Age-related dendritic and spine changes in corticocortically projecting neurons in macaque monkeys

Alterations in neuronal morphology occur in primate cerebral cortex during normal aging, vary depending on the neuronal type, region and cortical layer, and have been related to memory and cognitive impairment. We analyzed how such changes affect a specific subpopulation of cortical neurons forming long corticocortical projections from the superior temporal cortex to prefrontal area 46. These neurons were identified by retrograde transport in young and old macaque monkeys. Dendritic arbors of retrogradely labeled neurons were visualized in brain slices by intracellular injection of Lucifer Yellow, and reconstructed three-dimensionally using computer-assisted morphometry. Total dendritic length, numbers of segments, numbers of spines, and spine density were analyzed in layer III pyramidal neurons forming the projection considered. Sholl analysis was used to determine potential age-related changes in dendritic complexity. We observed statistically significant age-related decreases in spine numbers and density on both apical and basal dendritic arbors in these projection neurons. On apical dendrites, changes in spine numbers occurred mainly on the proximal dendrites but spine density decreased uniformly among the different branch orders. On basal dendrites, spine numbers and density decreased preferentially on distal branches. Regressive dendritic changes were observed only in one particular portion of the apical dendrites, with the general dendritic morphology and extent otherwise unaffected by aging. In view of the fact that there is no neuronal loss in neocortex and hippocampus in old macaque monkeys, it is possible that the memory and cognitive decline known to occur in these animals is related to rather subtle changes in the morphological and molecular integrity of neurons subserving identifiable neocortical association circuits that play a critical role in cognition.     

Functional brain mapping of the macaque related to spatial working memory as revealed by PET

To define the cortical areas that subserve spatial working memory in a nonhuman primate, we measured regional cerebral blood flow (rCBF) with [(15)O]H(2)O and positron emission tomography while monkeys performed a visually guided saccade (VGS) task and an oculomotor delayed-response (ODR) task. Both Statistical Parametric Mapping and regions of interest-based analyses revealed an increase of rCBF in the area surrounding the principal sulcus (PS), the superior convexity, the anterior bank of the arcuate sulcus (AS), the lateral orbitofrontal cortex (lOFC), the frontal pole (FP), the anterior cingulate cortex (ACC), the lateral bank of the intraparietal sulcus (lIPS) and the prestriate cortex. In the prefrontal cortex (PS, superior convexity, AS, lOFC and FP), rCBF values correlated positively with ODR task performance scores. From the hippocampus, rCBF values correlated negatively with ODR task performance. From the AS, superior convexity, lOFC, FP, ACC and lIPS, rCBF values of the PS correlated positively with rCBF values and negatively with hippocampus rCBF values. These results suggest that neural circuitry in the prefrontal cortex directly contributes the spatial working memory processes and that, in spatial working memory processes, the posterior parietal cortex and hippocampus have a different role to the prefrontal cortex.     

The effects of aging on layer 1 of primary visual cortex in the rhesus monkey

The effect of age on layer 1 in primary visual cortex was determined in 19 rhesus monkeys of various ages. Twelve of the monkeys had been behaviorally tested. With age layer 1 becomes thinner and the glial limiting membrane becomes thicker. In the neuropil of layer 1 many of the dendrites in old monkeys appear to be degenerating and, as a consequence, electron micrographs from old monkeys display fewer dendritic and spine profiles per unit area than in young monkeys. As determined using both the disector and size-frequency methods, there is also a concomitant decrease in the numerical density of synapses with age. Although there is a significant correlation between the thinning of layer 1 in area 17 and age, there is no significant correlation between either the thinning of layer 1 or its loss of synapses and any of the behavioral measures of memory function obtained from the 12 behaviorally tested monkeys. Similar morphological changes with age occur in layer 1 of prefrontal cortex of these same monkeys, but in area 46 both the thinning of layer 1 and the loss of synapses show a significant correlation with behavioral measures of memory function. These differences between layer 1 in these two cortical areas presumably relate to the fact that prefrontal cortex has a greater role in subserving cognition than does primary visual cortex.     

Synaptic distinction of laminar-specific prefrontal-temporal pathways in primates

Prefrontal pathways exert diverse effects in widespread cortical areas, issuing projections both to the middle layers and to layer I, which are anatomically and functionally distinct. Here we addressed the still unanswered question of whether cortical pathways that terminate in different layers are distinct at the synaptic level. We addressed this issue using as a model system the robust and functionally significant pathways from prefrontal areas 10 and 32 to superior temporal areas in rhesus monkeys. Boutons from prefrontal axons synapsing in the middle layers of superior temporal cortex were significantly larger than boutons synapsing in layer I. Most synapses were on spines in both layers, which are found on dendrites of excitatory neurons. The less prevalent synapses on smooth dendrites, characteristic of inhibitory interneurons, were more common in the middle cortical layers than in layer I. Bouton volume was linearly related to vesicular and mitochondrial content in both layers, though a subset of small boutons, found mostly in layer I, contained no mitochondria. The systematic laminar-specific presynaptic differences in stable cortical synapses in adult primates were independent of their origin in the functionally distinct prefrontal areas 10 and 32, or their destination in architectonically distinct superior temporal areas. This synaptic distinction suggests differences in efficacy of synaptic transmission and metabolic demands in laminar-specific pathways that may be selectively recruited in behavior.     

Low CA1 spine synapse density is further reduced by castration in male non-human primates

The hippocampus plays a major role in learning and memory and its morphology and function are readily affected by gonadal hormones in female non-human primates. We sought to determine whether the gonads also affect pyramidal cell spine synapse density in the CA1 hippocampal area of male primates. Unbiased electron microscopic stereological calculations were performed to determine the volumetric density of pyramidal cell spine synapses and semiquantitative analyses on the surface density of glial fibrillary acidic protein-containing glia processes and the diameter of pyramidal cell apical dendrites in the CA1 area of intact and orchidectomized (1 month) St Kitts vervet monkeys (Chlorocebus aethiops sabaeus). The volumetric density (number of spine synapse/ micro m(3)) of spine synapses was significantly lower (40%) in the gonadectomized animals than in control monkeys; conversely, the density of glia processes was significantly higher (15%) and the diameter of dendritic shafts located in this area was also larger (30%) in the orchidectomized animals than in the controls. Strikingly, when compared to female values, intact male primates had lower spine synapse densities than either intact or ovariectomized females. Since the primate hippocampus is very similar to that of a human's, the present observations suggest that physiological levels of circulating androgen hormones are necessary to support normal spine synapse density in the CA1 stratum radiatum of human male hippocampus.     

Search for color 'center(s)' in macaque visual cortex

It is often stated that color is selectively processed in cortical area V4, in both macaques and humans. However most recent data suggests that color is instead processed in region(s) antero-ventral to V4. Here we tested these two hypotheses in macaque visual cortex, where 'V4' was originally defined, and first described as color selective. Activity produced by equiluminant color-varying (versus luminance-varying) gratings was measured using double-label deoxyglucose in awake fixating macaques, in multiple areas of flattened visual cortex. Much of cortex was activated near-equally by both color- and luminance-varying stimuli. In remaining cortical regions, discrete color-biased columns were found in many cortical visual areas, whereas luminance-biased activity was found in only a few specific regions (V1 layer 4B and area MT). Consistent with a recent hypothesis, V4 was not uniquely specialized for color processing, but areas located antero-ventral to V4 (in/near TEO and anterior TE) showed more color-biased activity.     

A study of pyramidal cell structure in the cingulate cortex of the macaque monkey with comparative notes on inferotemporal and primary visual cortex

Recent studies have revealed a marked degree of variation in the pyramidal cell phenotype in visual, somatosensory, motor and prefrontal cortical areas in the brain of different primates, which are believed to subserve specialized cortical function. In the present study we carried out comparisons of dendritic structure of layer III pyramidal cells in the anterior and posterior cingulate cortex and compared their structure with those sampled from inferotemporal cortex (IT) and the primary visual area (V1) in macaque monkeys. Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors was determined, and somal areas measured. We found that pyramidal cells in anterior cingulate cortex were more branched and more spinous than those in posterior cingulate cortex, and cells in both anterior and posterior cingulate were considerably larger, more branched, and more spinous than those in area V1. These data show that pyramidal cell structure differs between posterior dysgranular and anterior granular cingulate cortex, and that pyramidal neurons in cingulate cortex have different structure to those in many other cortical areas. These results provide further evidence for a parallel between structural and functional specialization in cortex.     

Self-organization model of cytochrome oxidase blobs and ocular dominance columns in the primary visual cortex

There are regularly arranged blobs that contain neurons labeled by cytochrome oxidase (CO) in the supragranular layer of the primary visual cortex (V1) of monkeys and cats. This theoretical study demonstrates that CO-blob-like patterns can be reproduced based on the thermodynamic model for the activity-dependent self-organization of afferent inputs from two different groups of neurons to the supragranular layer of the visual cortex. Computer simulation based on the model shows that within a particular parameter range each blob is centered in the ocular dominance (OD) band, as observed in macaque monkeys and galagos. Furthermore, by increasing the strength of correlation in activity between inputs from the two eyes, nearby blobs merge across OD borders, as seen in the cat visual cortex. Finally, for monocular deprivation, blobs in the deprived eyes shrink as observed in monkeys and cats. For binocular deprivation, less intensely labeled blobs were reproduced, while the blob density did not change as observed in monkeys.     

Volumetric correlates of spatiotemporal working and recognition memory impairment in aged rhesus monkeys

Spatiotemporal and recognition memory are affected by aging in humans and macaque monkeys. To investigate whether these deficits are coupled with atrophy of memory-related brain regions, T(1)-weighted magnetic resonance images were acquired and volumes of the cerebrum, ventricles, prefrontal cortex (PFC), calcarine cortex, hippocampus, and striatum were quantified in young and aged rhesus monkeys. Subjects were tested on a spatiotemporal memory procedure (delayed response [DR]) that requires the integrity of the PFC and a medial temporal lobe-dependent recognition memory task (delayed nonmatching to sample [DNMS]). Region of interest analyses revealed that age inversely correlated with striatal, dorsolateral prefrontal cortex (dlPFC), and anterior cingulate cortex volumes. Hippocampal volume predicted acquisition of the DR task. Striatal volume correlated with DNMS acquisition, whereas total prefrontal gray matter, prefrontal white matter, and dlPFC volumes each predicted DNMS accuracy. A regional covariance analysis revealed that age-related volumetric changes could be captured in a distributed network that was coupled with declining performance across delays on the DNMS task. This volumetric analysis adds to growing evidence that cognitive aging in primates arises from region-specific morphometric alterations distributed across multiple memory-related brain systems, including subdivisions of the PFC.     

The effect of ovariectomy on spine bone mineral density in rhesus monkeys

As part of a study on the effects of hormones on uterine biology and estrogen metabolism, 12 normal female rhesus (Macaca mulatta) monkeys were ovariectomized, and treated intermittently with estradiol and progesterone. In order to determine whether there were changes in bone density as a result of ovariectomy despite the hormone therapy, spine bone mineral density (BMD) was measured by dual-photon absorptiometry. The mean +/- SE time from ovariectomy was 26 +/- 3 months, the mean estrogen treatment time was 3.5 +/- 0.4 months and the mean time from last hormonal treatment was 4.1 +/- 0.6 months. In these 12 monkeys aged 7.7 +/- 0.2 years, the mean spine BMD, 0.825 +/- 0.008 g/cm2, was significantly less, p = 0.0011, than the spine BMD, 0.863 +/- 0.007 g/cm2, in 12 intact female rhesus of similar age, 7.6 +/- 0.1 years and weight. Ovariectomy in female rhesus monkeys results in a relatively rapid diminution of spine BMD which is not prevented by intermittent hormonal replacement. This species may be an excellent model for studies of human osteoporosis.     

The effects of aging on layer 1 in area 46 of prefrontal cortex in the rhesus monkey

The effect of age on layer 1 of area 46 of prefrontal cortex was determined in the cerebral cortices of 15 rhesus monkeys, 13 of which had been behaviorally tested. Five of the monkeys were young (5-7 years of age), three were middle-aged (9-12 years) and seven were old (24-32 years). It was found that with age, layer 1 becomes significantly thinner and the glial limiting membrane becomes thicker. Counts of synapses in layer 1 of seven of these monkeys using the physical disector method on thin sections revealed that compared to young monkeys, there is a 30-60% reduction in the density of synapses per unit volume in old monkeys. This loss of synapses is accompanied by a reduction in the frequency of profiles of postsynaptic dendrites and their spines from the neuropil of layer 1, indicating that some spiny dendrites that belong to the apical dendritic tufts of pyramidal cells are degenerating and being lost with age. Correlation of these morphological changes with the behavioral data shows that there is a significant correlation between the thickness of layer 1 and memory function, as measured by the 2 min delay condition of the delayed non- matching to sample task. Also, there is significant correlation between the numerical density of synapses in layer 1 and three of the behavioral measures used, as well as the Cognitive Impairment Index. Thus, the changes that occur with age in layer 1 provide one possible basis for the age-related cognitive impairment evidenced in monkeys and humans alike.      

Dual role of substance P/GABA axons in cortical neurotransmission: synaptic triads on pyramidal cell spines and basket-like innervation of layer II-III calbindin interneurons in primate prefrontal cortex

In spite of accumulating evidence on the potent neuromodulatory, neuroprotective, trophic and memory-enhancing effects of the neuropeptide substance P (SP) in the cerebral cortex, the excitatory or inhibitory nature of the cortical SP innervation remains unclear and the postsynaptic targets of SP fibers are not defined. To obtain further insight into these issues, we have examined SP-containing axons and their postsynaptic targets in the prefrontal cortex of adult monkeys with single- and double label immunocytochemistry combined with light and correlated electron microscopy. SP fibers in the primate prefrontal cortex, unlike those in the rat cortex, preferentially innervate cortical layers I, II and upper layer III. Our results demonstrate for the first time that all SP-immunoreactive boutons in all cortical layers contain GABA. Of the entire sample of SP boutons, 53% synapse on dendritic shafts, 39% on dendritic spines and 8% on cell bodies. Another new finding is that synapse-forming SP boutons, in addition to their known innervation of pyramidal cells, form pericellular baskets around interneurons in layers II and upper III, a subpopulation of which contains calbindin D28k. Finally, the study also revealed that SP boutons frequently participate in 'synaptic triads' with spines which receive another (asymmetric, putatively excitatory amino acid-utilizing) synapse. Our findings indicate that SP/GABA axons in the primate prefrontal cortex modulate excitatory amino acid- mediated neurotransmission and control feed-forward disinhibitory GABAergic circuits in supragranular cortical layers.      

Odanacatib reduces bone turnover and increases bone mass in the lumbar spine of skeletally mature ovariectomized rhesus monkeys

Odanacatib (ODN) is a selective and reversible inhibitor of cathepsin K (CatK) currently being developed as a once‐weekly treatment for osteoporosis. In this study, we evaluated the effects of ODN on bone turnover, bone mineral density (BMD), and bone strength in the lumbar spine of estrogen‐deficient, skeletally mature rhesus monkeys. Ovariectomized (OVX) monkeys were treated in prevention mode for 21 months with either vehicle, ODN 6 mg/kg, or ODN 30 mg/kg (p.o., q.d.) and compared with intact animals. ODN treatment persistently suppressed the bone resorption markers (urinary NTx [75% to 90%] and serum CTx [40% to 55%]) and the serum formation markers (BSAP [30% to 35%] and P1NP [60% to 70%]) versus vehicle‐treated OVX monkeys. Treatment with ODN also led to dose‐dependent increases in serum 1‐CTP and maintained estrogen deficiency–elevated Trap‐5b levels, supporting the distinct mechanism of CatK inhibition in effectively suppressing bone resorption without reducing osteoclast numbers. ODN at both doses fully prevented bone loss in lumbar vertebrae (L₁ to L₄) BMD in OVX animals, maintaining a level comparable to intact animals. ODN dose‐dependently increased L₁ to L₄ BMD by 7% in the 6 mg/kg group (p < 0.05 versus OVX‐vehicle) and 15% in the 30 mg/kg group (p < 0.05 versus OVX‐vehicle) from baseline. Treatment also trended to increase bone strength, associated with a positive and highly significant correlation (R = 0.838) between peak load and bone mineral content of the lumbar spine. Whereas ODN reduced bone turnover parameters in trabecular bone, the number of osteoclasts was either maintained or increased in the ODN‐treated groups compared with the vehicle controls. Taken together, our findings demonstrated that the long‐term treatment with ODN effectively suppressed bone turnover without reducing osteoclast number and maintained normal biomechanical properties of the spine of OVX nonhuman primates. © 2012 American Society for Bone and Mineral Research     

Neural activity in primate parietal area 7a related to spatial analysis of visual mazes

Cognitive psychological studies of humans and monkeys solving visual mazes have provided evidence that a covert analysis of the maze takes place during periods of eye fixation interspersed between saccades, or when mazes are solved without eye movements. We investigated the neural basis of this process in posterior parietal cortex by recording the activity of single neurons in area 7a during maze solution. Monkeys were required to determine from a single point of fixation whether a critical path through the maze reached an exit or a blind ending. We found that during this process the activity of approximately one in four neurons in area 7a was spatially tuned to maze path direction. We obtained evidence that path tuning did not reflect a covert saccade plan insofar as the majority of neurons active during maze solution were not active on a delayed-saccade control task, and the minority that were active on both tasks did not exhibit congruent spatial tuning in the two conditions. We also obtained evidence that path tuning during maze solution was not due to the locations of visual receptive fields mapped outside the behavioral context of maze solution, in that receptive field centers and preferred path directions were not spatially aligned. Finally, neurons tuned to path direction were not present in area 7a when a na?ve animal viewed the same visual maze stimuli but did not solve them. These data support the hypothesis that path tuning in parietal cortex is not due to the lower level visual features of the maze stimulus, but rather is associated with maze solution, and as such, reflects a cognitive process applied to a complex visual stimulus.     

Effects of synaptic activity on dendritic spine motility of developing cortical layer v pyramidal neurons

It is increasingly clear that dendritic spines play an important role in compartmentalizing post-synaptic signals and that their dynamic morphological properties have functional consequences. Here, we examine this issue using two-photon microscopy to characterize spine motility on layer V pyramidal neurons in acute slices of the developing mouse cortex. In this system, all spine classes except filopodia become less dynamic as development proceeds. General manipulations of activity (TTX or KCl treatment) do not alter spine dynamics, although increased glutamatergic transmission (AMPA or NMDA treatment) stabilizes developing cortical spines. These effects on spine dynamics do not appear to be related to AMPA or NMDA receptor expression as assessed with immunolabeling, as there is no correlation between spine motility and AMPA (GluR1/2) or NMDA (NR1/NR2B) receptor subunit expression on a spine by spine basis. These results indicate that activity through glutamatergic synapses is important for regulating spine motility in the developing mouse cortex, and that the relative complement of receptors, while different across morphological classifications, cannot account for differences in dynamic structural changes in dendritic spines.     

Regional brain activation during concurrent implicit and explicit sequence learning

We used event-related fMRI to identify the brain regions engaged during explicit and implicit sequence learning (ESL and ISL, respectively). Twenty-four subjects performed a concurrent ESL and ISL task. Behavior showed learning in both conditions. Prefrontal (PFC), striatal, anterior cingulate cortex (ACC) and visual regions (V1, V2 and V3) were engaged during both ESL and ISL. With ESL there was increased activity in the visual regions on the predictable (i.e. learned pattern) trials. With ISL, however, there was a relative decrease in activity in visual regions. The opposite patterns in the visual regions highlight the different effects of ESL and ISL. The learning process was distinguished from the result of learning, by fitting subjects' functional magnetic resonance imaging data to their learning curve. This analysis revealed more extensive PFC activity during ESL and caudal ACC activity specific for the result of learning analysis, when the expected response was violated. Our results suggest a relative dissociation of the brain regions engaged during ESL and ISL, whereby ESL and ISL can be viewed as partially distinct but overlapping parallel processes.     

Regional dendritic and spine variation in human cerebral cortex: a quantitative golgi study

The present study explored differences in dendritic/spine extent across several human cortical regions. Specifically, the basilar dendrites/spines of supragranular pyramidal cells were examined in eight Brodmann's areas (BA) arranged according to Benson's (1993, Behav Neurol 6:75-81) functional hierarchy: primary cortex (somatosensory, BA3-1-2; motor, BA4), unimodal cortex (Wernicke's area, BA22; Broca's area, BA44), heteromodal cortex (supple- mentary motor area, BA6beta; angular gyrus, BA39) and supramodal cortex (superior frontopolar zone, BA10; inferior frontopolar zone, BA11). To capture more general aspects of regional variability, primary and unimodal areas were designated as low integrative regions; heteromodal and supramodal areas were designated as high integrative regions. Tissue was obtained from the left hemisphere of 10 neurologically normal individuals (M(age) = 30 +/- 17 years; five males, five females) and stained with a modified rapid Golgi technique. Ten neurons were sampled from each cortical region (n = 800) and evaluated according to total dendritic length, mean segment length, dendritic segment count, dendritic spine number and dendritic spine density. Despite considerable inter-individual variation, there were significant differences across the eight Brodmann's areas and between the high and low integrative regions for all dendritic and spine measures. Dendritic systems in primary and unimodal regions were consistently less complex than in heteromodal and supramodal areas. The range within these rankings was substantial, with total dendritic length in BA10 being 31% greater than that in BA3-1-2, and dendritic spine number being 69% greater. These findings demonstrate that cortical regions involved in the early stages of processing (e.g. primary sensory areas) generally exhibit less complex dendritic/spine systems than those regions involved in the later stages of information processing (e.g. prefrontal cortex). This dendritic progression appears to reflect significant differences in the nature of cortical processing, with spine-dense neurons at hierarchically higher association levels integrating a broader range of synaptic input than those at lower cortical levels.     

The effects of age on the cells in layer 1 of primate cerebral cortex

Although there is significant thinning of layer 1 with age in both occipital area 17 and prefrontal area 46 of the rhesus monkey, there are no significant age-related changes in the numbers of neurons, astrocytes, or microglia and oligodendrocytes in this layer. A few profiles of degenerating neurons have been encountered in old monkeys, but they are uncommon. Some astrocytes undergo hypertrophy with age, as evidenced by the increased thickness of the glial limiting membrane, and throughout layer 1 the amount of filaments in the cytoplasm of both their cell bodies and processes increases. The astrocytes also come to contain phagocytic material in the old monkeys, as do the microglial cells. We have previously shown that in both areas 17 and 46 there is an age-related loss of synapses from layer 1 and a concomitant loss of dendritic branches from the apical tufts of pyramidal cells from layer 1. These may be the sources of the material phagocytosed by the astrocytes and microglial cells.     

Differential expression patterns of striate cortex-enriched genes among Old World, New World, and prosimian primates

A group of 5 genes, OCC1, testican-1, testican-2, 5-HT1B, and 5-HT2A, are selectively expressed in layer 4 (4C of Brodmann) of striate cortex (visual area V1) of both Old World macaques and New World marmoset monkeys. The expression of these genes is activity dependent, as expression is reduced after blocking retinal activity. Surprisingly, the pronounced expression pattern has not been found in rodents or carnivores. Thus, these genes may be highly expressed in V1 of some but perhaps not all primates. Here, we compared the gene expression in members of 3 major branches of primate evolution: prosimians, New World monkeys, and Old World monkeys. Although the expression pattern of 5-HT1B was well conserved, those of the other genes varied from the least distinct in prosimian galagos to successively more in New World owl monkeys, marmosets, squirrel monkeys, and Old World macaque monkeys. In owl monkeys, the expression of 5-HT2A was significantly reduced by monocular tetrodotoxin injection, while those of OCC1 and 5-HT1B were not. Thus, we propose that early primates had low levels of expression and higher levels emerged with anthropoid primates and became further enhanced in the Old World catarrhine monkeys that are more closely related to humans.     

Neural responses during interception of real and apparent circularly moving stimuli in motor cortex and area 7a

We recorded the neuronal activity in the arm area of the motor cortex and parietal area 7a of two monkeys during interception of stimuli moving in real and apparent motion. The stimulus moved along a circular path with one of five speeds (180-540 degrees/s), and was intercepted at 6 o'clock by exerting a force pulse on a semi-isometric joystick which controlled a cursor on the screen. The real stimuli were shown in adjacent positions every 16 ms, whereas in the apparent motion situation five stimuli were flashed successively at the vertices of a regular pentagon. The results showed, first, that a group of neurons in both areas above responded not only during the interception but also during a NOGO task in which the same stimuli were presented in the absence of a motor response. This finding suggests these areas are involved in both the processing of the stimulus as well as in the preparation and production of the interception movement. In addition, a group of motor cortical cells responded during the interception task but not during a center --> out task, in which the monkeys produced similar force pulses towards eight stationary targets. This group of cells may be engaged in sensorimotor transformations more specific to the interception of real and apparent moving stimuli. Finally, a multiple regression analysis revealed that the time-varying neuronal activity in area 7a and motor cortex was related to various aspects of stimulus motion and hand force in both the real and apparent motion conditions, with stimulus-related activity prevailing in area 7a and hand-related activity prevailing in motor cortex. In addition, the neural activity was selectively associated with the stimulus angle during real motion, whereas it was tightly correlated to the time-to-contact in the apparent motion condition, particularly in the motor cortex. Overall, these observations indicate that neurons in motor cortex and area 7a are processing different parameters of the stimulus depending on the kind of stimulus motion, and that this information is used in a predictive fashion in motor cortex to trigger the interception movement.