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.     

Color discrimination involves ventral and dorsal stream visual areas

We used positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) in human subjects to investigate whether the ventral and dorsal visual stream cooperate when active judgements about color have to be made. Color was used as the attribute, because it is processed primarily in the ventral stream. The centrally positioned stimuli were equiluminant shades of brown. The successive color discrimination task was contrasted to a dimming detection task, in which retinal input was identical but with double the number of motor responses. The stimulus presentation rate was parametrically varied and a constant performance level was obtained for all conditions. The visual activation sites were identified by retinotopic mapping and cortical flattening. In addition, one psychophysical and two fMRI experiments were performed to control for differences in visuospatial attention and motor output. Successive color discrimination involved early visual areas, including V1 and VP and the ventral color-responsive region, as well as anterior and middle dorsal intraparietal sulcus, dorsal premotor cortex and pre-SMA. Cortical regions involved in dimming detection and motor output included area V3A, hMT/V5+, lateral occipital sulcus, posterior dorsal intraparietal sulcus, primary motor cortex and SMA. These experiments demonstrated that even with color as the attribute, successive discrimination, in which a decision process has to link visual signals to motor responses, involves both ventral and dorsal visual stream areas.     

Enhanced temporal non-linearities in human object-related occipito-temporal cortex

To what extent does neural activation in human visual cortex follow the temporal dynamics of the optical retinal stimulus? Specifically, to what extent does stimulus evoked neural activation persist after stimulus termination? In the present study, we used functional magnetic resonance imaging (fMRI) to explore the resulting temporal non-linearities across the entire constellation of human visual areas. Gray-scale images of animals, houses and faces were presented at two different presentation rates - 1 and 4 Hz - and the fMRI signal was analyzed in retinotopic and in high order occipito-temporal visual areas. In early visual areas and the motion sensitive area MT/V5, a fourfold increase in stimulus presentation rate evoked a twofold increase in signal amplitude. However, in high order visual areas, signal amplitude increased only by 25%. A control experiment ruled out the possibility that this difference was due to signal saturation ('ceiling') effects. A likely explanation for the stronger non-linearities in occipito-temporal cortex is a persistent neuronal activation that continues well after stimulus termination in the 1 Hz condition. These persistent activations might serve as a short term (iconic) memory mechanism for preserving a trace of the stimulus even in its absence and for future integration with temporally correlated stimuli. Two alternative models of persistence (inhibitory and excitatory) are proposed to explain the data.     

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.     

Estrogen replacement increases spinophilin-immunoreactive spine number in the prefrontal cortex of female rhesus monkeys

While studies have shown that estrogen affects hippocampal spine density and function, behavioral studies in humans and nonhuman primates have also implicated the prefrontal cortex in the effects of estrogen on cognition. However, the potential for similar estrogen-induced increases in spines and synapses in the prefrontal cortex has not been investigated in primates. Moreover, it is not known if such an estrogen effect would be manifested throughout the neocortex or primarily in the regions involved in cognition. Therefore, we investigated the effects of estrogen on dendritic spines in the prefrontal and primary visual cortices of young rhesus monkeys. Young female monkeys were ovariectomized and administered either estradiol cypionate or vehicle by intramuscular injection. Using an antibody against the spine-associated protein, spinophilin, spine numbers were estimated in layer I of area 46 and in layer I of the opercular portion of area V1 (V1o). Spine numbers in layer I of area 46 were significantly increased (55%) in the ovariectomy + estrogen group compared to the ovariectomy + vehicle group, yet spine numbers in layer I of area V1o were equivalent across the two groups. The present results suggest that estrogen's effects on synaptic organization influence select neocortical layers and regions in a primate model, and provide a morphological basis for enhanced prefrontal cortical functions following estrogen replacement.     

Cortical projections of area V2 in the macaque

To determine the locus, extent and topograhic organization of cortical projections of area V2, we injected tritiated amino acids under electrophysiological control into 15 V2 sites in 14 macaques. The injection sites included the foveal representation and representations ranging from central to far peripheral eccentricities in both the upper and lower visual fields. The results indicated that all V2 sites project topographically back to V1 and forward to V3, V4 and MT. There is also a topographically organized projection from V2 to V4t, but this projection is limited to the lower visual field representation. V2 thus appears to project to virtually all the visual cortex within the occipital lobe. In addition to these projections to occipital visual areas, V2 sites representing eccentricities of approximately 30 degrees and greater project to three visual areas in parietal cortex-the medial superior temporal (MST), parieto-occipital (PO) and ventral intraparietal (VIP) areas. This peripheral field representation of V2 also projects to area VTF, a visual area located in area TF on the posterior parahippocampal gyrus. Projections from the peripheral field representation of V2 of parietal areas could provide a direct route for rapid activation of circuits serving spatial vision and spatial attention.      

Color architecture in alert macaque cortex revealed by FMRI

The contribution that different brain areas make to primate color vision, especially in the macaque, is debated. Here we used functional magnetic resonance imaging in the alert macaque, giving a whole brain perspective of color processing in the healthy brain. We identified color-biased and luminance-biased activity and color-afterimage activity. Color-biased activity was found in V1, V2, and parts of V4 and not in V3a, MT, or other dorsal stream areas, in which a luminance bias predominated. Color-biased activity and color-afterimage activity were also found in a region on the posterior bank of the superior temporal sulcus. We review anatomical and physiological studies that describe this region, PITd, and postulate that it is distinct from areas V4 and TEO. When taken together with single-unit studies and lesion studies, our results suggest that color depends on a connected ventral-stream pathway involving at least V1, V2, V4, and PITd.     

The distribution of immunoreactivity for intracellular androgen receptors in the cerebral cortex of hormonally intact adult male and female rats: localization in pyramidal neurons making corticocortical connections

Gonadal hormones are known to broadly influence cortical information processing. Findings from this study in rats suggest that for androgens, this influence may include stimulation of underlying corticocortical connections. First, immunoreactivity for intracellular androgen receptors, while present in all regions and layers examined, was found to be particularly abundant in sensory and motor regions, and within these, within their major pyramidal cell layers, i.e. layers II/III and V/VI. Double labeling immunocytochemical studies for androgen receptors and for neuron-specific markers then confirmed that the majority of receptor-bearing cortical cells were pyramidal neurons. Finally, combined analyses of cortical receptor immunoreactivity and retrograde labeling produced by tracer injections made in specific subcortical (caudate, nucleus accumbens, superior colliculus, thalamus) areas yielded only isolated examples of receptor/tracer overlap. However, injections made within the cortex itself (sensory, motor, associational areas) retrogradely labeled cortical cells some 50% or more - especially within injected hemispheres, were receptor-immunoreactive. Thus, the regional, laminar, and cellular distributions of immunoreactivity in the rat cerebrum largely identify pyramidal neurons with connectional signatures aligning intracellular androgen receptors with the local, associational, and to a lesser degree, callosal circuits that interlink territories of the cortical mantle and play key roles in cortical information processing.     

Degradation of signal timing in cortical areas V1 and V2 of senescent monkeys

Senescence in monkeys results in a degradation of the functional properties of cortical cells as well as prolonged hyperactivity. We have now compared the spontaneous and visually evoked activity levels, as well as the visual response latencies of cells in cortical areas V1 and V2 of young and very old monkeys. We found that V1 cells within layer 4 exhibit normal latencies. In contrast, in other parts of V1 and throughout V2 hyperactivity in old monkeys is accompanied by dramatic delays in both the intracortical and intercortical transfer of information. Extrastriate cortex (area V2) is affected more severely than striate cortex (V1). Delayed information processing in cerebral cortex should contribute to the declines in cortical function that accompany old age.     

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.     

Cortical connections of area V4 in the macaque

To determine the locus, full extent, and topographic organization of cortical connections of area V4 (visual area 4), we injected anterograde and retrograde tracers under electrophysiological guidance into 21 sites in 9 macaques. Injection sites included representations ranging from central to far peripheral eccentricities in the upper and lower fields. Our results indicated that all parts of V4 are connected with occipital areas V2 (visual area 2), V3 (visual area 3), and V3A (visual complex V3, part A), superior temporal areas V4t (V4 transition zone), MT (medial temporal area), and FST (fundus of the superior temporal sulcus [STS] area), inferior temporal areas TEO (cytoarchitectonic area TEO in posterior inferior temporal cortex) and TE (cytoarchitectonic area TE in anterior temporal cortex), and the frontal eye field (FEF). By contrast, mainly peripheral field representations of V4 are connected with occipitoparietal areas DP (dorsal prelunate area), VIP (ventral intraparietal area), LIP (lateral intraparietal area), PIP (posterior intraparietal area), parieto-occipital area, and MST (medial STS area), and parahippocampal area TF (cytoarchitectonic area TF on the parahippocampal gyrus). Based on the distribution of labeled cells and terminals, projections from V4 to V2 and V3 are feedback, those to V3A, V4t, MT, DP, VIP, PIP, and FEF are the intermediate type, and those to FST, MST, LIP, TEO, TE, and TF are feedforward. Peripheral field projections from V4 to parietal areas could provide a direct route for rapid activation of circuits serving spatial vision and spatial attention. By contrast, the predominance of central field projections from V4 to inferior temporal areas is consistent with the need for detailed form analysis for object vision.     

Cortical specialization for processing first- and second-order motion

Distinct mechanisms underlying the visual perception of luminance-(first-order) and contrast-defined (second-order) motion havebeen proposed from electrophysiological, human psychophysicaland neurological studies; however a cortical specializationfor these mechanisms has proven elusive. Here human brain imaging combined with psychophysical methods was used to assess corticalspecializations for processing these two kinds of motion. Acommon stimulus construction was employed, controlling for differencesin spatial and temporal properties, psychophysical performanceand attention. Distinct cortical regions have been found preferentiallyprocessing either first- or second-order motion, both in occipitaland parietal lobes, producing the first physiological evidencein humans to support evidence from psychophysical studies, brainlesion sites and computational models. These results provideevidence for the idea that first-order motion is computed inV1 and second-order motion in later occipital visual areas,and additionally suggest a functional dissociation between thesetwo kinds of motion beyond the occipital lobe.     

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.     

Attention to form or surface properties modulates different regions of human occipitotemporal cortex

We carried out 2 functional magnetic resonance imaging experiments to investigate the cortical mechanisms underlying the contribution of form and surface properties to object recognition. In experiment 1, participants performed same-different judgments in separate blocks of trials on pairs of unfamiliar "nonsense" objects on the basis of their form, surface properties (i.e., both color and texture), or orientation. Attention to form activated the lateral occipital (LO) area, whereas attention to surface properties activated the collateral sulcus (CoS) and the inferior occipital gyrus (IOG). In experiment 2, participants were required to make same-different judgments on the basis of texture, color, or form. Again attention to form activated area LO, whereas attention to texture activated regions in the IOG and the CoS, as well as regions in the lingual sulcus and the inferior temporal sulcus. Within these last 4 regions, activation associated with texture was higher than activation associated with color. No color-specific cortical areas were identified in these regions, although parts of V1 and the cuneus yielded higher activation for color as opposed to texture. These results suggest that there are separate form and surface-property pathways in extrastriate cortex. The extraction of information about an object's color seems to occur relatively early in visual analysis as compared with the extraction of surface texture, perhaps because the latter requires more complex computations.     

Perception-related modulations of local field potential power and coherence in primary visual cortex of awake monkey during binocular rivalry

Cortical synchronization at gamma-frequencies (35-90 Hz) has been proposed to define the connectedness among the local parts of a perceived visual object. This hypothesis is still under debate. We tested it under conditions of binocular rivalry (BR), where a monkey perceived alternations among conflicting gratings presented singly to each eye at orthogonal orientations. We made multi-channel microelectrode recordings of multi-unit activity (MUA) and local field potentials (LFP) from striate cortex (V1) during BR while the monkey indicated his perception by pushing a lever. We analyzed spectral power and coherence of MUA and LFP over 4-90 Hz. As in previous work, coherence of gamma-signals in most pairs of recording locations strongly depended on grating orientation when stimuli were presented congruently in both eyes. With incongruent (rivalrous) stimulation LFP power was often consistently modulated in consonance with the perceptual state. This was not visible in MUA. These perception-related modulations of LFP occurred at low and medium frequencies (< 30 Hz), but not at gamma-frequencies. Perception-related modulations of LFP coherence were also restricted to the low-medium range. In conclusion, our results do not support the expectation that gamma-synchronization in V1 is related to the perceptual state during BR, but instead suggest a perception-related role of synchrony at low and medium frequencies.     

Category-specific conceptual processing of color and form in left fronto-temporal cortex

To investigate the cortical basis of color and form concepts, we examined event-related functional magnetic resonance imaging (fMRI) responses to matched words related to abstract color and form information. Silent word reading elicited activity in left temporal and frontal cortex, where category-specific activity differences were also observed. Whereas color words preferentially activated anterior parahippocampal gyrus, form words evoked category-specific activity in fusiform and middle temporal gyrus as well as premotor and dorsolateral prefrontal areas in inferior and middle frontal gyri. These results demonstrate that word meanings and concepts are not processed by a unique cortical area, but by different sets of areas, each of which may contribute differentially to conceptual semantic processing. We hypothesize that the anterior parahippocampal activation to color words indexes computation of the visual feature conjunctions and disjunctions necessary for classifying visual stimuli under a color concept. The predominant premotor and prefrontal activation to form words suggests action-related information processing and may reflect the involvement of neuronal elements responding in an either-or fashion to mirror neurons related to adumbrating shapes.     

The intrinsic shape of human and macaque primary visual cortex

Previous studies have reported considerable variability in primary visual cortex (V1) shape in both humans and macaques. Here, we demonstrate that much of this variability is due to the pattern of cortical folds particular to an individual and that V1 shape is similar among individual humans and macaques as well as between these 2 species. Human V1 was imaged ex vivo using high-resolution (200 microm) magnetic resonance imaging at 7 T. Macaque V1 was identified in published histological serial section data. Manual tracings of the stria of Gennari were used to construct a V1 surface, which was computationally flattened with minimal metric distortion of the cortical surface. Accurate flattening allowed investigation of intrinsic geometric features of cortex, which are largely independent of the highly variable cortical folds. The intrinsic shape of V1 was found to be similar across human subjects using both nonparametric boundary matching and a simple elliptical shape model fit to the data and is very close to that of the macaque monkey. This result agrees with predictions derived from current models of V1 topography. In addition, V1 shape similarity suggests that similar developmental mechanisms are responsible for establishing V1 shape in these 2 species.     

Retinotopic organization in human visual cortex and the spatial precision of functional MRI

A method of using functional magnetic resonance imaging (fMRI) to measure retinotopic organization within human cortex is described. The method is based on a visual stimulus that creates a traveling wave of neural activity within retinotopically organized visual areas. We measured the fMRI signal caused by this stimulus in visual cortex and represented the results on images of the flattened cortical sheet. We used the method to locate visual areas and to evaluate the spatial precision of fMRI. Specifically, we: (i) identified the borders between several retinotopically organized visual areas in the posterior occipital lobe; (ii) measured the function relating cortical position to visual field eccentricity within area V1; (iii) localized activity to within 1.1 mm of visual cortex; and (iv) estimated the spatial resolution of the fMRI signal and found that signal amplitude falls to 60% at a spatial frequency of 1 cycle per 9 mm of visual cortex. This spatial resolution is consistent with a linespread whose full width at half maximum spreads across 3.5 mm of visual cortex.      

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 perceptual and functional consequences of parietal top-down modulation on the visual cortex

The posterior parietal cortex (PPC) has been proposed to play a critical role in exerting top-down influences on occipital visual areas. By inducing activity in the PPC (angular gyrus) using transcranial magnetic stimulation (TMS), and using the phosphene threshold as a measure of visual cortical excitability, we investigated the functional role of this region in modulating the activity of the visual cortex. When triple-pulses of TMS were applied over the PPC unilaterally, the intensity of stimulation required to elicit a phosphene from the visual cortex (area V1/V2) was reduced, indicating an increase in visual cortical excitability. The increased excitability that was observed with unilateral TMS was abolished when TMS was applied over the PPC bilaterally. Our results provide a demonstration of the top-down modulation exerted by the PPC on the visual cortex and show that these effects are subject to interhemispheric competition.