Nadim Joni Shah

Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex : intersubject variability and probability maps

Probabilistic maps of neocortical areas and subcortical fiber tracts, warped to a common reference brain, have been published using microscopic architectonic parcellations in ten human postmortem brains. The maps have been successfully applied as topographical references for the anatomical localization of activations observed in functional imaging studies. Here, for the first time, we present stereotaxic, probabilistic maps of the hippocampus, the amygdala and the entorhinal cortex and some of their subdivisions. Cytoarchitectonic mapping was performed in serial, cell-body stained histological sections. The positions and the extent of cytoarchitectonically defined structures were traced in digitized histological sections, 3-D reconstructed and warped to the reference space of the MNI single subject brain using both linear and non-linear elastic tools of alignment. The probability maps and volumes of all structures were calculated. The precise localization of the borders of the mapped regions cannot be predicted consistently by macroanatomical landmarks. Many borders, e.g. between the subiculum and entorhinal cortex, subiculum and Cornu ammonis, and amygdala and hippocampus, do not match sulcal landmarks such as the bottom of a sulcus. Only microscopic observation enables the precise localization of the borders of these brain regions. The superposition of the cytoarchitectonic maps in the common spatial reference system shows a considerably lower degree of intersubject variability in size and position of the allocortical structures and nuclei than the previously delineated neocortical areas. For the first time, the present observations provide cytoarchitectonically verified maps of the human amygdala, hippocampus and entorhinal cortex, which take into account the stereotaxic position of the brain structures as well as intersubject variability. We believe that these maps are efficient tools for the precise microstructural localization of fMRI, PET and anatomical MR data, both in healthy and pathologically altered brains.

Line bisection judgments implicate right parietal cortex and cerebellum as assessed by fMRI

Objective: To use functional MRI (fMRI) to determine which brain regions are implicated when normal volunteers judge whether pretransected horizontal lines are correctly bisected (the Landmark test). Background: Manual line bisection and a variant thereof involving perceptual judgments of pretransected lines (the Landmark test) are widely used to assess unilateral visuospatial neglect in patients with neurologic disease. Although unilateral (left) neglect most often results from lesions to right temporoparietal cortex, the normal functional anatomy of the Landmark test has not been convincingly demonstrated. Methods: fMRI was carried out in 12 healthy right-handed male volunteers who judged whether horizontal lines were correctly prebisected. In the control task, subjects detected whether the horizontal lines contained a transection mark irrespective of the position of that mark. Response was by two-choice key press: on half the trials, subjects used the right, and on half, the left hand. Statistical analysis of evoked blood oxygenation level-dependent responses, measured with echoplanar imaging, employed statistical parametric mapping. Results: Performing the Landmark task showed neural activity (p < 0.05, corrected) in the right superior posterior and right inferior parietal lobe, early visual processing areas bilaterally, the cerebellar vermis, and the left cerebellar hemisphere. Only the latter area showed a significant interaction with hand used. Conclusions: The right hemispheric dominance observed in inferior parietal cortex is consistent with the results of lesion studies. Right superior parietal cortex, vermis, and left cerebellar hemisphere have not been implicated in neglect, but all appear to play a cognitive role in the Landmark task.

Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space—The roles of Brodmann areas 44 and 45

We investigated neural activations underlying a verbal fluency task and cytoarchitectonic probabilistic maps of Brocas speech region (Brodmanns areas 44 and 45). To do so, we reanalyzed data from a previous functional magnetic resonance imaging (fMRI) [Brain 125 (2002) 1024] and from a cytoarchitectonic study [J. Comp. Neurol. 412 (1999) 319] and developed a method to combine both data sets. In the fMRI experiment, verbal fluency was investigated in 11 healthy volunteers, who covertly produced words from predefined categories. A factorial design was used with factors verbal class (semantic vs. overlearned fluency) and switching between categories (no vs. yes). fMRI data analysis employed SPM99 (Statistical Parametric Mapping). Cytoarchitectonic maps of areas 44 and 45 were derived from histologic sections of 10 postmortem brains. Both the in vivo fMRI and postmortem MR data were warped to a common reference brain using a new elastic warping tool. Cytoarchitectonic probability maps with stereotaxic information about intersubject variability were calculated for both areas and superimposed on the functional data, which showed the involvement of left hemisphere areas with verbal fluency relative to the baseline. Semantic relative to overlearned fluency showed greater involvement of left area 45 than of 44. Thus, although both areas participate in verbal fluency, they do so differentially. Left area 45 is more involved in semantic aspects of language processing, while area 44 is probably involved in high-level aspects of programming speech production per se. The combination of functional data analysis with a new elastic warping tool and cytoarchitectonic maps opens new perspectives for analyzing the cortical networks involved in language.

BigBrain: an ultrahigh-resolution 3D human brain model.

Reconstructing the Human Brain Reference brains have become a standard tool in human brain research. Reference brains presently in the public domain provide a spatial framework at the macroscopic level. Amunts et al. (p. 1472) present a high-resolution (20 µm) three-dimensional reconstruction of a human brain. The tool will be freely available to help with interpreting functional neuroimaging studies, fiber tract analyses, and assigning molecular and gene expression data. A freely available microscopic model of human brain architecture with a spatial resolution of 20 micrometers is presented. Reference brains are indispensable tools in human brain mapping, enabling integration of multimodal data into an anatomically realistic standard space. Available reference brains, however, are restricted to the macroscopic scale and do not provide information on the functionally important microscopic dimension. We created an ultrahigh-resolution three-dimensional (3D) model of a human brain at nearly cellular resolution of 20 micrometers, based on the reconstruction of 7404 histological sections. “BigBrain” is a free, publicly available tool that provides considerable neuroanatomical insight into the human brain, thereby allowing the extraction of microscopic data for modeling and simulation. BigBrain enables testing of hypotheses on optimal path lengths between interconnected cortical regions or on spatial organization of genetic patterning, redefining the traditional neuroanatomy maps such as those of Brodmann and von Economo.

Performing allocentric visuospatial judgments with induced distortion of the egocentric reference frame: an fMRI study with clinical implications.

The temporary improvement of visuospatial neglect during galvanic vestibular stimulation (Scand. J. Rehabil. Med. 31 (1999)117) may result from correction of the spatial reference frame distorted by the responsible lesion. Prior to an investigation of the neural basis of this effect in neurological patients, exploration of the neural mechanisms underlying such procedures in normals is required to provide insight into the physiological basis thereof. Despite their clinical impact, the neural mechanisms underlying the interaction of galvanic (and other) vestibular manipulations with visuospatial processing (and indeed the neural bases of how spatial reference frames are computed in man) remain to be clarified. We accordingly used fMRI in normal volunteers to investigate the effect of galvanically induced interference with the egocentric spatial reference frame on the neural processes underlying allocentric visuospatial (line bisection) judgments. A significant specific interaction of galvanic vestibular stimulation with the neural mechanisms underlying allocentric visuospatial judgments was observed in right posterior parietal and ventral premotor cortex only. Activation of these areas previously found to be damaged in visuospatial neglect suggests that these effects reflect the increased processing demands when compensating for the distorted egocentric spatial reference frame while maintaining accurate performance during the allocentric spatial task. These results thus implicate right posterior parietal and right ventral premotor cortex in the computation of spatial reference frames. Furthermore, our data imply a specific physiological basis for the temporary improvement of visuospatial neglect in patients with right hemisphere lesions during galvanic vestibular stimulation and may thus impact upon the rehabilitation of neglect: understanding the interaction of galvanic vestibular stimulation with allocentric visuospatial judgments in healthy volunteers may lead to the more effective deployment of such techniques in neurological patients.

Probabilistic fibre tract analysis of cytoarchitectonically defined human inferior parietal lobule areas reveals similarities to macaques

The human inferior parietal lobule (IPL) is a multimodal brain region, subdivided in several cytoarchitectonic areas which are involved in neural networks related to spatial attention, language, and higher motor processing. Tracer studies in macaques revealed differential connectivity patterns of IPL areas as the respective structural basis. Evidence for comparable differential fibre tracts of human IPL is lacking. Here, anatomical connectivity of five cytoarchitectonic human IPL areas to 64 cortical targets was investigated using probabilistic tractography. Connection likelihood was assessed by evaluating the number of traces between seed and target against the distribution of traces from that seed to voxels in the same distance as the target. The main fibre tract pattern shifted gradually from rostral to caudal IPL: Rostral areas were predominantly connected to somatosensory and superior parietal areas while caudal areas more strongly connected with auditory, anterior temporal and higher visual cortices. All IPL areas were strongly connected with inferior frontal, insular and posterior temporal areas. These results showed striking similarities with connectivity patterns in macaques, providing further evidence for possible homologies between these two species. This shift in fibre tract pattern supports a differential functional involvement of rostral (higher motor functions) and caudal IPL (spatial attention), with probable overlapping language involvement. The differential functional involvement of IPL areas was further supported by hemispheric asymmetries of connection patterns which showed left-right differences especially with regard to connections to sensorimotor, inferior frontal and temporal areas.

Cortical Representations of Personally Familiar Objects and Places: Functional Organization of the Human Posterior Cingulate Cortex

The recognition of both personally familiar objects and places involves nonspatial memory retrieval processes, but only personally familiar places are represented as space. Although the posterior cingulate cortex (PCC) is considered to process both types of such memories, its functional organization is poorly understood. In this event-related fMRI study, normal subjects judged familiar/unfamiliar pictures in four categories: familiar places (FP), familiar objects (FO), unfamiliar places (UP), and unfamiliar objects (UO), thus constituting a two-factorial design. A significant main effect of stimuli with greater activation in the place (FP and UP) than object (FO and UO) trials was observed bilaterally in several medial temporo-occipito-parietal regions, including the caudal PCC (cPCC) and parahippocampal gyrus. The reverse comparison revealed greater activation in the lateral inferior occipito-temporal junctions and intraparietal sulci bilaterally. A significant main effect of familiarity with greater activation in the familiar (FP and FO) than unfamiliar (UP and UO) trials was observed in the mid-dorsal PCC (mPCC), retrosplenial cortex, posterior precuneus, and the left intraparietal sulcus. Activation specific to the FP trials (as assessed by the interaction) was observed in the right posterodorsal PCC (pPCC) only. Together with data from previous functional imaging studies, the results suggest a functional segregation of human PCC with differential involvement of pPCC in spatial representations of personally familiar places and of the mPCC and retrosplenial cortex in episodic retrieval of personally familiar places and objects. Activation of the left intraparietal sulcus may reflect retrieval of memories related to object manipulation.

Human cortical connectome reconstruction from diffusion weighted MRI: The effect of tractography algorithm

Reconstructing the macroscopic human cortical connectome by Diffusion Weighted Imaging (DWI) is a challenging research topic that has recently gained a lot of attention. In the present work, we investigate the effects of intra-voxel fiber direction modeling and tractography algorithm on derived structural network indices (e.g. density, small-worldness and global efficiency). The investigation is centered on three semi-independent distinctions within the large set of available diffusion models and tractography methods: i) single fiber direction versus multiple directions in the intra-voxel diffusion model, ii) deterministic versus probabilistic tractography and iii) local versus global measure-of-fit of the reconstructed fiber trajectories. The effect of algorithm and parameter choice has two components. First, there is the large effect of tractography algorithm and parameters on global network density, which is known to strongly affect graph indices. Second, and more importantly, there are remaining effects on graph indices which range in the tens of percent even when global density is controlled for. This is crucial for the sensitivity of any human structural network study and for the validity of study comparisons. We then investigate the effect of the choice of tractography algorithm on sensitivity and specificity of the resulting connections with a connectome dissection quality control (QC) approach. In this approach, evaluation of Tract Specific Density Coefficients (TSDCs) measures sensitivity while careful inspection of tractography path results assesses specificity. We use this to discuss interactions in the combined effects of these methods and implications for future studies.

A parametric analysis of the 'rate effect' in the sensorimotor cortex : a functional magnetic resonance imaging analysis in human subjects

We studied the effects of different movement speeds of unimanual right hand movements on functional magnetic resonance signal changes in the sensorimotor cortex using echo planar imaging (EPI). Six healthy right-handed subjects were scanned at rest and while executing a finger tapping task with their right index finger. Movement frequency was visually paced at rates ranging from 0.5 to 5 Hz, separated by 0.5 Hz steps. The blood oxygen level dependent (BOLD) response within the left sensorimotor cortex was linearly and positively related to movement frequency. However, this relation holds (r2 = 0.91) only for movement frequencies faster than 1 Hz (1.5-5 Hz). For the slower frequencies there was an initial sharp increase of the BOLD response from 0.5 to 1 Hz followed by an activity drop for 1.5 Hz. These results are compatible with the idea that two different motor control modes are operative during slow or fast movements. During slow movements a computational demanding on-line feedback control mode is operative resulting in strong BOLD signals indicating extensive neural activity. During faster movements on the other hand a program-like motor control mode is operative resulting in less demanding neural computations. The amount of neural computation for the latter control mode increases with increasing movement speed.

Multiple Movement Representations in the Human Brain: An Event-Related fMRI Study

Neurovascular correlates of response preparation have been investigated in human neuroimaging studies. However, conventional neuroimaging cannot distinguish, within the same trial, between areas involved in response selection and/ or response execution and areas specifically involved in response preparation. The specific contribution of parietal and frontal areas to motor preparation has been explored in electrophysiological studies in monkey. However, the associative nature of sensorimotor tasks calls for the additional contributions of other cortical regions. In this article, we have investigated the functional anatomy of movement representations in the context of an associative visuomotor task with instructed delays. Neural correlates of movement representations have been assessed by isolating preparatory activity that is independent from the performance of an actual motor act, or from the presence of a responses target. Movement instruction (specified by visual cues) and motor performance (specified by an auditory cue) were separated by a variable delay period. We have used whole-brain event-related fMRI to measure human brain activity during the performance of such a task. We have focused our analysis on specific preparatory activity, defined as a sustained response over variable delay periods between a transient visual instruction cue and a brief motor response, temporally independent from the transient events. Behavioral and electrophysiological controls ensured that preparatory activity was not contaminated by overt motor responses or working memory processes. We report suggestive evidence for multiple movement representations in the human brain. Specific sustained activity in preparation for an action was found not only in parieto-frontal regions but also in extrastriate areas and in the posterior portion of the superior temporal sulcus. We suggest that goal-directed preparatory activity relies on both visuo-motor and visuoperceptual areas. These findings point to a functional anatomical basis for the integration of perceptual and executive processes.