Thalamic and temporal cortex input to medial prefrontal cortex in rhesus monkeys

 To determine the source of thalamic input to the medial aspect of the prefrontal cortex, we injected retrograde tracers (wheat germ agglutinin conjugated to horseradish peroxidase, nuclear yellow, and/or bisbenzimide) into seven medial prefrontal sites and anterograde tracers (tritiated amino acids) into six thalamic sites, in a total of nine rhesus monkeys. The results indicated that ventral precallosal and subcallosal areas 14 and 25, and the ventral, subcallosal part of area 32, all receive projections from the mediodorsal portion of the magnocellular division of the medial dorsal nucleus (MDmc). The dorsal, precallosal part of area 32 receives projections mainly from the dorsal portion of the parvocellular division of the medial dorsal nucleus (MDpc), which also provides some input to area 14. Polar area 10 receives input from both MDpc and the densocellular division of the medial dorsal nucleus (MDdc), as does supracallosal area 24. Area 24 receives additional input from the anterior medial nucleus and midline nuclei. All medial prefrontal cortical areas were also found to receive projections from a number of cortical regions within the temporal lobe, such as the temporal pole, superior temporal gyrus, and parahippocampal gyrus. Areas 24, 25, and 32 receive, in addition, input from the entorhinal cortex. Combining these results with prior anatomical and behavioral data, we conclude that medial temporal areas that are important for object recognition memory send information directly both to dorsal medial prefrontal areas 24 and 32 and to ventral medial prefrontal areas 14 and 25. Only the latter two areas have additional access to this information via projections from the mediodorsal part of MDmc. Received: 1 March 1996 / Accepted: 13 January 1997     

Topography of commissural fibers of the prefrontal cortex in the rhesus monkey

Summary The topography of commissural fibers of the prefrontal cortex was studied in the rhesus monkey using autoradiography. Commissural fibers originating in the medial prefrontal and the caudal orbital regions course through the anterior portion of the genu and the rostrum of the corpus callosum, while those from the arcuate concavity travel at the rostral border of the body of the corpus callosum. Fibers emanating from the peri-principalis region occupy an intermediate position in the genu of the corpus callosum.     

Functional interactions among neurons in inferior temporal cortex of the awake macaque

Summary Functional interactions among inferior temporal cortex (IT) neurons were studied in the awake, fixating macaque monkey during the presentation of visual stimuli. Extracellular recordings were obtained simultaneously from several microelectrodes, and in many cases, spike trains from more than one neuron were extracted from each electrode by the use of spike shape sorting technology. Functional interactions between pairs of neurons were measured using cross-correlation. Discharge patterns of single neurons were evaluated using auto-correlation and PST histograms. Neurons recorded on the same electrode (within about 100 n) had more similar stimulus selectivity and were more likely to show functional interactions than those recorded on different electrodes spaced about 250 to 500 microns apart. Most neurons tended to fire in bursts tens to hundreds of milliseconds in duration, and asynchronously from the stimulus induced rate changes. Correlated neuronal firing indicative of shared inputs and direct interactions was observed. Occurrence of shared input was significantly lower for neuron pairs recorded on different electrodes than for neurons recorded on the same electrode. Direct connections occurred about as often for neurons on different electrodes as for neurons on the same electrode. These results suggest that input projections are usually restricted to less than 500 m patches and are then distributed over greater distances by intrinsic connections. Measurements of synaptic contribution suggest that typically more than 5 near-simultaneous inputs are required to cause an IT neuron to discharge.     

Laminar origin of striatal and thalamic projections of the prefrontal cortex in rhesus monkeys

Prefrontostriatal and prefrontothalamic connections in rhesus monkeys have been shown to be organized in a topographic manner. These projections originate largely from infragranular layers V and VI. To examine whether the striatal and thalamic connections from the prefrontal cortex arise from separate neuronal populations or are collateralized, two different fluorescent retrograde tracers (diamidino yellow and fast blue) were injected into topographically similar regions of the head of the caudate nucleus and the mediodorsal nucleus in the same animal. The results show that although prefrontostriatal and prefrontothalamic projections arise from similar topographic regions, their laminar origins are distinctive. The connections to the head of the caudate nucleus originate mainly from layer Va, to a lesser extent from layer Vb, with a minor contribution from layers III and VI. In contrast, the projections to the mediodorsal nucleus emanate largely from layer VI, and also from layer Vb. Only occasional double-labeled neurons were observed, indicating that prefrontostriatal and prefrontothalamic connections originate from separate neuronal populations. The differential laminar distributions of neurons projecting to the head of the caudate nucleus and the mediodorsal nucleus suggest that these structures may receive independent types of information from the prefrontal cortex.     

Free behavior of rhesus monkeys following lesions of the dorsolateral and orbital prefrontal cortex in infancy

Summary The present study sought to determine whether differential effects could be found in the free behavior of early-operated monkeys with selective removal of the dorsolateral and orbital prefrontal cortex. The early-operated monkeys were first observed in their home cages in stable living groups which had existed for at least 6 1/2 months (together condition) and then again immediately after they had been separated from one another (separated condition). The major results indicated that the monkeys with orbital lesions differed from unoperated controls in more ways than did the dorsolateral monkeys: in the together condition, the orbital group slept more and were more sedentary even when awake; in the separated condition, by contrast, they became hyperactive and spent most of their time in locomotion. These findings lend support to the notion, derived from studies of cognitive behavior in infant-operated monkeys, that functions of the orbital cortex, unlike those of the dorsolateral cortex, are not spared following brain damage in infancy. Further, the nature of the behavior exhibited by the impaired monkeys led to the suggestion that the orbital cortex may play an important role in modulating arousal mechanisms in the infant and adult monkey alike.Now at: Department of Psychiatry and Regional Primate Research Center, University of Washington Medical School, Seattle, USA.Now at: Department of Biostatistics, Johns Hopkins University, Baltimore. Maryland, USA.     

Perseverative interference in monkeys following selective lesions of the inferior prefrontal convexity

Summary Monkeys with lesions of the inferior frontal convexity were impaired relative to controls in retaining an auditory frequency differentiation (although subsequent thresholds were normal) and in learning object and spatial reversals. Performance was characterized by perseverative interference, a frontal symptom which now seems attributable to damage to the inferior convexity.This work was performed while the senior author was a visiting scientist at NIMH, Bethesda supported by postdoctoral fellowships from the Federation of University Women and the Science Research Council. Portions of the paper were presented at the meetings of the Eastern Psychological Association, 1966. We thank H.E. Rosvold for his active encouragement of this research.     

Comparison of human infants and rhesus monkeys on Piaget's AB task: evidence for dependence on dorsolateral prefrontal cortex

Summary This paper reports evidence linking dorsolateral prefrontal cortex with one of the cognitive abilities that emerge between 7.5–12 months in the human infant. The task used was Piaget's Stage IV Object Permanence Test, known as AB (pronounced A not B). The AB task was administered (a) to human infants who were followed longitudinally and (b) to intact and operated adult rhesus monkeys with bilateral prefrontal and parietal lesions. Human infants displayed a clear developmental progression in AB performance, i.e., the length of delay required to elicit the AB error pattern increased from 2–5 s at 7.5–9 months to over 10 s at 12 months of age. Monkeys with bilateral ablations of dorsolateral prefrontal cortex performed on the AB task as did human infants of 7.5–9 months; i.e., they showed the AB error pattern at delays of 2–5 s and chance performance at 10 s. Unoperated and parietally operated monkeys succeeded at delays of 2, 5, and 10 s; as did 12 month old human infants. AB bears a striking resemblance to Delayed Response, the classic test for dorsolateral prefrontal function in the rhesus monkey, and indeed performance on AB and Delayed Response in the same animals in the present study was fully comparable. These findings provide direct evidence that AB performance depends upon dorsolateral prefrontal cortex in rhesus monkeys and indicates that maturation of dorsolateral prefrontal cortex may underlie the developmental improvement in AB performance of human infants from 7.5–12 months of age. This improvement marks the development of the ability to hold a goal in mind in the absence of external cues, and to use that remembered goal to guide behavior despite the pull of previous reinforcement to act otherwise. This confers flexibility and freedom to choose and control what one does.     

Corticocortical projections to the prefrontal cortex in the rhesus monkey investigated with horseradish peroxidase techniques

The corticocortical afferents innervating the prefrontal cortex in the monkey were studied by means of the retrograde axonal transport of horseradish peroxidase. After injection of small amounts (0.3-0.5 microliter) of this enzyme into various parts of the prefrontal cortex, many labeled neurons (mostly pyramids of 15-25 microns in diameter) were found in various cortical regions of the ipsilateral hemisphere. A small part of the prefrontal cortex received fibers from other parts of the same cortex. For example, area 8 receives many fibers from both the rostral part of area 9 and a small area adjacent to the inferior branch of the arcuate sulcus. On the other hand, area 9 in the inferior prefrontal convexity receives fibers from localized parts of areas 8 and 9 in the dorsolateral convexity as well as from area 6. It is also apparent that association connections from the dorsolateral to the inferior convexity are stronger than those going in the opposite direction. The prefrontal afferents from other cortical regions include many fibers originating from the posterior association cortex as well as some fibers arising in the cingulate and orbital gyri. The prefrontal cortex does not receive direct corticocortical fibers from the motor and "primary" sensory cortices. There is a topographic pattern in the prefrontal projections from the cortical walls (STs area) surrounding the superior temporal sulcus. Thus, the caudal half of the STs area projects to area 8 and a small adjacent part of area 9. The dorsal wall of the rostral half of the STs area projects to areas 9-12, the fundus to the inferior convexity, and the ventral wall only to the caudal part of the convexity. Projections from the circumjacent association cortex of the STs area to the prefrontal cortex as well as to the STs area are likewise found to be topographically organized. This suggests that certain parts of the posterior association cortex projecting to particular areas of the prefrontal cortex, also send fibers to those parts of the STs area which project to the same prefrontal areas.     

Visual cortex ablation and thresholds for successively presented stimuli in rhesus monkeys: II. Hue

Summary Rhesus monkeys were trained to discriminate successively presented hues. The smallest difference they could reliably detect was determined before and after either inferotemporal ablation, or a lesion intended to remove as much as possible of prestriate area V4 (Zeki, 1973).As a group, the animals with lesions of V4 showed good but not perfect retention of their preoperative performance, and their thresholds were unaltered. The inferotemporal group showed no retention of the simplest successive task, red versus green, but after relearning their thresholds too were unaltered. It appears that animals without inferotemporal cortex can form precise internal representations of hues, and that the basis of the inferotemporal learning impairment may depend upon the nature of the stimuli to be discriminated.     

Projections from the medial nucleus of the inferior pulvinar complex to the middle temporal area of the visual cortex

Medial, central and posterior nuclei have been previously identified within the inferior pulvinar complex of owl monkeys (Lin & Kaas, 1979). In the present experiments injections of [³H]-proline into the posterior thalamus, including the medial nucleus, produced densely labeled terminals in the middle temporal area of the visual cortex (Allman & Kaas, 1971). Injections of the retrograde tracer, horseradish peroxidase, into the middle temporal area labeled most of the neurons in the medial nucleus and only occasional neurons in the central and posterior nuclei. The posterior nucleus appeared to project to the cortex rostral to the middle temporal area in the temporal lobe, and the central nucleus projects to the visual cortex caudal to the middle temporal area. We conclude that the middle temporal area is the major cortical target of the medial nucleus in the inferior pulvinar complex and that the central and posterior nuclei have other cortical targets.Thus, these findings support the view that the inferior pulvinar complex consists of three distinct nuclei, which should lead to further progress in understanding its connections and functions.     

Responses of neurons in the inferior temporal cortex in short term and serial recognition memory tasks

Summary Gaffan and Weiskrantz (1980) and Mishkin (1982) have shown that lesions to the inferior temporal visual cortex can impair the performance of serial visual recognition memory tasks. In order to provide evidence on whether the inferior temporal visual cortex contains a mechanism which enables memory to span the intervening items in a serial recognition task, or whether the inferior temporal cortex is merely afferent to such recent memory mechanisms, we analysed the activity of single neurons in the inferior temporal visual cortex and the adjacent cortex in the superior temporal sulcus in both delayed match to sample and serial recognition memory tasks. In the serial recognition task, various numbers of stimuli intervened between the first and second presentations of a stimulus. A considerable proportion (64/264 or 26%) of visually responsive inferotemporal neurons showed a different response to the novel and familiar presentations of a stimulus in the serial recognition memory task, and often a corresponding difference in response between the sample and match presentations of a stimulus in the delayed match to sample task. For the majority of neurons this difference was not sustained across even one intervening stimulus in the serial recognition task, and no neurons bridged more than 2 intervening stimuli. These results show that neurons in the inferior temporal cortex have responses which would be useful for a short term visual memory for stimuli, but would not be useful in recency memory tasks in which more than one stimulus intervenes between the first and second presentations of a stimulus. In this investigation, neurons were recorded both in the cortex on the inferior temporal gyrus (commonly called inferior temporal visual cortex, and consisting of areas TE3,TE2 and TE1 of Seltzer and Pandya 1978), and in the cortex in the adjacent anterior part of the superior temporal sulcus, in which a number of different temporal cortical visual areas have now been described (see Baylis et al. 1986).     

Subcortical afferents to the prefrontal cortex in rabbits

Summary The origins of cells projecting to the prefrontal cortex of the rabbit were studied, using horseradish peroxidase (HRP) technique. HRP injected into the prefrontal cortex labeled cells in the basal forebrain, lateral hypothalamus, raphe nuclei and locus coeruleus area on both sides. Labeled cells appeared also in the nucleus medialis dorsalis of the thalamus and other thalamic nuclei on the injection side.     

Interactions of visual stimuli in the receptive fields of inferior temporal neurons in awake macaques

Summary Monkeys were trained to perform a fixation task and a visual discrimination task. During the fixation task, one or two light bars were presented at different positions in the receptive fields of TE neurons. During the discrimination task, the animal was required to detect the positive stimulus when one or two of the paired small colored spots or two-dimensional patterns were presented. In both behavioral conditions, when the two light stimuli were presented simultaneously, almost none of the TE neurons showed an increase in responding over the single stimulus condition; the response was usually similar or less than the stronger response in the single stimulus condition. In the neurons that responded selectively to the discriminanda during the discrimination task, various interactions between the two antagonistic stimuli occurred depending on the location or the effectiveness of the two stimuli. These results may be related to gain control mechanisms in the wide receptive fields of TE neurons.     

Posterior cingulate and retrosplenial cortex connections of the caudal superior temporal region in the rhesus monkey

The rostral part of the superior temporal gyrus (STG) is known to project to ventral temporal cortex, but analogous paralimbic connections of the caudal STG have received comparatively less attention. The present study of the connections of the STG with medial paralimbic cortex showed that the caudal part of the STG (area Tpt and caudal area paAlt) and adjacent cortex of the upper bank of the superior temporal sulcus (caudal area TPO) have reciprocal connections with the caudal cingulate gyrus (areas 23a, b and c), retrosplenial cortex (area 30), and area 31. By contrast, cortex of the rostral-to-mid STG (areas Ts2, Ts3, and the rostral part of area paAlt) and adjacent upper bank of the STS (mid-area TPO) have few, if any, such interconnections. It is suggested that this connectional pattern of the caudal STG is consistent with its putative role of localizing sounds in space as proposed in recent studies.     

Object-centered encoding by face-selective neurons in the cortex in the superior temporal sulcus of the monkey

Summary Neurophysiological studies have shown that some neurons in the cortex in the superior temporal sulcus and in the inferior temporal cortex respond to faces. To determine if some face responsive neurons encode stimuli in an object-centered coordinate system rather than a viewer-centered coordinate system, a large number of neurons were tested for sensitivity to head movement in 3 macaque monkeys. Ten neurons responded only when a head undergoing rotatory movements was shown. All of these responded to a particular movement independently of the orientation of the moving head in relation to the viewer, maintaining specificity even when the moving head was inverted or shown from the back, thereby reversing viewer-centered movement vectors. This was taken as evidence that the movement was encoded in object-centered coordinates. In tests of whether there are neurons in this area which respond differently to the faces of different individuals relatively independently of viewing angle, it was found that a further 18 neurons responded more to one static face than another across different views. However, for 16 of these 18 cells there was still some modulation of the neuronal response with viewing angle. These 16 neurons thus did not respond perfectly in relation to the object shown independently of viewing angle, and may represent an intermediate stage between a viewercentered and an object-centered representation. In the same area as these neurons, other cells were found which responded on the basis of viewercentered coordinates. These neurophysiological findings provide evidence that some neurons in the inferior temporal visual cortex respond to faces (or heads) on the basis of object-centered coordinates, and that others have responses which are intermediate between object-centered and viewer-centered representations. The results are consistent with the hypothesis that object-centered representations are built in the inferior temporal visual cortex.     

Spatio-temporal integration in the substrate for self-stimulation of the prefrontal cortex

The number of stimulation pulses required to maintain a half maximal rate of self-stimulation of the prefrontal cortex (PFC) was determined for various currents. Over a restricted range, the effects of decreasing the stimulation frequency could be compensated for by increasing the current. This finding cannot easily be reconciled with the hypothesis that the rewarding impact of PFC stimulation is unaffected by increments in current. The minimum current that would support self-stimulation of the PFC at high frequencies was larger than has been reported at medial forebrain bundle sites.     

Interactions between two different visual stimuli in the receptive fields of inferior temporal neurons in macaques during matching behaviors

Macaque monkeys were trained to determine whether shapes or colors of two visual stimuli were the same or different (matched/non-matched). Two stimuli were presented at different locations while the monkey fixated a small spot. In one paradigm, two stimuli were presented simultaneously for 0.5 s (Sml-SO task). In the other paradigm, one of the stimuli was turned on 0.5 s before the onset of another stimulus, then the two stimuli were present for the following 0.5 s (Scc SO task). The aim of the later task was to analyze the responses of TE neurons to a single presentation of each stimulus and the effects of successive onsets of two stimuli. Of 232 responsive neurons tested in both tasks, 143 showed a significant selectivity between paired stimuli (termed selective neurons). During the Sml-SO task, some selective neurons showed a larger response to the different (non-matched) stimuli than to the double optimal stimuli (matched), even though one of the different stimuli was inhibitory. This effect was more prominent in neurons that showed a smaller response to the double presentations of the optimal stimulus than to the single presentation. Since another group of selective neurons showed smaller responses for the different stimuli, the average response amplitudes were similar between the identical and the different stimuli. During the Scc-SO task, when the optimal stimulus was turned on after the non-optimal stimulus (non-matched), the response to the second stimulus was mostly enhanced above the response level to the single presentation of the first stimulus. Since the responses to the second stimulus identical to the first stimulus tended to decrease, the difference in the responses between the matched and non-matched stimuli became significantly larger in the Scc-SO task. The reaction times of the monkeys were shorter during the Scc-SO task than the Sml-SO task. These changes in response amplitude between the different and the identical stimuli were not prominent in the non-selective neurons. These results suggest that non-linear interactions between two different stimuli play an important role in the discrimination of groups of visual stimuli, particularly in successive analysis.     

Role of the lateral prefrontal cortex in visual object-based selective attention

We demonstrate that attention to object representations is vitally dependent on the prefrontal cortex. Object-based selective attention was compared in neurologic patients with unilateral damage to either the dorsolateral prefrontal cortex (DLPFC) or the parietal cortex and in healthy controls. Our task required a top–down attentional modulation of object representations in which spatial location played no role. All groups could invoke top–down object-based selection, but the DLPFC patients showed a selective deficit when target stimuli were in the hemifield contralateral to the lesioned hemisphere. Our findings indicate that in the healthy brain, anterior cortical mechanisms are crucial for attending to object-centered representations, whereas posterior cortical mechanisms are necessary for attending to objects at locations in the visual scene.

Transient projections from the fronto-parietal and temporal cortex to areas 17, 18 and 19 in the kitten

Summary Using the retrograde tracers, fast blue and horseradish peroxidase we have shown the presence of projections from extensive regions of the frontoparietal and temporal cortex to areas 17, 18 and 19 in the newborn kitten. These projections are transitory as they do not exist in the adult cat. The anterograde transport of horseradish peroxidase conjugated with wheat germ agglutinin after injections in frontoparietal and temporal cortex revealed that these transitory projections terminate in the gray matter and that they could therefore play a functional role in the development of the visual cortex.