Improving Pediatric Delirium Assessment Documentation and Implementation of a Nonpharmacologic Delirium Management Bundle in the Cardiovascular Intensive Care Unit.

BACKGROUND: Pediatric delirium is common, associated with negative patient outcomes, and infrequently assessed in the ICU. Locally, pediatric delirium assessments in the cardiac PICU were infrequently documented resulting in an initiative to increase assessment documentation and implement a nurse-driven management protocol, the Bundle to Eliminate Delirium (BED). METHODS: This was a nurse-driven, quality improvement project in an eleven-bed cardiac PICU at a large academic health care facility. A pre- and postimplementation survey evaluating delirium management perceptions, knowledge, and assessment barriers was emailed to 113 nurses. Nurses received education about general delirium principles and assessment followed by weekly emails that included delirium assessment documentation rates and targeted education. Subsequently, BED education was provided via email followed by BED implementation, inclusion of BED completion rates in weekly emails, and observational audits of BED implementation. FINDINGS: 1522 delirium assessment opportunities were evaluated. Assessment documentation increased by 33%. Nurses reported greater confidence in their ability to manage delirium (P < .05 for numerous aspects of delirium care) and were less likely to report 'positive delirium assessments not acted upon' as a barrier to delirium assessment. BED implementation was inconsistent. DISCUSSION: Nursing education and feedback can increase delirium assessment rates and confidence in management but the impact of BED on these outcomes is not clear. APPLICATION TO PRACTICE: Improvement in pediatric delirium care may be obtained through a nurse-driven quality improvement project but an interprofessional approach is needed for optimal management. More studies are needed to identify effective pediatric delirium management strategies such as the BED.

Cortical cell and neuron density estimates in one chimpanzee hemisphere.

The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

Distributions of Cells and Neurons across the Cortical Sheet in Old World Macaques.

According to previous research, cell and neuron densities vary across neocortex in a similar manner across primate taxa. Here, we provide a more extensive examination of this effect in macaque monkeys. We separated neocortex from the underlying white matter in 4 macaque monkey hemispheres (1 Macaca nemestrina, 2 Macaca radiata, and 1 Macaca mulatta), manually flattened the neocortex, and divided it into smaller tissue pieces for analysis. The number of cells and neurons were determined for each piece across the cortical sheet using flow cytometry. Primary visual cortex had the most densely packed neurons and primary motor cortex had the least densely packed neurons. With respect to differences in brain size between cases, there was little variability in the total cell and neuron numbers within specific areas, and overall trends were similar to what has been previously described in Old World baboons and other primates. The average hemispheric total cell number per hemisphere ranged from 2.9 to 3.7 billion, while the average total neuron number ranged from 1.3 to 1.7 billion neurons. The visual cortex neuron densities were predictably higher, ranging from 18.2 to 34.7 million neurons/cm2 in macaques, in comparison to a range of 9.3-17.7 million neurons/cm2 across cortex as a whole. The results support other evidence that neuron surface densities vary across the cortical sheet in a predictable pattern within and across primate taxa.

Epileptic baboons have lower numbers of neurons in specific areas of cortex.

Epilepsy is characterized by recurrent seizure activity that can induce pathological reorganization and alter normal function in neocortical networks. In the present study, we determined the numbers of cells and neurons across the complete extent of the cortex for two epileptic baboons with naturally occurring seizures and two baboons without epilepsy. Overall, the two epileptic baboons had a 37% average reduction in the number of cortical neurons compared with the two nonepileptic baboons. The loss of neurons was variable across cortical areas, with the most pronounced loss in the primary motor cortex, especially in lateral primary motor cortex, representing the hand and face. Less-pronounced reductions of neurons were found in other parts of the frontal cortex and in somatosensory cortex, but no reduction was apparent in the primary visual cortex and little in other visual areas. The results provide clear evidence that epilepsy in the baboon is associated with considerable reduction in the numbers of cortical neurons, especially in frontal areas of the cortex related to motor functions. Whether or not the reduction of neurons is a cause or an effect of seizures needs further investigation.

Faster scaling of auditory neurons in cortical areas relative to subcortical structures in primate brains.

Allometric studies in primates have shown that the cerebral cortex, cerebellum, and remaining brain structures increase in size as a linear function of their numbers of neurons and nonneuronal cells across primates. Whether such scaling rules also apply to functionally related structures such as those of the auditory system is unknown. Here, we investigate the scaling of brain structures in the auditory pathway of six primate species and the closely related tree shrew. Using the isotropic fractionator method to estimate the numbers of neurons and nonneuronal cells in the inferior colliculus, medial geniculate nucleus, and auditory cortex (Ac), we assessed how they scaled across species and examined the relative scaling relationships among them. As expected, each auditory structure scales in mass as a linear function of its number of neurons, with no significant changes in neuronal density across species. The Ac scales proportionately with the cerebral cortex as a whole, maintaining a relative mass of approximately 1% and a relative number of neurons of 0.7%. However, the Ac gains neurons faster than both subcortical structures examined. As a result, larger primate brains have increased ratios of cortical to subcortical neurons involved in processing auditory information.

Functional organization of motor cortex of adult macaque monkeys is altered by sensory loss in infancy.

When somatosensory cortex (S1) is deprived of some of its inputs after section of ascending afferents in the dorsal columns of the spinal cord, it reorganizes to overrepresent the surviving inputs. As somatosensory cortex provides guiding sensory information to motor cortex, such sensory loss and representational reorganization could affect the development of the motor map in primary motor cortex (M1), especially if the sensory loss occurs early in development. To address this possibility, the dorsal columns of the spinal cord were sectioned between cervical levels (C3-5) 3-12 days after birth in five macaque monkeys. After 3-5 years of maturation (young adults), we determined how movements were represented in M1 contralateral to the lesion by using microelectrodes to electrically stimulate sites in M1 to evoke movements. Although the details of the motor maps in these five monkeys varied, the forelimb motor maps were abnormal. The representations of digit movements were reduced and abnormally arranged. Current levels for evoking movements from the forelimb region of M1 were in the normal range, but the lowest mean stimulation thresholds were for wrist or elbow instead of digit movements. Incomplete lesions and bilateral lesions produced fewer abnormalities. The results suggest that the development of normal motor cortex maps in M1 depends on sensory feedback from somatosensory maps.

Neuron densities vary across and within cortical areas in primates.

The numbers and proportion of neurons in areas and regions of cortex were determined for a single cortical hemisphere from two prosimian galagos, one New World owl monkey, one Old World macaque monkey, and one baboon. The results suggest that there is a common plan of cortical organization across the species examined here and also differences that suggest greater specializations in the Old World monkeys. In all primates examined, primary visual cortex (V1) was the most neuron-dense cortical area and the secondary visual areas had higher-than-average densities. Primary auditory and somatosensory areas tended to have high densities in the Old World macaque and baboon. Neuronal density varies less across cortical areas in prosimian galagos than in the Old World monkeys. Thus, cortical architecture varies greatly within and across primate species, but cell density is greater in cortex devoted to the early stages of sensory processing.

Variability in neuron densities across the cortical sheet in primates.

The function of any area of the brain is a product of its unique population of neurons and nonneurons and their local and long-range connectional architecture. At the present time, we have inadequate data about numbers of neurons and the distribution patterns of neurons in the cortex and other parts of the brain. Numbers and densities of neurons and nonneurons provide the foundation for the assembly of a cortical and whole-brain neuronal network, yet the majority of studies reporting neuron densities for the primate cortex estimate the number of neurons in the cortex as a whole or in specific areas for comparisons between treatment groups or species. While this is valuable information for studies of scaling or comparative studies of specific pathways or functions, a more detailed examination of cell and neuron number distribution across the entire cortical expanse is needed. Two studies reviewed here use the isotropic fractionator method for the determination of cell and neuron numbers to investigate the distribution of cells and neurons across the entire cortical sheet of 4 primate species, taking into consideration cortical areal boundaries. Neuron and total cell numbers were found to vary as much as 5 times between different functional areas across the cortical sheet. Numbers were also variable across representational zones within cortical areas like V1 and S1. The overall distribution of cells and neurons appears to be conserved across the species examined, suggesting a common plan for cell distribution in primates, with more areas of high neuron density in macaques and baboons compared to the smaller and less differentiated cortex of prosimian galagos and the New World owl monkey.

Comparison of area 17 cellular composition in laboratory and wild-caught rats including diurnal and nocturnal species.

In this study we examine the size of primary sensory areas in the neocortex and the cellular composition of area 17/V1 in three rodent groups: laboratory nocturnal Norway rats (Long-Evans; Rattus norvegicus), wild-caught nocturnal Norway rats (R. norvegicus), and laboratory diurnal Nile grass rats (Arvicanthis niloticus). Specifically, we used areal measures of myeloarchitecture of the primary sensory areas to compare area size and the isotropic fractionator method to estimate the number of neurons and nonneurons in area 17 in each species. Our results demonstrate that the percentage of cortex devoted to area 17 is significantly greater and the percentage of cortex devoted to S1 is significantly smaller in the diurnal Nile grass rat compared with the nocturnal Norway rat groups. Further, the laboratory rodent groups have a greater percentage of cortex devoted to auditory cortex compared with the wild-caught group. We also demonstrate that wild-caught rats have a greater density of neurons in area 17 compared to laboratory-reared animals. However, there were no other clear cellular composition differences in area 17 or differences in the percentage of brain weight devoted to area 17 between nocturnal and diurnal rats. Thus, there are differences in primary sensory area size between diurnal versus nocturnal and laboratory versus wild-caught rat groups and cellular density between wild-caught and laboratory rat groups. Our results demonstrate that the differences in the size and cellular composition of cortical areas do not fit with what would be expected based on brain scaling differences alone, and have a consistent relationship with lifestyle and sensory morphology.

The basic nonuniformity of the cerebral cortex.

Evolutionary changes in the size of the cerebral cortex, a columnar structure, often occur through the addition or subtraction of columnar modules with the same number of neurons underneath a unit area of cortical surface. This view is based on the work of Rockel et al. [Rockel AJ, Hiorns RW, Powell TP (1980) The basic uniformity in structure of the neocortex. Brain 103:221-244], who found a steady number of approximately 110 neurons underneath a surface area of 750 microm(2) (147,000 underneath 1 mm(2)) of the cerebral cortex of five species from different mammalian orders. These results have since been either corroborated or disputed by different groups. Here, we show that the number of neurons underneath 1 mm(2) of the cerebral cortical surface of nine primate species and the closely related Tupaia sp. is not constant and varies by three times across species. We found that cortical thickness is not inversely proportional to neuronal density across species and that total cortical surface area increases more slowly than, rather than linearly with, the number of neurons underneath it. The number of neurons beneath a unit area of cortical surface varies linearly with neuronal density, a parameter that is neither related to cortical size nor total number of neurons. Our finding of a variable number of neurons underneath a unit area of the cerebral cortex across primate species indicates that models of cortical organization cannot assume that cortical columns in different primates consist of invariant numbers of neurons.

Cellular scaling rules for the brains of an extended number of primate species.

What are the rules relating the size of the brain and its structures to the number of cells that compose them and their average sizes? We have shown previously that the cerebral cortex, cerebellum and the remaining brain structures increase in size as a linear function of their numbers of neurons and non-neuronal cells across 6 species of primates. Here we describe that the cellular composition of the same brain structures of 5 other primate species, as well as humans, conform to the scaling rules identified previously, and that the updated power functions for the extended sample are similar to those determined earlier. Accounting for phylogenetic relatedness in the combined dataset does not affect the scaling slopes that apply to the cerebral cortex and cerebellum, but alters the slope for the remaining brain structures to a value that is similar to that observed in rodents, which raises the possibility that the neuronal scaling rules for these structures are shared among rodents and primates. The conformity of the new set of primate species to the previous rules strongly suggests that the cellular scaling rules we have identified apply to primates in general, including humans, and not only to particular subgroups of primate species. In contrast, the allometric rules relating body and brain size are highly sensitive to the particular species sampled, suggesting that brain size is neither determined by body size nor together with it, but is rather only loosely correlated with body size.

Large-scale reorganization in the somatosensory cortex and thalamus after sensory loss in macaque monkeys.

Adult brains undergo large-scale plastic changes after peripheral and central injuries. Although it has been shown that both the cortical and thalamic representations can reorganize, uncertainties exist regarding the extent, nature, and time course of changes at each level. We have determined how cortical representations in the somatosensory area 3b and the ventroposterior (VP) nucleus of thalamus are affected by long standing unilateral dorsal column lesions at cervical levels in macaque monkeys. In monkeys with recovery periods of 22-23 months, the intact face inputs expanded into the deafferented hand region of area 3b after complete or partial lesions of the dorsal columns. The expansion of the face region could extend all the way medially into the leg and foot representations. In the same monkeys, similar expansions of the face representation take place in the VP nucleus of the thalamus, indicating that both these processing levels undergo similar reorganizations. The receptive fields of the expanded representations were similar in somatosensory cortex and thalamus. In two monkeys, we determined the extent of the brain reorganization immediately after dorsal column lesions. In these monkeys, the deafferented regions of area 3b and the VP nucleus became unresponsive to the peripheral touch immediately after the lesion. No reorganization was seen in the cortex or the VP nucleus. A comparison of the extents of deafferentation across the monkeys shows that even if the dorsal column lesion is partial, preserving most of the hand representation, it is sufficient to induce an expansion of the face representation.

Geometric morphometrics defines shape differences in the cortical area map of C57BL/6J and DBA/2J inbred mice.

BACKGROUND: We previously described planar areal differences in adult mouse visual, somatosensory, and neocortex that collectively discriminated C57BL/6J and DBA/2J inbred strain identity. Here we use a novel application of established methods of two-dimensional geometric morphometrics to examine shape differences in the cortical area maps of these inbred strains. RESULTS: We used Procrustes superimposition to align a reliable set of landmarks in the plane of the cortical sheet from tangential sections stained for the cytochrome oxidase enzyme. Procrustes superimposition translates landmark configurations to a common origin, scales them to a common size, and rotates them to minimize an estimate of error. Remaining variation represents shape differences. We compared the variation in shape between C57BL/6J and DBA/2J relative to that within each strain using a permutation test of Goodall's F statistic. Significant differences in shape in the posterior medial barrel subfield (PMBSF), as well as differences in shape across primary sensory areas, characterize the cortical area maps of these common inbred, isogenic strains. CONCLUSION: C57BL/6J and DBA/2J have markedly different cortical area maps, in both size and shape. These differences suggest polymorphism in genetic factors underlying cortical specification, even between common isogenic strains. Comparing cortical phenotypes between normally varying inbred mice or between genetically modified mice can identify genetic contributions to cortical specification. Geometric morphometric analysis of shape represents an additional quantitative tool for the study of cortical development, regardless of whether it is studied from phenotype to gene or gene to phenotype.

Responses of neurons in the middle temporal visual area after long-standing lesions of the primary visual cortex in adult new world monkeys.

The retinotopic organization of the middle temporal visual area (MT) was determined in six adult owl monkeys and one adult marmoset 69 d to 10 months after lesions of the dorsolateral primary visual cortex (V1). The lesions removed were limited to extensive parts of the representation of the lower visual quadrant in V1. Microelectrodes were used to record from neurons at numerous sites in MT to determine whether parts of MT normally devoted to the lower visual quadrant (1) were unresponsive to visual stimuli, (2) acquired responsiveness to inputs from intact portions of V1, or (3) became responsive to some other visually driven input such as a relay from the superior colliculus via the pulvinar to MT. All monkeys (n = 6) with moderate to moderately large lesions had unresponsive portions of MT even after 10 months of recovery. These unresponsive regions were retinotopically equivalent to the removed parts of V1 in normal animals. Thus, there was no evidence for an alternative source of activation. In addition, these results indicate that any retinotopic reorganization of MT based on inputs from intact portions of V1 was not extensive, yet neurons near the margins of responsive cortex may have acquired new receptive fields, and the smallest 5 degrees lesion of V1 failed to produce an unresponsive zone. Deprived portions of MT were not remarkably changed in histological appearance in cytochrome oxidase, Nissl, and Wisteria floribunda agglutinin preparations. Nevertheless, some reduction in myelin staining and other histological changes were suggested. We conclude that MT is highly dependent on V1 for activation in these monkeys, and alternative sources do not become effective over months when normal activation is absent. Additionally, remaining V1 inputs have only a limited capacity to expand their activation territory into deprived portions of MT.

Variation in the cortical area map of C57BL/6J and DBA/2J inbred mice predicts strain identity.

BACKGROUND: Recent discoveries suggest that arealization of the mammalian cortical sheet develops in a manner consonant with principles established for embryonic patterning of the body. Signaling centers release morphogens that determine regional growth and tissue identity by regulating regional expression of transcription factors. Research on mouse cortex has identified several candidate morphogens that affect anteroposterior or mediolateral cortical regionalization as well as mitogenesis. Inbred strains of laboratory mice can be exploited to study cortical area map formation if there are significant phenotypic differences with which to correlate gene polymorphism or expression data. Here we describe differences in the cortical area map of two commonly used inbred strains of laboratory mice, C57BL/6J and DBA/2J. Complete cortical hemispheres from adult mice were dissected and stained for the cytochrome oxidase enzyme in order to measure histochemically defined cortical areas. RESULTS: C57BL/6J has the larger neocortex, relatively larger primary visual cortex (V1), but relatively smaller posterior medial barrel subfield of the primary somatosensory cortex (PMBSF). The sample of C57BL/6J and DBA/2J mice can be discriminated with 90% accuracy on the basis of these three size dimensions. CONCLUSION: C57BL/6J and DBA/2J have markedly different cortical area maps, suggesting that inbred strains harbor enough phenotypic variation to encourage a forward genetic approach to understanding cortical development, complementing other approaches.

Overview of the visual system of Tarsius.

Tarsiers, which are currently considered to constitute the sister group of anthropoid primates, exhibit a number of morphological specializations such as remarkably large eyes, big ears, long hind legs, and a nearly naked tail. Here we provide an overview of the current state of knowledge on the tarsier visual system and describe recent anatomical observations from our laboratory. Its large eyes notwithstanding, the most remarkable feature of the tarsier brain is the large size and distinct lamination of area V1. Based on the need of tarsier for optimal scotopic vision and acuity to detect small prey in low lighting conditions, tarsiers may have preserved a high level of visual acuity by enlarging V1 at the expense of other areas. The other classically described visual regions are present in tarsier, albeit many borders are not clearly distinct on histochemical or immunohistochemical preparations. Tarsiers also have a large number and unusual distributions of cones in the retina, with high numbers of M/L-cones in the central retina and S-cones surprisingly at the periphery, which may be sensitive to UV light and may be useful for prey detection. These adaptive specializations may together account for the unique nocturnal predatory requirements of tarsiers.

Distribution across cortical areas of neurons projecting to the superior colliculus in new world monkeys.

Surprisingly little is known about the proportions of projections of different areas and regions of neocortex to the superior colliculus in primates. To obtain an overview of such projection patterns, we placed a total of 10 injections of retrograde tracers in the superior colliculus of three New World monkeys (Callithrix, Callicebus, and Aotus). Because cortex was flattened and cut parallel to the surface, labeled corticotectal neurons could be accurately located relative to architectonic boundaries and surface features. While there was variability across cases and injection sites, the summed results clearly support several conclusions. One, three well-defined visual areas, V1 (18%), V2 (14%), and MT (11%), contributed nearly half of the total of labeled cells. Two, several other visual areas (V3, DL, DM, and FST) that are early in the processing hierarchy provided another fifth of the total. Three, inferior temporal visual areas of the ventral stream provided only minor projections. Four, visuomotor fields (FEF, FV, cortex in the region of SEF, and posterior parietal cortex) contained less than 10% of the labeled neurons. Five, few labeled neurons were in auditory or somatosensory areas. The results indicate that cortical inputs to the superior colliculus originate predominantly from early visual areas rather than from multimodal or visuomotor areas.

Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer.

CONTEXT: The accurate identification and interpretation of germline mutations in mismatch repair genes in colorectal cancer cases is critical for clinical management. Current data suggest that mismatch repair mutations are highly heterogeneous and that many mutations are not detected when conventional DNA sequencing alone is used. OBJECTIVE: To evaluate the potential of conversion analysis compared with DNA sequencing alone to detect heterogeneous germline mutations in MLH1, MSH2, and MSH6 in colorectal cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Multicenter study with patients who participate in the Colon Cancer Family Registry. Mutation analyses were performed in participant samples determined to have a high probability of carrying mismatch repair germline mutations. Samples from a total of 64 hereditary nonpolyposis colorectal cancer cases, 8 hereditary nonpolyposis colorectal cancer-like cases, and 17 cases diagnosed prior to age 50 years were analyzed from June 2002 to June 2003. MAIN OUTCOME MEASURES: Classification of family members as carriers or noncarriers of germline mutations in MLH1, MSH2, or MSH6; mutation data from conversion analysis compared with genomic DNA sequencing. RESULTS: Genomic DNA sequencing identified 28 likely deleterious exon mutations, 4 in-frame deletion mutations, 16 missense changes, and 22 putative splice site mutations. Conversion analysis identified all mutations detected by genomic DNA sequencing--plus an additional exon mutation, 12 large genomic deletions, and 1 exon duplication mutation--yielding an increase of 33% (14/42) in diagnostic yield of deleterious mutations. Conversion analysis also showed that 4 of 16 missense changes resulted in exon skipping in transcripts and that 17 of 22 putative splice site mutations affected splicing or mRNA transcript stability. Conversion analysis provided an increase of 56% (35/63) in the diagnostic yield of genetic testing compared with genomic DNA sequencing alone. CONCLUSIONS: The data confirm the heterogeneity of mismatch repair mutations and reveal that many mutations in colorectal cancer cases would be missed using conventional genomic DNA sequencing alone. Conversion analysis substantially increases the diagnostic yield of genetic testing for mismatch repair mutations in patients diagnosed as having colorectal cancer.

Anatomical and functional organization of somatosensory areas of the lateral fissure of the New World titi monkey (Callicebus moloch).

The organization of anterior and lateral somatosensory cortex was investigated in titi monkeys (Callicebus moloch). Multiunit microelectrode recordings were used to identify multiple representations of the body, and anatomical tracer injections were used to reveal connections. (1) Representations of the face were identified in areas 3a, 3b, 1, S2, and the parietal ventral area (PV). In area 3b, the face was represented from chin/lower lip to upper lip and neck/upper face in a rostrocaudal sequence. The representation of the face in area 1 mirrored that of area 3b. Another face representation was located in area 3a. Adjoining face representations in S2 and PV exhibited mirror-image patterns to those of areas 3b and 1. (2) Two representations of the body, the rostral and caudal ventral somatosensory areas (VSr and VSc), were found in the dorsal part of the insula. VSc was roughly a reversal image of the S2 body representation, and VSr was roughly a reversal of PV. (3) Neurons in the insula next to VSr and VSc responded to auditory stimuli or to both auditory and somatosensory stimuli. (4) Injections of tracers within the hand representations in areas 3b, 1, and S2 revealed reciprocal connections between these three areas. Injections in areas 3b and 1 labeled the ventroposterior nucleus, whereas injections in S2 labeled the inferior ventroposterior nucleus. The present study demonstrates features of somatosensory cortex of other monkeys in titi monkeys, while revealing additional features that likely apply to other primates.

Cortical inputs to the middle temporal visual area in New World owl monkeys.

We made eight retrograde tracer injections into the middle temporal visual area (MT) of three New World owl monkeys (Aotus nancymaae). These injections were placed across the representation of the retina in MT to allow us to compare the locations of labeled cells in other areas in order to provide evidence for any retinotopic organization in those areas. Four regions projected to MT: 1) early visual areas, including V1, V2, V3, the dorsolateral visual area, and the dorsomedial visual area, provided topographically organized inputs to MT; 2) all areas in the MT complex (the middle temporal crescent, the middle superior temporal area, and the fundal areas of the superior temporal sulcus) projected to MT. Somewhat variably across injections, neurons were labeled in other parts of the temporal lobe; 3) regions in the location of the medial visual area, the posterior parietal cortex, and the lateral sulcus provided other inputs to MT; 4) finally, projections from the frontal eye field, frontal visual field, and prefrontal cortex were also labeled by our injections. These results further establish the sources of input to MT, and provide direct evidence within and across cases for retinotopic patterns of projections from early visual areas to MT.