Interlaminar differences in the pyramidal cell phenotype in cortical areas 7m and STP (the superior temporal polysensory area) of the macaque monkey

Pyramidal neurones were injected with Lucifer Yellow in slices cut tangential to the surface of area 7m and the superior temporal polysensory area (STP) of the macaque monkey. Comparison of the basal dendritic arbors of supra- and infragranular pyramidal neurones (n=139) that were injected in the same putative modules in the different cortical areas revealed variation in their structure. Moreover, there were relative differences in dendritic morphology of supra- and infragranular pyramidal neurones in the two cortical areas. Shell analyses revealed that layer III pyramidal neurones in area STP had considerably higher peak complexity (maximum number of dendritic intersections per Shell circle) than those in layer V, whereas peak complexities were similar for supra- and infragranular pyramidal neurones in area 7m. In both cortical areas, the basal dendritic trees of layer m pyramidal neurones were characterized by a higher spine density than those in layer V. Calculations of the total number of dendritic spines in the average basal dendritic arbor revealed that layer V pyramidal neurones in area 7m had twice as many spines as cells in layer III. (4535 and 2294, respectively). A similar calculation for neurones in area STP revealed that layer III pyramidal neurones had approximately the same number of spines as cells in layer V (3585 and 3850 spines, respectively). Relative differences in the branching patterns of, and the number of spines in, the basal dendritic arbors of supra- and infragranular pyramidal neurones in the different cortical areas may allow for integration of different numbers of inputs, and different degrees of dendritic processing. These results support the thesis that intra-areal circuitry differs in different cortical areas.

A medial to lateral shift in pre-movement cortical activity in hemi-Parkinson's disease

Objective: Recent evidence suggests that cortical activity associated with voluntary movement is relatively shifted from medial to lateral premotor areas in Parkinson's disease. This shift occurs bilaterally even for unilateral responses. It is not clear whether the shift in processing reflects an overall change in movement strategy, thereby involving alternate cortical areas, or reflects a compensatory change whereby, given the appropriate conditions, less impaired cortical areas are able to provide a similar function in compensation for those areas which are more impaired. This issue was examined in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. Methods: Fourteen patients with hemi-Parkinson's disease and 15 age-matched control subjects performed a Go/NoGo finger movement task and the contingent negative variation (CNV) was recorded from 21 scalp positions. Results and conclusions: Maximal CNV amplitudes were found over central medial regions for control subjects, but were shifted more frontally for Parkinson's disease patients, reduced in amplitude over the midline and lateralized towards the side ipsilateral to the greatest basal ganglia impairment. This shift in cortical activity from medial to lateral areas in Parkinson's disease patients appears to reflect a compensatory mechanism operating predominantly on the side of greatest basal ganglia impairment. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Identifying rate-limiting nodes in large-scale cortical networks for visuospatial processing: an illustration using fMRI

With the advent of functional neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), we have gained greater insight into the neural correlates of visuospatial function. However, it may not always be easy to identify the cerebral regions most specifically associated with performance on a given task. One approach is to examine the quantitative relationships between regional activation and behavioral performance measures. In the present study, we investigated the functional neuroanatomy of two different visuospatial processing tasks, judgement of line orientation and mental rotation. Twenty-four normal participants were scanned with fMRI using blocked periodic designs for experimental task presentation. Accuracy and reaction time (RT) to each trial of both activation and baseline conditions in each experiment was recorded. Both experiments activated dorsal and ventral visual cortical areas as well as dorsolateral prefrontal cortex. More regionally specific associations with task performance were identified by estimating the association between (sinusoidal) power of functional response and mean RT to the activation condition; a permutation test based on spatial statistics was used for inference. There was significant behavioral-physiological association in right ventral extrastriate cortex for the line orientation task and in bilateral (predominantly right) superior parietal lobule for the mental rotation task. Comparable associations were not found between power of response and RT to the baseline conditions of the tasks. These data suggest that one region in a neurocognitive network may be most strongly associated with behavioral performance and this may be regarded as the computationally least efficient or rate-limiting node of the network.

The dorsomedial visual areas in New World and Old World monkeys: homology and function

The extrastriate cortex near the dorsal midline has been described as part of an 'express' pathway that provides visual input to the premotor cortex. This pathway is considered important for the integration of sensory information about the visual field periphery and the skeletomotor system, especially in relation to the control of arm movements. However, a better understanding of the functional contributions of different parts of this complex has been hampered by the lack of data on the extent and boundaries of its constituent visual areas. Recent studies in macaques have provided the first detailed view of the topographical organization of this region in Old World monkeys. Despite differences in nomenclature, a comparison of the visuotopic organization, myeloarchitecture and connections of the relevant visual areas with those previously studied in New World monkeys reveals a remarkable degree of similarity and helps to clarify the subdivision of function between different areas of the dorsomedial complex. A caudal visual area, named DM or V6, appears to be important for the detection of coherent patterns of movement across wide regions of the visual field, such as those induced during self-motion. A rostral area, named M or V6A, is more directly involved with visuomotor integration. This area receives projections both from DM/V6 and from a separate motion analysis channel, centred on the middle temporal visual area (or V5), which detects the movement of objects in extrapersonal space. These results support the suggestion, made earlier on the basis of more fragmentary evidence, that the areas rostral to the second visual area in dorsal cortex are homologous in all simian primates. Moreover, they emphasize the importance of determining the anatomical organization of the cortex as a prerequisite for elucidating the function of different cortical areas.

Parvalbumin-, calbindin-, and calretinin-immunoreactive neurons in the prefrontal cortex of the owl monkey (Aotus trivirgatus): A standardized quantitative comparison with sensory and motor areas

Recent studies have revealed regional variation in the density and distribution of inhibitory neurons in different cortical areas, which are thought to reflect area-specific specializations in cortical circuitry. However, there are as yet few standardized quantitative data regarding how the inhibitory circuitry in prefrontal cortex (PFC), which is thought to be involved in executive functions such as cognition, emotion and decision making, compares to that in other cortical areas. Here we used immunohistochemical techniques to determine the density and distribution of parvalbumin (PV)-, calbindin (CB)-, and calretinin (CR)-immunoreactive (ir) neurons and axon terminals in the dorsolateral and orbital PFC of the owl monkey (Aotus trivirgatus), and compared them directly with data obtained using the same techniques in 11 different visual, somatosensory and motor areas. We found marked differences in the density of PV-ir, CB-ir, and CR-ir interneurons in several cortical areas. One hundred and twenty eight of all 234 possible between-area pairwise comparisons were significantly different. The density of specific subpopulations of these cells also varied among cortical areas, as did the density of axon terminals. Comparison of PFC with other cortical areas revealed that 40 of all 66 possible statistical comparisons of the density of PV-ir, CB-ir, and CR-ir cells were significantly different. We also found evidence for heterogeneity in the pattern of labeling of PV-ir, CB-ir, and CR-ir cells and axon terminals between the dorsolateral and orbital subdivisions of PFC. These data are likely to reflect basic differences in interneuron circuitry, which are likely to influence inhibitory function in the cortex. Copyright (C) 2003 S. Karger AG, Basel.

Fractal analysis of pyramidal cells in the visual cortex of the galago (Otolemur garnetti): Regional variation in dendritic branching patterns between visual areas

Previously it has been shown that the branching pattern of pyramidal cells varies markedly between different cortical areas in simian primates. These differences are thought to influence the functional complexity of the cells. In particular, there is a progressive increase in the fractal dimension of pyramidal cells with anterior progression through cortical areas in the occipitotemporal (OT) visual stream, including the primary visual area (V1), the second visual area (V2), the dorsolateral area (DL, corresponding to the fourth visual area) and inferotemporal cortex (IT). However, there are as yet no data on the fractal dimension of these neurons in prosimian primates. Here we focused on the nocturnal prosimian galago (Otolemur garnetti). The fractal dimension (D), and aspect ratio (a measure of branching symmetry), was determined for I I I layer III pyramidal cells in V1, V2, DL and IT. We found, as in simian primates, that the fractal dimension of neurons increased with anterior progression from V1 through V2, DL, and IT. Two important conclusions can be drawn from these results: (1) the trend for increasing branching complexity with anterior progression through OT areas was likely to be present in a common primate ancestor, and (2) specialization in neuron structure more likely facilitates object recognition than spectral processing.

Areal specialization of pyramidal cell structure in the visual cortex of the tree shrew: a new twist revealed in the evolution of cortical circuitry

Cortical pyramidal cells, while having a characteristic morphology, show marked phenotypic variation in primates. Differences have been reported in their size, branching structure and spine density between cortical areas. In particular, there is a systematic increase in the complexity of the structure of pyramidal cells with anterior progression through occipito-temporal cortical visual areas. These differences reflect area-specific specializations in cortical circuitry, which are believed to be important for visual processing. However, it remains unknown as to whether these regional specializations in pyramidal cell structure are restricted to primates. Here we investigated pyramidal cell structure in the visual cortex of the tree shrew, including the primary (V1), second (V2) and temporal dorsal (TD) areas. As in primates, there was a trend for more complex branching structure with anterior progression through visual areas in the tree shrew. However, contrary to the trend reported in primates, cells in the tree shrew tended to become smaller with anterior progression through V1, V2 and TD. In addition, pyramidal cells in V1 of the tree shrew are more than twice as spinous as those in primates. These data suggest that variables that shape the structure of adult cortical pyramidal cells differ among species.

Regional specialization in pyramidal cell structure in the visual cortex of the galago: An intracellular injection study of striate and extrastriate areas with comparative notes on New World and Old World monkeys

Recent studies have revealed marked differences in the basal dendritic structure of layer III pyramidal cells in the cerebral cortex of adult simian primates. In particular, there is a consistent trend for pyramidal cells of increasing complexity with anterior progression through occipitotemporal cortical visual areas. These differences in pyramidal cell structure, and their systematic nature, are believed to be important for specialized aspects of visual processing within, and between, cortical areas. However, it remains unknown whether this regional specialization in the pyramidal cell phenotype is unique to simians, is unique to primates in general or is widespread amongst mammalian species. In the present study we investigated pyramidal cell structure in the prosimian galago (Otolemur garnetti). We found, as in simians, that the basal dendritic arbors of pyramidal cells differed between cortical areas. More specifically, pyramidal cells became progressively more spinous through the primary (V1), second (V2), dorsolateral (DL) and inferotemporal ( IT) visual areas. Moreover, pyramidal neurons in V1 of the galago are remarkably similar to those in other primate species, in spite of large differences in the sizes of this area. In contrast, pyramidal cells in inferotemporal cortex are quite variable among primate species. These data suggest that regional specialization in pyramidal cell phenotype was a likely feature of cortex in a common ancestor of simian and prosimian primates, but the degree of specialization varies between species. Copyright (C) 2005 S. Karger AG, Basel.

Brain maps, great and small: lessons from comparative studies of primate visual cortical organization

In this paper, we review evidence from comparative studies of primate cortical organization, highlighting recent findings and hypotheses that may help us to understand the rules governing evolutionary changes of the cortical map and the process of formation of areas during development. We argue that clear unequivocal views of cortical areas and their homologies are more likely to emerge for 'core' fields, including the primary sensory areas, which are specified early in development by precise molecular identification steps. In primates, the middle temporal area is probably one of these primordial cortical fields. Areas that form at progressively later stages of development correspond to progressively more recent evolutionary events, their development being less firmly anchored in molecular specification. The certainty with which areal boundaries can be delimited, and likely homologies can be assigned, becomes increasingly blurred in parallel with this evolutionary/developmental sequence. For example, while current concepts for the definition of cortical areas have been vindicated in allowing a clarification of the organization of the New World monkey 'third tier' visual cortex (the third and dorsomedial areas, V3 and DM), our analyses suggest that more flexible mapping criteria may be needed to unravel the organization of higher-order visual association and polysensory areas.

Ipsilateral corticocortical projections to the primary and middle temporal visual areas of the primate cerebral cortex: area-specific variations in the morphology of connectionally identified pyramidal cells

We quantified the morphology of over 350 pyramidal neurons with identified ipsilateral corticocortical projections to the primary (V1) and middle temporal (MT) visual areas of the marmoset monkey, following intracellular injection of Lucifer Yellow into retrogradely labelled cells. Paralleling the results of studies in which randomly sampled pyramidal cells were injected, we found that the size of the basal dendritic tree of connectionally identified cells differed between cortical areas, as did the branching complexity and spine density. We found no systematic relationship between dendritic tree structure and axon target or length. Instead, the size of the basal dendritic tree increased roughly in relation to increasing distance from the occipital pole, irrespective of the length of the connection or the cortical layer in which the neurons were located. For example, cells in the second visual area had some of the smallest and least complex dendritic trees irrespective of whether they projected to V1 or MT, while those in the dorsolateral area (DL) were among the largest and most complex. We also observed that systematic differences in spine number were more marked among V1-projecting cells than MT-projecting cells. These data demonstrate that the previously documented systematic differences in pyramidal cell morphology between areas cannot simply be attributed to variable proportions of neurons projecting to different targets, in the various areas. Moreover, they suggest that mechanisms intrinsic to the area in which neurons are located are strong determinants of basal dendritic field structure.

Movement-related potentials in Huntington's disease: movement preparation and execution

Movement-related potentials (MRPs) reflect increasing cortical activity related to the preparation and execution of voluntary movement. Execution and preparatory components may be separated by comparing MRPs recorded from actual and imagined movement. Imagined movement initiates preparatory processes, but not motor execution activity. MRPs are maximal over the supplementary motor area (SMA), an area of the cortex involved in the planning and preparation of movement. The SMA receives input from the basal ganglia, which are affected in Huntington's disease (HD), a hyperkinetic movement disorder. In order to further elucidate the effects of the disorder upon the cortical activity relating to movement, MRPs were recorded from ten HD patients, and ten age-matched controls, whilst they performed and imagined performing a sequential button-pressing task. HD patients produced MRPs of significantly reduced size both for performed and imagined movement. The component relating to movement execution was obtained by subtracting the MRP for imagined movement from the MRP for performed movement, and was found to be normal in HD. The movement preparation component was found by subtracting the MRP found for a control condition of watching the visual cues from the MRP for imagined movement. This preparation component in HD was reduced in early slope, peak amplitude, and post-peak slope. This study therefore reported abnormal MRPs in HD. particularly in terms of the components relating to movement preparation, and this finding may further explain the movement deficits reported in the disease.

Motor imagery in Parkinson's disease: A PET study

We used positron emission tomography (PET) with O-15-labelled water to record patterns of cerebral activation in six patients with Parkinson's disease (PD), studied when clinically off and after turning on as a result of dopaminergic stimulation. They were asked to imagine a Finger opposition movement performed with their right hand. externally paced at a rate of 1 Hz. Trials alternating between motor imagery and rest were measured. A pilot study of three age-matched controls was also performed. We chose the task as a robust method of activating the supplementary motor area (SMA), defects of which have been reported in PD. The PD patients showed normal de-rees of activation of the SMA (proper) when both off and on. Significant activation with imagining movement also occurred in the ipsilateral inferior parietal cortex (both off and when on) and ipsilateral premotor cortex (when off only). The patients showed significantly greater activation of the rostral anterior cingulate and significantly less activation of the left lingual gyrus and precuneus when performing the task on compared with their performance when off. PD patients when imagining movement and off showed less activation of several sites including the right dorsolateral prefrontal cortex (DLPFC) when compared to the controls performing the same task. No significant differences from controls were present when the patients imagined when on. Our results are consistent with other studies showing deficits of pre-SMA function in PD with preserved function of the SMA proper. In addition to the areas of reduced activation (anterior cingulate, DLPFC), there were also sites of activation (ipsilateral premotor and inferior parietal cortex) previously reported as locations of compensatory overactivity for PD patients performing similar tasks. Both failure of activation and compensatory changes a-re likely to contribute to the motor deficit in PD. (C) 2001 Movement Disorder Society.

The preparation and execution of self-initiated and externally-triggered movement: A study of event-related fMRI

Studies of functional brain imaging in humans and single cell recordings in monkeys have generally shown preferential involvement of the medially located supplementary motor area (SMA) in self-initiated movement and the lateral premotor cortex in externally cued movement. Studies of event-related cortical potentials recorded during movement preparation, however, generally show increased cortical activity prior to self-initiated movements but little activity at early stages prior to movements that are externally cued at unpredictable times. In this study, the spatial location and relative timing of activation for self-initiated and externally triggered movements were examined using rapid event-related functional MRI. Twelve healthy right-handed subjects were imaged while performing a brief finger sequence movement (three rapid alternating button presses: index-middle-index finger) made either in response to an unpredictably timed auditory cue (between 8 to 24 s after the previous movement) or at self-paced irregular intervals. Both movement conditions involved similar strong activation of medial motor areas including the pre-SMA, SMA proper, and rostral cingulate cortex, as well as activation within contralateral primary motor, superior parietal, and insula cortex. Activation within the basal ganglia was found for self-initiated movements only, while externally triggered movements involved additional bilateral activation of primary auditory cortex. Although the level of SMA and cingulate cortex activation did not differ significantly between movement conditions, the timing of the hemodynamic response within the pre-SMA was significantly earlier for self-initiated compared with externally triggered movements. This clearly reflects involvement of the pre-SMA in early processes associated with the preparation for voluntary movement. (C) 2002 Elsevier Science.

Attentional modulation of neural responses to action observation: Implications for models of the human 'mirror' system

In primates, the observation of meaningful, goaldirected actions engages a network of cortical areas located within the premotor and inferior parietal lobules. Current models suggest that activity within these regions arises relatively automatically during passive action observation without the need for topdown control. Here we used functional magnetic resonance imaging to determine whether cortical activit)' associated with action observation is modulated by the strategic allocation of selective attention. Normal observers viewed movie clips of reach-to-grasp actions while performing an easy or difficult visual discrimination at the fovea. A wholebrain analysis was performed to determine the effects of attentional load on neural responses to observed hand actions. Our results suggest that cortical areas involved in action observation are significantiy modulated by attentional load. These findings have important implications for recent attempts to link the human action-observation system to response properties of "mirror neurons" in monkeys.