Neurochemistry and circuit organization of the lateral spiriform nucleus of birds: A uniquely nonmammalian direct pathway component of the basal ganglia.

We used diverse methods to characterize the role of avian lateral spiriform nucleus (SpL) in basal ganglia motor function. Connectivity analysis showed that SpL receives input from globus pallidus (GP), and the intrapeduncular nucleus (INP) located ventromedial to GP, whose neurons express numerous striatal markers. SpL-projecting GP neurons were large and aspiny, while SpL-projecting INP neurons were medium sized and spiny. Connectivity analysis further showed that SpL receives inputs from subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr), and that the SNr also receives inputs from GP, INP, and STN. Neurochemical analysis showed that SpL neurons express ENK, GAD, and a variety of pallidal neuron markers, and receive GABAergic terminals, some of which also contain DARPP32, consistent with GP pallidal and INP striatal inputs. Connectivity and neurochemical analysis showed that the SpL input to tectum prominently ends on GABAA receptor-enriched tectobulbar neurons. Behavioral studies showed that lesions of SpL impair visuomotor behaviors involving tracking and pecking moving targets. Our results suggest that SpL modulates brainstem-projecting tectobulbar neurons in a manner comparable to the demonstrated influence of GP internus on motor thalamus and of SNr on tectobulbar neurons in mammals. Given published data in amphibians and reptiles, it seems likely the SpL circuit represents a major direct pathway-type circuit by which the basal ganglia exerts its motor influence in nonmammalian tetrapods. The present studies also show that avian striatum is divided into three spatially segregated territories with differing connectivity, a medial striato-nigral territory, a dorsolateral striato-GP territory, and the ventrolateral INP motor territory.

Deep-learning based fully automatic segmentation of the globus pallidus interna and externa using ultra-high 7 Tesla MRI.

Deep brain stimulation (DBS) surgery has been shown to dramatically improve the quality of life for patients with various motor dysfunctions, such as those afflicted with Parkinson's disease (PD), dystonia, and essential tremor (ET), by relieving motor symptoms associated with such pathologies. The success of DBS procedures is directly related to the proper placement of the electrodes, which requires the ability to accurately detect and identify relevant target structures within the subcortical basal ganglia region. In particular, accurate and reliable segmentation of the globus pallidus (GP) interna is of great interest for DBS surgery for PD and dystonia. In this study, we present a deep-learning based neural network, which we term GP-net, for the automatic segmentation of both the external and internal segments of the globus pallidus. High resolution 7 Tesla images from 101 subjects were used in this study; GP-net is trained on a cohort of 58 subjects, containing patients with movement disorders as well as healthy control subjects. GP-net performs 3D inference in a patient-specific manner, alleviating the need for atlas-based segmentation. GP-net was extensively validated, both quantitatively and qualitatively over 43 test subjects including patients with movement disorders and healthy control and is shown to consistently produce improved segmentation results compared with state-of-the-art atlas-based segmentations. We also demonstrate a postoperative lead location assessment with respect to a segmented globus pallidus obtained by GP-net.

Connections between the internal and the external capsules and the globus pallidus in the sheep: A dichromate stain X-ray microtomographic study.

Sheep are recognized as useful species for translational neurodegeneration research, in particular for the study of Huntington disease. There is a lack of information regarding the detailed anatomy and connections of the basal ganglia of sheep, in normal myeloarchitectonics and in tract-tracing studies. In this work, the organization of the corticostriatal projections at the level of the putamen and globus pallidus (GP) are explored. For the first time, the myeloarchitectonic pattern of connections between the internal (IC) and the external (EC) capsules with the GP have been investigated in the sheep. Formaldehyde-fixed blocks of the striatum were treated with a metallic stain containing potassium dichromate and visualized using micro-CT (µ-CT). The trivalent chromium (Cr3+), attached to myelin phospholipids, imparts a differential contrast to the grey and white matter compartments, which allows the visualization of myelinated fascicles in µ-CT images. The fascicles were classified according to their topographical location in dorsal supreme fascicles (X, Y, apex) arising from the IC and EC; pre-commissurally, basal fascicles connecting the ventral part of the EC with the lateral zone of the ventral pallidum (VP) and, post-commissurally, superior (Z1 ), middle (Z2 ) and lower (Z3 ) fascicles, connecting at different levels the EC with the GP. The results suggest that the presumptive cortical efferent and afferent fibres to the pallidum could be organized according to a dorsal to ventrolateral topography in the sheep, similar to that seen in other mammals. The proposed methodology has the potential to delineate the myeloarchitectonic patterns of nervous systems and tracts.

Subthalamic Nucleus: Neuroanatomical Review

Discovered in 1865 by Jules Bernard Luys, the subthalamic nucleus is a set of small nuclei located in the diencephalon, inferior to the thalamus and superior to the substantia nigra, that can be visualized in a posterior coronal section. Histologically, it consists of neurons compactly distributed and filled with a large number of blood vessels and sparse myelinated fibers. This review presents an analysis of this anatomical region, considering what is most recent in the literature. Subthalamic neurons are excitatory and use glutamate as the neurotransmitter. In healthy individuals, these neurons are inhibited by nerve cells located in the side globus pallidus. However, if the fibers that make up the afferent circuit are damaged, the neurons become highly excitable, thus causing motor disturbances that can be classified as hyperkinetic, for example ballism and chorea, or hypokinetic, for example Parkinson disease (PD). The advent of deep brain stimulation has given the subthalamic nucleus great visibility. Studies reveal that the stimulation of this nucleus improves themotor symptoms of PD.

Structural variation within the left globus pallidus is associated with task-switching, not stimulus updating or distractor filtering.

Cognitive control is a pivotal aspect of cognition and it is impaired in many clinical populations. To date, several distinct types of cognitive control have been proposed, and prior work demonstrated the instrumental role of basal ganglia, frontal and parietal regions. However, the role of the structural variation of these regions in cognitive control functions is poorly understood. Here, we examined in 39 adults the association between regional brain volume and three major types of cognitive control: (i) stimulus updating, (ii) task-switching, and (iii) distractor filtering. The volume of the globus pallidus was positively correlated with individual variation in task-switching , and was anatomically specific to the left hemisphere. Importantly, this region did not track performance in distractor filtering or stimulus updating. We then aimed to use transcranial direct current stimulation to target the left midline subcortical structures. However, we did not find an effect on task-switching. While the null effect in the brain stimulation prevents us from drawing causal inference from the role of globus pallidus on task-switching, our structural results reveal a novel and highly specific neurostructural mechanism for task-switching and provide a further understanding of the link between cognitive control functions and the human brain.

Spatially coherent and topographically organized pathways of the human globus pallidus.

Internal and external segments of globus pallidus (GP) exert different functions in basal ganglia circuitry, despite their main connectional systems share the same topographical organization, delineating limbic, associative, and sensorimotor territories. The identification of internal GP sensorimotor territory has therapeutic implications in functional neurosurgery settings. This study is aimed at assessing the spatial coherence of striatopallidal, subthalamopallidal, and pallidothalamic pathways by using tractography-derived connectivity-based parcellation (CBP) on high quality diffusion MRI data of 100 unrelated healthy subjects from the Human Connectome Project. A two-stage hypothesis-driven CBP approach has been carried out on the internal and external GP. Dice coefficient between functionally homologous pairs of pallidal maps has been computed. In addition, reproducibility of parcellation according to different pathways of interest has been investigated, as well as spatial relations between connectivity maps and existing optimal stimulation points for dystonic patients. The spatial organization of connectivity clusters revealed anterior limbic, intermediate associative and posterior sensorimotor maps within both internal and external GP. Dice coefficients showed high degree of coherence between functionally similar maps derived from the different bundles of interest. Sensorimotor maps derived from the subthalamopallidal pathway resulted to be the nearest to known optimal pallidal stimulation sites for dystonic patients. Our findings suggest that functionally homologous afferent and efferent connections may share similar spatial territory within the GP and that subcortical pallidal connectional systems may have distinct implications in the treatment of movement disorders.

The Amsterdam Ultra-high field adult lifespan database (AHEAD): A freely available multimodal 7 Tesla submillimeter magnetic resonance imaging database.

Normative databases allow testing of novel hypotheses without the costly collection of magnetic resonance imaging (MRI) data. Here we present the Amsterdam Ultra-high field adult lifespan database (AHEAD). The AHEAD consists of 105 7 Tesla (T) whole-brain structural MRI scans tailored specifically to imaging of the human subcortex, including both male and female participants and covering the entire adult life span (18-80 yrs). We used these data to create probability maps for the subthalamic nucleus, substantia nigra, internal and external segment of the globus pallidus, and the red nucleus. Data was acquired at a submillimeter resolution using a multi-echo (ME) extension of the second gradient-echo image of the MP2RAGE sequence (MP2RAGEME) sequence, resulting in complete anatomical alignment of quantitative, R1-maps, R2*-maps, T1-maps, T1-weighted images, T2*-maps, and quantitative susceptibility mapping (QSM). Quantitative MRI maps, and derived probability maps of basal ganglia structures are freely available for further analyses.

Probabilistic tractography in the ventrolateral thalamic nucleus: cerebellar and pallidal connections.

The ventrolateral thalamic nucleus (VL), as part of the 'motor thalamus', is main relay station of cerebellar and pallidal projections. It comprises anterior (VLa) and posterior (VLpd and VLpv) subnuclei. Though the fibre architecture of cerebellar and pallidal projections to of the VL nucleus has already been focus in a numerous amount of in vitro studies mainly in animals, probabilistic tractography now offers the possibility of an in vivo comparison in healthy humans. In this study we performed a (a) qualitative and (b) quantitative examination of VL-cerebellar and VL-pallidal pathways and compared the probability distributions between both projection fields in the VL after an (I) atlas-based and (II) manual-based segmentation procedure. Both procedures led to high congruent results of cerebellar and pallidal connectivity distributions: the maximum of pallidal projections was located in anterior and medial parts of the VL nucleus, whereas cerebellar connectivity was more located in lateral and posterior parts. The median connectivity for cerebellar connections in both approaches (manual and atlas-based segmentation) was VLa > VLpv > VLpd, whereas the pallidal median connectivity was VLa ~ VLpv > VLpd in the atlas-based approach and VLpv > VLa > VLpd in the manual approach.

Pallidal lead placement in dystonia: leads of non-responders are contained within an anatomical range defined by responders.

BACKGROUND: Deep brain stimulation (DBS) within the pallidum represents an effective and well-established treatment for isolated dystonia. However, clinical outcome after surgery may be variable with limited response in 10-25% of patients. The effect of lead location on clinical improvement is still under debate. OBJECTIVE: To identify stimulated brain regions associated with the most beneficial clinical outcome in dystonia patients. METHODS: 18 patients with cervical and generalized dystonia with chronic DBS of the internal pallidum were investigated. Patients were grouped according to their clinical improvement into responders, intermediate responders and non-responders. Magnetic resonance and computed tomography images were co-registered, and the volume of tissue activated (VTA) with respect to the pallidum of individual patients was analysed. RESULTS: VTAs in responders (n = 11), intermediate responders (n = 3) and non-responders (n = 4) intersected with the posterior internal (GPi) and external (GPe) pallidum and the subpallidal area. VTA heat maps showed an almost complete overlap of VTAs of responders, intermediate and non-responders. VTA coverage of the GPi was not higher in responders. In contrast, VTAs of intermediate and non-responders covered the GPi to a significantly larger extent in the left hemisphere (p < 0.01). CONCLUSIONS: DBS of ventral parts of the posterior GPi, GPe and the adjacent subpallidal area containing pallidothalamic output projections resulted in favourable clinical effects. Of note, non-responders were also stimulated within the same area. This suggests that factors other than mere lead location (e.g., clinical phenotype, genetic background) have determined clinical outcome in the present cohort.

Whole course of pallidothalamic tracts identified on the sectioned images and surface models.

The anatomy of the pallidothalamic tracts, including the ansa lenticularis, lenticular fasciculus, and thalamic fasciculus (field H1 of Forel), should be elucidated by neurosurgeons and neuroscientists who study deep brain stimulation. In this study, serially sectioned images of a human cadaver head were employed to overcome the limitations of existing methods to observe the pallidothalamic tracts. Owing to the high resolution and real color of the sectioned images, 28 structures, including the pallidothalamic tracts and mammillothalamic fasciculus, were identified. The structures were segmented and made into surface models, which are helpful in improving the stereoscopic understanding. Observing the sectioned images and surface models may help in understanding the detailed anatomy of the pallidothalamic tracts. The new findings, such as the spatial relationship of the tracts, were summarized in a schematic figure. Moreover, to elucidate the anatomical structures along the course of deep brain stimulation, virtual electrodes were inserted into the surface models. The sectioned images and surface models of this study are expected to enhance the understanding of the pallidothalamic tract anatomy. A portable document format file containing the surface models and the sectioned images can be freely downloaded from the authors' homepage. Clin. Anat. 32:66-76, 2019. © 2019 Wiley Periodicals, Inc.

Role of T1 mapping to evaluate brain aging in a healthy population.

PURPOSE: To investigate the relationship between healthy brain aging and T1 relaxation time obtained by T1 mapping. MATERIALS AND METHODS: A total of 211 (102 males, 109 females; age range: 20-89 years; mean age: 54 years) healthy volunteers underwent T1 mapping between July 2018 and January 2019. Regions of interest (ROIs) were placed on T1 maps in different anatomical regions, including the thalamus, putamen, globus pallidus, head of the caudate nucleus, nucleus accumbens, genu of the corpus callosum, and frontal lobe white matter (WM). Additionally, linear and quadratic regression analyses of ROIs were performed. RESULTS: There were significant quadratic and negative linear correlations between T1 relaxation times in the thalamus, putamen, and age (p < .001). Although the nucleus accumbens did not show a significant relationship between T1 relaxation times and age by linear regression (p = .624), a statistically significant relationship was obtained by quadratic regression (p < .001). For the globus pallidus, head of the caudate nucleus, genu of the corpus callosum and frontal lobe WM the quadratic regression analysis showed a better relationship than the linear correlation analysis. CONCLUSION: Age-related changes in T1 relaxation time vary by location in GM and WM.

Motor cortex can directly drive the globus pallidus neurons in a projection neuron type-dependent manner in the rat.

The basal ganglia are critical for the control of motor behaviors and for reinforcement learning. Here, we demonstrate in rats that primary and secondary motor areas (M1 and M2) make functional synaptic connections in the globus pallidus (GP), not usually thought of as an input site of the basal ganglia. Morphological observation revealed that the density of axonal boutons from motor cortices in the GP was 47% and 78% of that in the subthalamic nucleus (STN) from M1 and M2, respectively. Cortical excitation of GP neurons was comparable to that of STN neurons in slice preparations. FoxP2-expressing arkypallidal neurons were preferentially innervated by the motor cortex. The connection probability of cortico-pallidal innervation was higher for M2 than M1. These results suggest that cortico-pallidal innervation is an additional excitatory input to the basal ganglia, and that it can affect behaviors via the cortex-basal ganglia-thalamus motor loop.

Structural organization, GABAergic and tyrosine hydroxylase expression in the striatum and globus pallidus of the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha).

The striatum is an essential component of the basal ganglia that regulatessensory processing, motor, cognition, and behavior. Depending on the species, the striatum shows a unique structure called caudate-putamen as in mice, or its separation into two regions called caudate and lenticular nuclei, the latter formed by putamen and globus pallidus areas, as in primates. These structures have two compartments, striosome and matrix. We investigated the structural organization, GABAergic and tyrosine hydroxylase (TH) expression in the striatum and globus pallidus of the South American plains vizcacha, Lagostomus maximus. Its striatum showed regionalization arising from the presence of an internal capsule, and a similar organization to a striosome-matrix compartmentalization. GABAergic neurons in the matrix of caudate exhibited parvalbumin, calretinin, calbindin, GAD65, and NADPH-d-immunoreactivity. These were also expressed in cells of the putamen with the exception of calretinin showing neurofibers localization. Globus pallidus showed parvalbumin- and GAD65-immunoreactive cells, and calretinin- and calbindin-immunoreactive neuropil, plus GABA-A-immunoreactive neurofibers. NADPH-d-, GAD65- and GABA-A-immunoreactive neurons were larger than parvalbumin-, calretinin-, and calbindin-immunoreactive cells, whereas calbindin-immunoreactive cells were the most abundant. In addition, TH-immunoreactive neuropil was observed in the matrix of the striatum. A significant larger TH-immunoreactive area and neuron number was found in females compared to males. The presence of an internal capsule suggests an adaptive advantage concerning motor and cognitive abilities favoring reaction time in response to predators. In an anatomy-evolutive perspective, the striatum of vizcacha seems to be closer to that of humans than to that of laboratory traditional models such as mouse.

Subcortical amyloid load is associated with shape and volume in cognitively normal individuals.

Amyloid-beta (Aß) deposition is one of the main hallmarks of Alzheimer's disease. The study assessed the associations between cortical and subcortical 11 C-Pittsburgh Compound B (PiB) retention, namely, in the hippocampus, amygdala, putamen, caudate, pallidum, and thalamus, and subcortical morphology in cognitively normal individuals. We recruited 104 cognitive normal individuals who underwent extensive neuropsychological assessment, PiB-positron emission tomography (PET) scan, and 3-T magnetic resonance imaging (MRI) acquisition of T1-weighted images. Global, cortical, and subcortical regional PiB retention values were derived from each scan and subcortical morphology analyses were performed to investigate vertex-wise local surface and global volumes, including the hippocampal subfields volumes. We found that subcortical regional Aß was associated with the surface of the hippocampus, thalamus, and pallidum, with changes being due to volume and shape. Hippocampal Aß was marginally associated with volume of the whole hippocampus as well as with the CA1 subfield, subiculum, and molecular layer. Participants showing higher subcortical Aß also showed worse cognitive performance and smaller hippocampal volumes. In contrast, global and cortical PiB uptake did not associate with any subcortical metrics. This study shows that subcortical Aß is associated with subcortical surface morphology in cognitively normal individuals. This study highlights the importance of quantifying subcortical regional PiB retention values in these individuals.

Valence-encoding in the lateral habenula arises from the entopeduncular region.

Lateral habenula (LHb) neurons are activated by negative motivational stimuli and play key roles in the pathophysiology of depression. Prior reports suggested that rostral entopeduncular nucleus (rEPN) neurons drive these responses in the LHb and rostromedial tegmental nucleus (RMTg), but these influences remain untested. Using rabies viral tracers, we demonstrate disynaptic projections from the rEPN to RMTg, but not VTA, via the LHb in rats. Using in vivo electrophysiology, we find that rEPN or LHb subpopulations exhibit activation/inhibition patterns after negative/positive motivational stimuli, similar to the RMTg, while temporary inactivation of a region centered on the rEPN decreases LHb basal and burst firing, and reduces valence-related signals in LHb neurons. Additionally, excitotoxic rEPN lesions partly diminish footshock-induced cFos in the LHb and RMTg. Together, our findings indicate an important role of the rEPN, and possibly immediately adjacent hypothalamus, in driving basal activities and valence processing in LHb and RMTg neurons.

Morphometric Study of the Internal Globus Pallidus Using the Robert, Barnard, and Brown Staining Method.

BACKGROUND: The globus pallidus internus (Gpi) is a major target in functional neurosurgery. Anatomical studies are crucial for correct planning and good surgical outcomes in this region. The present study described the anatomical coordinates of the Gpi and its relationship with other brain structures and compared the findings with those from previous anatomical studies. METHODS: We obtained 35 coronal and 5 horizontal brain specimens from the Department of Anatomy and stained them using the Robert, Barnard, and Brown technique. After excluding defective samples, 60 nuclei were analyzed by assessing their distances to the anatomical references and the trajectories to these nuclei. RESULTS: The barycenter of the Gpi was identified at the level of the mammillary bodies and 1 cm above the intercommissural plane. Thereafter, the distances to other structures were found. The mean ± standard deviation distance was 15.62 ± 2.66 mm to the wall of the third ventricle and 17.02 ± 2.69 mm to its midline, 4.74 ± 1.12 mm to the optic tract, 2.51 ± 0.8 mm and 13.56 ± 2 mm to the internal and external capsule, and 21.3 ± 2.44 mm to the insular cortex. The cortical point of entry should be located 22.03 ± 4.34 mm to 48.74 ± 4.44 mm from the midline. CONCLUSION: The Gpi has less variability in distance to closer anatomical references, such as the optic tract and internal capsule. Distant locations showed a more inhomogeneous pattern. Anatomical studies such as ours are important for the development of new therapeutic approaches and can be used as a basis for new research involving volumetric and specific group analyses.

Corticopallidal Connectome of the Globus Pallidus Externus in Humans: An Exploratory Study of Structural Connectivity Using Probabilistic Diffusion Tractography.

BACKGROUND AND PURPOSE: Electrophysiologic abnormalities of the globus pallidus externus have been shown in several disease processes including Parkinson disease, dystonia, and Huntington disease. However, the connectivity, nuclear structure, and function of the globus pallidus externus are still not well-understood. Increasing evidence for the existence of direct corticopallidal connections challenges traditional understanding of the connectivity of the globus pallidus externus; nevertheless, these corticopallidal connections have yet to be fully characterized in humans. The objective of this study was to assess the corticopallidal connections of the globus pallidus externus by means of probabilistic diffusion-weighted MR imaging tractography using high-resolution, multishell data. MATERIALS AND METHODS: Imaging data from the open-access Human Connectome Project data base were used to perform probabilistic tractography between the globus pallidus externus and the cerebral cortex using 34 distinct cortical regions. Group averages were calculated for normalized percentages of tracts reaching each of the cortical targets, and side-to-side comparison was made. RESULTS: Cortical connectivity was demonstrated between the globus pallidus externus and multiple cortical regions, including direct connection to putative sensorimotor, associative, and limbic areas. Connectivity patterns were not significantly different between the right and left hemispheres with the exception of the frontal pole, which showed a greater number of connections on the right (P = .004). CONCLUSIONS: Our in vivo study of the human globus pallidus externus using probabilistic tractography supports the existence of extensive corticopallidal connections and a tripartite functional division, as found in animal studies. A better understanding of the connectivity of the globus pallidus externus may help to understand its function and elucidate the effects of programming the higher contacts in pallidal deep brain stimulation.

Human Motor Thalamus Reconstructed in 3D from Continuous Sagittal Sections with Identified Subcortical Afferent Territories.

Classification and delineation of the motor-related nuclei in the human thalamus have been the focus of numerous discussions for a long time. Difficulties in finding consensus have for the most part been caused by paucity of direct experimental data on connections of individual nuclear entities. Kultas-Ilinsky et al. (2011) showed that distribution of glutamic acid decarboxylase isoform 65 (GAD65), the enzyme that synthesizes inhibitory neurotransmitter γ-aminobutyric acid, is a reliable marker that allows to delineate connectionally distinct nuclei in the human motor thalamus, namely the territories innervated by nigral, pallidal, and cerebellar afferents. We compared those immunocytochemical staining patterns with underlying cytoarchitecture and used the latter to outline the three afferent territories in a continuous series of sagittal Nissl-stained sections of the human thalamus. The 3D volume reconstructed from the outlines was placed in the Talairach stereotactic coordinate system relative to the intercommissural line and sectioned in three stereotactic planes to produce color-coded nuclear maps. This 3D coordinate-based atlas was coregistered to the Montreal Neurological Institute (MNI-152) space. The current report proposes a simplified nomenclature of the motor-related thalamic nuclei, presents images of selected histological sections and stereotactic maps illustrating topographic relationships of these nuclei as well as their relationship with adjacent somatosensory afferent region. The data are useful in different applications such as functional MRI and diffusion tractography. The 3D dataset is publicly available under an open license and can also be applicable in clinical interventions in the thalamus.

How do cortico-striatal projections impact on downstream pallidal circuitry?

The frontal cortico-basal ganglia network plays a central role in action selection, associative learning, and motivation, processes requiring the integration of information from functionally distinct cortical regions. The cortico-striatal projection is a likely substrate of information integration, as terminal fields from different cortical regions converge in the striatum. These intersecting projections form complex zones of unique cortical inputs. Here, our goal was to follow these projection zones downstream in the basal ganglia to the globus pallidus. We combined a sizable database of 3D models of striato-pallidal chartings in macaques with maps of frontal cortical inputs to determine the topography of the striato-pallidal projection and the indirect cortical influence over the pallidum. We found that the striato-pallidal projection is highly topographic, with the location of the striatal injection site strongly predicting the location of the resulting pallidal terminal fields. Furthermore, striato-pallidal projections are specific and largely nonoverlapping. Thus, striatal hubs receiving unique combinations of cortical inputs have distinct projections to the pallidum. However, because of the strong convergence of cortical terminal fields in the striatum, the indirect pallidal representation of any given frontal cortical region remains broad. We illustrate this arrangement by contrasting the pallidal projections from two nearby striatal cases: one a putative hub for cortical attentional bias signals, and the other with a different, more ventral set of cortical inputs. Thus, the striato-pallidal projection faithfully conveys unique combinations of cortical inputs to different locations within the pallidum via the striatum.