Corticostriatal Circuits Research Articles

Differential impact of optogenetic stimulation of direct and indirect pathways from dorsolateral and dorsomedial striatum on motor symptoms in Huntington's disease mice

The alterations in the basal ganglia circuitry are core pathological hallmark in Huntington's Disease (HD) and traditionally linked to its sever motor symptoms. Recently it was shown that optogenetic stimulation of cortical afferences to the striatum is able to reverse motor symptoms in HD mice. However, the specific contribution of the direct and indirect striatal output pathways from the dorsolateral (DLS) and dorsomedial striatum (DMS) to the motor phenotype is still not clear. Here, we aim to uncover the contributions of these striatal subcircuits to motor control in wild type (WT) and HD mice by using the symptomatic R6/1 mice. We systematically evaluated locomotion, exploratory behavior, and motor learning effects of the selective optogenetic stimulation of D1 or A2A expressing neurons (direct and indirect pathway, respectively), in DLS or DMS. Bilateral optogenetic stimulation of the direct pathway from DLS and the indirect pathway from DMS resulted in subtle locomotor enhancements, while unaltering exploratory behavior. Additionally, bilateral stimulation of the indirect pathway from the DLS improved performance in the accelerated rotarod task, suggesting a role in motor learning. In contrast, in HD mice, stimulation of these pathways did not modulate any of these behaviors. Overall, this study highlights that selective stimulation of direct and indirect pathways from DLS and DMS have subtle impact in locomotion, exploratory activity nor motor learning. The lack of responses in HD mice also suggests that strategies involving cortico-striatal circuits rather than striatal output circuits might be a better strategy for managing motor symptoms in movement disorders.

Cross-species striatal hubs: Linking anatomy to resting-state connectivity

Corticostriatal connections are essential for motivation, cognition, and behavioral flexibility. There is broad interest in using resting-state functional magnetic resonance imaging (rs-fMRI) to link circuit dysfunction in these connections with neuropsychiatric disorders. In this paper, we used tract-tracing data from non-human primates (NHPs) to assess the likelihood of monosynaptic connections being represented in rs-fMRI data of NHPs and humans. We also demonstrated that existing hub locations in the anatomical data can be identified in the rs-fMRI data from both species. To characterize this in detail, we mapped the complete striatal projection zones from 27 tract-tracer injections located in the orbitofrontal cortex (OFC), dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (vmPFC), ventrolateral PFC (vlPFC), and dorsal PFC (dPFC) of macaque monkeys. Rs-fMRI seeds at the same regions of NHP and homologous regions of human brains showed connectivity maps in the striatum mostly consistent with those observed in the tracer data. We then examined the location of overlap in striatal projection zones. The medial rostral dorsal caudate connected with all five frontocortical regions evaluated in this study in both modalities (tract-tracing and rs-fMRI) and species (NHP and human). Other locations in the caudate also presented an overlap of four frontocortical regions, suggesting the existence of different locations with lower levels of input diversity. Small retrograde tracer injections and rs-fMRI seeds in the striatum confirmed these cortical input patterns. This study sets the ground for future studies evaluating rs-fMRI in clinical samples to measure anatomical corticostriatal circuit dysfunction and identify connectional hubs to provide more specific treatment targets for neurological and psychiatric disorders.

A shared spatial topography links the functional connectome correlates of cocaine use disorder and dopamine D2/3 receptor densities

The biological mechanisms that contribute to cocaine and other substance use disorders involve an array of cortical and subcortical systems. Prior work on the development and maintenance of substance use has largely focused on cortico-striatal circuits, with relatively less attention on alterations within and across large-scale functional brain networks, and associated aspects of the dopamine system. Here, we characterize patterns of functional connectivity in cocaine use disorder and their spatial association with neurotransmitter receptor densities and transporter bindings assessed through PET. Profiles of functional connectivity in cocaine use disorder reliably linked with spatial densities of dopamine D2/3 receptors across independent datasets. These findings demonstrate that the topography of dopamine receptor densities may underlie patterns of functional connectivity in cocaine use disorder, as assessed through fMRI.

Functional and free-water imaging in rapid eye movement behaviour disorder and Parkinson's disease.

It is established that one of the best predictors of a future diagnosis of Parkinson's disease is a current diagnosis of rapid eye movement behaviour disorder (RBD). In such patients, this provides a unique opportunity to study brain physiology and behavioural motor features of RBD that may precede early-stage Parkinson's disease. Based on prior work in early-stage Parkinson's disease, we aim to determine if the function of corticostriatal and cerebellar regions are impaired in RBD using task-based functional MRI and if structural changes can be detected within the caudate, putamen and substantia nigra in RBD using free-water imaging. To assess motor function, we measured performance on the Purdue Pegboard Test, which is affected in patients with RBD and Parkinson's disease. A cohort of 24 RBD, 39 early-stage Parkinson's disease and 25 controls were investigated. All participants were imaged at 3 Telsa. Individuals performed a unimanual grip force task during functional imaging. Participants also completed scales to assess cognition, sleep and motor symptoms. We found decreased functional activity in both RBD and Parkinson's disease within the motor cortex, caudate, putamen and thalamus compared with controls. There was elevated free-water-corrected fractional anisotropy in the putamen in RBD and Parkinson's disease and elevated free-water in the putamen and posterior substantia nigra in Parkinson's disease compared with controls. Participants with RBD and Parkinson's disease performed significantly worse on all tasks of the Purdue Pegboard Test compared with controls. The both hands task of the Purdue Pegboard Test was most sensitive in distinguishing between groups. A subgroup analysis of early-stage RBD (<2 years diagnosis) confirmed similar findings as those in the larger RBD group. These findings provide new evidence that the putamen is affected in early-stage RBD using both functional and free-water imaging. We also found evidence that the striatum, thalamus and motor cortex have reduced functional activity in early-stage RBD and Parkinson's disease. While the substantia nigra shows elevated free-water in Parkinson's disease, we did not observe this effect in early-stage RBD. These findings point to the corticostriatal and thalamocortical circuits being impaired in RBD patients.

Difference in Laterality of the Dorsal Striatum in Schizoaffective Disorder.

Recent research has demonstrated that the dorsal striatum is directly associated with the integration of cognitive, sensory-motor, and motivational/emotional data. Disruptions in the corticostriatal circuit have been implicated in the pathophysiology of psychosis. The dorsal striatum was reported to show lateralized pathology in psychotic disorders. In this study, we aimed to analyze the laterality of the dorsal striatum with texture analysis of T2-weighted magnetic resonance imaging (MRI) images from schizoaffective disorder (SAD) patients. Twenty SAD patients, met the inclusion criteria and had available cranial MRI data were assigned as the patient group. Twenty healthy individuals were determined as the control group. Texture analysis values were obtained from striatum region of interests (ROI) generated from T2-weighted MRI images. Data are presented as mean and standard deviation. The suitability of the data for normal distribution was analyzed with the Kolmogorov-Smirnov test. Analysis of variance (ANOVA) test (Post Hoc TUKEY) was employed to compare the group data based on test findings. There was no significant difference between the groups in terms of gender and age. There were differences in the values of texture analysis parameters of both caudate and putamen nuclei in comparison to controls. We identified differences in the left dorsal striatum nuclei in SAD. The differences in the putamen were more and more pronounced than in the caudate. Texture analyses suggest that the left dorsal striatum nuclei may be different in SAD patients. Further studies are needed to determine the pathophysiology of SAD and how it may affect disease treatment.

WAY-208466, a 5-HT6 receptor agonist, increases food motivation in primates: A behavioural and PET imaging study opening perspectives in eating disorders

The 5-HT6 receptor (5-HT6R) is highly expressed in the anterior striatum, a region involved in food-intake and anxiety-related behaviours that shows abnormal activity in anorexia nervosa (AN) patients. Indeed, 5-HT6R antagonists decrease food motivation across species. Rodent studies have shown the acute anxiolytic properties of WAY-208466, a selective 5-HT6R agonist. Thus, we hypothesized that this agent could increase food motivation and decrease anxiety-related behaviours by impacting cortico-striatal circuits. We administered acute (0.1 mg/kg) and subchronic (0.03 and 0.1 mg/kg) intramuscular injections to four macaques performing a food-choice task and expressing spontaneous behaviours. We used PET imaging with the [18F]2FNQ1P specific tracer to determine 5-HT6R occupancy in several regions that could be linked with the induced behavioural changes. Acute and subchronic activation of 5-HT6R transmission led to a reversible increase in food motivation. WAY-208466 also decreased anxiety-like behaviours when given acutely but not subchronically. However, in the subchronic protocol, the higher dose led to increased activity characterized by movements and object-related behaviour expression. PET imaging revealed that these behavioural changes could be sustained by cortico-striatal circuits involved in food intake. These findings demonstrate that this 5-HT6R agonist subchronic treatment successfully increases food motivation but does not fully achieve the expected anxiolytic effect in monkeys. It suggests that targeting 5-HT6Rs may be a promising approach for treating the restrictive subtype of AN, which, unlike anxiety, has not been shown to benefit from treatment with selective serotonin reuptake inhibitors.

Oxytocin pathway gene variation and corticostriatal resting-state functional connectivity

Genetic variations in single nucleotide polymorphisms (SNPs) within oxytocin pathway genes have been linked to social behavior and neurodevelopmental conditions. However, the neurobiological mechanisms underlying these associations remain elusive. In this study, we investigated the relationship between variations of 10 SNPs in oxytocin pathway genes and resting-state functional connectivity among 55 independent components using a large sample from the UK Biobank (N ≈ 30,000). Our findings revealed that individuals with the GG genotype at rs4813627 within the oxytocin structural gene (OXT) exhibited weaker resting-state functional connectivity in the corticostriatal circuit compared to those with the GA/AA genotypes. Empirical evidence has linked the GG genotype at OXT rs4813627 with a behavioral tendency of insensitivity to others. These results inform the neural mechanisms by which oxytocin-related genetic factors can influence social behavior.

A multi-region recurrent circuit for evidence accumulation in rats.

Decision-making based on noisy evidence requires accumulating evidence and categorizing it to form a choice. Here we evaluate a proposed feedforward and modular mapping of this process in rats: evidence accumulated in anterodorsal striatum (ADS) is categorized in prefrontal cortex (frontal orienting fields, FOF). Contrary to this, we show that both regions appear to be indistinguishable in their encoding/decoding of accumulator value and communicate this information bidirectionally. Consistent with a role for FOF in accumulation, silencing FOF to ADS projections impacted behavior throughout the accumulation period, even while nonselective FOF silencing did not. We synthesize these findings into a multi-region recurrent neural network trained with a novel approach. In-silico experiments reveal that multiple scales of recurrence in the cortico-striatal circuit rescue computation upon nonselective FOF perturbations. These results suggest that ADS and FOF accumulate evidence in a recurrent and distributed manner, yielding redundant representations and robustness to certain perturbations.

Neuron type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct

Cortical neuromodulation (CNM) is widely used to promote recovery after stroke. Despite the beneficial results of CNM, the roles played by different neuron types in the effects of current CNM techniques are unable to be differentiated. Our aim was to use selective optogenetic cortical stimulation to explore how different subpopulations of neuronal cells contribute to poststroke recovery. We transduced the sensory-parietal cortex (SPC) of rats with CamKII-ChR2 (pyramidal neurons), PV-ChR2 (parvalbumin-expressing inhibitory neurons), or hSyn-ChR2 (pan-neuronal population) before inducing photothrombotic capsular infarct lesions. We found that selective stimulation of inhibitory neurons resulted in significantly greater motor recovery than stimulation of excitatory neurons or the pan-neuronal population. Furthermore, 2-deoxy-2-[18F] fluoro-D-glucose microPET (FDG-microPET) imaging revealed a significant reduction in cortical diaschisis and activation of the corticostriatal neural circuit, which were correlated with behavioral recovery in the PV-ChR2 group. The spatial pattern of brain-derived neurotrophic factor (BDNF) expression was evident in the stimulated cortex and underlying cortico-subcortical circuit. Our results indicate that the plasticity of inhibitory neurons is crucial for functional recovery after capsular infarct. Modifying CNM parameters to potentiate the stimulation of inhibitory neurons could improve poststroke outcomes.

Striatal Dopamine Contributions to Skilled Motor Learning.

Coordinated multijoint limb and digit movements-"manual dexterity"-underlie both specialized skills (e.g., playing the piano) and more mundane tasks (e.g., tying shoelaces). Impairments in dexterous skill cause significant disability, as occurs with motor cortical injury, Parkinson's disease, and a range of other pathologies. Clinical observations, as well as basic investigations, suggest that corticostriatal circuits play a critical role in learning and performing dexterous skills. Furthermore, dopaminergic signaling in these regions is implicated in synaptic plasticity and motor learning. Nonetheless, the role of striatal dopamine signaling in skilled motor learning remains poorly understood. Here, we use fiber photometry paired with a genetically encoded dopamine sensor to investigate striatal dopamine release in both male and female mice as they learn and perform a skilled reaching task. Dopamine rapidly increases during a skilled reach and peaks near pellet consumption. In the dorsolateral striatum, dopamine dynamics are faster than in the dorsomedial and ventral striatum. Across training, as reaching performance improves, dopamine signaling shifts from pellet consumption to cues that predict pellet availability, particularly in medial and ventral areas of the striatum. Furthermore, performance prediction errors are present across the striatum, with reduced dopamine release after an unsuccessful reach. These findings show that dopamine dynamics during skilled motor behaviors change with learning and are differentially regulated across striatal subregions.

Treatment for OCD and Their Effectiveness

This research looks at a variety of aspects related to obsessive-compulsive disorder (OCD), such as symptoms, possible factors diagnosis, and treatment methods. OCD's distinctive ritualistic compulsions, which frequently manifest as uncontrollable thought and behavior patterns, are brought on by distressing obsessions. According to this study neurotransmitter and Corticostriatal circuits abnormalities have been linked to this disorder, although the exact cause is still unknown. Increased susceptibility among blood relations of sick individuals suggests a role for genetics. Obsessions and compulsions are diagnosed based on predetermined criteria that highlight their irrationality and disruptive nature. The connection between obsessive thoughts and anxiety can be broken by a number of treatments, the foundation of which is behavioral therapy. By gradually confronting anxiety-inducing circumstances, exposure and response prevention (ERP) has proven successful. According to this paper the main objectives of cognitive therapy are to address dysfunctional thought processes, such as overestimating threats or taking on excessive responsibility. This paper contends that by cognitive-behavioral therapy (CBT) combining behavioral and cognitive elements is both economical and efficient. The studies under review in this paper demonstrate differences in treatment effectiveness, accentuating the necessity for more studies with larger sample sizes in making definitive judgments on treatment outcomes.

Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism.

Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking. To this aim, preclinical studies can be really helpful to longitudinally study behavioural alterations resembling human symptoms and to investigate the underlying neurobiological correlates. In this regard, the BTBR T+ Itpr3tf/J (BTBR) mice are an inbred mouse strain that exhibits a pattern of behaviours well resembling human ASD-like behavioural features. In this study, the BTBR mice model was used to investigate neurochemical and biomolecular alterations, regarding Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), together with GABAergic, glutamatergic, cholinergic, dopaminergic and noradrenergic neurotransmissions and their metabolites in four different brain areas, i.e. prefrontal cortex, hippocampus, amygdala and hypothalamus. In our results, BTBR strain reported decreased noradrenaline, acetylcholine and GABA levels in prefrontal cortex, while hippocampal measurements showed reduced NGF and BDNF expression levels, together with GABA levels. Concerning hypothalamus, no differences were retrieved. As regarding amygdala, we found reduced dopamine levels, accompanied by increased dopamine metabolites in BTBR mice, together with decreased acetylcholine, NGF and GABA levels and enhanced glutamate content. Taken together, our data showed that the BTBR ASD model, beyond its face validity, is a useful tool to untangle neurotransmission alterations that could be underpinned to the heterogeneous ASD-like behaviours, highlighting the crucial role played by amygdala.

Dysfunctional feedback processing in male methamphetamine abusers: Evidence from neurophysiological and computational approaches

Methamphetamine use disorder (MUD) as a major public health risk is associated with dysfunctional neural feedback processing. Although dysfunctional feedback processing in people who are substance dependent has been explored in several behavioral, computational, and electrocortical studies, this mechanism in MUDs requires to be well understood. Furthermore, the current understanding of latent components of their behavior such as learning speed and exploration-exploitation dilemma is still limited. In addition, the association between the latent cognitive components and the related neural mechanisms also needs to be explored. Therefore, in this study, the underlying neurocognitive mechanisms of feedback processing of such impairment, and age/gender-matched healthy controls are evaluated within a probabilistic learning task with rewards and punishments. Mathematical modeling results based on the Q-learning paradigm suggested that MUDs show less sensitivity in distinguishing optimal options. Additionally, it may be worth noting that MUDs exhibited a slight decrease in their ability to learn from negative feedback compared to healthy controls. Also through the lens of underlying neural mechanisms, MUDs showed lower theta power at the medial-frontal areas while responding to negative feedback. However, other EEG measures of reinforcement learning including feedback-related negativity, parietal-P300, and activity flow from the medial frontal to lateral prefrontal regions, remained intact in MUDs. On the other hand, the elimination of the linkage between value sensitivity and medial-frontal theta activity in MUDs was observed. The observed dysfunction could be due to the adverse effects of methamphetamine on the cortico-striatal dopamine circuit, which is reflected in the anterior cingulate cortex activity as the most likely region responsible for efficient behavior adjustment. These findings could help us to pave the way toward tailored therapeutic approaches.

Annual Research Review: Neuroimmune network model of depression: adevelopmental perspective.

Depression is a serious public health problem, and adolescence is an 'age of risk' for the onset of Major Depressive Disorder. Recently, we and others have proposed neuroimmune network models that highlight bidirectional communication between the brain and the immune system in both mental and physical health, including depression. These models draw on research indicating that the cellular actors (particularly monocytes) and signaling molecules (particularly cytokines) that orchestrate inflammation in the periphery can directly modulate the structure and function of the brain. In the brain, inflammatory activity heightens sensitivity to threats in the cortico-amygdala circuit, lowers sensitivity to rewards in the cortico-striatal circuit, and alters executive control and emotion regulation in the prefrontal cortex. When dysregulated, and particularly under conditions of chronic stress, inflammation can generate feelings of dysphoria, distress, and anhedonia. This is proposed to initiate unhealthy, self-medicating behaviors (e.g. substance use, poor diet) to manage the dysphoria, which further heighten inflammation. Over time, dysregulation in these brain circuits and the inflammatory response may compound each other to form a positive feedback loop, whereby dysregulation in one organ system exacerbates the other. We and others suggest that this neuroimmune dysregulation is a dynamic joint vulnerability for depression, particularly during adolescence. We have three goals for the present paper. First, we extend neuroimmune network models of mental and physical health to generate a developmental framework of risk for the onset of depression during adolescence. Second, we examine how a neuroimmune network perspective can help explain the high rates of comorbidity between depression and other psychiatric disorders across development, and multimorbidity between depression and stress-related medical illnesses. Finally, we consider how identifying neuroimmune pathways to depression can facilitate a 'next generation' of behavioral and biological interventions that target neuroimmune signaling to treat, and ideally prevent, depression in youth and adolescents.

Optogenetic stimulation of corticostriatal circuits improves behavioral flexibility in mice with prenatal alcohol exposure

Fetal alcohol spectrum disorder (FASD) is the most common preventable form of developmental and neurobehavioral disability. Animal models have demonstrated that even low to moderate prenatal alcohol exposure (PAE) is sufficient to impair behavioral flexibility in multiple domains. Previously, utilizing a moderate limited access drinking in the dark paradigm, we have shown that PAE 1) impairs touchscreen pairwise visual reversal in male adult offspring 2) leads to small but significant decreases in orbitofrontal (OFC) firing rates 3) significantly increases dorsal striatum (dS) activity and 4) aberrantly sustains OFC-dS synchrony across early reversal. In the current study, we examined whether optogenetic stimulation of OFC-dS projection neurons would be sufficient to rescue the behavioral inflexibility induced by PAE in male C57BL/6J mice. Following discrimination learning, we targeted OFC-dS projections using a retrograde adeno-associated virus (AAV) delivered to the dS which expressed channel rhodopsin (ChR2). During the first four sessions of reversal learning, we delivered high frequency optogenetic stimulation to the OFC via optic fibers immediately following correct choice responses. Our results show that optogenetic stimulation significantly reduced the number of sessions, incorrect responses, and correction errors required to move past the early perseverative phase for both PAE and control mice. In addition, OFC-dS stimulation during early reversal learning reduced the increased sessions, correct and incorrect responding seen in PAE mice during the later learning phase of reversal but did not significantly alter later performance in control ChR2 mice. Taken together these results suggest that stimulation of OFC-dS projections can improve early reversal learning in PAE and control mice, and these improvements can persist even into later stages of the task days later. These studies provide an important foundation for future clinical approaches to improve executive control in those with FASD.This article is part of the Special Issue on “PFC circuit function in psychiatric disease and relevant models”.

Effects of Savoring Meditation on Positive Emotions and Pain-Related Brain Function: A Mechanistic Randomized Controlled Trial in People With Rheumatoid Arthritis

Positive emotions are a promising target for intervention in chronic pain, but mixed findings across trials to date suggest that existing interventions may not be optimized to efficiently engage the target. The aim of the current pilot mechanistic randomized controlled trial was to test the effects of a positive emotion-enhancing intervention called Savoring Meditation on pain-related neural and behavioral targets in patients with rheumatoid arthritis. Participants included 44 patients with a physician-confirmed diagnosis of rheumatoid arthritis (n = 29 included in functional magnetic resonance imaging (fMRI) analyses), who were randomized to either Savoring Meditation or a Slow Breathing control. Both meditation interventions were brief (four 20-minute sessions). Self-report measures were collected pre-and post-intervention. An fMRI task was conducted at post-intervention, during which participants practiced the meditation technique on which they had been trained while exposed to non-painful and painful thermal stimuli. Savoring significantly reduced experimental pain intensity ratings relative to rest (P < .001). Savoring also increased cerebral blood flow in the ventromedial prefrontal cortex and increased connectivity between the ventromedial prefrontal cortex and caudate during noxious thermal stimulation relative to Slow Breathing (z = 2.3 voxelwise, false discovery rate cluster corrected P = .05). Participants in the Savoring condition also reported significantly increased positive emotions (ps < .05) and reduced anhedonic symptoms (P < .01) from pre- to post-intervention. These findings suggest that Savoring recruits reward-enhancing corticostriatal circuits in the face of pain, and future work should extend these findings to evaluate if these mechanisms of Savoring are associated with improved clinical pain outcomes in diverse patient populations. PerspectiveSavoring Meditation is a novel positive emotion-enhancing intervention designed for patients with chronic pain. The present findings provide preliminary evidence that Savoring Meditation is acutely analgesic, and engages neural and subjective emotional targets that are relevant to pain self-management. Future work should evaluate the clinical translation of these findings.

The long-term impact of irradiation on functional connectivity in brain circuits involved in memory processes after pediatric posterior fossa tumor

PurposeMemory is one of the main specific cognitive domains impaired with attention and processing speed after a pediatric brain tumor. This work explored the long-term impact of radiotherapy in children with posterior fossa tumor (PFT) on brain connectivity in neural circuits involved in memory using resting-state functional magnetic resonance imaging (rs-fMRI). MethodsA total of 20 irradiated and 15 non-irradiated PFT survivors, and 21 healthy controls, prospectively included in the IMPALA study (NCT04324450), performed memory tests assessing episodic, procedural, and working memories and were subjected to an rs-fMRI. We manually contoured main structures involved in memory to explore connectivity at rest in a seed-to-voxel analysis. The groups were compared and differences in connectivity were correlated with behavioral scores and irradiation doses. ResultsThe performance of all mnesic tasks was lower in PFT survivors with a greater alteration in working and episodic memory in irradiated patients. Irradiated survivors had atypical connectivities in all memory circuits compared to controls and in cortico-caudate and cortico-cerebellar circuits compared to non-irradiated survivors. Non-irradiated survivors had only atypical connectivities in the cortico-cerebellar circuits compared to controls. In irradiated survivors, atypical connectivities in cortico-hippocampal circuits were linked with episodic memory scores and dose of irradiation to the left hippocampus and in cortico-striatal circuits with procedural memory scores and dose of irradiation to the striatum. ConclusionThe results of this study highlight that irradiation has a long-term impact on brain connectivity in brain circuits involved in memory after pediatric PFT with a specific radiation-dose effect in supratentorial structures.

Declarative Learning Mechanisms Support Declarative but Not Probabilistic Feedback-Based Learning in Children with Developmental Language Disorder (DLD).

Declarative and probabilistic feedback-based learning was evaluated in 8-12-year-old school-age children with developmental language disorder (DLD; n = 14) and age-matched children with typical development (TD; n = 15). Children performed a visual two-choice word-learning task and a visual probabilistic classification task while their electroencephalogram (EEG) was recorded non-invasively from the scalp. Behavioral measures of accuracy and response to feedback, and electrophysiological responses to feedback were collected and compared between the two groups. While behavioral data indicated poorer performance by children with DLD in both learning paradigms, and similar response patterns to positive and negative feedback, electrophysiological data highlighted processing patterns in the DLD group that differed by task. More specifically, in this group, feedback processing in the context of declarative learning, which is known to be dominated by the medial temporal lobe (MTL), was associated with enhanced N170, an event-related brain potential (ERP) associated with MTL activation. The N170 amplitude was found to be correlated with declarative task performance in the DLD group. During probabilistic learning, known to be governed by the striatal-based learning system, the feedback-related negativity (FRN) ERP, which is the product of the cortico-striatal circuit dominated feedback processing. Within the context of probabilistic learning, enhanced N170 was associated with poor learning in the TD group, suggesting that MTL activation during probabilistic learning disrupts learning. These results are interpreted within the context of a proposed feedback parity hypothesis suggesting that in children with DLD, the system that dominates learning (i.e., MTL during declarative learning and the striatum during probabilistic learning) dominates and supports feedback processing.

Neural circuit selective for fast but not slow dopamine increases in drug reward

The faster a drug enters the brain, the greater its addictive potential, yet the brain circuits underlying the rate dependency to drug reward remain unresolved. With simultaneous PET-fMRI we linked dynamics of dopamine signaling, brain activity/connectivity, and self-reported ‘high’ in 20 adults receiving methylphenidate orally (results in slow delivery) and intravenously (results in fast delivery) (trial NCT03326245). We estimated speed of striatal dopamine increases to oral and IV methylphenidate and then tested where brain activity was associated with slow and fast dopamine dynamics (primary endpoint). We then tested whether these brain circuits were temporally associated with individual ‘high’ ratings to methylphenidate (secondary endpoint). A corticostriatal circuit comprising the dorsal anterior cingulate cortex and insula and their connections with dorsal caudate was activated by fast (but not slow) dopamine increases and paralleled ‘high’ ratings. These data provide evidence in humans for a link between dACC/insula activation and fast but not slow dopamine increases and document a critical role of the salience network in drug reward.

Cortico-striatal activity associated with fidget spinner use: an fMRI study

Fidget spinners are said to be a very successful toy, and it's said that it has a good impact on attention for children with ADHD and hand motor control. However, there is limited scientific evidence to support these claims, and there is a lack of data on neurobiological responses to rotating fidget spinners. To better understand the mechanism whereby fidget spinners affect motor behavior, we tried to identify the neural correlates of rotating fidget spinners using functional magnetic resonance imaging and non-magnetic fidget spinners with five types of ease of rotation. As a result, we confirmed that the pre/postcentral gyrus, middle temporal gyrus, supplementary motor area (SMA), cerebellum, and striatum are activated when rotating spinners. Furthermore, the SMA was activated more with easier-to-rotate spinners. Additionally, a psychophysiological interaction analysis revealed increased functional connectivity between the SMA and the caudate while rotating fidget spinners compared to just holding them. These results suggest that the fine motor control associate with spinning a fidget spinner is supported by the cortico-striatal circuits involved in planning and reward.