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Background Methods Results Conclusions Adolescence is a critical developmental period for the study of anorexia nervosa (AN), an illness characterized by extreme restriction of food intake. The maturation of the reward system during adolescence combined with recent neurobiological models of AN led to the hypothesis that early on in illness, restrictive food choices would be associated with activity in nucleus accumbens reward regions, rather than caudate regions identified among adults with AN.Healthy adolescents (HC, n = 41) and adolescents with AN or atypical AN (atypAN, n = 76) completed a Food Choice Task during fMRI scanning. Selection of high‐fat foods and choice‐related activation in nucleus accumbens and anterior caudate regions‐of‐interest (ROIs) were compared between individuals with AN/atypAN and HC. Associations were examined between choice‐related activation and choice preferences among the AN group. Exploratory analyses examined associations between choice‐related activation and psychological assessments among the patient group.Adolescents with AN or atypAN selected fewer high‐fat foods than HC (t = −5.92, p < .001). Counter to predictions, there were no significant group differences in choice‐related activation in the ROIs. Among individuals with AN or atypAN, choice‐related neural activity in the anterior caudate was significantly negatively associated with high‐fat food selections in the task (r = −.32, p = .024). In exploratory analyses, choice‐related anterior caudate activation was positively associated with psychological measures of illness severity among patients (p's < .05, uncorrected).In this large cohort of adolescents with AN/atypAN, there was no evidence of altered reward system engagement during food choice. While there was no group difference in choice‐related caudate activation, the associations with choices and psychological measures continue to suggest that this neural region is implicated in illness. Longitudinal analyses will clarify whether neural variability relates to longer‐term course. [ABSTRACT FROM AUTHOR]

The dorsal striatum is composed of the caudate nucleus and the putamen in human and non‐human primates. These two regions receive different cortical projections and are functionally distinct. The caudate is involved in the control of goal‐directed behaviors, while the putamen is implicated in habit learning and formation. Previous reports indicate that ethanol differentially influences neurotransmission in these two regions. Because neurotransmitters primarily signal through G protein‐coupled receptors (GPCRs) to modulate neuronal activity, the present study aimed to determine whether ethanol had a region‐dependent impact on the expression of proteins that are involved in the trafficking and function of GPCRs, including G protein subunits and their effectors, protein kinases, and elements of the cytoskeleton. Western blotting was performed to examine protein levels in the caudate and the putamen of male cynomolgus macaques that self‐administered ethanol for 1 year under free access conditions, along with control animals that self‐administered an isocaloric sweetened solution under identical operant conditions. Among the 18 proteins studied, we found that the levels of one protein (PKCβ) were increased, and 13 proteins (Gαi1/3, Gαi2, Gαo, Gβ1γ, PKCα, PKCε, CaMKII, GSK3β, β‐actin, cofilin, α‐tubulin, and tubulin polymerization promoting protein) were reduced in the caudate of alcohol‐drinking macaques. However, ethanol did not alter the expression of any proteins examined in the putamen. These observations underscore the unique vulnerability of the caudate nucleus to changes in protein expression induced by chronic ethanol exposure. Whether these alterations are associated with ethanol‐induced dysregulation of GPCR function and neurotransmission warrants future investigation. [ABSTRACT FROM AUTHOR]

Classic research has shown a division in the neuroanatomical structures that support flexible (e.g., short‐cutting) and habitual (e.g., familiar route following) navigational behavior, with hippocampal–caudate systems associated with the former and putamen systems with the latter. There is, however, disagreement about whether the neural structures involved in navigation process particular forms of spatial information, such as associations between constellations of cues forming a cognitive map, versus single landmark‐action associations, or alternatively, perform particular reinforcement learning algorithms that allow the use of different spatial strategies, so‐called model‐based (flexible) or model‐free (habitual) forms of learning. We sought to test these theories by asking participants (N = 24) to navigate within a virtual environment through a previously learned, 9‐junction route with distinctive landmarks at each junction while undergoing functional magnetic resonance imaging (fMRI). In a series of probe trials, we distinguished knowledge of individual landmark‐action associations along the route versus knowledge of the correct sequence of landmark‐action associations, either by having absent landmarks, or "out‐of‐sequence" landmarks. Under a map‐based perspective, sequence knowledge would not require hippocampal systems, because there are no constellations of cues available for cognitive map formation. Within a learning‐based model, however, responding based on knowledge of sequence would require hippocampal systems because prior context has to be utilized. We found that hippocampal–caudate systems were more active in probes requiring sequence knowledge, supporting the learning‐based model. However, we also found greater putamen activation in probes where navigation based purely on sequence memory could be planned, supporting models of putamen function that emphasize its role in action sequencing. [ABSTRACT FROM AUTHOR]

Background: Intrastriatal delivery of potential therapeutics in Huntington's disease (HD) requires sufficient caudate and putamen volumes. Currently, volumetric magnetic resonance imaging is rarely done in clinical practice, and these data are not available in large research cohorts such as Enroll‐HD. Objective: The objective of this study was to investigate whether predictive models can accurately classify HD patients who exceed caudate and putamen volume thresholds required for intrastriatal therapeutic interventions. Methods: We obtained and merged data for 1374 individuals across three HD cohorts: IMAGE‐HD, PREDICT‐HD, and TRACK‐HD/TRACK‐ON. We imputed missing data for clinical variables with >72% non‐missing values and used the model‐building algorithm BORUTA to identify the 10 most important variables. A random forest algorithm was applied to build a predictive model for putamen volume >2500 mm3 and caudate volume >2000 mm3 bilaterally. Using the same 10 predictors, we constructed a logistic regression model with predictors significant at P < 0.05. Results: The random forest model with 1000 trees and minimal terminal node size of 5 resulted in 83% area under the curve (AUC). The logistic regression model retaining age, CAG repeat size, and symbol digit modalities test‐correct had 85.1% AUC. A probability cutoff of 0.8 resulted in 5.4% false positive and 66.7% false negative rates. Conclusions: Using easily obtainable clinical data and machine learning‐identified initial predictor variables, random forest, and logistic regression models can successfully identify people with sufficient striatal volumes for inclusion cutoffs. Adopting these models in prescreening could accelerate clinical trial enrollment in HD and other neurodegenerative disorders when volume cutoffs are necessary enrollment criteria. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Word finding difficulty is a frequent complaint in older age and disease states, but treatment options are lacking for such verbal retrieval deficits. Better understanding of the neurophysiological and neuroanatomical basis of verbal retrieval function may inform effective interventions. In this article, we review the current evidence of a neural retrieval circuit central to verbal production, including words and semantic memory, that involves the pre‐supplementary motor area (pre‐SMA), striatum (particularly caudate nucleus), and thalamus. We aim to offer a modified neural circuit framework expanded upon a memory retrieval model proposed in 2013 by Hart et al., as evidence from electrophysiological, functional brain imaging, and noninvasive electrical brain stimulation studies have provided additional pieces of information that converge on a shared neural circuit for retrieval of memory and words. We propose that both the left inferior frontal gyrus and fronto‐polar regions should be included in the expanded circuit. All these regions have their respective functional roles during verbal retrieval, such as selection and inhibition during search, initiation and termination of search, maintenance of co‐activation across cortical regions, as well as final activation of the retrieved information. We will also highlight the structural connectivity from and to the pre‐SMA (e.g., frontal aslant tract and fronto‐striatal tract) that facilitates communication between the regions within this circuit. Finally, we will discuss how this circuit and its correlated activity may be affected by disease states and how this circuit may serve as a novel target engagement for neuromodulatory treatment of verbal retrieval deficits. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The neuroanatomical changes driving both cognitive and mobility impairments, an emerging preclinical dementia syndrome, are not fully understood. We examined gray‐matter volumes (GMVs) and structural covariance networks (SCNs) abnormalities in community‐based older people preceding the conversion to physio‐cognitive decline syndrome (PCDS). METHODS: Voxel‐wise brain GMV and established SCNs were compared between PCDS and non‐PCDS converters. RESULTS: The study included 343 individuals (60.2 ± 6.9 years, 49.6% men) with intact cognitive and mobility functions. Over an average 5.6‐year follow‐up, 116 transitioned to PCDS. Identified regions with abnormal GMVs in PCDS converters were over cerebellum and caudate, which served as seeds for SCNs establishment. Significant differences in cerebellum‐based (to right frontal pole and left middle frontal gyrus) and caudate‐based SCNs (to right caudate putamen, right planum temporale, left precentral gyrus, right postcentral gyrus, and left parietal operculum) between converters and nonconverters were observed. DISCUSSION: This study reveals early neuroanatomic changes, emphasizing the cerebellum's role, in dual cognitive and mobility impairments. Highlights: Neuroanatomic precursors of dual cognitive and mobility impairments are identified.Cerebellar GMV reductions and increased right caudate GMV precede the onset of PCDS.Altered cerebellum‐ and caudate‐based SCNs drive PCDS transformation.This research establishes a foundation for understanding PCDS as a specific dementia syndrome. [ABSTRACT FROM AUTHOR]

Salinity (sodium chloride, NaCl) from anthropogenic sources is a persistent contaminant that negatively affects freshwater taxa. Amphibians can be susceptible to salinity, but some species are innately or adaptively tolerant. Physiological mechanisms mediating tolerance to salinity are still unclear, but changes in osmoregulatory hormones such as corticosterone (CORT) and aldosterone (ALDO) are prime candidates. We exposed larval barred tiger salamanders (Ambystoma mavortium) to environmentally relevant NaCl treatments (<32–4000 mg·L−1) for 24 days to test effects on growth, survival, and waterborne CORT responses. Of those sampled, we also quantified waterborne ALDO from a subset. Using a glucocorticoid antagonist (RU486), we also experimentally suppressed CORT signaling of some larvae to determine if CORT mediates effects of salinity. There were no strong differences in survival among salinity treatments, but salinity reduced dry mass, snout–vent length, and body condition while increasing water content of larvae. High survival and sublethal effects demonstrated that salamanders were physiologically challenged but could tolerate the experimental concentrations. CORT signaling did not attenuate sublethal effects of salinity. Baseline and stress‐induced (after an acute stressor, shaking) CORT were not influenced by salinity. ALDO was correlated with baseline CORT, suggesting it could be difficult to decouple the roles of CORT and ALDO. Future studies comparing ALDO and CORT responses of adaptively tolerant and previously unexposed populations could be beneficial to understand the roles of these hormones in tolerance to salinity. Nevertheless, our study enhances our understanding of the roles of corticosteroid hormones in mediating effects of a prominent anthropogenic stressor. [ABSTRACT FROM AUTHOR]

Introduction: The dorsal striatum, comprised of the caudate and putamen, is implicated in the pathophysiology of psychosis spectrum disorders. Given the high concentration of dopamine receptors in the striatum, striatal dopamine imbalance is a likely cause in cortico‐striatal dysconnectivity. There is great interest in understanding the relationship between striatal abnormalities in psychosis and antipsychotic treatment response, but few studies have considered differential involvement of the caudate and putamen. This study's goals were twofold. First, identify patterns of dorsal striatal dysconnectivity for the caudate and putamen separately in patients with a psychosis spectrum disorder; second, determine if these dysconnectivity patterns were predictive of treatment response. Methods: Using resting state functional connectivity, we evaluated dorsal striatal connectivity using separate bilateral caudate and putamen seed regions in two cohorts of subjects: a cohort of 71 medication‐naïve first episode psychosis patients and a cohort of 42 unmedicated patients with schizophrenia (along with matched controls). Patient and control connectivity maps were contrasted for each cohort. After receiving 6 weeks of risperidone treatment, patients' clinical response was calculated. We used regression analyses to determine the relationship between baseline dysconnectivity and treatment response. Results: This dysconnectivity was also predictive of treatment response in both cohorts. Discussion: These findings suggest that the caudate may be more of a driving factor than the putamen in early cortico‐striatal dysconnectivity. [ABSTRACT FROM AUTHOR]

Gray matter (GM) atrophy is frequently detected in persons living with HIV, even in the era of combination antiretroviral therapy (cART), but the specificity of regions affected remains elusive. For instance, which regions are consistently affected in HIV? In addition, atrophy at which regions is frequently associated with neurocognitive impairment in HIV? Resolving these questions can potentially help to establish the possible neural profiles of HIV‐associated neurocognitive disorders (HAND) severity, which currently is solely defined by neurobehavioral assessments. Here, we addressed these questions using a novel meta‐analysis technique, the colocalization‐likelihood estimation (CLE) technique, to quantitatively synthesize the findings of GM atrophy in HIV+ adults. Twenty‐one of 386 studies published between 1988 and November 2017 and identified in PubMed were selected, plus four identified in other resources. In the end, 25 studies (1,370 HIV+ adults, 889 HIV− controls) were included in the meta‐analysis. This technique revealed that GM atrophy in HIV+ adults was dominated by two distinct but nonexclusive profiles: frontal (including anterior cingulate cortex, [ACC]) atrophy, which was associated withHIV‐disease and consistently differentiated HIV+ adults from HIV− controls; and caudate/striatum atrophy, which was associated with neurocognitive impairment. The critical role of caudate/striatum atrophy in neurocognitive impairment was further supported by a separate data analysis, which examined the findings of correlation analyses between GM and neurocognitive performance. These results suggest that the frontal lobe and the striatum play critical but differential roles in HAND. A neural model of HAND severity was proposed with several testable predictions. [ABSTRACT FROM AUTHOR]

Although the activation of the prefrontal cortex (PFC) and the striatum had been found in smoking cue induced craving task, whether and how the functional interactions and white matter integrity between these brain regions contribute to craving processing during smoking cue exposure remains unknown. Twenty-five young male smokers and 26 age- and gender-matched nonsmokers participated in the smoking cue-reactivity task. Craving related brain activation was extracted and psychophysiological interactions (PPI) analysis was used to specify the PFC-efferent pathways contributed to smoking cue-induced craving. Diffusion tensor imaging (DTI) and probabilistic tractography was used to explore whether the fiber connectivity strength facilitated functional coupling of the circuit with the smoking cue-induced craving. The PPI analysis revealed the negative functional coupling of the left dorsolateral prefrontal cortex (DLPFC) and the caudate during smoking cue induced craving task, which positively correlated with the craving score. Neither significant activation nor functional connectivity in smoking cue exposure task was detected in nonsmokers. DTI analyses revealed that fiber tract integrity negatively correlated with functional coupling in the DLPFC-caudate pathway and activation of the caudate induced by smoking cue in smokers. Moreover, the relationship between the fiber connectivity integrity of the left DLPFC-caudate and smoking cue induced caudate activation can be fully mediated by functional coupling strength of this circuit in smokers. The present study highlighted the left DLPFC-caudate pathway in smoking cue-induced craving in smokers, which may reflect top-down prefrontal modulation of striatal reward processing in smoking cue induced craving processing. Hum Brain Mapp 38:4644-4656, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Restricted and repetitive behaviors are a defining feature of autism, which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT2A receptor activity is altered in autism, while recent work indicates that systemic 5HT2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT2A receptors are expressed in the orbitofrontal cortex and striatum. These two regions have been shown to be altered in autism. The present study investigated whether 5HT2A receptor blockade in the dorsomedial striatum or orbitofrontal cortex in the BTBR mouse strain, an idiopathic model of autism, affects the phenotype related to restricted and repetitive behaviors. Microinfusion of the 5HT2A receptor antagonist, M100907 into the dorsomedial striatum alleviated a reversal learning impairment and attenuated grooming behavior. M100907 infusion into the orbitofrontal cortex increased perseveration during reversal learning and potentiated grooming. These findings suggest that increased 5HT2A receptor activity in the dorsomedial striatum may contribute to behavioral inflexibility and stereotyped behaviors in the BTBR mouse. 5HT2A receptor signaling in the orbitofrontal cortex may be critical for inhibiting a previously learned response during reversal learning and expression of stereotyped behavior. The present results suggest which brain areas exhibit abnormalities underlying repetitive behaviors in an idiopathic mouse model of autism, as well as which brain areas systemic treatment with M100907 may principally act on in BTBR mice to attenuate repetitive behaviors. [ABSTRACT FROM AUTHOR]

Although specific brain regions have been implicated in long-term memory processes, the brain function responsible for correctly recollecting information remains incompletely understood. This study used a remember-recollection-recognition task to explore brain activities specifically associated with correct recollection. Seventy-eight subjects were first asked to remember 40 items and recollect them in the scanner. Comparison of correctly recollected trials to incorrectly recollected trials (when participants mistakenly believed they had recollected information correctly) identified greater activation of the caudate bilaterally. The involvement of caudate activation appears important in recollecting information correctly. Potential explanations and implications are discussed. Hum Brain Mapp 37:3999-4005, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Stress triggers impulsive and addictive behaviors, and alcoholism has been frequently associated with increased stress sensitivity and impulse control problems. However, neural correlates underlying the link between alcoholism and impulsivity in the context of stress in patients with alcohol use disorders ( AUD) have not been well studied. Methods This study investigated neural correlates and connectivity patterns associated with impulse control difficulties in abstinent AUD patients. Using functional magnetic resonance imaging, brain responses of 37 AUD inpatients, and 37 demographically matched healthy controls were examined during brief individualized imagery trials of stress, alcohol cue, and neutral-relaxing conditions. Stress-related impulsivity was measured using a subscale score of impulse control problems from Difficulties in Emotion Regulation Scale. Results Impulse control difficulties in AUD patients were significantly associated with hypo-active response to stress in the ventromedial prefrontal cortex (Vm PFC), right caudate, and left lateral PFC ( LPFC) compared to the neutral condition ( p < 0.01, whole-brain corrected). These regions were used as seed regions to further examine the connectivity patterns with other brain regions. With the VmPFC seed, AUD patients showed reduced connectivity with the anterior cingulate cortex compared to controls, which are core regions of emotion regulation, suggesting AUD patients' decreased ability to modulate emotional response under distressed state. With the right caudate seed, patients showed increased connectivity with the right motor cortex, suggesting increased tendency toward habitually driven behaviors. With the left LPFC seed, decreased connectivity with the dorsomedial PFC (Dm PFC), but increased connectivity with sensory and motor cortices were found in AUD patients compared to controls ( p < 0.05, whole-brain corrected). Reduced connectivity between the left LPFC and Dm PFC was further associated with increased stress-induced anxiety in AUD patients ( p < 0.05, with adjusted Bonferroni correction). Conclusions Hypo-active response to stress and altered connectivity in key emotion regulatory regions may account for greater stress-related impulse control problems in alcoholism. [ABSTRACT FROM AUTHOR]

Successful social interactions depend on the ability to anticipate other people's actions. Current conceptualizations of brain function propose that causes of sensory input are inferred through their integration with internal predictions generated in the observer's motor system during action observation. Less is known concerning how action prediction changes with age. Previously we showed that internal action representations are less specific in older compared with younger adults at behavioral and neural levels. Here, we characterize how neural activity varies while healthy older adults aged 56-71 years predict the time-course of an unfolding action as well as the relation to task performance. By using fMRI, brain activity was measured while participants observed partly occluded actions and judged the temporal coherence of the action continuation that was manipulated. We found that neural activity in frontoparietal and occipitotemporal regions increased the more an action continuation was shifted backwards in time. Action continuations that were shifted towards the future preferentially engaged early visual cortices. Increasing age was associated with neural activity that extended from posterior to anterior regions in frontal and superior temporal cortices. Lower sensitivity in action prediction resulted in activity increases in the caudate. These results imply that the neural implementation of predicting actions undergoes similar changes as the neural process of executing actions in older adults. The comparison between internal predictions and sensory input seems to become less precise with age leading to difficulties in anticipating observed actions accurately, possibly due to less specific internal action models. [ABSTRACT FROM AUTHOR]

Background Psychological factors are known to significantly modulate itch in patients suffering from chronic itch. Itch is also highly susceptible to both placebo and nocebo (negative placebo) effects. Brain activity likely supports nocebo-induced itch, but is currently unknown. Methods We collected functional MRI (fMRI) data from atopic dermatitis ( AD) patients, in a within-subject design, and contrast brain response to nocebo saline understood to be allergen vs open-label saline control. Exploratory analyses compared results to real allergen itch response and placebo responsiveness, evaluated in the same patients. Results Nocebo saline produced greater itch than open saline control ( P < 0.01). Compared to open saline, nocebo saline demonstrated greater fMRI response in caudate, dorsolateral prefrontal cortex (dl PFC), and intraparietal sulcus (iPS) - brain regions important for cognitive executive and motivational processing. Exploratory analyses found that subjects with greater dl PFC and caudate activation to nocebo-induced itch also demonstrated greater dl PFC and caudate activation, respectively, for real allergen itch. Subjects reporting greater nocebo-induced itch also demonstrated greater placebo reduction of allergen-evoked itch, suggesting increased generalized modulation of itch perception. Conclusions Our study demonstrates the capacity of nocebo saline to mimic both the sensory and neural effects of real allergens and provides an insight to the brain mechanisms supporting nocebo-induced itch in AD, thus aiding our understanding of the role that expectations and other psychological factors play in modulating itch perception in chronic itch patients. [ABSTRACT FROM AUTHOR]

Aim The simplified reference tissue model ( SRTM) is used for estimation of receptor occupancy assuming that the non-displaceable binding in the reference region is identical to the brain regions of interest. The aim of this work was to extend the SRTM to also account for inter-regional differences in non-displaceable concentrations, and to investigate if this model allowed estimation of receptor occupancy using white matter as reference. It was also investigated if an apparent higher affinity in caudate compared with other brain regions, could be better explained by a difference in the extent of non-displaceable binding. Methods The analysis was based on a PET study in six healthy volunteers using the 5- HT1B receptor radioligand [11C]- AZ10419369. The radioligand was given intravenously as a tracer dose alone and following different oral doses of the 5- HT1B receptor antagonist AZD3783. Non-linear mixed effects models were developed where differences between regions in non-specific concentrations were accounted for. The properties of the models were also evaluated by means of simulation studies. Results The estimate (95% CI) of KiPL was 10.2 ng ml−1 (5.4, 15) and 10.4 ng ml−1 (8.1, 13.6) based on the extended SRTM with white matter as reference and based on the SRTM using cerebellum as reference, respectively. The estimate (95% CI) of KiPL for caudate relative to other brain regions was 55% (48, 62%). Conclusions The extended SRTM allows consideration of white matter as reference region when no suitable grey matter region exists. AZD3783 affinity appears to be higher in the caudate compared with other brain regions. [ABSTRACT FROM AUTHOR]

This study examined the association between size of the caudate nuclei and intelligence. Based on the central role of the caudate in learning, as well as neuroimaging studies linking greater caudate volume to better attentional function, verbal ability, and dopamine receptor availability, we hypothesized the existence of a positive association between intelligence and caudate volume in three large independent samples of healthy adults (total N = 517). Regression of IQ onto bilateral caudate volume controlling for age, sex, and total brain volume indicated a significant positive correlation between caudate volume and intelligence, with a comparable magnitude of effect across each of the three samples. No other subcortical structures were independently associated with IQ, suggesting a specific biological link between caudate morphology and intelligence. Hum Brain Mapp 36:1407-1416, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Animal approach-avoidance conflict paradigms have been used extensively to operationalize anxiety, quantify the effects of anxiolytic agents, and probe the neural basis of fear and anxiety. Results from human neuroimaging studies support that a frontal-striatal-amygdala neural circuitry is important for approach-avoidance learning. However, the neural basis of decision-making is much less clear in this context. Thus, we combined a recently developed human approach-avoidance paradigm with functional magnetic resonance imaging (fMRI) to identify neural substrates underlying approach-avoidance conflict decision-making. Fifteen healthy adults completed the approach-avoidance conflict (AAC) paradigm during fMRI. Analyses of variance were used to compare conflict to nonconflict (avoid-threat and approach-reward) conditions and to compare level of reward points offered during the decision phase. Trial-by-trial amplitude modulation analyses were used to delineate brain areas underlying decision-making in the context of approach/avoidance behavior. Conflict trials as compared to the nonconflict trials elicited greater activation within bilateral anterior cingulate cortex, anterior insula, and caudate, as well as right dorsolateral prefrontal cortex (PFC). Right caudate and lateral PFC activation was modulated by level of reward offered. Individuals who showed greater caudate activation exhibited less approach behavior. On a trial-by-trial basis, greater right lateral PFC activation related to less approach behavior. Taken together, results suggest that the degree of activation within prefrontal-striatal-insula circuitry determines the degree of approach versus avoidance decision-making. Moreover, the degree of caudate and lateral PFC activation related to individual differences in approach-avoidance decision-making. Therefore, the approach-avoidance conflict paradigm is ideally suited to probe anxiety-related processing differences during approach-avoidance decision-making. Hum Brain Mapp 36:449-462, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim Major depressive disorder ( MDD) onset during childhood/adolescence is associated with a greater illness burden and distinct clinical profile. However, limited research exists on the effect of age of MDD onset on volumetric abnormalities in para/limbic structures during adulthood. Methods Subgenual anterior cingulate cortex ( sgACC), hippocampus and caudate nucleus volumes were measured by manual tracing in depressed individuals ( n = 45) and healthy controls ( HC; n = 19). Volumetric comparisons were carried out between HC and MDD patients divided into those with pediatric (≤18 years; n = 17) and adult onset (≥19 years; n = 28). Results The adult MDD-onset group had smaller sgACC volumes than the pediatric-onset and HC groups (age, sex controlled). No differences in caudate and hippocampus volumes existed. sgACC and hippocampal volumes were inversely correlated with depression severity. Conclusions Surprisingly, pediatric MDD-onset was not associated with more pronounced sgACC, hippocampus and caudate volume reductions. Nevertheless, age of illness onset appears to be a meaningful dimension of study in efforts to understand the neurobiological heterogeneity of MDD. [ABSTRACT FROM AUTHOR]

Amphetamine is a central nervous system psychostimulant with a high potential for abuse. Recent literature has shown that genetic and drug-induced elevations in dopamine transporter ( DAT) expression augment the neurochemical and behavioral potency of psychostimulant releasers. However, it remains to be determined if the well-documented differences in DAT levels across striatal regions drive regionally distinct amphetamine effects within individuals. DAT levels and dopamine uptake rates have been shown to follow a gradient in the striatum, with the highest levels in the dorsal regions and lowest levels in the nucleus accumbens shell; thus, we hypothesized that amphetamine potency would follow this gradient. Using fast scan cyclic voltammetry in mouse brain slices, we examined DAT inhibition and changes in exocytotic dopamine release by amphetamine across four striatal regions (dorsal and ventral caudate-putamen, nucleus accumbens core and shell). Consistent with our hypothesis, amphetamine effects at the DAT and on release decreased across regions from dorsal to ventral, and both measures of potency were highly correlated with dopamine uptake rates. Separate striatal subregions are involved in different aspects of motivated behaviors, such as goal-directed and habitual behaviors, that become dysregulated by drug abuse, making it critically important to understand regional differences in drug potencies. [ABSTRACT FROM AUTHOR]

The psychostimulant amphetamine (AMPH) is frequently used to increase catecholamine levels in attention disorders and positron emission tomography imaging studies. Despite the fact that most radiotracers for positron emission tomography studies are characterized in non-human primates (NHPs), data on regional differences of the effect of AMPH in NHPs are very limited. This study examined the impact of AMPH on extracellular dopamine (DA) levels in the medial prefrontal cortex and the caudate of NHPs using microdialysis. In addition to differences in magnitude, we observed striking differences in the temporal profile of extracellular DA levels between these regions that can likely be attributed to differences in the regulation of dopamine uptake and biosynthesis. The present data suggest that cortical DA levels may remain elevated longer than in the caudate which may contribute to the clinical profile of the actions of AMPH. [ABSTRACT FROM AUTHOR]

People make decisions by evaluating existing evidence against a threshold or level of confidence. Individuals vary widely in response times even when they perform a simple task in the laboratory. We examine the neural bases of this individual variation by combining computational modeling and brain imaging of 64 healthy adults performing a stop signal task. Behavioral performance was modeled by an accumulator model that describes the process of information growth to reach a threshold to respond. In this model, go trial reaction time (goRT) is jointly determined by the information growth rate, threshold, and movement time (MT). In a linear regression of activations in successful go and all stop (Go+Stop) trials against goRT across participants, the insula, supplementary motor area (SMA), pre-SMA, thalamus including the subthalamic nucleus (STN), and caudate head respond to increasing goRT. Among these areas, the insula, SMA, and thalamus including the STN respond to a slower growth rate, the caudate head responds to an elevated threshold, and the pre-SMA responds to a longer MT. In the regression of Go+Stop trials against the stop signal reaction time (SSRT), the pre-SMA shows a negative correlation with SSRT. These results characterize the component processes of decision making and elucidate the neural bases of a critical aspect of inter-subject variation in human behavior. These findings also suggest that the pre-SMA may play a broader role in response selection and cognitive control rather than simply response inhibition in the stop signal task. Hum Brain Mapp 35:2531-2542, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT Area V4 has numerous, topographically organized connections with multiple cortical areas, some of which are important for spatially organized visual processing, and others which seem important for spatial attention. Although the topographic organization of V4's connections with other cortical areas has been established, the detailed topography of its connections with subcortical areas is unclear. We therefore injected retrograde and anterograde tracers in different topographical regions of V4 in nine macaques to determine the organization of its subcortical connections. The injection sites included representations ranging from the fovea to far peripheral eccentricities in both the upper and lower visual fields. The topographically organized connections of V4 included bidirectional connections with four subdivisions of the pulvinar, two subdivisions of the claustrum, and the interlaminar portions of the lateral geniculate nucleus, and efferent projections to the superficial and intermediate layers of the superior colliculus, the thalamic reticular nucleus, and the caudate nucleus. All of these structures have a possible role in spatial attention. The nontopographic, or converging, connections included bidirectional connections with the lateral nucleus of the amygdala, afferent inputs from the dorsal raphe, median raphe, locus coeruleus, ventral tegmentum and nucleus basalis of Meynert, and efferent projections to the putamen. Any role of these structures in attention may be less spatially specific. J. Comp. Neurol. 522:1941-1965, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The precise pathogenic mechanisms of Huntington's disease (HD) are unknown but can be tested in vivo using proton magnetic resonance spectroscopy ((1)H MRS) to measure neurochemical changes. The objective of this study was to evaluate neurochemical differences in HD gene mutation carriers (HGMCs) versus controls and to investigate relationships among function, brain structure, and neurochemistry in HD. Because previous (1)H MRS studies have yielded varied conclusions about HD neurochemical changes, an additional goal was to compare two (1)H MRS data analysis approaches. HGMCs with premanifest to early HD and controls underwent evaluation of motor function, magnetic resonance imaging, and localized (1)H MRS in the caudate and the frontal lobe. Analytical approaches that were tested included absolute quantitation (unsuppressed water signal as an internal reference) and relative quantification (calculating ratios of all neurochemical signals within a voxel). We identified a suite of neurochemicals that were reduced in concentration proportionally to loss of caudate volume in HGMCs. Caudate concentrations of N-acetylaspartate (NAA), creatine, choline, and caudate and frontal lobe concentrations of glutamate plus glutamine (Glx) and glutamate were correlated with caudate volume in HGMCs. The relative, but not the absolute, quantitation approach revealed disease-related differences; the Glx signal was decreased relative to other neurochemicals in the caudate of HGMCs versus controls. This is the first study to demonstrate a correlation among structure, function, and chemical measures in HD brain. Additionally, we demonstrate that a relative quantitation approach may enable the magnification of subtle differences between groups. Observation of decreased Glx suggests that glutamate signaling may be disrupted relatively early in HD, which has important implications for therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Previous studies with a limited sample size suggested more severe dopaminergic transporter (DAT) lesions in the striatum of progressive supranuclear palsy (PSP) than those in Parkinson's disease (PD) and multiple system atrophy-parkinsonism (MSA-P). However, few studies had taken various subtypes of PSP into consideration, making the reanalysis of DAT imaging in larger PSP cohort with various subtypes in need., Objectives: To compare the dopaminergic lesion patterns of PSP with MSA-P and PD, and to explore the specific striatal subregional patterns of different PSP subtypes., Methods: 11 C-CFT positron emission tomography (PET) imaging was conducted in 83 PSP patients consisting of different subtypes, 61 patients with PD, 41 patients with MSA-P, and 43 healthy volunteers. Demographic and clinical data were compared by the chi-squared test or one-way analysis of variance. A generalized linear model was used to examine intergroup differences in tracer uptake values after adjusting for age, disease duration, and disease severity. Areas under the receiver operating characteristic curve were calculated to assess the diagnostic accuracy of subregional DAT binding patterns., Results: The patients with PSP presented more severe DAT loss in the striatum than in PD and MSA-P, especially in caudate. In PSP, the subregional lesion was still more severe in putamen than in caudate, similar to that in PD and MSA-P. Among detailed subtypes, no significant difference was detected., Conclusion: The dopaminergic lesions were more severe in PSP, and no difference was detected among subtypes., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The basal ganglia have traditionally been viewed as motor processing nuclei; however, functional neuroimaging evidence has implicated these structures in more complex cognitive and affective processes that are fundamental for a range of human activities. Using quantitative meta-analysis methods we assessed the functional subdivisions of basal ganglia nuclei in relation to motor (body and eye movements), cognitive (working-memory and executive), affective (emotion and reward) and somatosensory functions in healthy participants. We document affective processes in the anterior parts of the caudate head with the most overlap within the left hemisphere. Cognitive processes showed the most widespread response, whereas motor processes occupied more central structures. On the basis of these demonstrated functional roles of the basal ganglia, we provide a new comprehensive topographical model of these nuclei and insight into how they are linked to a wide range of behaviors. Hum Brain Mapp 34:3031-3054, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Multiple techniques exist for the automated segmentation of magnetic resonance images (MRIs). The validity of these techniques can be assessed by evaluating test-retest reliability, interscanner reliability, and consistency with manual segmentation. We evaluate these measures for the FSL/FIRST subcortical segmentation tool. We retrospectively analyzed 190 MRI scans from 87 subjects with mood or anxiety disorders and healthy volunteers scanned multiple times on different platforms ( N = 56) and/or the same platform ( N = 45, groups overlap), and 146 scans from subjects who underwent both high-resolution and whole brain imaging in a single session, for comparison with manual segmentation of the hippocampus. The thalamus, caudate, putamen, hippocampus, and pallidum were reliably segmented in different sessions on the same scanner (Intraclass correlation coefficient (ICC) > 0.83 scanners and diagnostic groups pooled). In these regions, the range of between platform reliabilities were lower (0.527 < ICC < 0.953), although values below 0.7 were due to systematic differences between platforms or low reliability in the hippocampus between eight- and single-channel coil platforms. Accumbens and amygdala segmentations were generally unreliable within and between scanning platforms. ICC values for hippocampal volumes between automated and manual segmentations were acceptable (ICC > 0.7, groups pooled), and both methods detected significant differences between genders. In addition, FIRST segmentations were consistent with manual segmentations (in a subset of images; N = 20) in the left caudate and bilateral putamen. This retrospective analysis assesses realistic performance of the algorithm in conditions like those found in multisite trials or meta-analyses. In addition, the inclusion of psychiatric patients establishes reliability in subjects exhibiting volumetric abnormalities, validating patient studies. Hum Brain Mapp 34:2313-2329, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives Executive function impairments are a core feature of bipolar I disorder ( BD-I), not only present during acute episodes but also persisting following remission of mood symptoms. Despite advances in knowledge regarding the neural basis of executive functions in healthy subjects, research into morphological abnormalities underlying the deficits in BD-I is lacking. Methods Patients with BD-I within three months of sustained remission from their first manic episode (n = 41) underwent neuropsychological testing and a 3T magnetic resonance imaging scan and were compared to healthy subjects matched for age, sex, and premorbid IQ (n = 30). Group dorsolateral prefrontal cortex ( DLPFC; Brodmann areas 9 and 46) and caudate volumes were examined and analyzed for relationships with the average score from three computerized tests of executive function: Spatial Working Memory, Stockings of Cambridge, and Intradimensional/Extradimensional Shift. Results Right caudate volumes were enlarged in patients ( z = 3.57, p < 0.05 corrected). No differences in DLPFC volumes were found. Patients showed large deficits in executive function relative to healthy subjects ( d = −0.92, p < 0.001). While in healthy subjects, a larger right ( r = +0.39, p < 0.05) and left ( r = +0.44, p < 0.05) caudate was associated with better executive function score, in patients, larger right ( r = −0.36, p < 0.05) and left ( r = −0.34, p < 0.05) volumes correlated with poorer performance. Conclusions Although the etiology of gray matter changes is unknown, volume increases in the right caudate may be an important factor underlying executive function impairments during remission in patients with BD-I. [ABSTRACT FROM AUTHOR]

The idea that humans use flexible map-like representations of their environment to guide spatial navigation has a long and controversial history. One reason for this enduring controversy might be that individuals vary considerably in their ability to form and utilize cognitive maps. Here we investigate the behavioral and neuroanatomical signatures of these individual differences. Participants learned an unfamiliar campus environment over a period of three weeks. In their first visit, they learned the position of different buildings along two routes in separate areas of the campus. During the following weeks, they learned these routes for a second and third time, along with two paths that connected both areas of the campus. Behavioral assessments after each learning session indicated that subjects formed a coherent representation of the spatial structure of the entire campus after learning a single connecting path. Volumetric analyses of structural MRI data and voxel-based morphometry (VBM) indicated that the size of the right posterior hippocampus predicted the ability to use this spatial knowledge to make inferences about the relative positions of different buildings on the campus. An inverse relationship between gray matter volume and performance was observed in the caudate. These results suggest that (i) humans can rapidly acquire cognitive maps of large-scale environments and (ii) individual differences in hippocampal anatomy may provide the neuroanatomical substrate for individual differences in the ability to learn and flexibly use these cognitive maps. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article discusses research on correlations of striatal dopamine synthesis with default network deactivations during working memory in younger adults. Study participants underwent positron emission tomography (PET) scans as well as functional magnetic resonance imaging (fMRI) while performing a delayed recognition working memory task. Based on the results, this synthesis assists in modulating default network activity in younger adults, and modifications to the dopamine system may contribute to age-related changes in working memory function.

The article presents a study that investigated the possible correlation between genetic factors and the volumes of subcortical brain structures. Several models for genetic factors namely a Basal Ganglia/Thalamus factor, a Ventricular factor, a Limbic factor, and a Nucleus Accumbens factor are found to fit the data generated. Genetic patterning among structures that differentiate between brain, different subcortical regions, and cerebrospinal fluid spaces was observed.

The ability to perform an appropriate response in the presence of competing alternatives is a critical facet of human behavioral control. This is especially important if a response is prepared for execution but then has to be changed suddenly. A popular hypothesis of basal ganglia (BG) function suggests that its direct and indirect pathways could provide a neural mechanism to rapidly switch from one planned response to an alternative. However, if one response is more dominant or ‘automatic’ than the other, the BG might have a different role depending on switch direction. We built upon the pro- and antisaccade tasks, two models of automatic and voluntary behavior, respectively, and investigated whether the BG are important for switching any planned response in general, or if they are more important for switching from a more automatic response to a response that is more difficult to perform. Subjects prepared either a pro- or antisaccade but then had to switch it unexpectedly on a subset of trials. The results revealed increased striatal activation for switching from a pro- to an antisaccade but this did not occur for switching from an anti- to a prosaccade. This activation pattern depended on the relative difficulty in switching, and it was distinct from frontal eye fields, an area shown to be more active for antisaccade trials than for prosaccade trials. This suggests that the BG are important for compensating for differences in response difficulty, facilitating the rapid switching of one response for another. [ABSTRACT FROM AUTHOR]

Hypothalamic orexin (hypocretin) neurons project to the key structures of the limbic system and orexin receptors, both orexin receptor type 1 (OXR1) and type 2 (OXR2), are expressed in most limbic regions. Emerging evidence suggests that orexin is among important neurotransmitters that regulate addictive properties of drugs of abuse. In this study, we examined the effect of psychostimulant cocaine on orexin receptor protein abundance in the rat limbic system in vivo. Intermittent administration of cocaine (20 mg/kg, i.p., once daily for 5 days) caused a typical behavioral sensitization response to a challenge cocaine injection at a 14-day withdrawal period. Repeated cocaine administration at the same withdrawal time also increased OXR2 protein levels in the nucleus accumbens while repeated cocaine had no effect on OXR1 and orexin neuropeptide (both orexin-A and orexin-B) levels in this region. In contrast to the nucleus accumbens, OXR2 levels in the frontal cortex, the ventral tegmental area, the hippocampus, and the dorsal striatum (caudate putamen) were not altered by cocaine. Remarkably, the up-regulated OXR2 levels in the nucleus accumbens showed a long-lasting nature as it persisted up to 60 days after the discontinuation of repeated cocaine treatments. In contrast to chronic cocaine administration, an acute cocaine injection was insufficient to modify levels of any orexin receptor and peptide. Our data identify the up-regulation of OXR2 in the nucleus accumbens as an enduring molecular event that is correlated well with behavioral plasticity in response to chronic psychostimulant administration. This OXR2 up-regulation may reflect a key adaptation of limbic orexinergic transmission to chronic drug exposure and may thus be critical for the expression of motor plasticity. [ABSTRACT FROM AUTHOR]

Previous studies investigating the development of place and cued learning using the Morris water task are in disagreement regarding the day in development that each type of learning emerges. Here, place and cued navigation in the water task were examined in differently aged groups of young male and female rats (P17, P18, P19, P20, and P24) during a single day of training. When only distal cues were present, P20 and P24 but not younger rats learned the location of the hidden platform. In contrast, when a proximal cue marked the platform location, rats as young as P17 showed evidence of cue-controlled navigation, although only P18 and older rats exhibited cued learning. In line with most previous studies, these results indicate that cued learning emerges earlier in development than place learning and support a dissociation of developmental trajectories for the neural systems underlying the two types of navigation. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 553-564, 2007. [ABSTRACT FROM AUTHOR]

Background Decreased caudate volumes and increased white matter lesions (WMLs) are associated both with aging and late-life depression, but the relationship between the two is unclear. We examined the association between WML and caudate volume, hypothesizing there would be a negative association, which would be stronger for WMLs located in anterior regions. We additionally hypothesized that this association would be stronger in depressed subjects. Method This MRI study included 182 elderly depressed and 64 elderly control subjects. Our imaging analysis procedures divided the brain into anterior and posterior halves. WML volume in each half was calculated, as were left and right caudate volumes. A statistical model incorporating WML volumes, age, total brain volume, diagnosis, and gender was used to examine caudate volumes. Results WML volume was negatively associated with total and right caudate volume. This association was stronger for WMLs in the anterior half of the brain. Anterior WML volume was additionally negatively associated with right caudate volume in depressed subjects, but not in controls. Conclusions Using unadjusted levels of significance, WML volume is negatively associated with right caudate volume in both older populations, but with left caudate volume only in depressed individuals. When statistical corrections for multiple comparisons are used, the finding is limited to a negative association between WML volume and right caudate volume, primarily in depressed subjects. This study demonstrates one mechanism by which WMLs may disrupt frontostriatal circuits. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine the volumetric and metabolic correlates of caudate nucleus in antipsychotic-naïve schizophrenia patients in comparison with healthy controls. Method: Twelve antipsychotic-naïve schizophrenia patients and 13 healthy controls underwent 31P magnetic resonance spectroscopy of basal ganglia. Magnetic resonance imaging volume of caudate nuclei was measured using scion image software. Results: Patients had significantly smaller caudate volume than healthy controls. Phosphocreatine (PCr)/total phosphorous and PCr/total adenosine tri-phosphate ratios of both caudate nuclei were significantly lower in patients than controls. Significant negative correlation was found between the left caudate volume and left PCr/total phosphorus ratio in the patients. Age at onset of psychosis had i) significant negative correlation with right and left caudate volumes and ii) significant positive correlation with left PCr/total phosphorus ratio. Conclusion: The metabolic and volumetric abnormalities of caudate nucleus in antipsychotic-naïve schizophrenia patients support neurodevelopmental etiopathogenesis. [ABSTRACT FROM AUTHOR]

Using optimized voxel-based morphometry, we studied the relationship between gray matter volume in brain areas associated with reward and scores on a behavioral activation system measure (the Sensitivity to Reward scale) in a sample of 50 male undergraduates. Voxel-based morphometry analysis revealed a negative correlation between Sensitivity to Reward scores and gray matter volume in the dorsal striatum and prefrontal cortex. Results indicate that a reduced volume in the striatum might be associated with enhanced reward sensitivity and deficits in inhibitory control. [ABSTRACT FROM AUTHOR]

Results of numerous human imaging studies and nonhuman neurophysiological studies on reward highlight a role for frontal, striatal, and thalamic regions in operant learning. By integrating operant and functional neuroimaging methodologies, the present investigation examined brain activation to two types of discriminative stimuli correlated with different contingencies. Prior to neuroimaging, 10 adult human subjects completed operant discrimination training in which money was delivered following button pressing (press-money contingency) in the presence of one set of discriminative stimuli, and termination of trials followed not responding (no response-next trial contingency) in the presence of a second set of discriminative stimuli. After operant training, subjects were instructed to memorize a third set of control stimuli unassociated with contingencies. Several hours after training, functional magnetic resonance imaging was performed while subjects viewed discriminative and control stimuli that were presented individually for 1,500 ms per trial, with stimulus presentations occurring, on average, every 6 s. Activation was found in frontal and striatal brain regions to both sets of discriminative stimuli relative to control stimuli. In addition, exploratory analyses highlighted activation differences between discriminative stimuli. The results demonstrate the utility of coupling operant and imaging technologies for investigating the neural substrates of operant learning in humans. [ABSTRACT FROM AUTHOR]

Background Decreased caudate volumes have been noted in unipolar depressed subjects, especially in the elderly and those with cognitive impairment. No differences have been noted in initial studies of multi-aged bipolar subjects; however, this region has not been examined in older bipolar subjects. Methods We examined the caudate nuclei volumes of 36 older bipolar subjects (mean age 58) and 35 older controls (mean age 62) using logistic regression analyses to control for age and gender differences. Differences between late- and early-onset (age-of-onset before age 45) bipolar subjects were also examined, as well as the effect of length of illness. Results The right caudate was noted to be smaller in older bipolar subjects compared with older controls when controlled for sex and age (p = 0.0448). No differences were noted in overall brain volume nor lateral ventricular volume between the bipolar and control subjects. Late-onset bipolar subjects had a decrease in brain volume (p = 0.035) compared with early-onset bipolar subjects. Late-onset bipolar subjects had a decrease in the right (p = 0.044) and total (p = 0.04) caudate size compared with older controls. Conclusions Right caudate volume is decreased in older bipolar subjects compared to controls. Bipolar subjects with late-onset illness have significantly decreased right and total caudate volumes compared to controls. This is affected by neither the length of illness nor the age of onset. Late-onset bipolar subjects have decreased total brain volume compared with early-onset bipolar subjects. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract Acute cocaine can inhibit catecholamine biosynthesis by regulating the enzymatic activity of tyrosine hydroxylase via alterations in the phosphorylation state of the enzyme. The mechanisms underlying acute cocaine-dependent regulation of tyrosine hydroxylase phosphorylation have not been determined. In this study, 0, 15 or 30 mg/kg cocaine was administered intraperitoneally to rats and the phosphorylation state of tyrosine hydroxylase in the brain was examined using antibodies specific for the phosphorylated forms of serine-19, -31 and -40 in tyrosine hydroxylase. In the caudate and nucleus accumbens, cocaine dose-dependently decreased the levels of phosphorylated serine-19, -31 and -40. In the ventral tegmental area, the levels of phosphorylated serine-19, but not serine-31 and -40, were decreased by 15 and 30 mg/kg cocaine. In the amygdala, the levels of phosphorylated serine-19, but not serine-31 or -40, were decreased. The functional effects of these alterations in phosphorylation state were assessed by measuring tyrosine hydroxylase activity in vivo(accumulation of DOPA after administration of the decarboxylase inhibitor NSD-1015). Acute administration of 30 mg/kg cocaine significantly decreased l-DOPA production in caudate and accumbens but not in amygdala. These data suggest that the phosphorylation of serine-31 or -40, but not serine-19, is involved in the regulation of tyrosine hydroxylase activity by acute cocaine. [ABSTRACT FROM AUTHOR]

Volumetric neuroimaging is increasingly being used by researchers of affective disorders to assess potential involvement of different brain structures in mood regulation and to test neuroanatomic models of mood disorders. In unipolar depression, findings suggest abnormalities in the frontal lobe (particularly the subgenual prefrontal cortex), basal ganglia (particularly the caudate and putamen), cerebellum, and hippocampus/amygdala complex. In bipolar disorder, abnormalities in the third ventricle, frontal lobe, cerebellum, and possibly the temporal lobe are noted. We review the findings for the various regions of the brain, and discuss the implications on the understanding of mood disorders. Directions for future research in volumetric imaging is then discussed. [ABSTRACT FROM AUTHOR]

Abstract Anterograde transport methods reveal an extensive thalamostriate projection from the extrageniculate visual thalamus. These projections distribute to approximately the same regions of the striatum innervated by the corticostriate projections from over a dozen higher visual cortical areas [visual-recipient sector; Updyke, B.V. (1993) J. Comp. Neurol., 327, 159–193.]. Like their cortical counterparts, the thalamostriate projections to the caudate distribute in a patchy manner that suggests potential overlap or intermingling spatial relationships between the two major afferents. All of the visually related thalamic nuclei projecting to the striatum receive ascending signals from the superior colliculus, suggesting that the constraints placed upon tectal processing by striatonigral control have important consequences for central perceptuomotor processing at the striatal and cortical levels. [ABSTRACT FROM AUTHOR]

Abstract In the dorsal striatum, there are two major populations of medium spiny projection neurons. One population is positive for dynorphin mRNA (DYN+), and these cells project preferentially to the substantia nigra, forming the so-called ‘direct pathway’. A second population is positive for enkephalin mRNA (ENK+), and these cells influence the substantia nigra indirectly, via the globus pallidus and subthalamic nucleus. Psychostimulant drugs, such as amphetamine and cocaine, are reported to induce immediate early genes (IEGs) in only one subpopulation of dorsal striatal projection neurons, DYN+ cells. However, this apparent selectivity appears to be a function of environmental context. We found that when given in the animal's home cage, amphetamine and cocaine increased expression of the IEG, c-fos, almost exclusively in DYN+ cells. However, when given in a novel environment, amphetamine and cocaine increased c-fos mRNA in both DYN+ and ENK+ cells. Furthermore, amphetamine and cocaine increased c-fos mRNA expression in the subthalamic nucleus when administered in the novel environment, but not when given at home. We conclude that the neural circuitry engaged by psychostimulant drugs, and their ability to induce specific patterns of gene expression, are determined by the environmental context in which they are experienced. This may be related to the ability of environmental novelty to facilitate psychostimulant drug-induced neuroplasticity. [ABSTRACT FROM AUTHOR]

Objectives . To investigate a presumed correlation between clock drawing ratings and linear measurements of computerized tomography (CT) studies in demented patients. Design . Blinded evaluations of clock drawing tests and CT studies of elderly dementia patients were conducted by a geriatric psychiatrist and a neuroradiologist. Subjects . Fifty-one community-dwelling elderly subjects meeting the criteria for DSM-IV diagnosis of dementia (Alzheimer's type dementia: N =31; vascular dementia: N =15; ‘mixed’ type dementia: N =5). Materials . Mini-Mental State Examination (MMSE), Cambridge Cognitive Examination (CAMCOG), Clinical Dementia Rating (CDR). CAMCOG derived scored clock drawings were evaluated using adaptations of Shulman et al .'s and Freedman et al .'s methods. CT studies were evaluated using six different linear measurements of brain atrophy described in the literature. Results . Of the CT linear measurements, only the Cerebro-Ventricular Index-2 (CVI-2; bicaudate index) significantly correlated with clock drawing ratings (CAMCOG's clock r =-0.407, p =0.003; Shulman's method r =0.357, p =0.01, Freedman's method r =-0.413, p =0.003) in the dementia group. There was no significant correlation between CVI-2 with demographic (age), cognitive (MMSE, CAMCOG) and clinical (duration of illness, CDR) ratings. Alzheimer's patients generally maintained a significant correlation between CVI-2 and clock drawings, but vascular dementia patients did not; CVI-2 also correlated significantly with the Praxis subtest of the CAMCOG in dementia and Alzheimer's patients but not in the vascular dementia group. Similarly, multiple stepwise regression analysis showed that only CVI-2 but not the other radiological measures studied, was selected as the significant variable to correlated with clock drawing test ratings in the dementia group and Alzheimer's patients. Partial correlation analysis controlling for demographic and clinical variables shows that controlled variables had no significant effect on the relationship between clock drawing ratings and CVI-2. Conclusion . A single and easy to perform measure of caudate atrophy correlates specifically and consistently with impairments revealed in the clock drawing test and with a Praxis subtest, suggesting possible caudate involvement with clock drawings in dementia in general and of the Alzheimer's type in particular. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract : This study directly assessed striatal dopamine (DA) uptake rates and peak release in response to KCl in normal, symptomatic, and recovered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cats using in vivo electrochemistry. DA uptake rates measured after direct application of known concentrations of DA to the striatum were slowed significantly in both dorsal and ventral striatum in symptomatic cats compared with rates recorded in normal animals. DA uptake rates remained significantly slowed in recovered cats and were not significantly different from the rates recorded in symptomatic animals. In symptomatic cats, both DA uptake rates and the signal recorded in response to KCl stimulation were significantly decreased from normal in all dorsal and ventral striatal regions sampled. Reduction/oxidation (redox) ratios recorded in response to KCl stimulation suggested DA to be the predominant electroactive species. In spontaneously recovered MPTP-treated cats, recordings in the ventral striatum subsequent to KCl stimulation again suggested DA to be the predominant electroactive species released, and peak levels were significantly higher than those recorded in symptomatic animals. In the dorsal striatum of recovered cats, redox ratios recorded subsequent to KCl stimulation suggested serotonin rather than DA to be the predominant electroactive species released. Peak levels of release in the dorsal striatum were not significantly greater than those recorded in symptomatic animals. These results suggest that in spontaneously recovered MPTP-treated cats, there is partial recovery of ventral striatal DAergic terminals, persistent loss of dorsal striatal DAergic terminals, and a down-regulation of DA transporter number/function throughout the striatum. These processes may contribute to volume transmission of DA in the striatum and promote functional recovery. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging was conducted on six children and adolescents with fetal alcohol syndrome and seven matched normal controls. Detailed volumetric analyses demonstrated significant reductions in the cerebral vault, basal ganglia, and diencephalon in the children with fetal alcohol syndrome, compared with control children. In addition, the volume of the cerebellar vault was smaller than controls in 4 of the 6 children with fetal alcohol syndrome, although the group difference did not reach significance. When the basal ganglia were divided into the caudate and lenticular nuclei, both of these regions were significantly reduced in the children with fetal alcohol syndrome. Finally, when the overall reduction in brain size was controlled, the proportional volume of the basal ganglia and, more specificatly, the caudate nucleus was reduced in the children with fetal alcohol syndrome. These results may relate to behavioral findings in both humans and animals exposed to alcohol prenatally. [ABSTRACT FROM AUTHOR]

The function of subcortical nuclei in partial epilepsy was investigated using positron emission tomography (PET) to measure metabolism in the basal ganglia and thalamus. Sixteen patients undergoing surgical evaluation were studied with 18F-fluorodeoxyglucose (FDG) interictally and had intensive extracranial and intracranial electrophysiologic evaluations. Eight patients had left temporal lobe seizure foci, six had right temporal lobe foci, and two had right posterotemporal or parietal foci. The PET data were analyzed visually and quantitatively, using a multivariate analysis of variance on the quantitative data. Hypometabolism of subcortical nuclei was Present ipsilateral to the cortical seizure focus. Cortical hypometabolism was noted focally in the temporal lobe in patients with left temporal lobe seizure foci, whereas patients with right temporal lobe seizure foci had diffuse hemispheric hypometabolism. We postulate that the subcortical hypometabolism is secondary to decreased efferent activity from temporal lobe structures, in particular amygdala and hippocampus, to subcortical nuclei. Diminished subcortical activity may then lead to defective regulation of cortical excitability in the temporal lobe, increasing the likelihood of seizure development and spread. RÉSUMÉ Les auteurs ont étudiés le fonctionnement des noyaux sous-corticaux dans l'épilepsie partielle, en utilisant la tomographic à émission de positrons (PET) pour mesurer le métabolisme des noyaux de la base et du thalamus. Seize patients qui bénéficiaient d'une évaluation pré-chirurgicale ont été étudiés au moyen du 18-F-fluorodéoxyglucose (FDG) en intercritique, et au moyen d'un monitorage intensif et électrophysiologique intra et extracrânien. Huit patients présentaient un foyer critique du lobe temporal gauche, 2 du lobe temporal droit, et 2 présentaient un foyer temporal postérieur ou pariétal droit. Les données du PET ont été analysées visuellement et quantitativement, au moyen d'une analyse de multivariances des données quantitatives. Un hypométabolisme des noyaux de la base ipsilatéraux au foyer cortical a été observé. Un hypométabolisme cortical focal a été constaté au niveau du lobe temporal de patients présentant un foyer critique temporal gauche, alors que les patients présentant un foyer critique temporal droit présentaient un hypométabolisme hémisphérique diffus. Les auteurs émettent le postulat selon lequel l'hypométabolisme sous-cortical est secondaire à une diminution de l'activité efférente des structures du lobe temporal, en particulier de l'amygdale et de l'hippocampe, vers les noyaux de la base. Une activité sous-corticale diminuée peut entraîner un déficit de régulation de l'excitabilité corticale du lobe temporal, ce qui augmente la probabilité du développement et de l'extension des crises. RESUMEN Utilizando la tomografia por emisión de positrones (PET) se ha medido el matabolismo de los ganglios basales y tálamo para medir la función de los núcleos subcorticales en la epilépsia, Dieciseis enfermos sometidos a una valoración quirúrgica han sido estudiados con 18-F-fluorodeoxiglucosa (FDG) durante los periodos interictales y fueron sometidos a intensas evaluaciones electrofisiológicas intra y extracraneales. Ocho pacientes tenían un foco epiléptico en el lóbulo temporal izquierdo, 6 tenían un foco en el lóbulo temporal derecho y 2 un foco temporal posterior derecho o parietal. La información conseguida con el PET fue analizada visual y cuantitativamente, utilizando un análisis multivariado de las varianzas en la información cuantitativa. Se observó un hipometabolismo subcortical ipsilateral correspondiente al foco cortical epiléptico. Se detectó un hipometabolismo cortical focal en el lóbulo temporal en enfermos con focos epilépticos del lóbulo temporal izquierdo mientras que los enfermos con focos epilépticos del lóbulo temporal derecho tenían un hipometabolismo hemisférico difuso. Postulamos que el hipometabolismo subcortical es secundario a una reducción de la actividad eferente del lóbulo temporal desde las estructuras del lóbulo temporal, en particular la amigdala y el hipocampo, hacía los núcleos subcorticales. La reducción de la actividad subcortical puede conducir a una regulación defectuosa de la excitabilidad cortical en el lóbulo temporal incrementando la posibilidad de un desarrollo de los ataques y de su dispersión. ZUSAMMENFASSUNG Mit Hilfe der Positronenemissionstomographie (PET) wurde durch Messung des Metabolismus in den basalen Ganglien und dem Thalamus die Funktion der subkortikalen Kerne bei Partialepilepsien untersucht. 16 für eine chirurgische Evaluation ausgewählte Patienten wurden mit der 18-Fluorodeoxyglucose-Methode (FDG) interiktal untersucht und intensiven extrakraniellen und intrakraniellen elektrophysiologischen Auswertungen unterworfen. 8 Patienten zeigten einen linken Temporallappenfokus, 6 Patienten einen rechten Temporallappenfokus und 2 Patienten rechtsseitige, hintere Temporallappenoder parietale Foci. Die PET-Daten wurden visuell und quantitativ mit einer multivarianten Variananalyse ausgewertet. Ipsilateral zum kortikalen Anfallsfokus war ein Hypometabolismus der subkortikalen Kerne zu finden. Ein kortikaler Hypometabolismus trat fokal im Temporallappen auf bei zwei Patienten mit linksseitigen Temporallappenanfällen. Patienten mit rechtsseitigen Temporallappenfoci zeigten einen diffusen hemisphärischen Metabolismus. Wir vermuten, daß der subkortikale Hypometabolismus sekundär durch eine herabgesetzte Efferenz von Temporallappenstrukturen, speziell vom Amygdalon und Hippokampus zu subkortikalen Kernen entsteht. Die herabgesetzte, subkortikale Aktivität führt dann zu einer fehlerhaften Regulation der kortikalen Erregbarkeit in den Temporallappen und erhöht somit die Wahrscheinlichkeit der Anfallsentstehung und Ausbreitung. [ABSTRACT FROM AUTHOR]

This case report describes a patient with Huntington’s Disease (HD) who allegedly stalked her therapist. The patient developed recurrent thoughts about her therapist as well as amorous feelings towards her therapist. She engaged in stalking behavior including unwelcome gifts, multiple telephone calls to the therapist’s office and home, and making threats towards the therapist. The patient continued to contact the therapist after the therapist filed a Personal Protection Order. The patient was successfully treated with risperidone and fluvoxamine. Through a focused review of the relevant literature, the authors explore the potential relationship between the patient’s obsessional thoughts, amorous feelings towards her therapist, the basal ganglia dysfunction, and the stalking behavior. The authors posit a hypothesis of stalking as a novel early manifestation of HD in this patient. To the best of the authors’ knowledge, this is the first reported case of stalking occurring with potentially causal organic lesions. [ABSTRACT FROM AUTHOR]

Bolitoglossa mombachoensis is an endemic neotropical salamander of the Mombacho Volcano, Nicaragua. Canopy communities within the tropics are hubs for biodiversity, and many tropical plethodontids have a foraging preference for epiphytic plants, such as bromeliads, which provide moist microclimates for shelter, foraging, and nesting. Habitat loss continues to be the biggest threat to amphibians worldwide. This species is highly dependent on nocturnal arboreal climbing. We describe their plant preference, which extends beyond bromeliads, and their arboreal dependence used for refuge and foraging. Foraging behavior is constricted to nighttime, plant availability, geography, and altitude. [ABSTRACT FROM AUTHOR]