Neural Changes Research Articles

The effect of movement representation techniques on ankle function and performance in persons with or without a lateral ankle sprain: a systematic review and meta-analysis

BackgroundLateral ankle sprains are highly prevalent and result in tissue damage, impairments of muscle strength, instability, and muscle activation. Up to 74% will experience ongoing symptoms after a lateral ankle sprain. In healthy subjects, motor imagery might induce neural changes in the somatosensory and motor areas of the brain, yielding favourable enhancements in muscular force. However, during motor imagery, difficulties in building a motor image, no somatosensory feedback, and the absence of structural changes at the level of the muscle might explain the differences found between motor imagery and physical practice. In rehabilitation, motor imagery might be supportive in rebuilding motor networks or creating new networks to restore impairments in muscle activation and movement patterns. This systematic review was undertaken to summarize the current body of evidence about the effect on motor imagery, or action observation, on lower leg strength, muscle performance, ankle range of motion, balance, and edema in persons with, and without, a lateral ankle sprain compared to usual care, a placebo intervention, or no intervention.MethodsA systematic review with meta-analysis of randomized controlled trials was conducted in healthy participants and participants with a lateral ankle sprain. Motor imagery or action observation in isolation, or in combination with usual care were compared to a placebo intervention, or no intervention. An electronic search of MEDLINE, EMBASE, Cinahl, Psychinfo, Sportdiscus, Web of Science, Cochrane and Google Scholar was conducted, and articles published up to 7th June 2023 were included. Two reviewers individually screened titles and abstracts for relevancy using the inclusion criteria. Variables related to muscle strength, muscle function, range of motion, balance, return to sports tests, or questionnaires on self-reported function or activities were extracted. A risk of bias assessment was done using the Cochrane Risk-of-Bias tool II by two reviewers. Meta-analysis using a random effects model was performed when two or more studies reported the same outcome measures. The Standardized Mean Difference (SMD) was calculated over the change from baseline scores. Review manager 5.4 was used to perform analysis of subgroup differences and test for statistically significant differences. Confidence intervals were visually checked for overlap between subgroups.ResultsNine studies, six examining healthy participants and three examining participants with an acute lateral ankle sprain, were included. All studies were rated with moderate to high risk of bias overall. Quality of the motor imagery interventions differed largely between studies. Meta-analysis showed a large and significant effect of motor imagery on lower leg strength (SMD 1.47, 95% CI 0.44 to 2.50); however, the evidence was downgraded to very low certainty due to substantial heterogeneity (I2 = 73%), limitations in the studies (some concerns in risk of bias in all studies), and imprecision (n = < 300). Evidence showed no association with ankle range of motion (SMD 0.25, 95% CI -0.43 to 0.93), edema (SMD -1.11, 95% CI -1.60 to 3.81), the anterior reach direction of the Star Excursion Balance Test (SEBT) (SMD 0.73, 95% CI -0.62 to 2.08), the posterolateral direction (SMD 0.32, 95% CI -0.94 to 1.57), and the posteromedial direction (SMD 0.52, 95% CI -0.07 to 1.10). The certainty of evidence for the different comparisons was very low.ConclusionsThere is a low certainty, significant, positive effect for motor imagery being able to improve lower leg muscle strength in healthy participants. The effect on balance, range of motion and edema was uncertain and of very low certainty.Systematic review registrationPROSPERO CRD42021243258.

Neural evidence for procedural automatization during cognitive development: Intraparietal response to changes in very-small addition problem-size increases with age

Cognitive development is often thought to depend on qualitative changes in problem-solving strategies, with early developing algorithmic procedures (e.g., counting when adding numbers) considered being replaced by retrieval of associations (e.g., between operands and answers of addition problems) in adults. However, algorithmic procedures might also become automatized with practice. In a large cross-sectional fMRI study from age 8 to adulthood (n = 128), we evaluate this hypothesis by measuring neural changes associated with age-related reductions in a behavioral hallmark of mental addition, the problem-size effect (an increase in solving time as problem sum increases). We found that age-related decreases in problem-size effect were paralleled by age-related increases of activity in a region of the intraparietal sulcus that already supported the problem-size effect in 8- to 9-year-olds, at an age the effect is at least partly due to explicit counting. This developmental effect, which was also observed in the basal ganglia and prefrontal cortex, was restricted to problems with operands ≤ 4. These findings are consistent with a model positing that very-small arithmetic problems–and not larger problems–might rely on an automatization of counting procedures rather than a shift towards retrieval, and suggest a neural automatization of procedural knowledge during cognitive development.

Neck Muscle Vibration Alters Cerebellar Processing Associated with Motor Skill Acquisition of a Proprioceptive-Based Task.

Experimentally induced neck fatigue and neck pain have been shown to impact cortico-cerebellar processing and sensorimotor integration, assessed using a motor learning paradigm. Vibration specifically impacts muscle spindle feedback, yet it is unknown whether transient alterations in neck sensory input from vibration impact these neural processing changes following the acquisition of a proprioceptive-based task. Twenty-five right-handed participants had electrical stimulation over the right median nerve to elicit short- and middle-latency somatosensory evoked potentials (SEPs) pre- and post-acquisition of a force matching tracking task. Following the pre-acquisition phase, controls (CONT, n = 13, 6 F) received 10 min of rest and the vibration group (VIB, n = 12, 6 F) received 10 min of 60 Hz vibration on the right sternocleidomastoid and left cervical extensors. Task performance was measured 24 h later to assess retention. Significant time by group interactions occurred for the N18 SEP peak, 21.77% decrease in VIB compared to 58.74% increase in CONT (F(1,23) = 6.475, p = 0.018, np2 = 0.220), and the N24 SEP peak, 16.31% increase in VIB compared to 14.05% decrease in CONT (F(1,23) = 5.787, p = 0.025, np2 = 0.201). Both groups demonstrated improvements in motor performance post-acquisition (F(1,23) = 52.812, p < 0.001, np2 = 0.697) and at retention (F(1,23) = 35.546, p < 0.001, np2 = 0.607). Group-dependent changes in the SEP peaks associated with cerebellar input (N18) and cerebellar processing (N24) suggests that an altered proprioceptive input from neck vibration impacts cerebellar pathways.

Adaptive Neuroplasticity in Brain Injury Recovery: Strategies and Insights.

This review addresses the relationship between neuroplasticity and recovery from brain damage. Neuroplasticity's ability to adapt becomes crucial since brain injuries frequently result in severe impairments. We begin by describing the fundamentals of neuroplasticity and how it relates to rehabilitation. Examining different forms of brain injuries and their neurological effects highlights the complex difficulties in rehabilitation. By revealing cellular processes, we shed light on synaptic adaptability following damage. Our study of synaptic plasticity digs into axonal sprouting, dendritic remodeling, and the balance of long-term potentiation. These processes depict neural resilience amid change. Then, after damage, we investigate immediate and slow neuroplastic alterations, separating reorganizations that are adaptive from those that are maladaptive. As we go on to rehabilitation, we evaluate techniques that use neuroplasticity's potential. These methods take advantage of the brain's plasticity for healing, from virtual reality and brain-computer interfaces to constraint-induced movement therapy. Ethics and individualized neurorehabilitation are explored. We scrutinize the promise of combination therapy and the difficulties in putting new knowledge into clinical practice. In conclusion, this analysis highlights neuroplasticity's critical role in brain injury recovery, providing sophisticated approaches to improve life after damage.

Neural functional network of early Parkinson's disease based on independent component analysis.

This work explored neural network changes in early Parkinson's disease: Resting-state functional magnetic resonance imaging was used to investigate functional alterations in different stages of Parkinson's disease (PD). Ninety-five PD patients (50 early/mild and 45 early/moderate) and 37 healthy controls (HCs) were included. Independent component analysis revealed significant differences in intra-network connectivity, specifically in the default mode network (DMN) and right frontoparietal network (RFPN), in both PD groups compared to HCs. Inter-network connectivity analysis showed reduced connectivity between the executive control network (ECN) and DMN, as well as ECN-left frontoparietal network (LFPN), in early/mild PD. Early/moderate PD exhibited decreased connectivity in ECN-LFPN, ECN-RFPN, ECN-DMN, and DMN-auditory network, along with increased connectivity in LFPN-cerebellar network. Correlations were found between ECN-DMN and ECN-LFPN connections with UPDRS-III scores in early/mild PD. These findings suggest that PD progression involves dysfunction in multiple intra- and inter-networks, particularly implicating the ECN, and a wider range of abnormal functional networks may mark the progression of the disease.

Rapid neural changes during novel speech-sound learning: An fMRI and DTI study

While the functional and microstructural changes that occur when we learn new language skills are well documented, relatively little is known about the time course of these changes. Here a combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) study that tracks neural change over three days of learning Arabic phonetic categorization as a new language (L-training) is presented. Twenty adult native English-speaking (L-native) participants are scanned before and after training to perceive and produce L-training phonetic contrasts for one hour on three consecutive days. A third (Chinese) language is used as a control language (L-control). Behavioral results show significant performance improvement for L-training in both learnt tasks; the perception and production task. Imaging analysis reveals that, training-related hemodynamic fMRI signal and fractional anisotropy (FA) value increasing can be observed, in the left inferior frontal gyrus (LIFG) and positively correlated with behavioral improvement. Moreover, post training functional connectivity findings show a significant increasing between LIFG and left inferior parietal lobule for L-training. These results indicate that three hours of phonetic categorization learning causes functional and microstructural changes that are typically associated with much more long-term learning.

Mediodorsal thalamus-projecting anterior cingulate cortex neurons modulate helping behavior in mice

Many species living in groups can perform prosocial behaviors via voluntarily helping others with or without benefits for themselves. To provide a better understanding of the neural basis of such prosocial behaviors, we adapted a preference lever-switching task in which mice can prevent harm to others by switching from using a lever that causes shocks to a conspecific one that does not. We found the harm avoidance behavior was mediated by self-experience and visual and social contact but not by gender or familiarity. By combining single-unit recordings and analysis of neural trajectory decoding, we demonstrated the dynamics of anterior cingulate cortex (ACC) neural activity changes synchronously with the harm avoidance performance of mice. In addition, ACC neurons projected to the mediodorsal thalamus (MDL) to modulate the harm avoidance behavior. Optogenetic activation of the ACC-MDL circuit during non-preferred lever pressing (nPLP) and inhibition of this circuit during preferred lever pressing (PLP) both resulted in the loss of harm avoidance ability. This study revealed the ACC-MDL circuit modulates prosocial behavior to avoid harm to conspecifics and may shed light on the treatment of neuropsychiatric disorders with dysfunction of prosocial behavior.

Sensory cortex plasticity supports auditory social learning

Social learning (SL) through experience with conspecifics can facilitate the acquisition of many behaviors. Thus, when Mongolian gerbils are exposed to a demonstrator performing an auditory discrimination task, their subsequent task acquisition is facilitated, even in the absence of visual cues. Here, we show that transient inactivation of auditory cortex (AC) during exposure caused a significant delay in task acquisition during the subsequent practice phase, suggesting that AC activity is necessary for SL. Moreover, social exposure induced an improvement in AC neuron sensitivity to auditory task cues. The magnitude of neural change during exposure correlated with task acquisition during practice. In contrast, exposure to only auditory task cues led to poorer neurometric and behavioral outcomes. Finally, social information during exposure was encoded in the AC of observer animals. Together, our results suggest that auditory SL is supported by AC neuron plasticity occurring during social exposure and prior to behavioral performance.

Terahertz label-free detection of nicotine-induced neural cell changes and the underlying mechanisms

Nicotine exposure can lead to neurological impairments and brain tumors, and a label-free and nondestructive detection technique is urgently required by the scientific community to assess the effects of nicotine on neural cells. Herein, a terahertz (THz) time-domain attenuated total reflection (TD-ATR) spectroscopy approach is reported, by which the effects of nicotine on normal and cancerous neural cells, i.e., HEB and U87 cells, are successfully investigated in a label/stain-free and nondestructive manner. The obtained THz absorption coefficients of HEB cells exposed to low-dose nicotine and high-dose nicotine are smaller and larger, respectively, than the untreated cells. In contrast, the THz absorption coefficients of U87 cells treated by nicotine are always smaller than the untreated cells. The THz absorption coefficients can be well related to the proliferation properties (cell number and compositional changes) and morphological changes of neural cells, by which different types of neural cells are differentiated and the viabilities of neural cells treated by nicotine are reliably assessed. Collectively, this work sheds new insights on the effects of nicotine on neural cells, and provides a useful tool (THz TD-ATR spectroscopy) for the study of chemical-cell interactions.

Cortical changes during the learning of sequences of simultaneous finger presses

Abstract The cortical alterations underpinning the acquisition of motor skills remain debated. In this longitudinal study in younger adults, we acquired performance and neuroimaging (7 T MRI) measures weekly over the course of 6 weeks to investigate neural changes associated with learning sequences of simultaneous finger presses executed with the non-dominant hand. Both the intervention group (n = 33), which practiced the finger sequences at home, and the control group (n = 30, no home practice) showed general performance improvements, but performance improved more and became more consistent for sequences that were intensively trained by the intervention group, relative to those that were not. Brain activity for trained sequences decreased compared with untrained sequences in the bilateral parietal and premotor cortices. No training-related changes in the primary sensorimotor areas were detected. The similarity of activation patterns between trained and untrained sequences decreased in secondary, but not primary, sensorimotor areas, while the similarity of the activation patterns between different trained sequences did not show reliable changes. Neither the variability of activation patterns across trials, nor the estimates of brain structure displayed practice-related changes that reached statistical significance. Overall, the main correlate of learning configural sequences was a reduction in brain activity in secondary motor areas.

When shapes are more than shapes: perceptual, developmental, and neurophysiological basis for attributions of animacy and theory of mind.

Among a variety of entities in their environment, what do humans consider alive or animate and how does this attribution of animacy promote development of more abstract levels of mentalizing? By decontextualizing the environment of bodily features, we review how physical movements give rise to perceived animacy in Heider-Simmel style animations. We discuss the developmental course of how perceived animacy shapes our interpretation of the social world, and specifically discuss when and how children transition from perceiving actions as goal-directed to attributing behaviors to unobservable mental states. This transition from a teleological stance, asserting a goal-oriented interpretation to an agent's actions, to a mentalistic stance allows older children to reason about more complex actions guided by hidden beliefs. The acquisition of these more complex cognitive behaviors happens developmentally at the same time neural systems for social cognition are coming online in young children. We review perceptual, developmental, and neural evidence to identify the joint cognitive and neural changes associated with when children begin to mentalize and how this ability is instantiated in the brain.

Teleosts as behaviour test models for social stress.

Stress is an important aspect of our everyday life and exposure to it is an unavoidable occurrence. In humans, this can come in the form of social stress or physical stress from an injury. Studies in animal models have helped researchers to understand the body's adaptive response to stress in human. Notably, the use of behavioural tests in animal models plays a pivotal role in understanding the neural, endocrine and behavioural changes induced by social stress. Under socially stressed conditions, behavioural parameters are often measured physiological and molecular parameters as changes in behaviour are direct responses to stress and are easily assessed by behavioural tests. Throughout the past few decades, the rodent model has been used as a well-established animal model for stress and behavioural changes. Recently, more attention has been drawn towards using fish as an animal model. Common fish models such as zebrafish, medaka, and African cichlids have the advantage of a higher rate of reproduction, easier handling techniques, sociability and most importantly, share evolutionary conserved genetic make-up, neural circuitry, neuropeptide molecular structure and function with mammalian species. In fact, some fish species exhibit a clear diurnal or seasonal rhythmicity in their stress response, similar to humans, as opposed to rodents. Various social stress models have been established in fish including but not limited to chronic social defeat stress, social stress avoidance, and social stress-related decision-making. The huge variety of behavioural patterns in teleost also aids in the study of more behavioural phenotypes than the mammalian species. In this review, we focus on the use of fish models as alternative models to study the effects of stress on different types of behaviours. Finally, fish behavioural tests against the typical mammalian model-based behavioural test are compared and discussed for their viability.

The Audiovisual Mismatch Negativity in Predictive and Non-Predictive Speech Stimuli in Older Adults With and Without Hearing Loss.

Adults with aging-related hearing loss (ARHL) experience adaptive neural changes to optimize their sensory experiences; for example, enhanced audiovisual (AV) and predictive processing during speech perception. The mismatch negativity (MMN) event-related potential is an index of central auditory processing; however, it has not been explored as an index of AV and predictive processing in adults with ARHL. In a pilot study we examined the AV MMN in two conditions of a passive oddball paradigm- one AV condition in which the visual aspect of the stimulus can predict the auditory percept and one AV control condition in which the visual aspect of the stimulus cannot predict the auditory percept. In adults with ARHL, evoked responses in the AV conditions occurred in the early MMN time window while the older adults with normal hearing showed a later MMN. Findings suggest that adults with ARHL are sensitive to AV incongruity, even when the visual is not predictive of the auditory signal. This suggests that predictive coding for AV speech processing may be heightened in adults with ARHL. This paradigm can be used in future studies to measure treatment related changes, for example via aural rehabilitation, in older adults with ARHL.

Supplementary Motor Area Activity Differs in Parkinson's Disease with and without Freezing of Gait.

The study aimed to investigate the neural changes that differentiate Parkinson's disease patients with freezing of gait and age-matched controls, using ambulatory electroencephalography event-related features. Compared to controls, definite freezers exhibited significantly less alpha desynchronization at the motor cortex about 300 ms before and after the start of overground walking and decreased low-beta desynchronization about 300 ms before and about 300 and 700 ms after walking onset. The late slope of motor potentials also differed in the sensory and motor areas between groups of controls, definite, and probable freezers. This difference was found both in preparation and during the execution of normal walking. The average frontal peak of motor potential was also found to be largely reduced in the definite freezers compared with the probable freezers and controls. These findings provide valuable insights into the underlying structures that are affected in patients with freezing of gait, which could be used to tailor drug development and personalize drug care for disease subtypes. In addition, the study's findings can help in the evaluation and validation of nonpharmacological therapies for patients with Parkinson's disease.

TMS over the pre-SMA enhances semantic cognition via remote network effects on task-based activity and connectivity

BackgroundThe continuous decline of executive abilities with age is mirrored by increased neural activity of domain-general networks during task processing. So far, it remains unclear how much domain-general networks contribute to domain-specific processes such as language when cognitive demands increase. The current neuroimaging study explored the potential of intermittent theta-burst stimulation (iTBS) over a domain-general hub to enhance executive and semantic processing in healthy middle-aged to older adults. MethodsWe implemented a cross-over within-subject study design with three task-based neuroimaging sessions per participant. Using an individualized stimulation approach, each participant received once effective and once sham iTBS over the pre-supplementary motor area (pre-SMA), a region of domain-general control. Subsequently, task-specific stimulation effects were assessed in functional MRI using a semantic and a non-verbal executive task with varying cognitive demand. ResultsEffective stimulation increased activity only during semantic processing in visual and dorsal attention networks. Further, iTBS induced increased seed-based connectivity in task-specific networks for semantic and executive conditions with high cognitive load but overall reduced whole-brain coupling between domain-general networks. Notably, stimulation-induced changes in activity and connectivity related differently to behavior: While stronger activity of the parietal dorsal attention network was linked to poorer semantic performance, its enhanced coupling with the pre-SMA was associated with more efficient semantic processing. ConclusionsiTBS modulates networks in a task-dependent manner and generates effects at regions remote to the stimulation site. These neural changes are linked to more efficient semantic processing, which underlines the general potential of network stimulation approaches in cognitive aging.

Abstract P434: Insights Into Blood Pressure Control In Primary Aldosteronism Using Physiological Modeling

For the last 20 years, we have observed that patients with drug resistant hypertension due to primary aldosteronism (PA) have significant lowering of blood pressure (BP) and improved hypokalemia when moving to a DASH dietary intervention (≤65 mEq/day Na + / ≥120 mEq/day K + ). However, current guidelines for PA treatment briefly recommend lowering Na + intake and make no specific mention of supplementing potassium intake or using DASH in PA. Because continuous monitoring of cardiovascular, neural, and hormonal changes during developing PA cannot be achieved experimentally, we used the mathematical model of human physiology, HumMod, to test the responses to a DASH diet during PA. Starting from baseline conditions with normal Na + /K + intake (150 and 50 mmol/day, respectively), we simulated an aldosterone secreting tumor to gradually increase plasma aldosterone to 20 ng/dL over 3 years. Baseline PA was associated with hypertension (150 mmHg systolic BP), very low endogenous renin and aldosterone secretion, hypokalemia (2.9 mmol/L K + ), and tumor aldosterone secretion of 43 μg/day. We simulated a chronic change in dietary intake: 1) Low Na + diet - Na + intake fixed at 65 mmol/day, 2) High K + diet - 120 mmol/day K + intake, or 3) DASH diet - Low Na + intake and high K + intake. Lowering Na + intake without or with high K + intake (DASH) were associated with lower systolic BP (-12 mmHg and -25 mmHg, respectively) over the first 4 weeks and persisted for up to 2 years despite continued activation of the renin-angiotensin system and increasing tumor aldosterone. Simulating mineralocorticoid blockade (MCB) was associated with reductions in systolic BP (-17 mmHg) and correction of hypokalemia (4.0 mmol/L) but BP still remained uncontrolled (134/81 mmHg), partly due to the compensatory increase in renin secretion. However, adding low Na + or DASH to the MCB simulation were associated with greater antihypertensive effects (-26 and -30, mmHg respectively). These current simulations may help better understand the sequence of physiological events in PA and yield new insights into its diagnosis and management. The physiological effects of the DASH diet desperately need to be tested in patients with PA as the simulation suggests beneficial effects beyond current treatment guidelines.

Functional Connectivity Mechanisms Underlying Symptom Reduction Following Lisdexamfetamine Treatment in Binge-Eating Disorder: A Clinical Trial

BackgroundSpeculation exists as to whether lisdexamfetamine dimesylate (LDX) acts on the functional connectivity (FC) of brain networks that modulate appetite, reward, or inhibitory control in binge-eating disorder (BED). Better insights into its action may help guide the development of more targeted therapeutics and identify who will benefit most from this medication. Here, we use a comprehensive data-driven approach to investigate the brain FC changes that underlie the therapeutic action of LDX in patients with BED. MethodsForty-six participants with moderate to severe BED received LDX titrated to 50 or 70 mg for an 8-week period. Twenty age-matched healthy control participants were also recruited. Resting-state functional magnetic resonance imaging was used to probe changes in brain FC pre- and post treatment and correlated with change in clinical measures. ResultsNinety-seven percent of trial completers (n = 31) experienced remission or a reduction to mild BED during the 8-week LDX trial. Widespread neural FC changes occurred, with changes in default mode to limbic, executive control to subcortical, and default mode to executive control networks associated with improvements in clinical outcomes. These connections were not distinct from control participants at pretreatment but were different from control participants following LDX treatment. Pretreatment connectivity did not predict treatment response. ConclusionsFC between networks associated with self-referential processing, executive function, and reward seem to underlie the therapeutic effect of LDX in BED. This suggests that LDX activates change via multiple systems, with most changes in compensatory networks rather than in those characterizing the BED diagnosis.

Role of insula and its subregions in progression from recent onset to chronic idiopathic tinnitus.

We determined the structural and functional alterations in the insula and its subregions in patients with idiopathic tinnitus in order to identify the neural changes involved in the progression from recent onset to chronic tinnitus. We recruited 24 recent-onset tinnitus patients, 32 chronic tinnitus patients and 36 healthy controls. We measured the grey matter volume and fractional amplitude of low-frequency fluctuation of the insula and its subregions and the functional connectivity within the insula and between the insula and the rest of the brain. Relationships between MRI and clinical characteristics were estimated using partial correlation analysis. Both recent-onset and chronic tinnitus patients showed decreased fractional amplitude of low-frequency fluctuation in the insula and its subregions, but only chronic tinnitus patients showed bilateral grey matter atrophy in the ventral anterior insula. Abnormal functional connectivity was detected in recent-onset and chronic tinnitus patients relative to the healthy controls, but functional connectivity differences between recent-onset and chronic tinnitus patients were found in only the auditory-related cortex, frontal cortex and limbic system. Functional alterations (fractional amplitude of low-frequency fluctuation and functional connectivity of the left ventral anterior insula), but not structural changes, were correlated with clinical severity. Bilateral grey matter atrophy in the ventral anterior insula decreased regional activities in the left ventral anterior insula and left posterior insula, and abnormal functional connectivity of the insula subregions with auditory and non-auditory areas were implicated in the progression from recent onset to chronic tinnitus. This suggests that tinnitus generation and development occur in a dynamic manner and involve aberrant multi-structural and functional (regional brain activity and abnormal functional connectivity) reorganization of the insula.

Sex-dependent noradrenergic modulation of premotor cortex during decision making.

Rodent premotor cortex (M2) integrates information from sensory and cognitive networks for action planning during goal-directed decision making. M2 function is regulated by cortical inputs and ascending neuromodulators, including norepinephrine (NE) released from the locus coeruleus (LC). LC-NE has been shown to modulate the signal to noise ratio of neural representations in target cortical regions, increasing the salience of relevant stimuli. Using rats performing a two-alternative forced choice task after administration of a β noradrenergic antagonist (propranolol), we show that β noradrenergic signaling is necessary for effective action plan signals in anterior M2. Loss of β noradrenergic signaling results in failure to suppress irrelevant action plans in anterior M2 disrupting decoding of cue related information, delaying decision times, and increasing trial omissions, particularly in females. Furthermore, we identify a potential mechanism for the sex bias in behavioral and neural changes after propranolol administration via differential expression of β2 noradrenergic receptor RNA across sexes in anterior M2, particularly on local inhibitory neurons. Overall, we show a critical role for β noradrenergic signaling in anterior M2 during decision making by suppressing irrelevant information to enable efficient action planning and decision making.

Healthcare experience affects pain-specific responses to others' suffering in the anterior insula.

Medical students and professional healthcare providers often underestimate patients' pain, together with decreased neural responses to pain information in the anterior insula (AI), a brain region implicated in self-pain processing and negative affect. However, the functional significance and specificity of these neural changes remains debated. Across two experiments, we recruited university medical students and emergency nurses to test the role of healthcare experience on the brain reactivity to other's pain, emotions, and beliefs, using both pictorial and verbal cues. Brain responses to self-pain was also assessed and compared with those to observed pain. Our results confirmed that healthcare experience decreased the activity in AI in response to others' suffering. This effect was independent from stimulus modality (pictures or texts), but specific for pain, as it did not generalize to inferences about other mental or affective states. Furthermore, representational similarity and multivariate pattern analysis revealed that healthcare experience impacted specifically a component of the neural representation of others' pain that is shared with that of first-hand nociception, and related more to AI than to other pain-responsive regions. Taken together, our study suggests a decreased propensity to appraise others' suffering as one's own, associated with a reduced recruitment of pain-specific information in AI. These findings provide new insights into neural mechanisms leading to pain underestimation by caregivers in clinical settings.