Old neurochemical markers, new functional directions?: An Editorial for 'Distinct gradients of various neurotransmitter markers in caudate nucleus and putamen of the human brain' on page 650.

Authors: Philippe De Deurwaerdere, Silvana Gaetani, Roxanne A Vaughan...

The dorsal striatum coordinates input-output processing of numerous functions including those related to motor activity, motivation, and learning. Considerable anatomical and biochemical heterogeneity across striatal subregions has long been known to result in distinct functional outcomes, and for imbalances in these pathways to contribute to many complex disorders. Here we highlight the study of Hörtnagl et al. (2019) who utilize precision dissection of human caudate nucleus and putamen for detailed measurement of major neurochemical markers to address the question of anatomical heterogeneity of neurotransmitter distribution and turnover in these regions. The findings identify gradients of neurotransmitter markers in rostro-caudal, dorso-lateral, and anterior-posterior directions with a precision that has not been previously determined in humans. Correlative analyses of the results also suggest tentative links between content of various neurotransmitters in specific subregions, raising the intriguing possibility that neurotransmitter quantity in one territory may correlate with the quantity of the same or different transmitter from another territory. This suggests the presence of a functional anatomy over extensive brain regions and networks that can be studied through multiple correlative analyses, and identify a possible basis for a new approach for postmortem analysis of neurotransmitter distribution and function.

Topics: Aged; Biomarkers; Caudate Nucleus; Female; Humans; Male; Neurotransmitter Agents; Postmortem Changes; Putamen

PubMed: 31917872
DOI: 10.1111/jnc.14929

Authors: Paul A Yushkevich, Joseph Piven, Heather Cody Hazlett...

Active contour segmentation and its robust implementation using level set methods are well-established theoretical approaches that have been studied thoroughly in the image analysis literature. Despite the existence of these powerful segmentation methods, the needs of clinical research continue to be fulfilled, to a large extent, using slice-by-slice manual tracing. To bridge the gap between methodological advances and clinical routine, we developed an open source application called ITK-SNAP, which is intended to make level set segmentation easily accessible to a wide range of users, including those with little or no mathematical expertise. This paper describes the methods and software engineering philosophy behind this new tool and provides the results of validation experiments performed in the context of an ongoing child autism neuroimaging study. The validation establishes SNAP intrarater and interrater reliability and overlap error statistics for the caudate nucleus and finds that SNAP is a highly reliable and efficient alternative to manual tracing. Analogous results for lateral ventricle segmentation are provided.

Topics: Brain; Caudate Nucleus; Dominance, Cerebral; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Mathematical Computing; Software; Software Validation; User-Computer Interface

PubMed: 16545965
DOI: 10.1016/j.neuroimage.2006.01.015

Authors: Jae Hyun Yoo, Ji-Won Chun, Mi Ran Choi...

BACKGROUND AND AIMS

Problematic smartphone use (PSU) is growing rapidly among teens. It has similar presentations as other behavioral addictions in terms of excessive use, impulse control problems, and negative consequences. However, the underlying neurobiological mechanisms remain undiscovered. We hypothesized that structural changes in the striatum might serve as an important link between alteration in glutamate signaling and development of PSU.

METHODS

Among 88 participants, twenty (F:M, 12:8; age 16.2 ± 1.1) reported high scores in the smartphone addiction proneness scale (SAPS) with a cut-off score of 42; the other 68 (F:M, 19:49; age 15.3 ± 1.7) comprised the control group. Sociodemographic data and depression, anxiety, and impulsivity traits were measured. Striatal volumes (caudate, putamen, and nucleus accumbens) were estimated from T1 imaging data. Serum glutamate levels were estimated from peripheral blood samples. Group comparisons of each data were performed after controlling for age and gender. Mediation analyses were conducted to test the indirect effects of glutamate level alteration on PSU through striatal volumetric alteration.

RESULTS

The PSU group showed a decrease in both caudate volumes than the control group. Left caudate volume was positively correlated with serum glutamate level, and negatively with impulsivity traits and SAPS scores. The mediation model revealed a significant indirect effect of serum glutamate on SAS scores through the reduced left caudate volume.

DISCUSSION AND CONCLUSIONS

This study suggests that altered glutamatergic neurotransmission may be associated with PSU among teens, possibly through reduced left caudate volume. Current findings might support neural mechanisms of smartphone addiction.

Topics: Adolescent; Behavior, Addictive; Caudate Nucleus; Glutamic Acid; Humans; Smartphone; Synaptic Transmission

PubMed: 33905351
DOI: 10.1556/2006.2021.00024

Authors: Étienne Aumont, Caroll-Ann Blanchette, Veronique D Bohbot...

When people navigate, they use strategies dependent on one of two memory systems. The hippocampus-based spatial strategy consists of using multiple landmarks to create a cognitive map of the environment. In contrast, the caudate nucleus-based response strategy is based on the memorization of a series of turns. Importantly, response learners display more gray matter and functional activity in the caudate nucleus and less gray matter in the hippocampus. In parallel, the caudate nucleus is involved in decision-making by mediating attention toward rewards and in set-shifting by mediating preparatory actions. The present study, therefore, examined the link between navigational strategy use, that are associated with gray matter differences in the caudate nucleus and hippocampus, and decision-making and set-shifting performance. Fifty-three participants completed the 4 on 8 virtual maze, the Iowa Gambling Task (IGT), the Wisconsin Card Sorting Test-64 (WCST-64), and a task-switching test. The results revealed that people who use response strategies displayed increased risk-taking behavior in the IGT compared to the people using hippocampus-dependent spatial strategies. Response strategy was also associated with enhanced set-shifting performance in the WCST-64 and task-switching test. These results confirm that risk-taking and set-shifting behavior, that are differentially impacted by the caudate nucleus and hippocampus memory systems, can be predicted by navigational strategy.

Topics: Adolescent; Adult; Caudate Nucleus; Decision Making; Female; Hippocampus; Humans; Male; Memory; Risk-Taking; Spatial Navigation; Young Adult

PubMed: 30898972
DOI: 10.1101/lm.048306.118

Authors: Mikhail Votinov, Artem Myznikov, Maya Zheltyakova...

The organization of socio-cognitive processes is a multifaceted problem for which many sophisticated concepts have been proposed. One of these concepts is social intelligence (SI), i.e., the set of abilities that allow successful interaction with other people. The theory of mind (ToM) human brain network is a good candidate for the neural substrate underlying SI since it is involved in inferring the mental states of others and ourselves and predicting or explaining others' actions. However, the relationship of ToM to SI remains poorly explored. Our recent research revealed an association between the gray matter volume of the caudate nucleus and the degree of SI as measured by the Guilford-Sullivan test. It led us to question whether this structural peculiarity is reflected in changes to the integration of the caudate with other areas of the brain associated with socio-cognitive processes, including the ToM system. We conducted seed-based functional connectivity (FC) analysis of resting-state fMRI data for 42 subjects with the caudate as a region of interest. We found that the scores of the Guilford-Sullivan test were positively correlated with the FC between seeds in the right caudate head and two clusters located within the right superior temporal gyrus and bilateral precuneus. Both regions are known to be nodes of the ToM network. Thus, the current study demonstrates that the SI level is associated with the degree of functional integration between the ToM network and the caudate nuclei.

Topics: Brain; Brain Mapping; Caudate Nucleus; Emotional Intelligence; Humans; Magnetic Resonance Imaging; Theory of Mind

PubMed: 34720887
DOI: 10.3389/fncir.2021.727960

Authors: Leonardo D Garma, Lisbeth Harder, Juan M Barba-Reyes...

Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangling the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq and spatial transcriptomics of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their inherent transcriptional structure in the human dorsal striatum. We propose a comprehensive taxonomy of striatal interneurons with eight main classes and fourteen subclasses, providing their full transcriptomic identity and spatial expression profile as well as additional quantitative FISH validation for specific populations. We have also delineated the correspondence of our taxonomy with previous standardized classifications and shown the main transcriptomic and class abundance differences between caudate nucleus and putamen. Notably, based on key functional genes such as ion channels and synaptic receptors, we found matching known mouse interneuron populations for the most abundant populations, the recently described PTHLH and TAC3 interneurons. Finally, we were able to integrate other published datasets with ours, supporting the generalizability of this harmonized taxonomy.

Topics: Humans; Interneurons; Transcriptome; Male; Female; Corpus Striatum; Caudate Nucleus; Putamen; Middle Aged; Animals; Aged; Mice; Gene Expression Profiling; Adult

PubMed: 39039043
DOI: 10.1038/s41467-024-50414-w

Authors: Dimitrios Andreou, Kjetil Nordbø Jørgensen, Stener Nerland...

The caudate nucleus is a part of the striatum, and striatal hyperdopaminergia is considered central to the pathophysiology of schizophrenia. How caudate volume is affected in schizophrenia and what role antipsychotics play remains unclear. In early-onset schizophrenia (EOS), where psychosis emerges during a neurodevelopmentally critical phase, the caudate may exhibit a heightened vulnerability to the effects of antipsychotic medications. We hypothesized effects of both antipsychotic medication use and age of onset on caudate in schizophrenia. We included adult patients with EOS (n = 83) and adult-onset schizophrenia (AOS) (n = 246), adult healthy controls (HC, n = 774), adolescent patients with non-affective psychosis (n = 56) and adolescent HC (n = 97). We obtained T1-weighted MRI scans using a 1.5T Siemens scanner and General Electric 3T scanners. In our main analysis, we tested for main and interaction effects of diagnosis and current antipsychotic medication use on caudate volume. Adult patients with EOS (p < 0.001) and AOS (p = 0.002) had both larger caudate than HC. Age of onset (EOS/AOS) interacted with antipsychotic use (p = 0.004) which was associated with larger caudate in EOS (p < 0.001) but not in AOS (p = 0.654). Conversely, among medicated patients only, EOS had larger caudate than AOS (p < 0.001). No other subcortical structures showed differences between medicated EOS and AOS. Medicated adolescent patients with non-affective psychosis and medicated adult patients with EOS showed similar caudate volumes. The results may indicate a schizophrenia-related and a medication-induced caudate increase, the latter restricted to patients with EOS and possibly occurring already in adolescence shortly after disease onset.

Topics: Humans; Caudate Nucleus; Schizophrenia; Adult; Female; Male; Antipsychotic Agents; Adolescent; Age of Onset; Magnetic Resonance Imaging; Young Adult; Organ Size; Case-Control Studies

PubMed: 39353988
DOI: 10.1038/s41598-024-73322-x

Authors: Takahiro Doi, Yunshu Fan, Joshua I Gold...

Our decisions often balance what we observe and what we desire. A prime candidate for implementing this complex balancing act is the basal ganglia pathway, but its roles have not yet been examined experimentally in detail. Here, we show that a major input station of the basal ganglia, the caudate nucleus, plays a causal role in integrating uncertain visual evidence and reward context to guide adaptive decision-making. In monkeys making saccadic decisions based on motion cues and asymmetric reward-choice associations, single caudate neurons encoded both sources of information. Electrical microstimulation at caudate sites during motion viewing affected the monkeys' decisions. These microstimulation effects included coordinated changes in multiple computational components of the decision process that mimicked the monkeys' similarly coordinated voluntary strategies for balancing visual and reward information. These results imply that the caudate nucleus plays causal roles in coordinating decision processes that balance external evidence and internal preferences.

Topics: Animals; Caudate Nucleus; Decision Making; Macaca mulatta; Male; Photic Stimulation; Reward; Uncertainty; Visual Perception

PubMed: 32568068
DOI: 10.7554/eLife.56694

Authors: Kei Oyama, Yukiko Hori, Koki Mimura...

The orbitofrontal cortex (OFC) and its major downstream target within the basal ganglia-the rostromedial caudate nucleus (rmCD)-are involved in reward-value processing and goal-directed behavior. However, a causal contribution of the pathway linking these two structures to goal-directed behavior has not been established. Using the chemogenetic technology of designer receptors exclusively activated by designer drugs with a crossed inactivation design, we functionally and reversibly disrupted interactions between the OFC and rmCD in two male macaque monkeys. We injected an adeno-associated virus vector expressing an inhibitory designer receptor, hM4Di, into the OFC and contralateral rmCD, the expression of which was visualized by positron emission tomography and confirmed by postmortem immunohistochemistry. Functional disconnection of the OFC and rmCD resulted in a significant and reproducible loss of sensitivity to the cued reward value for goal-directed action. This decreased sensitivity was most prominent when monkeys had accumulated a certain amount of reward. These results provide causal evidence that the interaction between the OFC and the rmCD is needed for motivational control of action on the basis of the relative reward value and internal drive. This finding extends the current understanding of the physiological basis of psychiatric disorders in which goal-directed behavior is affected, such as obsessive-compulsive disorder. In daily life, we routinely adjust the speed and accuracy of our actions on the basis of the value of expected reward. Abnormalities in these kinds of motivational adjustments might be related to behaviors seen in psychiatric disorders such as obsessive-compulsive disorder. In the current study, we show that the connection from the orbitofrontal cortex to the rostromedial caudate nucleus is essential for motivational control of action in monkeys. This finding expands our knowledge about how the primate brain controls motivation and behavior and provides a particular insight into disorders like obsessive-compulsive disorder in which altered connectivity between the orbitofrontal cortex and the striatum has been implicated.

Topics: Animals; Caudate Nucleus; Goals; Humans; Male; Motivation; Prefrontal Cortex; Reward

PubMed: 35794012
DOI: 10.1523/JNEUROSCI.0229-22.2022

Authors: Gabor Perlaki, Reka Horvath, Szilvia Anett Nagy...

Although several methods have been developed to automatically delineate subcortical gray matter structures from MR images, the accuracy of these algorithms has not been comprehensively examined. Most of earlier studies focused primarily on the hippocampus. Here, we assessed the accuracy of two widely used non-commercial programs (FSL-FIRST and Freesurfer) for segmenting the caudate and putamen. T1-weighted 1 mm isotropic resolution MR images were acquired for thirty healthy subjects (15 females). Caudate nucleus and putamen were segmented manually by two independent observers and automatically by FIRST and Freesurfer (v4.5 and v5.3). Utilizing manual labels as reference standard the following measures were studied: Dice coefficient (D), percentage volume difference (PVD), absolute volume difference as well as intraclass correlation coefficient (ICC) for consistency and absolute agreement. For putamen segmentation, FIRST achieved higher D, lower PVD and higher ICC for absolute agreement with manual tracing than either version of Freesurfer. Freesurfer overestimated the putamen, while FIRST was not statistically different from manual tracing. The ICC for consistency with manual tracing was similar between the two methods. For caudate segmentation, FIRST and Freesurfer performed more similarly. In conclusion, Freesurfer and FIRST are not equivalent when comparing to manual tracing. FIRST was superior for putaminal segmentation.

Topics: Adult; Caudate Nucleus; Female; Humans; Magnetic Resonance Imaging; Male; Observer Variation; Putamen; Reproducibility of Results; Young Adult

PubMed: 28546533
DOI: 10.1038/s41598-017-02584-5