Using diffusion MRI data acquired with ultra-high gradient strength to improve tractography in routine-quality data.

The development of scanners with ultra-high gradient strength, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today's state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols.

[Secondary surgeries in craniosynostosis and faciocraniosynostosis]. / Chirurgie secondaire des craniosténoses et faciocraniosténoses.

Secondary surgeries for single craniosynostosis surgeries are mainly esthetic refinements rather than functional indications. However, cranioplasties for bone defects correction or insufficient corrections may be undertaken. Management of syndromic craniosynostoses usually requires multiple surgical interventions, the sequence of which might vary per the genetic mutation. It is commonplace to start with posterior vault expansion before age 6 months, then treat cerebellar tonsillar herniation by the age of twelve months, and delay fronto-facial monobloc advancement until at least 18-24 months of age. Ventricular shunting is preferably avoided or delayed. Failure to respect these guidelines can significantly complicate the subsequent management. Primary fronto-orbital advancement or early facial osteotomy type Le Fort3, may compromise the subsequent fronto-facial monobloc advancement. However, this salvage secondary monobloc may be undertaken in some instances despite previous anterior osteotomies with a higher morbidity.

Temperature-Sensitive Resistance to Wheat streak mosaic virus in CO960333 and KS06HW79 Wheat.

Temperature-sensitive resistance (TSR) that can protect against losses to Wheat streak mosaic virus (WSMV) has been described in elite wheat germplasm. A TSR identified in the advanced breeding line CO960333 and its derivative KS06HW79 was examined in growth-chamber tests conducted under constant temperature regimes of 18, 21, and 24°C against an array of WSMV isolates. At 18°C, all tested isolates systemically infected the pedigree parents, while the progeny line CO960333 remained free of symptoms; at 24°C, all lines were susceptible. At the intermediate temperature of 21°C, the TSR of KS06HW79 was effective in contrast to the TSRs of KS03HW12 and 'RonL'. In field trials conducted in 2011 and 2012, the TSR expressed in KS06HW79 conferred complete protection against yield losses from inoculation with the Sidney 81 isolate of WSMV, while the TSR of RonL conferred similar protection in 2012 but allowed small losses in 2011. The resistance expressed by KS06HW79 is likely not due to the Wsm1 gene because it did not contain the tightly linked J15 sequence-characterized amplified region (SCAR) DNA marker. These findings suggest that KS06HW79 could be an additional TSR source of value to wheat-breeding programs seeking to control losses from WSMV.

The simultaneous role of an alveolus as flow mixer and flow feeder for the deposition of inhaled submicron particles.

In an effort to understand the fate of inhaled submicron particles in the small sacs, or alveoli, comprising the gas-exchange region of the lung, we calculated the flow in three-dimensional (3D) rhythmically expanding models of alveolated ducts. Since convection toward the alveolar walls is a precursor to particle deposition, it was the goal of this paper to investigate the streamline maps' dependence upon alveoli location along the acinar tree. On the alveolar midplane, the recirculating flow pattern exhibited closed streamlines with a stagnation saddle point. Off the midplane we found no closed streamlines but nested, funnel-like, spiral, structures (reminiscent of Russian nesting dolls) that were directed towards the expanding walls in inspiration, and away from the contracting walls in expiration. These nested, funnel-like, structures were surrounded by air that flowed into the cavity from the central channel over inspiration and flowed from the cavity to the central channel over expiration. We also found that fluid particle tracks exhibited similar nested funnel-like spiral structures. We conclude that these unique alveolar flow structures may be of importance in enhancing deposition. In addition, due to inertia, the nested, funnel-like, structures change shape and position slightly during a breathing cycle, resulting in flow mixing. Also, each inspiration feeds a fresh supply of particle-laden air from the central channel to the region surrounding the mixing region. Thus, this combination of flow mixer and flow feeder makes each individual alveolus an effective mixing unit, which is likely to play an important role in determining the overall efficiency of convective mixing in the acinus.

TAP, a novel T cell-activating protein involved in the stimulation of MHC-restricted T lymphocytes.

Five mAbs have been generated and used to characterize TAP (T cell activating protein) a novel, functional murine T cell membrane antigen. The TAP molecule is a 12-kD protein that is synthesized by T cells. By antibody crossblocking, it appears to be closely associated with a 16-kD protein on the T cell membrane also identified with a novel mAb. These molecules are clearly distinct from the major well-characterized murine T cell antigens previously described. Antibody binding to TAP can result in the activation of MHC-restricted, antigen-specific inducer T cell hybridomas that is equivalent in magnitude to maximal antigen or lectin stimulation. This is a direct effect of soluble antibody and does not require accessory cells or other factors. The activating anti-TAP mAbs are also mitogenic for normal heterogeneous T lymphocytes in the presence of accessory cells or IL-1. In addition, these antibodies are observed to modulate specific immune stimulation. Thus, the activating anti-TAP mAbs synergise with antigen-specific stimulation of T cells, while a nonactivating anti-TAP mAb inhibits antigen driven activation. These observations suggest that the TAP molecule may participate in physiologic T cell activation. The possible relationship of TAP to known physiologic triggering structures, the T3-T cell receptor complex, is considered. TAP is expressed on 70% of peripheral T cells and therefore defines a major T cell subset, making it perhaps the first example of a murine subset-specific activating protein.

Identification of Variants of the High Plains virus Infecting Wheat in Kansas.

The properties of two virus isolates (U04-82 and U04-83) obtained from two wheat (Triticum aestivum) plants expressing mosaic symptoms were investigated using enzyme-linked immunosorbent assay (ELISA), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), time-of-flight mass spectrometry (TOFMS), and infection of wheat with resistance to Wheat streak mosaic virus (WSMV). The coat protein mass was estimated by SDS-PAGE as approximately 32 kDa for U04-82 and 30 kDa for U04-83. The amino acid sequence of the coat protein of U04-82 was 99.6 and 85.5% identical to two isolates, ABC58222 and TX96, respectively, of High Plains virus (HPV) described from Texas. U04-82 was transmitted by wheat curl mites and caused significant yield reductions in wheat resistant to WSMV. U04-83 was actually two distinct virus isolates whose capsid protein amino acid sequences were only 57 and 50% similar to that of TX96. Antiserum prepared to a synthetic peptide from the sequence of the U04-83 isolate recognized the two U04-83 isolates, but not the U04-82 isolate.

Reduced focal fiber collinearity in the cingulum bundle in adults with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a disabling condition, often associated with a chronic course. Given its role in attentional control, decision-making, and emotional regulation, the anterior cingulate cortex is considered to have a key role in the pathophysiology of the disorder. Notably, the cingulum bundle, being the major white matter tract connecting to this region, has been historically a target for the surgical treatment of intractable OCD. In this study, we aimed to identify the extent to which focal-more than diffuse-abnormalities in fiber collinearity of the cingulum bundle could distinguish 48 adults with OCD (mean age [SD] = 23.3 [4.5] years; F/M = 30/18) from 45 age- and sex-matched healthy control adults (CONT; mean age [SD] = 23.2 [3.8] years; F/M = 28/17) and further examine if these abnormalities correlated with symptom severity. Use of tract-profiles rather than a conventional diffusion imaging approach allowed us to characterize white matter microstructural properties along (100 segments), as opposed to averaging these measures across, the entire tract. To account for these 100 different segments of the cingulum bundle, a repeated measures analysis of variance revealed a main effect of group (OCD < CONT; F[1,87] = 5.3; P = 0.024) upon fractional anisotropy (FA, a measure of fiber collinearity and/or white matter integrity), in the cingulum bundle, bilaterally. Further analyses revealed that these abnormalities were focal (middle portion) within the left and right cingulum bundle, although did not correlate with symptom severity in OCD. Findings indicate that focal abnormalities in connectivity between the anterior cingulate cortex and other prefrontal cortical regions may represent neural mechanisms of OCD.

Temperature-Sensitive Wheat streak mosaic virus Resistance Identified in KS03HW12 Wheat.

Wheat streak mosaic virus (WSMV) infection reduces seed yield and quality in wheat. These losses can be alleviated significantly by exploiting genetic host plant resistance. A new source of temperature-sensitive resistance to WSMV, KS03HW12, and its parental lines (KS97HW29/ KS97HW131//KS96HW100-5) were evaluated in both greenhouse and field conditions. Parental wheat lines were exposed to WSMV pressure under different temperatures in growth chambers to determine the stability of the resistance, and 2 years of field yield trials were conducted to confirm effectiveness. To determine the effectiveness of its resistance against a spectrum of isolates, KS03HW12 was tested against six different WSMV isolates of different geographic origins. Among the three pedigree parents, only one, KS97HW29, was resistant. The parental lines of KS97HW29 are not available for testing; therefore, the presumed origin of the resistance could not be further confirmed. None of the six tested WSMV isolates systemically infected KS03HW12 at 18°C. Yield of KS03HW12 in field tests was not different from healthy controls. Thus, the elite winter wheat KS03HW12 appears to be a stable and effective source of temperature-sensitive resistance to WSMV and should be useful for wheat breeding programs.

Dissipative particle dynamics simulation of flow generated by two rotating concentric cylinders: boundary conditions.

The dissipative particle dynamics (DPD) method was used to simulate the flow in a system comprised of a fluid occupying the space between two cylinders rotating with equal angular velocities. The fluid, initially at rest, ultimately reaches a steady, linear velocity distribution (a rigid-body rotation). Since the induced flow field is solely associated with the no-slip boundary condition at the walls, we employed this system as a benchmark to examine the effect of bounce-back reflections, specular reflections, and Pivkin-Karniadakis no-slip boundary conditions, upon the steady-state velocity, density, and temperature distributions. An additional advantage of the foregoing system is that the fluid occupies inherently a finite bounded domain so that the results are affected by the prescribed no-slip boundary conditions only. Past benchmark systems such as Couette flow between two infinite parallel plates or Poiseuille flow in an infinitely long cylinder must employ artificial periodic boundary conditions at arbitrary upstream and downstream locations, a possible source of spurious effects. In addition, the effect of the foregoing boundary conditions on the time evolution of the simulated velocity profile was compared with that of the known, time-dependent analytical solution. It was shown that bounce-back reflection yields the best results for the velocity distributions with small fluctuations in density and temperature at the inner fluid domain and larger deviations near the walls. For the unsteady solutions a good fit is obtained if the DPD friction coefficient is proportional to the kinematic viscosity. Based on dimensional analysis and the numerical results a universal correlation is suggested between the friction coefficient and the kinematic viscosity.

Temperature Sensitivity and Efficacy of Wheat streak mosaic virus Resistance Derived from CO960293 Wheat.

Wheat yields often are limited by infection by Wheat streak mosaic virus (WSMV). Host plant resistance to WSMV can reduce losses. This study was conducted to characterize a new source of temperature-sensitive resistance found in CO960293 wheat. The source of the temperature-sensitive resistance in CO960293 is unknown. Parental and other wheat lines were tested for WSMV resistance using 51 WSMV isolates under different temperatures to determine the stability of the resistance, and yield trials were conducted in the field for 3 years. All parental wheat lines became infected by WSMV at all temperatures and were infective in back assay to 'Tomahawk' wheat. No WSMV isolate defeated the resistance of CO960293 at 18°C. Yield of CO960293 in field trials was reduced in only 1 of 3 years. Our data demonstrate that this wheat line can be a valuable source of resistance to WSMV in wheat programs, particularly in areas where temperatures are cool following planting in the fall.

Convergent inputs from thalamic motor nuclei and frontal cortical areas to the dorsal striatum in the primate.

Current models of basal ganglia circuitry primarily associate the ventral thalamic nuclei with relaying basal ganglia output to the frontal cortex. However, some studies have demonstrated projections from the ventral anterior (VA) and ventral lateral (VL) thalamic nuclei to the striatum, suggesting that these nuclei directly modulate the striatum. VA/VL nuclei have specific connections with primary, supplementary, premotor, and cingulate motor cortices indicating their involvement in motor function. These areas mediate different aspects of motor control such as movement execution, motor learning, and sensorimotor integration. Increasing evidence indicates that functionally related motor areas have convergent projections to the dorsal striatum, suggesting that integration of different aspects of motor control occur at the level of the striatum. This study examines the organization of VA/VL thalamic inputs to the dorsal "motor" striatum to determine how this afferent projection is organized with respect to corticostriatal afferents from motor, premotor, and cingulate motor areas. Motor cortical projections to specific dorsal striatal regions arose from multiple areas, including components from primary motor, premotor, supplementary, and cingulate motor areas. Diverse motor cortical projections to a given dorsal striatal region indicated convergence of functionally related corticostriatal motor pathways. Most dorsal striatal sites received dense thalamic inputs from the VL pars oralis nucleus. Additional thalamostriatal projections arose from VA, VL pars caudalis, and ventral posterior lateral pars oralis nuclei and Olszewski's Area X. Our results provide evidence for convergent striatal projections from interconnected ventral thalamic and cortical motor areas, suggesting that these afferents modulate the same striatal output circuits.

Striatal responses to partial dopaminergic lesion: evidence for compensatory sprouting.

Dopaminergic lesions result in the acute loss of striatal dopamine content, the loss of tyrosine hydroxylase-immunoreactive fibers, upregulation of preproenkephalin mRNA expression, and compensatory changes in the synthesis and metabolism of dopamine. Despite the severe loss of fine tyrosine hydroxylase-immunoreactive fibers, larger fibers persist. We found that some tyrosine hydroxylase fiber types increase their branching and become thicker after partial lesion. To determine whether the remaining tyrosine hydroxylase fibers were degenerative or part of a compensatory response, we morphologically characterized striatal tyrosine hydroxylase fibers and compared them to silver-stained degenerative structures. Branched and large tyrosine hydroxylase fiber types were nondegenerative. Furthermore, normal preproenkephalin mRNA expression was maintained despite severe overall loss of tyrosine hydroxylase fibers in striatal regions with abundant branching, whereas preproenkephalin mRNA expression increased in severely depleted regions that lacked branched fibers, indicating that branching or sprouting was involved in the compensation for dopamine depletion and the maintenance of normal preproenkephalin expression. In support of compensatory sprouting by tyrosine hydroxylase fibers, mRNA for growth associated protein-43 was upregulated in dopaminergic midbrain cells. We conclude that an important compensatory response to partial dopaminergic depletion is the formation of new branches or sprouting.

Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum.

Clinical manifestations in diseases affecting the dopamine system include deficits in emotional, cognitive, and motor function. Although the parallel organization of specific corticostriatal pathways is well documented, mechanisms by which dopamine might integrate information across different cortical/basal ganglia circuits are less well understood. We analyzed a collection of retrograde and anterograde tracing studies to understand how the striatonigrostriatal (SNS) subcircuit directs information flow between ventromedial (limbic), central (associative), and dorsolateral (motor) striatal regions. When viewed as a whole, the ventromedial striatum projects to a wide range of the dopamine cells and receives a relatively small dopamine input. In contrast, the dorsolateral striatum (DLS) receives input from a broad expanse of dopamine cells and has a confined input to the substantia nigra (SN). The central striatum (CS) receives input from and projects to a relatively wide range of the SN. The SNS projection from each striatal region contains three substantia nigra components: a dorsal group of nigrostriatal projecting cells, a central region containing both nigrostriatal projecting cells and its reciprocal striatonigral terminal fields, and a ventral region that receives a specific striatonigral projection but does not contain its reciprocal nigrostriatal projection. Examination of results from multiple tracing experiments simultaneously demonstrates an interface between different striatal regions via the midbrain dopamine cells that forms an ascending spiral between regions. The shell influences the core, the core influences the central striatum, and the central striatum influences the dorsolateral striatum. This anatomical arrangement creates a hierarchy of information flow and provides an anatomical basis for the limbic/cognitive/motor interface via the ventral midbrain.

Early dipyridamole (99m)Tc-sestamibi single photon emission computed tomographic imaging 2 to 4 days after acute myocardial infarction predicts in-hospital and postdischarge cardiac events: comparison with submaximal exercise imaging.

BACKGROUND: Because of its brief hemodynamic effects and minor effect on determinants of myocardial oxygen demand, vasodilator stress myocardial perfusion imaging (MPI) can be applied very early after acute myocardial infarction (AMI) for risk stratification, allowing management decisions to be made earlier and thus potentially shortening hospitalization stays, reducing costs, and preventing early cardiac events. This multicenter randomized trial compared the prognostic value of early dipyridamole MPI and standard predischarge submaximal exercise MPI in patients who presented with AMI. METHODS AND RESULTS: Patients who presented with their first AMI (n=451) were randomized in a 3:1 ratio to undergo either both an early (day 2 to 4) dipyridamole (99m)Tc-sestamibi MPI study and a predischarge (day 6 to 12) submaximal exercise (99m)Tc-sestamibi MPI study or only the predischarge study. Multivariate predictors of in-hospital cardiac events included nuclear imaging summed stress and summed reversibility scores and peak creatine kinase. For postdischarge cardiac events, multivariate predictors in patients undergoing dipyridamole MPI included only the summed stress, reversibility, and rest imaging scores and anterior MI. For a given summed stress score, the interaction of reversibility score further improved the predictive value. Dipyridamole MPI showed better risk stratification than submaximal exercise MPI. CONCLUSIONS: Dipyridamole MPI very early after MI predicts early and late cardiac events, with superior prognostic value compared with submaximal exercise imaging. The extent and severity of the stress defect and reversibility of the defect were the most important predictors of cardiac death and recurrent MI. This technique can allow management decisions to be made earlier with regard to AMI patients and could have important economic impact if applied widely.

The place of the thalamus in frontal cortical-basal ganglia circuits.

The thalamus has long been thought to convey subcortical information to the cortex. Indeed, models of basal ganglia function attribute the primary role for the thalamus to a simple relay of information processed in the basal ganglia to the cortex. The thalamic nuclear groups that are associated primarily with this function are the ventral anterior and ventral lateral nuclei and the mediodorsal thalamic nucleus. However, recent studies have shown that the corticothalamic projection is important for the dynamics of the thalamocortical processing. Furthermore, the relay nuclei that carry basal ganglia output to the cortex have recently been shown to project back to the basal ganglia directly. These two recent developments indicate a more dynamic role for the thalamus in basal ganglia information processing than a passive relay.

A primate analogue of amphetamine-induced behaviors in humans.

The effects of amphetamine on individual and social behaviors were studied in two colonies of rhesus monkeys. After an initial base-line period, each animal, in turn, received low chronic drug administration for 3 weeks. Between each drug period new base-line data were collected. During amphetamine administration, there was a significant increase in the following behaviors: time spent in "sit tense" postures, frequency of orienting, and frequency of agonistic behaviors. In addition, significant changes were seen in the time spent in proximity with other members of the group. The results are discussed both in terms of across-animal changes as well as with regard to social factors, rank in the hierarchy, and affiliative relationships.

Primate cingulostriatal projection: limbic striatal versus sensorimotor striatal input.

The organization of the projections from the cingulate cortex to the striatum in the monkey was studied using the retrograde tracers Lucifer Yellow conjugated to dextran amines and horseradish peroxidase conjugated to wheat germ agglutinin. These tracers were injected into the different regions of the ventral (limbic) striatum and the dorsal (sensorimotor) striatum. The shell region of the nucleus accumbens was defined using calbindin-D28K immunohistochemistry. Following injections into the ventral striatum, there are numerous retrogradely labeled neurons in the various regions of the primate cingulate cortex, most of which are derived from layer V. The cytoarchitectural subdivisions of cingulate cortex include the anterior cingulate cortex, areas 25, 24a-c, and 24a'-c', and the posterior cingulate cortex, areas 23a-c, 29, 30, and 31. There is a topographical organization of the projections from these different cingulate areas to the ventral and dorsal striatum. The medial ventral striatum receives input from the rostral part of the anterior cingulate cortex (areas 25 and 24a,b). The shell region of the nucleus accumbens receives fibers from areas 25, 24a,b, and 24a',b'. Projections to the central ventral striatum including the core of the nucleus accumbens are derived primarily from areas 25, 24a, 24b, and the medial part of area 24c. However, few labeled cells are detected in areas 24c and 24c'. The lateral ventral striatum receives input primarily from areas 24b, 24b' and 23b and medial portion of area 24c. The medial ventral striatum and the shell of the nucleus accumbens have a similar distribution of labeled cells, such that these regions derive their input almost entirely from the rostral anterior cingulate cortex. In contrast to the ventral striatum, the dorsal sensorimotor striatum receives projections from areas 24c, 24c' 23c and 31. These arise primarily from the lateral portion of lower bank and the fundus of the cingulate sulcus. Our results demonstrate that areas 24c, 24c' and 23c, the lateral portion of the lower bank and the fundus of the cingulate sulcus project to the dorsal sensorimotor striatum. The medial portion of the lower bank of the cingulate cortex projects to the ventral striatum including the core of the nucleus accumbens. Different projections to striatum from discrete subdivisions of cingulate cortex indicate that these areas are heterogeneous and have different functions such that the fundus of the cingulate sulcus is related to skeletomotor function, whereas the medial portion of the lower bank of the cingulate sulcus is associated with the limbic-related and association cortical function.(ABSTRACT TRUNCATED AT 400 WORDS)

Primate striatonigral projections: a comparison of the sensorimotor-related striatum and the ventral striatum.

The striatum receives topographic cortical inputs with the limbic lobe terminating in the ventral striatum and sensorimotor cortical regions terminating in the dorsolateral striatum. The organization of striatonigral projections originating from these different striatal territories was examined in primate by using several anterograde tracers. The ventral striatum innervates a large area of the substantia nigra, including the medial pars reticulata and much of the pars compacta. Moreover, projections from separate areas of the ventral striatum overlap considerably in the substantia nigra. No mediolateral or rostrocaudal topographic order is apparent, and the area of the substantia nigra associated with the ventral striatum is extensive. In contrast, the sensorimotor-related striatum innervates a limited region of the ventrolateral substantia nigra. Similar to ventral striatonigral projections, projections originating from different areas of the sensorimotor-related striatum send converging inputs to the substantia nigra. Sensorimotor-related striatonigral projections avoid the region of the dopaminergic neurons in the dorsal pars compacta. Striatonigral projections from the sensorimotor-related and ventral striatum do not overlap in the substantia nigra. Examination of the outputs of discrete striatal loci indicates that the organization of striatonigral projections is more related to corticostriatal inputs than to a simple rostrocaudal, dorsoventral, or mediolateral topography of the striatum. Striatal projections that originate from different striatal territories are distinct and nonoverlapping, thus supporting the concept of segregated striatonigral circuits. However, areas of the striatum that receive common cortical inputs send converging inputs to the substantia nigra. This suggests that the substantia nigra is also an important link for integrating information between functionally related (sub)circuits.

Interrelationship of the distribution of neuropeptides and tyrosine hydroxylase immunoreactivity in the human substantia Nigra.

The relationship in the human substantia nigra of peptidergic fibers with intrinsic dopaminergic neurons was studied in adjacent coronal sections of the mesencephalon immunohistochemically stained for enkephalin (ENK), substance P (SP), and tyrosine (TH) hydroxylase immunoreactivity. TH-positive elements are present in the substantia nigra in at least two different arrangements: 1) a dorsal tier of rather loosely arranged neurons, which is continuous medially with the ventral tegmental area and laterally with the retrorubral area, 2) a ventral tier of more closely packed neurons, clusters of which frequently form finger-like extensions deep into the pars reticulata. This ventral region contains TH-positive dendrites extending ventrally into the pars reticulata. The distribution of ENK is mainly restricted to the medial half of the ventral aspect of the substantia nigra, while SP occupies its entire rostral-caudal and medial-lateral extents. Peptide-positive fibers vary in density from dense to light. There is very little overlap between the dorsal tier of the TH-positive neurons and the ENK or SP staining. The dorsal part of the peptide-immunoreactive area extensively overlaps with the TH-positive neurons of the ventral tier of cells. The ventral part of the peptide-positive area overlaps with the pars reticulata of the substantia nigra in which the TH-positive dendrites extend. The overlap between the neuropeptide fibers and the TH-positive cells of the ventral tier is not complete, with cells found both within and outside peptide-positive fiber networks. Three patterns of overlap emerge. In dorsal regions elongated cell clusters lie partially within and partially outside the dense peptide-positive fiber networks. In the ventral regions TH-positive cells are either completely embedded within peptide fibers or clusters of cells are present in peptide-free zones. These data suggest that specific peptidergic pathways differentially innervate the substantia nigra. TH cells which lie within or outside these fibers may reflect functionally different subsystems in the striatonigral pathways in the human.

Organization of thalamostriatal terminals from the ventral motor nuclei in the macaque.

This study examines the organization of thalamostriatal projections from ventral tier nuclei that relay basal ganglia output to the frontal cortex. Although previous thalamostriatal studies emphasize projections from the intralaminar nuclei, studies in primates show a substantial projection from the ventral anterior (VA) and ventral lateral (VL) nuclei. These nuclei make up the main efferent projection from the basal ganglia to frontal cortical areas, including primary motor, supplementary, premotor, and cingulate motor areas. Functionally related motor areas of the frontal cortex and VA/VL have convergent projections to specific regions of the dorsal striatum. The distribution of VA/VL terminals within the striatum is crucial to understanding their relationship to motor cortical afferents. We placed anterograde tracer injections into discrete VA/VL thalamic areas. VA/VL thalamostriatal projections terminate in broad, rostrocaudal regions of the dorsal striatum, corresponding to regions innervated by functionally related cortical motor areas. The pars oralis division of VL projects primarily to the dorsolateral, postcommissural putamen, whereas the parvicellular VA targets more medial and rostral putamen regions, and the magnocellular division of VA targets the dorsal head of the caudate nucleus. Whereas these results demonstrate a general functional topography, specific VA/VL projections overlap extensively, suggesting that functionally distinct VA/VL projections may also converge in dorsal striatal areas. Within striatal territories, VA/VL projections terminate in a patchy, nonhomogeneous manner, indicating another level of complexity. Moreover, terminal fields contain both terminal clusters and scattered, long, unbranched fibers with many varicosities. These fiber morphologies resemble those from the cortex and raise the possibility that VA/VL thalamostriatal projections neurons have divergent connectional features.