Syracuse VA Medical Center

BACKGROUND: The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known. METHODS: From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality. RESULTS: During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death. CONCLUSIONS: Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.).

Our goal in this review is to provide an anatomical framework for the analysis of the motor functions of the medial wall of the hemisphere in humans and laboratory primates. Converging evidence indicates that this region of the frontal lobe contains multiple areas involved in motor control. In the monkey, the medial wall contains four premotor areas that project directly to both the primary motor cortex and the spinal cord. These are the supplementary motor area (SMA) on the superior frontal gyrus and three motor areas buried within the cingulate sulcus. In addition, there is evidence that a fifth motor field. the pre-SMA. lies rostral to the SMA proper. Recent physiological observations provide evidence for functional differences among these motor fields. In the human, no consensus exists on the number of distinct motor fields on the medial wall. In this review, we summarize the results of positron emission tomography (PET) studies that examined functional activation on the medial wall of humans. Our analysis suggests that it is possible to identify at least four separate cortical areas on the medial wall. Each area appears to be relatively more involved in some aspects of motor behavior than others. These cortical areas in the human appear to be analogous to the pre-SMA, the SMA proper, and two of the cingulate motor areas of the monkey. We believe that these correspondences and the anatomical framework we describe will be important for unraveling the motor functions of the medial wall of the hemisphere.

We determined the origin of corticospinal neurons in the frontal lobe. These neurons were labeled by retrograde transport of tracers after injections into either the dorsolateral funiculus at the second cervical segment or the gray matter of the spinal cord throughout the cervical enlargement. Using retrograde transport of tracer from the arm area of the primary motor cortex, we defined the arm representation in each premotor area in another set of animals. We found that corticospinal projections to cervical segments of the spinal cord originate from the primary motor cortex and from the 6 premotor areas in the frontal lobe. These are the same premotor areas that project directly to the arm area of the primary motor cortex. The premotor areas are located in parts of cytoarchitectonic area 6 on the lateral surface and medial wall of the hemisphere, as well as in subfields of areas 23 and 24 in the cingulate sulcus. The total number of corticospinal neurons in the arm representations of the premotor areas equals or exceeds the total number in the arm representation of the primary motor cortex. The premotor areas collectively comprise more than 60% of the cortical area in the frontal lobe that projects to the spinal cord. Like the primary motor cortex, each of the premotor areas contains local regions that have a high density of corticospinal neurons. These observations indicate that a substantial component of the corticospinal system originates from the premotor areas in the frontal lobe. Each of the premotor areas has direct access to the spinal cord, and as a consequence, each has the potential to influence the generation and control of movement independently of the primary motor cortex. These findings raise serious questions about the utility of viewing the primary motor cortex as the "upper motoneuron" or "final common pathway" for the central control of movement.

The possibility that neurons in the basal ganglia and cerebellum innervate areas of the cerebral cortex that are involved in cognitive function has been a controversial subject. Here, retrograde transneuronal transport of herpes simplex virus type 1 (HSV1) was used to identify subcortical neurons that project via the thalamus to area 46 of the primate prefrontal cortex. This cortical area is known to be involved in spatial working memory. Many neurons in restricted regions of the dentate nucleus of the cerebellum and in the internal segment of the globus pallidus were labeled by transneuronal transport of virus from area 46. The location of these neurons was different from those labeled after HSV1 transport from motor areas of the cerebral cortex. These observations define an anatomical substrate for the involvement of basal ganglia and cerebellar output in higher cognitive function.

We examined the topographic organization of corticospinal neurons in the primary motor cortex and in the two premotor areas on the lateral surface of the hemisphere [i.e., the dorsal premotor area (PMd) and the ventral premotor area (PMv)]. In two macaques, we labeled corticospinal neurons that project beyond T7 or S2 by placing crystals of HRP into the dorsolateral funiculus at these segmental levels. In another seven macaques, we labeled corticospinal neurons that project to specific segmental levels of the spinal cord by injecting the fluorescent tracers fast blue and diamidino yellow into the gray matter of the cervical and lumbosacral segments. In one set of experiments (n = 2), we defined the representations of the arm and leg in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other fluorescent tracer into lower lumbosacral segments (L6-S1) of the same animal. In another set of experiments (n = 5), we defined the representations of distal and proximal parts of the forelimb in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other tracer into upper cervical segments (C2-C4) of the same animal. In the primary motor cortex and the PMd, cortical regions that project to lower cervical segments were largely separate from those that project to lower lumbosacral segments. In the PMv, few neurons were labeled after tracer injections into lower cervical segments or lower lumbosacral segments. However, corticospinal neurons were labeled in the PMv after tracer injections into upper cervical segments and after HRP placement in the dorsolateral funiculus at T7. The region of the PMv that projects to upper cervical segments was separate from that which projects below T7. Cortical regions that project to upper and lower cervical segments of the spinal cord overlapped considerably in the primary motor cortex and in the PMd. Despite this overlap, we found that the regions of the primary motor cortex and PMd that project most densely to upper cervical segments were largely separate from those that project most densely to lower cervical segments. Furthermore, we found two separate regions within area 4 that send corticospinal projections primarily to the lower cervical segments. One of these regions was located within the classical “hand” area of the primary motor cortex. The other was located at the medial edge of arm representation in the primary motor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Three distinct clinical syndromes occur in patients with increased numbers of circulating LGL. Patients with T-LGL leukemia have clonal proliferations of CD3+ LGL typically associated with chronic neutropenia and autoimmune features. NK-LGL leukemia is characterized by clonal CD3- LGL proliferation with an acute clinical presentation marked by massive hepatosplenomegaly and systemic illness. However, most patients with increased numbers of CD3- LGL do not have clinical features of NK-LGL leukemia and have a chronic clinical course. X-linked gene analyses have supported a polyclonal LGL lymphocytosis in this syndrome. Further studies are needed to determine whether clonal progression can occur in these patients.

AIMS: To synthesize continuous associations between delayed reward discounting (DRD) and both addiction severity and quantity-frequency (QF); to examine moderators of these relationships; and to investigate publication bias. METHODS: Meta-analysis of published studies examining continuous associations between DRD and addictive behaviors. Published, peer-reviewed studies on addictive behaviors (alcohol, tobacco, cannabis, stimulants, opiates and gambling) were identified via PubMed, MEDLINE and PsycInfo. Studies were restricted to DRD measures of monetary gains. Random-effects meta-analysis was conducted using Pearson's r as the effect size. Publication bias was evaluated using fail-safe N, Begg-Mazumdar and Egger's tests, meta-regression of publication year and effect size and imputation of missing studies. RESULTS: ). Significantly larger effect sizes were observed for studies examining severity compared with QF (P = 0.01), but not between the type of addictive behavior (P = 0.30) or DRD assessment (P = 0.90). Indices of publication bias suggested a modest impact of unpublished findings. CONCLUSIONS: Delayed reward discounting is associated robustly with continuous measures of addiction severity and quantity-frequency. This relation is generally robust across type of addictive behavior and delayed reward discounting assessment modality.

The neural circuits that link the basal ganglia with the cerebral cortex are critically involved in the generation and control of voluntary movement. Retrograde transneuronal transport of herpes simplex virus type 1 was used to examine the organization of connections in the cebus monkey between an output nucleus of the basal ganglia, the internal segment of the globus pallidus (GPi), and three cortical areas: the primary motor cortex, the supplementary motor ara, and the ventral premotor area. Spatially separate regions of the GPi were labeled after virus injections into each cortical area. The GPi projects to multiple cortical motor areas, and this pallidal output is organized into discrete channels. This information provides a new anatomical framework for examining the function of the basal ganglia in skeletomotor control.

Traumatic brain injury (TBI) presents in various forms ranging from mild alterations of consciousness to an unrelenting comatose state and death. In the most severe form of TBI, the entirety of the brain is affected by a diffuse type of injury and swelling. Treatment modalities vary extensively based on the severity of the injury and range from daily cognitive therapy sessions to radical surgery such as bilateral decompressive craniectomies. Guidelines have been set forth regarding the optimal management of TBI, but they must be taken in context of the situation and cannot be used in every individual circumstance. In this review article, we have summarized the current status of treatment for TBI in both clinical practice and basic research. We have put forth a brief overview of the various subtypes of traumatic injuries, optimal medical management, and both the noninvasive and invasive monitoring modalities, in addition to the surgical interventions necessary in particular instances. We have overviewed the main achievements in searching for therapeutic strategies of TBI in basic science. We have also discussed the future direction for developing TBI treatment from an experimental perspective.

Magnetic resonance imaging was used to examine the involvement of the dentate nucleus of the cerebellum in cognitive operations. All seven people examined displayed a large bilateral activation in the dentate during their attempts to solve a pegboard puzzle. The area activated was three to four times greater than that activated during simple movements of the pegs. These results provide support for the concept that the computational power of the cerebellum is applied not only to the control of movement but also to cognitive functions.

We examined interconnections between a portion of the prefrontal cortex and the premotor areas in the frontal lobe to provide insights into the routes by which the prefrontal cortex gains access to the primary motor cortex and the central control of movement. We placed multiple injections of one retrograde tracer in the arm area of the primary motor cortex to define the premotor areas in the frontal lobe. Then, in the same animal, we placed multiple injections of another retrograde tracer in and around the principal sulcus (Walker's area 46). This double labeling strategy enabled us to determine which premotor areas are interconnected with the prefrontal cortex. There are three major results of this study. First, we found that five of the six premotor areas in the frontal lobe are interconnected with the dorsolateral prefrontal cortex. Second, the major site for interactions between the prefrontal cortex and the premotor areas is the ventral premotor area. Third, the prefrontal cortex is interconnected with only a portion of the arm representation in three premotor areas (supplementary motor area, the caudal cingulate motor area on the ventral bank of the cingulate sulcus, and the dorsal premotor area), whereas it is interconnected with the entire arm representation in the ventral premotor area and the rostral cingulate motor area. These observations indicate that the output of the prefrontal cortex targets specific premotor areas and even subregions within individual premotor areas.

Rhesus monkeys were trained on a conditional orientation discrimination task in order to assess whether attentive selection for a color or luminance stimulus feature would affect visual processing in extrastriate area V4. The task required monkeys to select a bar stimulus based on its color or luminance and then to discriminate the angular tilt of the selected stimulus. The majority of neurons (74%) were selectively activated when the color or luminance of the stimulus in the receptive field matched the color or luminance of the cue. The activity was attenuated when there was not a match between the stimulus and the cue. The differential activation was based on the presence or absence of the stimulus feature and was independent of spatial location. Across the population of V4 neurons, optimal stimuli that matched the selected color or luminance elicited about twice the activity as stimuli that did not match the selected feature. The feature-selective changes in activity were observed to develop beginning about 200 msec after the stimulus onset and were maintained over the remainder of the behavioral trial. In this task the activity of V4 neurons reflected a selection based on the cued feature and not simply the physical color or luminance of the receptive field stimulus. Under these conditions, the topographic representation of the neural activity in area V4 highlights the potential targets in the visual scene at the expense of background objects. These observations offer a physiological counterpart to psychophysical studies suggesting that stimuli can be preferentially selected in parallel across the visual field on the basis of a unique color or luminance feature.

PURPOSE: Perirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation. METHODS AND MATERIALS: Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months. RESULTS: Spacer application was rated as "easy" or "very easy" 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption. CONCLUSIONS: Spacer application was well tolerated. Increased perirectal space reduced rectal irradiation, reduced rectal toxicity severity, and decreased rates of patients experiencing declines in bowel quality of life. The spacer appears to be an effective tool, potentially enabling advanced prostate RT protocols.

We used anterograde transport of wheat germ agglutinin-horseradish peroxidase to examine the pattern of spinal termination of efferents from the supplementary motor area (SMA) and the two caudal cingulate motor areas (CMAd and CMAv). Our analysis was limited to cervical segments of the macaque. For comparison, we also examined the pattern of termination of efferents from the primary motor cortex (M1). The SMA, CMAd, CMAv, and M1 all terminate in the ventral horn (lamina IX). Thus, all of these motor areas appear to have direct connections with spinal motoneurons, particularly those innervating muscles of the fingers and wrist. All of the motor areas also terminate in the intermediate zone of the spinal cord (laminae V-VIII). Terminations from the SMA and M1 were densest in three regions: (1) dorsolaterally within laminae V-VII; (2) dorsomedially within lamina VI; and (3) ventromedially within lamina VII and adjacent lamina VIII. In contrast, efferents from the CMAd terminate most densely in the dorsolateral portion of the intermediate zone, whereas those from the CMAv were concentrated in the dorsomedial region. Thus, the CMAd and CMAv may innervate distinct sets of interneurons that project directly to motoneurons, and thereby influence specific aspects of segmental motor control. These results suggest that corticospinal projections from the SMA, CMAd, and CMAv are in many respects similar to those of efferents from M1. Consequently, each of the motor areas on the medial wall has the potential to generate and control movement at the level of the spinal cord and may provide an anatomical substrate for the recovery of motor function that follows damage to M1.

IMPORTANCE: Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. OBJECTIVE: To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS: A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. INTERVENTIONS: The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES: Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. RESULTS: The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). CONCLUSIONS AND RELEVANCE: Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00740714.

CONTEXT Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions and lower access to care. OBJECTIVES To examine the effectiveness of a telemedicine intervention to achieve clinical management goals in older, ethnically diverse, medically underserved patients with diabetes. DESIGN, Setting, and Patients A randomized controlled trial was conducted, comparing telemedicine case management to usual care, with blinded outcome evaluation, in 1,665 Medicare recipients with diabetes, aged >/= 55 years, residing in federally designated medically underserved areas of New York State. Interventions Home telemedicine unit with nurse case management versus usual care. Main Outcome Measures The primary endpoints assessed over 5 years of follow-up were hemoglobin A1c (HgbA1c), low density lipoprotein (LDL) cholesterol, and blood pressure levels. RESULTS Intention-to-treat mixed models showed that telemedicine achieved net overall reductions over five years of follow-up in the primary endpoints (HgbA1c, p = 0.001; LDL, p < 0.001; systolic and diastolic blood pressure, p = 0.024; p < 0.001). Estimated differences (95% CI) in year 5 were 0.29 (0.12, 0.46)% for HgbA1c, 3.84 (-0.08, 7.77) mg/dL for LDL cholesterol, and 4.32 (1.93, 6.72) mm Hg for systolic and 2.64 (1.53, 3.74) mm Hg for diastolic blood pressure. There were 176 deaths in the intervention group and 169 in the usual care group (hazard ratio 1.01 [0.82, 1.24]). CONCLUSIONS Telemedicine case management resulted in net improvements in HgbA1c, LDL-cholesterol and blood pressure levels over 5 years in medically underserved Medicare beneficiaries. Mortality was not different between the groups, although power was limited. Trial Registration http://clinicaltrials.gov Identifier: NCT00271739.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is upregulated in androgen-dependent prostate carcinoma and it has been targeted for immunotherapy and diagnosis of this cancer. However, this protein is also expressed in other tissues. The objective of this study is to investigate its expression in normal and malignant human tissues. METHODS: Using monoclonal antibodies 24.4E6 (specific for residues 638-657) and 7E11.C5 (specific for the transmembrane domain of PSMA), immunohistochemical detection of PSMA was performed in surgical specimens. RESULTS: Prostate-specific membrane antigen was detected in the epithelium of prostate, urinary bladder, proximal tubules of kidney, liver, esophagus, stomach, small intestine, colon, breast, fallopian tubes and testicular seminiferous tubules, hippocampal neurons and astrocytes, ependyma, cortex and medulla of the adrenal gland, and ovary stroma. It was also detected in neoplasms of the prostate, kidney, urinary bladder, stomach, small intestine, colon, lung, adrenal gland, and testis. It was not detected in normal seminal vesicles or the lung. CONCLUSIONS: These findings demonstrate that PSMA is widely distributed in normal tissues, and, depending on the tumors, its expression is up- or down-regulated, or unchanged. The broad distribution of PSMA may make it suitable for the diagnosis and therapy of a wide variety of tumors.

BACKGROUND: Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions who experience barriers to access to care or a high burden of illness. METHODS: The authors conducted a randomized, controlled trial comparing telemedicine case management to usual care, with blinding of those obtaining outcome data, in 1,665 Medicare recipients with diabetes, aged 55 years or greater, and living in federally designated medically underserved areas of New York State. The primary endpoints were HgbA1c, blood pressure, and low-density lipoprotein (LDL) cholesterol levels. RESULTS: In the intervention group (n = 844), mean HgbA1c improved over one year from 7.35% to 6.97% and from 8.35% to 7.42% in the subgroup with baseline HgbA1c > or =7% (n = 353). In the usual care group (n = 821) mean HgbA1c improved over one year from 7.42% to 7.17%. Adjusted net reductions (one-year minus baseline mean values in each group, compared between groups) favoring the intervention were as follows: HgbA1c, 0.18% (p = 0.006), systolic and diastolic blood pressure, 3.4 (p = 0.001) and 1.9 mm Hg (p < 0.001), and LDL cholesterol, 9.5 mg/dL (p < 0.001). In the subgroup with baseline HgbA1c > or =7%, net adjusted reduction in HgbA1c favoring the intervention group was 0.32% (p = 0.002). Mean LDL cholesterol level in the intervention group at one year was 95.7 mg/dL. The intervention effects were similar in magnitude in the subgroups living in New York City and upstate New York. CONCLUSION: Telemedicine case management improved glycemic control, blood pressure levels, and total and LDL cholesterol levels at one year of follow-up.

The basal ganglia are known to receive inputs from widespread regions of the cerebral cortex, such as the frontal, parietal, and temporal lobes. Of these cortical areas, only the frontal lobe is thought to be the target of basal ganglia output. One of the cortical regions that is a source of input to the basal ganglia is area TE, in inferotemporal cortex. This cortical area is thought to be critically involved in the recognition and discrimination of visual objects. Using retrograde transneuronal transport of herpes simplex virus type 1, we have found that one of the output nuclei of the basal ganglia, the substantia nigra pars reticulata, projects via the thalamus to TE. Thus, TE is not only a source of input to the basal ganglia, but also is a target of basal ganglia output. This result implies that the output of the basal ganglia influences higher order aspects of visual processing. In addition, we propose that dysfunction of the basal ganglia loop with TE leads to alterations in visual perception, including visual hallucinations.

Anterograde transport of 2-10% WGA-HRP was used to examine the pattern of termination of efferents from the primary motor cortex to cervical segments of the spinal cord in cebus (Cebus apella) and squirrel (Saimiri sciureus) monkeys. We have compared the pattern of termination in these monkeys because of marked differences in their manipulative abilities. Both primates have pseudo-opposable thumbs; however, only cebus monkeys use independent finger movements to pick up small objects. We found that corticospinal terminations in cervical segments of the cebus monkey are located in three main zones: a dorsolateral region of the intermediate zone, a dorsomedial region of the intermediate zone, and the ventral horn. The projection to the ventral horn in these monkeys is particularly dense at C8-T1 segments, where terminations form a "ring" that encircles the lateral motoneuronal cell group. In contrast, there are only two main zones of terminations in the squirrel monkey: a dorsolateral region of the intermediate zone and a dorsomedial region of the intermediate zone. As others have noted, efferents from the primary motor cortex of squirrel monkeys have, at best, only sparse terminations within the ventral horn. Thus, there are marked differences between cebus and squirrel monkeys in the extent of corticospinal terminations within the ventral horn. These observations provide further support for the concept that monosynaptic projections from the primary motor cortex to motoneurons in the ventral horn provide part of the neural substrate for dexterous movements of the fingers.