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There has been a recent major upsurge in the concerns about reproducibility in many areas of science. Within the neuroimaging domain, one approach is to promote reproducibility is to target the re-executability of the publication. The information supporting such re-executability can enable the detailed examination of how an initial finding generalizes across changes in the processing approach, and sampled population, in a controlled scientific fashion. ReproNim: A Center for Reproducible Neuroimaging Computation is a recently funded initiative that seeks to facilitate the "last mile" implementations of core re-executability tools in order to reduce the accessibility barrier and increase adoption of standards and best practices at the neuroimaging research laboratory level. In this report, we summarize the overall approach and tools we have developed in this domain.

There has been a recent major upsurge in the concerns about reproducibility in many areas of science. Within the neuroimaging domain, one approach is to promote reproducibility is to target the re-executability of the publication. The information supporting such re-executability can enable the detailed examination of how an initial finding generalizes across changes in the processing approach, and sampled population, in a controlled scientific fashion. ReproNim: A Center for Reproducible Neuroimaging Computation is a recently funded initiative that seeks to facilitate the ‘last mile’ implementations of core re-executability tools in order to reduce the accessibility barrier and increase adoption of standards and best practices at the neuroimaging research laboratory level. In this report, we summarize the overall approach and tools we have developed in this domain.

Functional magnetic resonance imaging (fMRI) was used to study memory-associated activation of medial temporal lobe (MTL) regions in 32 nondemented elderly individuals with mild cognitive impairment (MCI). Subjects performed a visual encoding task during fMRI scanning and were tested for recognition of stimuli afterward. MTL regions of interest were identified from each individual's structural MRI, and activation was quantified within each region. Greater extent of activation within the hippocampal formation and parahippocampal gyrus (PHG) was correlated with better memory performance. There was, however, a paradoxical relationship between extent of activation and clinical status at both baseline and follow-up evaluations. Subjects with greater clinical impairment, based on the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right PHG during encoding, even after accounting for atrophy. Moreover, those who subsequently declined over the 2.5 years of clinical follow-up (44% of the subjects) activated a significantly greater extent of the right PHG during encoding, despite equivalent memory performance. We hypothesize that increased activation in MTL regions reflects a compensatory response to accumulating AD pathology and may serve as a marker for impending clinical decline.

We describe a system for parcellation of the human cerebral white matter and nuclei, based upon magnetic resonance images. An algorithm for subdivision of the cerebral central white matter according to topographic criteria is developed in the companion manuscript. In the present paper we provide a rationale for this system of parcellation of the central white matter and we extend the system of cerebral parcellation to include principal subcortical gray structures such as the thalamus and the basal ganglia. The volumetric measures of the subcortical gray and white matter parcellation units in 20 young adult brains are computed and reported here as well. In addition, with the comprehensive system for cerebral gray and white matter structure parcellation as reference, we formulate a systematics of forebrain connectivity. The degree to which functionally specific brain areas correspond to topographically specific areas is an open empirical issue. The resolution of this issue requires the development of topographically specific anatomic analyses, such as presented in the current system, and the application of such systems to a comprehensive set of functional-anatomic correlation studies in order to establish the degree of structural-functional correspondence. This system is expected to be applied in both cognitive and clinical neuroscience as an MRI-based topographic systematics of human forebrain anatomy with normative volumetric reference and also as a system of reference for the anatomic organization of specific neural systems as disrupted by focal lesions in lesion-deficit correlations.

We describe a virtually automatic comprehensive parcellation of the human cerebral central white matter, which is based upon T1-weighted MRI scans. The system, which is “rule-based,” is developed from prior anatomic studies of the human brain and experimental studies of connectivity in animals as elaborated in the companion manuscript. Boundaries which delineate anatomic subregions of the white matter are computed from the geometric features of anatomic landmarks visible in the imaging data. The fiber systems of the central white matter are ordered topographically into three compartments, reflecting the inferred arrangements of principal neural systems pathways. These include an outer radiate (fibers principally radially aligned), an intermediate sagittal (fibers principally sagittally aligned), and deep bridging (fibers bridging hemispheres or cortex and deep structures) compartments. Each of these compartments is secondarily parcellated into smaller units to increase the anatomic specificity and spatial resolution of the system. The principal intended uses for this system of anatomic subdivision are for the volumetric characterization of forebrain white matter in normal and abnormal brains and for precision and specificity of localization in focal lesion-deficit correlation studies.

Although neuroimaging has a limited role in the diagnostic assessment of obsessive-compulsive disorder (OCD), neuroimaging research has contributed crucial information regarding the pathophysiology of OCD and related diseases. OCD may be one of a spectrum of disorders that all involve corticostriatal pathology, in which the clinical presentation reflects the topography of dysfunction within the striatum. Structural neuroimaging studies of OCD have indicated volumetric abnormalities in the caudate nucleus. Functional imaging studies of OCD have shown increased activity in the corticostriatal pathway involving anterior orbitofrontal cortex and the caudate nucleus, both at rest and during symptom provocation, which is attenuated following effective treatment. Paralimbic elements, such as the anterior cingulate and posterior orbitofrontal cortex, may play a role in mediating anxiety or arousal nonspecifically. Taken together, these imaging data support the “striatal topography” model of OCD and suggest directions for future research, focusing on processes involving anterior orbitofrontal cortex and the caudate nucleus.

The medial nucleus of the pulvinar complex (PM) has widespread connections with association cortex. We investigated the connections of the PM with the prefrontal cortex (PFC) in macaque monkeys, with tracers placed into the PM and the PFC, respectively. Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) placed into the PM resulted in widespread anterograde terminal labeling in layers III and IV, and retrograde cellular labeling in layer VI of the PFC. Injections of tracers centered on the central/lateral PM resulted in labeling of dorsolateral and orbital regions, whereas injections centered on caudal, medial PM resulted in labeling of dorsomedial and medial PFC. Since injections of the PM included neighboring thalamic nuclei, retrograde tracers were placed into distinct cytoarchitectonic regions of the PFC and retrogradely labeled cells in the posterior thalamus were charted. The results of this series of tracer injections confirmed the results of the thalamic injections. Injections placed into areas 8a, 12 (lateral and orbital), 45, 46 and 11, retrogradely labeled neurons in the central/lateral PM, while tracer injections placed into areas 9, 12 (lateral), 10 and 24, labeled medial PM. The connections of the PM with temporal, parietal, insular, and cingulate cortices were also examined. The central/lateral PM has reciprocal connections with posterior parietal areas 7a, 7ip, and 7b, insular cortex, caudal superior temporal sulcus (STS), caudal superior temporal gyrus (STG), and posterior cingulate, whereas medial PM is connected mainly with the anterior STS and STG, as well as the cingulate cortex and the amygdala. These connectional studies suggest that the central/lateral and medial PM have divergent connections which may be the substrate for distinct functional circuits. J. Comp. Neurol. 379:313–332, 1997. © 1997 Wiley-Liss, Inc.

Magnetic resonance imaging (MRI) has revolutionized the practical demands of clinical neurology. This technology promises now to advance neurology in theoretical and applied realms of fundamental human brain science. We emphasize here two domains in which these advances will occur. The first is volumetric morphometry of the human brain. With MRI the multiple levels of processing of the brain may be characterized in terms of their absolute volumes and their relative sizes, perspectives indispensable for our understanding of the development and operation of neural systems. Volumetric morphometry also promises substantial increases in the specificity and sensitivity of neurological diagnosis, particularly where applied to disorders where structural abnormalities will be reflected only in volumetric abnormalities. The second direction of advance considered here is application of MRI in cortical mapping in support of cognitive neuroscience. In this application MRI provides means to map at high resolution the distribution of subcomponents of neural systems activated by behavioral paradigms. This line of investigation will carry forward rapidly our understanding of how the information processing algorithms of the brain are mapped upon the coordinates of the various gray matter structures of the brain. Among the practical consequences of this application will be a reasoned design of surgical field in tumor and epilepsy surgery.

Objective: To examine alterations in patterns of brain activation seen in normal aging and in mild Alzheimer's disease by functional magnetic resonance imaging (fMRI) during an associative encoding task. Methods: 10 young controls, 10 elderly controls, and seven patients with mild Alzheimer's disease were studied using fMRI during a face–name association encoding task. The fMRI paradigm used a block design with three conditions: novel face–name pairs, repeated face–name pairs, and visual fixation. Results: The young and elderly controls differed primarily in the pattern of activation seen in prefrontal and parietal cortices: elderly controls showed significantly less activation in both superior and inferior prefrontal cortices but greater activation in parietal regions than younger controls during the encoding of novel face–name pairs. Compared with elderly controls, the Alzheimer patients showed significantly less activation in the hippocampal formation but greater activation in the medial parietal and posterior cingulate regions. Conclusions: The pattern of fMRI activation during the encoding of novel associations is differentially altered in the early stages of Alzheimer's disease compared with normal aging.

Background and Purpose— The clinical diagnosis and treatment of stroke, as well as investigations into the underlying pathophysiology of the disease, hinge on inferences from the anatomy of the stroke lesion. We describe an MRI-based system of topographic and volumetric analysis that considers distribution of infarct with respect to neuroanatomic structures, superficial and deep perfusion compartments, and gray and white matter tissue types. Methods— MRI-based 3-dimensional topographic and volumetric analysis of presumed MCA embolic stroke was performed months after the acute event in 21 subjects ranging in age from 34 to 75 years. Results— The topography of infarction was greatly variable, with virtually all regions of the MCA territory involved in at least 1 stroke in the series. In 14, there was involvement of the M1 as well as the M2 through M4 territories; in 6, there was involvement of only the M2 through M4 territories; and in 2, there was involvement of only the M1 territory. The volumes varied from 3.1 to 256 cm 3 , corresponding approximately to a range of 1% to 90% of the total MCA territory. Conclusions— The system of topographic and volumetric analysis is generally applicable to all strokes in the forebrain where the infarct is visualized in MRI, independent of vascular territory, clinical correlates, and interval between stroke and MRI. The results emphasize the variety of topographic patterns and lesion volumes of strokes. Intended long-range applications include correlation of outcome of stroke with predictions from acute-phase diffusion- and perfusion-weighted imaging and investigations of the potential benefit of therapeutic agents.

The process of forming new associations between previously unrelated items of information, such as a name and a face, likely requires the integration of activity within multiple brain regions. The hippocampus and related structures in the medial temporal lobe are thought to be particularly critical in binding together items of information. We studied eight healthy young subjects with functional magnetic resonance imaging (fMRI) during the encoding of novel face‐name associations compared to viewing repeated face‐name pairs. A consistent pattern of activation was observed in the hippocampus, pulvinar nucleus of the thalamus, fusiform and dorsolateral prefrontal cortices across individual subjects. The location of the activation within the hippocampus was more anterior than previously reported in studies using similar novel vs. repeated paradigms with stimuli that did not specifically require relational processing among unrelated items. These data suggest that the process of forming new face‐name associations is supported by a distributed network of brain regions, and provide additional evidence for the essential role of the hippocampus in associative memory processes. Hum. Brain Mapping 14:129–139, 2001. © 2001 Wiley‐Liss, Inc.

This magnetic resonance imaging (MRI)-based morphometric analysis of cortical topography in the human brain is based upon the segmentation and parcellation of volumetric T1-weighted MRI data for a set of 20 young adult brains including 10 males and 10 females. For the most part, each parcellation unit (PU) of the neocortex corresponds to a single or a portion of a single gyrus. The volumes of each PU were computed for each brain. Subsets of PUs were also grouped so as to represent the neocortex for the frontal, temporal, parietal and occipital lobes. The coefficient of variation of the mean volume of total neocortex and that of the neocortex assigned to individual lobes cluster around 10%, whereas that of neocortex assigned to the individual gyri (PU) is more than twice that value. Approximately 80% of the total variance in gyral volume arises from determinants interactive for individual and specific gyri, while only approximately 10% of the total variance appears to be a reflection of uniform scaling to total neocortical volume. Sexual dimorphism contributes a pervasive though relatively small component of this variance. These results have implications for the study of structure-function correlation, and the proper statistical methods of handling volumetric data in morphometric studies. In addition, the nature of the covariance structure of the data will lead to future hypotheses regarding the relationships between the various potential genetic and epigenetic gyral influencing factors.

We described a patient, BG, who exhibited a striking pattern of false recognition after an infarction of the right frontal lobe. Seven experiments document the existence of the phenomenon, explore its characteristics, and demonstrate how it can be eliminated. BG showed pathologically high false alarm rates when stimuli were visual words (experiments 1 and 4), auditory words (experiment 2), environmental sounds (experiment 3), pseudowords (experiment 5), and pictures (experiment 7). His false alarms were not merely attributable to the semantic or physical similarity of studied and non-studied items (experiments 4 and 5). However, BG's false recognitions were virtually eliminated by presenting him with categorized stimuli and testing him with new stimuli from non-studied categories (experiments 6 and 7). The results suggest that BG's false alarms may be attributable to an over-reliance on memory for general characteristics of the study episode, along with impaired memory for specific items. The damaged right frontal lobe mechanisms may normally support the monitoring and/or retrieval processes that are necessary for item-specific recognition.

Several areas on the medial surface of the frontal lobe in both monkeys and humans, including the supplementary motor area and specific areas within the ventral bank of the cingulate sulcus called the cingulate motor areas, have been implicated in the initiation and execution of skiled movements. These areas project directly to the motor cortex and spinal cord, and, on this basis alone, can be considered premotor areas. The present study investigated whether these premotor areas are specific targets of prefrontal cortical projections in the rhesus monkey and thereby provide links between this association cortex and motor effector pathways. Circumscribed injections of wheat germ agglutinin-conjugated horseradish peroxidase were placed into different cytoarchitectonic subdivisions of prefrontal cortex, and resultant retrograde and anterograde labeling examined with respect to designated premotor targets. Conversely, injections were also made in the supplementary and cingulate motor areas and labeled cells and terminals charted in the prefrontal cortex. A principal finding in this study is the identification of multiple prefrontal regions that project to the supplementary motor area, the cingulate motor areas, or both. Areas 46, 8a, 9, 11, and 12 are reciprocally connected with an area of the superior frontal gyrus in or near the supplementary motor area at its rostral margin. A smaller constellation of prefrontal areas, areas 46, 8a, and 11, is reciprocally connected with portions of cingulate cortex that have been classified as premotor arm and/or leg representations (Hutchins et al., Exp Brain Res 71:667–672, 1988). In accordance with numerous previous reports, prefrontal areas 46, 8a, 9, 10, 11, and 12 are reciprocally connected with “nonmotor” subdivisions of cingulate cortex. The results presented here specify the corticocortical connections by which prefrontal cortex may influence motor output. © 1993 Wiley-Liss, Inc.

The relationship between the termination zones of projections from paired homotopic areas of the frontal lobes was examined in the caudate nucleus and the putamen of the macaque monkey. Injections of WGA-HRP and tritiated amino acids were made in topographically matched regions of the principal sulcus (PS) or of the supplementary motor area (SMA) in each hemisphere, such that the projections from the same area on each side were differentially labeled in the same animal. Adjacent sections through the neostriatum were processed for the respective tracers, permitting the relationship between the converging projections to be defined. The topographic distribution and strength of ipsilateral corticostriatal projections observed for separately labeled left and right hemispheres were strikingly similar. Projections from the left and the right PS terminated preferentially in central parts of the left and right neostriata, respectively, while projections of the left and right SMAs terminated preferentially in dorsolateral parts of respective left and right neostriata. Therefore, little evidence for asymmetry of corticostriatal projections was found. The projections of the left and the right PS to the same neostriatum were also compared. Remarkably, whether in the left or right hemisphere, projections from the left and the right PS were in precise register in topographically specific territories of the caudate and putamen. Likewise, projections of the left and right SMAs converged in both the left and right neostriata. Such convergence allows for a remarkable degree of interhemispheric integration in the descending corticostriatal networks.

The relationship between the termination zones of projections from paired homotopic areas in the frontal lobe was examined in the cerebral cortex of the macaque monkey. Injections of WGA-HRP and tritiated amino acids were made in topographically matched regions of the principal sulcus (PS) or the supplementary motor area (SMA) in each hemisphere, such that the projections from the same area on each side were differentially labeled in the same animal. Adjacent sections through the cortical regions that received bilateral inputs from these areas were processed for the respective tracers, permitting the relationship between the converging projections to be defined. Comparison of the cortical connections of the left and right PS or of the left and right SMA yielded two major findings. First, only minor differences in the topographic distribution and strength of connections of homotopic areas were observed, providing little evidence of asymmetry in the connections of either the PS or the SMA in the macaque. Second, with the exception of interdigitation observed in a portion of the dorsal bank of the PS, the cortical projections from both the left and the right PS and SMA converged (overlapped) in common columnar territories. These termination patterns allow for a remarkable degree of interhemispheric integration.