whole brain connectome exists in 12 years old adolescents, with 92% individuals having a whole brain uniqueness value greater than one. The cingulo-opercular network (CON; a long-acting 'brain control network' configuring information processing) demonstrated marginal uniqueness in early adolescence with 56% of individuals showing uniqueness greater than one (i.e., more similar to her/his own CON four months later than those from any other subjects) and this increased longitudinally. Notably, the low uniqueness of the CON correlates (β = -18.6, FDR-Q < < 0.001) with K10 levels at the subsequent time point. This association suggests that the individualisation of CON network is related to psychological distress levels. Our findings highlight the potential of longitudinal neuroimaging to capture mental health problems in young people who are undergoing profound neuroplasticity and environment sensitivity period. [ABSTRACT FROM AUTHOR]

• Number of thought probes may effect measurement of mind wandering during a task. • Number of thought probes differentially effect mind wandering based on task demands. • More thought probes result in more mind wandering during a working memory task. • More thought probes result in less mind wandering during a video lecture. • Thought probes interact with attentional control demands, influence mind wandering. Mind wandering is a topic of great interest in many areas, but as with all psychological constructs, the interpretation of experimental results might depend on the way it is measured. A common way of measuring mind wandering in experiments is with self-report thought probes. An important question with this methodology is if the probe itself may be influencing participants' mind wandering. Previous research suggests that multiple thought probes throughout a task may lead to less mind wandering. However, in some studies (e.g., Schubert et al, 2019) the probes occurred during a recorded lecture video and in the others (e.g., Seli et al, 2016) the probes occurred during a sustained attention to response task (SART). What is missing in the current literature is a comparison of the effect the number of thought probes has on mind wandering during a task that requires a greater deal of thought control throughout the task to perform well, such as a complex span task or working memory. As such, in the two experiments presented here we randomly assigned participants to one of four conditions. Conditions contained a minimum of one and a maximum of six probes. In the first experiment, we found that participants who had received fewer probes mind wandered less during an operation span task, supporting our hypothesis. In the second experiment, we found that participants who had received fewer probes mind wandered more during a video lecture. The results suggest that thought probes interact with attentional control demands to influence mind wandering. [ABSTRACT FROM AUTHOR]

Abstract: One of the most unexpected findings by functional neuroimaging has been the discovery of the brain''s default network — a set of brain regions that is spontaneously active during passive moments. The default network''s discovery was a fortunate accident that occurred due to the inclusion of rest control conditions in early PET and functional MRI studies. At first, the network was ignored. Later, its presence was shunned as evidence of an experimental confound. Finally, it emerged as a mainstream target of focused study. Here, I describe a personal perspective of the default network''s serendipitous discovery. [Copyright &y& Elsevier]

Abstract: Given that the brain evolved to function in the real world then it seems reasonable to want to examine how it operates in that context. But of course the world is complex, as are the brain''s responses to it, and MRI scanners are inherently restrictive environments. This combination of challenges makes the prospect of studying the freely-behaving brain with fMRI disconcerting to anyone sensible. When designing naturalistic fMRI experiments it is necessary to ensure that the thoughts or behaviours under scrutiny are not unduly perturbed or constrained by the imaging process, while still being amenable to experimental manipulation and control, and result in meaningful and interpretable data. This is difficult to achieve. Here, briefly, and in a highly subjective and selective manner, I consider: why we might want to deploy free-behaviour designs in an fMRI context, how to go about it, review some examples of it in action, and decide finally whether it is worth it (it is). [Copyright &y& Elsevier]

Abstract: Can one be fooled into believing that one intended an action that one in fact did not intend? Past experimental paradigms have demonstrated that participants, when provided with false perceptual feedback about their actions, can be fooled into misperceiving the nature of their intended motor act. However, because veridical proprioceptive/perceptual feedback limits the extent to which participants can be fooled, few studies have been able to answer our question and induce the illusion to intend. In a novel paradigm addressing this question, participants were instructed to move a line on the computer screen by use of a phony brain–computer interface. Line movements were actually controlled by computer program. Demonstrating the illusion to intend, participants reported more intentions to move the line when it moved frequently than when it moved infrequently. Consistent with ideomotor theory, the finding illuminates the intimate liaisons among ideomotor processing, the sense of agency, and action production. [Copyright &y& Elsevier]

While seeking new functional methods to reassess the concept of hemisphericity, a two-hand line-bisection task was investigated because of reports of large, stable differences among the general population. These were found to be due to hemispheric differences in judgment of the midpoint of horizontal lines, made visible due to the unilateral brain control of each hand. By use of a two-hand line-bisection test (Best-Hand Test), university workers (n=412) were readily sorted into theoretical response categories, resulting in the production of two large groups. These two groups correlated well with those produced by four independent hemisphericity assessments, two physiological and two psychological. This is the third biophysical method whose performance-based group separations significantly correlated with those produced by preference-based hemisphericity-type questionnaires. It is rapid and avoids language, education, or cultural bias. [Copyright &y& Elsevier]

The control of the brain system has received increasing attention in the domain of brain science. Most brain control studies have been conducted to explore the brain network's graph-theoretic properties or to produce the desired state based on neural state dynamics, regarding the brain as a passively responding system. However, the self-adjusting nature of neural system after treatment has not been fully considered in the brain control. In the present study, we propose a computational framework for optimal control of the brain with a self-adjustment process in the effective connectivity after treatment. The neural system is modeled to adjust its outgoing effective connectivity as activity-dependent plasticity after treatment, followed by synaptic rescaling of incoming effective connectivity. To control this neural system to induce the desired function, the system's self-adjustment parameter is first estimated, based on which the treatment is optimized. Utilizing this framework, we conducted simulations of optimal control over a functional hippocampal circuitry, estimated using dynamic causal modeling of voltage-sensitive dye imaging from the wild type and mutant mice, responding to consecutive electrical stimuli. Simulation results for optimal control of the abnormal circuit toward a healthy circuit using a single node treatment, neural-type specific treatment as an analogy of medication, and combined treatments of medication and nodal treatment suggest the plausibility of the current framework in controlling the self-adjusting neural system within a restricted treatment setting. We believe the proposed computational framework of the self-adjustment system would help optimal control of the dynamic brain after treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Research has shown that difficulties with emotion regulation abilities in childhood and adolescence increase the risk for developing symptoms of mental disorders, e.g anxiety. We investigated whether functional magnetic resonance imaging (fMRI)-based neurofeedback (NF) can modulate brain networks supporting emotion regulation abilities in adolescent females. We performed three experiments (Experiment 1: N ​= ​18; Experiment 2: N ​= ​30; Experiment 3: N ​= ​20). We first compared different NF implementations regarding their effectiveness of modulating prefrontal cortex (PFC)-amygdala functional connectivity (fc). Further we assessed the effects of fc-NF on neural measures, emotional/metacognitive measures and their associations. Finally, we probed the mechanism underlying fc-NF by examining concentrations of inhibitory and excitatory neurotransmitters. Results showed that NF implementations differentially modulate PFC-amygdala fc. Using the most effective NF implementation we observed important relationships between neural and emotional/metacognitive measures, such as practice-related change in fc was related with change in thought control ability. Further, we found that the relationship between state anxiety prior to the MRI session and the effect of fc-NF was moderated by GABA concentrations in the PFC and anterior cingulate cortex. To conclude, we were able to show that fc-NF can be used in adolescent females to shape neural and emotional/metacognitive measures underlying emotion regulation. We further show that neurotransmitter concentrations moderate fc–NF–effects. • Neurofeedback implementations differentially modulate PFC-amygdala connectivity. • Functional connectivity neurofeedback affect measures of emotion regulation. • Neurotransmitter concentrations moderate neurofeedback effects. [ABSTRACT FROM AUTHOR]

As the speech apparatus is also involved in producing non-speech movements, understanding whether speech and non-speech planning are controlled by the same brain mechanisms is central to the comprehension of motor speech planning. A crucial issue is whether a specialized motor planning/control system is dedicated to speech or if the motor planning/control system is shared across oromotor behaviors. We investigated the EEG/ERP spatio-temporal dynamics of the motor planning processes preceding articulation by comparing the production of non-speech gestures matched to monosyllabic words and non-words. To isolate motor from pre-motor planning, we used a delayed production task combined with an articulatory suppression task. Results suggest that the planning processes preceding articulation for non-speech, words and non-words recruit the same neural networks but with different involvement for non-speech and speech. The results support the idea of shared motor planning/control systems for speech and non-speech but with different dynamics for each oromotor behavior. [ABSTRACT FROM AUTHOR]

The APOE4 protein affects the primary neuropathological markers of Alzheimer's disease (AD): amyloid plaques, neurofibrillary tangles, and gliosis. These interactions have been investigated to understand the strong effect of APOE genotype on risk of AD. However, APOE genotype has strong effects on processes in normal brains, in the absence of the hallmarks of AD. We propose that CNS APOE is involved in processes in the normal brains that in later years apply specifically to processes of AD pathogenesis. We review the differences of the APOE protein found in the CNS compared to the plasma, including post-translational modifications (glycosylation, lipidation, multimer formation), focusing on ways that the common APOE isoforms differ from each other. We also review structural and functional studies of young human brains and control APOE knock-in mouse brains. These approaches demonstrate the effects of APOE genotype on microscopic neuron structure, gross brain structure, and behavior, primarily related to the hippocampal areas. By focusing on the effects of APOE genotype on normal brain function, approaches can be pursued to identify biomarkers of APOE dysfunction, to promote normal functions of the APOE4 isoform, and to prevent the accumulation of the pathologic hallmarks of AD with aging. [ABSTRACT FROM AUTHOR]

Lactate is now recognized as an important intermediate in brain metabolism, but its role is still under investigation. In this work we mapped the distribution of lactate and bicarbonate produced from intravenously injected 13C-pyruvate over the whole brain using a new imaging method, hyperpolarized 13C MRI (N = 14, ages 23 to 77). Segmenting the 13C-lactate images into brain atlas regions revealed a pattern of lactate that was preserved across individuals. Higher lactate signal was observed in cortical grey matter compared to white matter and was highest in the precuneus, cuneus and lingual gyrus. Bicarbonate signal, indicating flux of [1–13C]pyruvate into the TCA cycle, also displayed consistent spatial distribution. One-way ANOVA to test for significant differences in lactate among atlas regions gave F = 87.6 and p < 10−6. This report of a "lactate topography" in the human brain and its consistent pattern is evidence of region-specific lactate biology that is preserved across individuals. Image 1 • Hyperpolarized 13C MRI was used to acquire human brain images in control subjects. • 13C-lactate images were segmented into brain atlas regions. • The 13C-lactate topography was found to be consistent across individuals. • The preserved pattern provides evidence of region-specific lactate biology. [ABSTRACT FROM AUTHOR]

Spatial selective attention enables listeners to process a signal of interest in natural settings. However, most past studies on auditory spatial attention used impoverished spatial cues: presenting competing sounds to different ears, using only interaural differences in time (ITDs) and/or intensity (IIDs), or using non-individualized head-related transfer functions (HRTFs). Here we tested the hypothesis that impoverished spatial cues impair spatial auditory attention by only weakly engaging relevant cortical networks. Eighteen normal-hearing listeners reported the content of one of two competing syllable streams simulated at roughly +30° and −30° azimuth. The competing streams consisted of syllables from two different-sex talkers. Spatialization was based on natural spatial cues (individualized HRTFs), individualized IIDs, or generic ITDs. We measured behavioral performance as well as electroencephalographic markers of selective attention. Behaviorally, subjects recalled target streams most accurately with natural cues. Neurally, spatial attention significantly modulated early evoked sensory response magnitudes only for natural cues, not in conditions using only ITDs or IIDs. Consistent with this, parietal oscillatory power in the alpha band (8–14 ​Hz; associated with filtering out distracting events from unattended directions) showed significantly less attentional modulation with isolated spatial cues than with natural cues. Our findings support the hypothesis that spatial selective attention networks are only partially engaged by impoverished spatial auditory cues. These results not only suggest that studies using unnatural spatial cues underestimate the neural effects of spatial auditory attention, they also illustrate the importance of preserving natural spatial cues in assistive listening devices to support robust attentional control. • Neural responses are weak or even absent with impoverished spatial auditory cues. • Spatial cue realism affects parietal alpha activity and early evoked cortical responses. • Differences due to cue realism disappear by the next level of neural processing. • Robust engagement of spatial attention mechanisms requires realistic spatial cues. [ABSTRACT FROM AUTHOR]

• Prenatal estrogens defeminize but postnatal estrogens feminize rodent behavior. • Genes differentiate behavior by modifying gonadal hormones but also in a more direct manner. • Steroids mediate sexual differentiation by affecting microglia and prostanoids. • Activation of sex behavior depends on steroids produced in the gonads but also in the brain. • Estrogen production changes rapidly in the brain and this impacts behavior activation. Since the beginning of this century, research methods in neuroendocrinology enjoyed extensive refinements and innovation. These advances allowed collection of huge amounts of new data and the development of new ideas but have not led to this point, with a few exceptions, to the development of new conceptual advances. Conceptual advances that took place largely resulted from the ingenious insights of several investigators. I summarize here some of these new ideas as they relate to the sexual differentiation and activation by sex steroids of reproductive behaviors and I discuss how our research contributed to the general picture. This selective review clearly demonstrates the importance of conceptual changes that have taken place in this field since beginning of the 21st century. The recent technological advances suggest that our understanding of hormones, brain and behavior relationships will continue to improve in a very fundamental manner over the coming years. [ABSTRACT FROM AUTHOR]

How can people persuade and influence others? One option is to directly target others' behavior through rules and incentives. Another increasingly popular option, however, is to focus on modifying what others think rather than how they behave, and hoping behaviors will then change as a result. The assumption underlying this latter approach is that targeting thoughts and attitudes might be easier or more effective than targeting behaviors. Drawing from psychological reactance theory (Brehm, 1966), we investigate whether efforts targeted at controlling what people think, rather than how they behave, will indeed be met with differing levels of psychological reactance. Across four studies, we find that people experience greater psychological reactance towards efforts to control their thoughts compared to efforts to control their behaviors. Specifically, thought control, compared to behavioral control, led people to experience greater anger and negativity, and to report lowered motivation to engage in requested behaviors (Study 1). These effects occurred, at least in part, because people perceived that those who try to control their thoughts are likely to try to control their behaviors too, but not vice versa. As a result, thought control elicited greater reactance than behavioral control because the former was perceived as more restrictive than the latter (Studies 2 & 3). We also address other explanations for why thought control may elicit more reactance than behavioral control (Study 4). [ABSTRACT FROM AUTHOR]