Deficits in attentional orienting following damage to the perirhinal or postrhinal cortices

The authors used an associative learning paradigm to assess the effects of perirhinal or postrhinal damage on attentional orienting. Control rats and rats with lesions of either the perirhinal or postrhinal cortex initially displayed high levels of orienting behavior (rearing) to presentations of a light cue. Continued nonreinforced presentations resulted in normal habituation of the response. In addition, orienting reemerged in control rats, indicating increased attentional processing of the cue. This conditioned orienting did not reemerge in rats with either perirhinal or postrhinal lesions, providing direct evidence that the rat perirhinal and postrhinal cortices each play a role in attention. These results are consistent with an emerging view that some structures within the medial temporal lobe have nonmnemonic functions.     

Topographic maps of visual spatial attention in human parietal cortex

Functional magnetic resonance imaging (fMRI) was used to measure activity in human parietal cortex during performance of a visual detection task in which the focus of attention systematically traversed the visual field. Critically, the stimuli were identical on all trials (except for slight contrast changes in a fully randomized selection of the target locations) whereas only the cued location varied. Traveling waves of activity were observed in posterior parietal cortex consistent with shifts in covert attention in the absence of eye movements. The temporal phase of the fMRI signal in each voxel indicated the corresponding visual field location. Visualization of the distribution of temporal phases on a flattened representation of parietal cortex revealed at least two distinct topographically organized cortical areas within the intraparietal sulcus (IPS), each representing the contralateral visual field. Two cortical areas were proposed based on this topographic organization, which we refer to as IPS1 and IPS2 to indicate their locations within the IPS. This nomenclature is neutral with respect to possible homologies with well-established cortical areas in the monkey brain. The two proposed cortical areas exhibited relatively little response to passive visual stimulation in comparison with early visual areas. These results provide evidence for multiple topographic maps in human parietal cortex.     

The human mast cell receptor binding site maps to the third constant domain of immunoglobulin E.

The characterization of the site on the IgE molecule which accommodates the high affinity receptor for IgE (Fc epsilon RI) should allow the design of IgE analogues which can be utilized to block allergic responses. Using chimeric human IgE molecules in which different constant region domains were exchanged with their murine homologues, we demonstrate here that the C epsilon 3 in its native configuration is essential for the binding to the alpha subunit of the human Fc epsilon RI. Deletion of the human C epsilon 2 from such chimeric molecules did not impair their ability to interact with the Fc epsilon RI, indicating that C epsilon 2 is not directly involved in the human Fc epsilon RI binding site and that C epsilon 3 alone is necessary and sufficient to account for most of the human Fc epsilon RI-binding capacity.     

Object exploration and reactions to spatial and nonspatial changes in hooded rats following damage to parietal cortex or hippocampal formation.

Hooded rats with bilateral lesions of the anterior part of the hippocampal formation (HIP), anterior region of the posterior parietal cortex (APC), or posterior region of the posterior parietal cortex (PPC) were compared with controls for their exploration of 5 objects in an open field, habituation of locomotion and object investigation, and response to spatial and nonspatial change. First, all groups displayed habituation of both locomotor and exploratory activity. Second, controls selectively reexplored displaced objects, and APC-lesioned rats reexplored all objects, whereas PPC- and HIP-lesioned rats failed to react to the spatial change. Third, a novel object induced reexploration in all groups. The results are consistent with the roles of the HIP and PPC in spatial information processing. Moreover, the APC and PPC are involved in attentional effortful processing and visuospatial information processing necessary for spatial representation, respectively.     

Deficits in fixed-interval performance following prenatal and postnatal lead exposure.

Female rats were exposed daily to 750 mg/kg of lead acetate via a restricted watering schedule for 70-80 days prior to mating and then throughout pregnancy and nursing. At weaning, litters from half of the lead dams were placed directly on treatment for the duration of the experiment. These manipulations yielded 3 groups: Group Pb/Pb, offspring exposed during pre- and postweaning periods; Group Pb/C, offspring exposed only during preweaning periods: and Group C/C, control offspring. Beginning at 42-49 days of age, postnatal, offspring were shaped to bar press under a fixed-interval, 1-min schedule (FI1) and then given 20 sessions, each 45 min in length. Analyses revealed that Group Pb/Pb received fewere reinforcements across sessions than the other 2 groups, which did not differ. However, when the Pb/Pb offspring did receive reinforcement, they exhibited the scalloped pattern of responding characteristic of fixed-interval schedules.     

Plasticity of tonotopic maps in auditory midbrain following partial cochlear damage in the developing chinchilla

 There is substantial reorganization of the midbrain (inferior colliculus) tonotopic map following neonatally induced partial cochlear lesions in the chinchilla. The most obvious feature of this remapping is a large ”iso-frequency” region in the ventral sector of the central nucleus of inferior colliculus (ICC). Neurons in this region exhibit similar threshold and tuning properties, with a common characteristic frequency which corresponds to the high-frequency audiometric cutoff. This overrepresented frequency range also corresponds to the high-frequency border of the cochlear lesion. Alterations to the tonotopic map corresponding to lower frequencies, in more dorsal regions of ICC, depend on the extent and degree of the cochlear lesion. When there is minimal damage to apical (low-frequency) cochlear areas, the dorsal ICC has relatively normal frequency representations. With more extensive apical cochlear lesions there is a corresponding disruption of ICC tonotopic representation of the low frequencies. We conclude that the tonotopic map within the ICC can become (re)organized postnatally according to the abnormal pattern of neural activity from the auditory periphery. Similar reorganization can be expected to occur in human infants with a partial cochlear hearing loss from birth. Received: 2 February 1998 / Accepted: 3 July 1998     

Contralateral visual hemifield representations in the human pulvinar nucleus

The pulvinar is a major nucleus of the thalamus. Macaque pulvinar includes two subregions that are connected to the visual cortex and are retinotopically organized, but the organizing principles of the visual portions of the human pulvinar are unknown. We employed two tasks to address the question of whether human pulvinar exhibits spatial organization using event-related functional magnetic resonance imaging. The first was a global-motion discrimination with a rich visual stimulus and the second a luminance-discrimination task of similar difficulty that used a minimal visual stimulus. Both tasks required central fixation and covert peripheral attention. A group analysis of blood-oxygen-level-dependent responses elicited in the motion-discrimination task revealed activity bilaterally in the ventral pulvinar (z = 2 in Talairach space). Clear position specificity was observed with activity elicited only by contralateral stimuli. Ipsilateral stimuli caused suppression. This locus of activity is distinct from the more dorsal (z = 10) region of the pulvinar that has previously been reported to be visually responsive but not retinotopic. In the luminance-discrimination task, similar activity was seen, but it was weaker and detectable only in the left pulvinar. In additional experiments with no task, passively viewed global-motion stimuli also activated the ventral pulvinar bilaterally. Our results show for the first time a distinct, bilateral visual representation in human inferior pulvinar that appears to be contralaterally organized.     

Topographic maps in human frontal cortex revealed in memory-guided saccade and spatial working-memory tasks

We used fMRI at 3 Tesla and improved spatial resolution (2 x 2 x 2 mm(3)) to investigate topographic organization in human frontal cortex using memory-guided response tasks performed at 8 or 12 peripheral locations arranged clockwise around a central fixation point. The tasks required the location of a peripheral target to be remembered for several seconds after which the subjects either made a saccade to the remembered location (memory-guided saccade task) or judged whether a test stimulus appeared in the same or a slightly different location by button press (spatial working-memory task). With these tasks, we found two topographic maps in each hemisphere, one in the superior branch of precentral cortex and caudalmost part of the superior frontal sulcus, in the region of the human frontal eye field, and a second in the inferior branch of precentral cortex and caudalmost part of the inferior frontal sulcus, both of which greatly overlapped with activations evoked by visually guided saccades. In each map, activated voxels coded for saccade directions and memorized locations predominantly in the contralateral hemifield with neighboring saccade directions and memorized locations represented in adjacent locations of the map. Particular saccade directions or memorized locations were often represented in multiple locations of the map. The topographic activation patterns showed individual variability from subject to subject but were reproducible within subjects. Notably, only saccade-related activation, but no topographic organization, was found in the region of the human supplementary eye field in dorsomedial prefrontal cortex. Together these results show that topographic organization can be revealed outside sensory cortical areas using more complex behavioral tasks.     

Functional imaging of the human lateral geniculate nucleus and pulvinar

In the human brain, little is known about the functional anatomy and response properties of subcortical nuclei containing visual maps such as the lateral geniculate nucleus (LGN) and the pulvinar. Using functional magnetic resonance imaging (fMRI) at 3 tesla (T), collective responses of neural populations in the LGN were measured as a function of stimulus contrast and flicker reversal rate and compared with those obtained in visual cortex. Flickering checkerboard stimuli presented in alternation to the right and left hemifields reliably activated the LGN. The peak of the LGN activation was found to be on average within +/-2 mm of the anatomical location of the LGN, as identified on high-resolution structural images. In all visual areas except the middle temporal (MT), fMRI responses increased monotonically with stimulus contrast. In the LGN, the dynamic response range of the contrast function was larger and contrast gain was lower than in the cortex. Contrast sensitivity was lowest in the LGN and V1 and increased gradually in extrastriate cortex. In area MT, responses were saturated at 4% contrast. Response modulation by changes in flicker rate was similar in the LGN and V1 and occurred mainly in the frequency range between 0.5 and 7.5 Hz; in contrast, in extrastriate areas V4, V3A, and MT, responses were modulated mainly in the frequency range between 7.5 and 20 Hz. In the human pulvinar, no activations were obtained with the experimental designs used to probe response properties of the LGN. However, regions in the mediodorsal right and left pulvinar were found to be consistently activated by bilaterally presented flickering checkerboard stimuli, when subjects attended to the stimuli. Taken together, our results demonstrate that fMRI at 3 T can be used effectively to study thalamocortical circuits in the human brain.     

Cognitive impairment following frontal lobe damage and its relevance to human amnesia

Whether frontal lobe pathology can account for some of the cognitive impairment observed in amnesic patients with Korsakoff's syndrome was investigated. Various cognitive and memory tests were given to patients with circumscribed frontal lobe lesions, patients with Korsakoff's syndrome, non-Korsakoff amnesic patients, and control Ss. Patients with frontal lobe lesions were not amnesic. Nevertheless they exhibited 2 deficits that were also exhibited by patients with Korsakoff's syndrome but not by other amnesic patients: (a) impairment on the Wisconsin Card Sorting Test and (b) impairment on the Initiation and Preservation subscale of the Dementia Rating Scale. Thus, frontal lobe pathology can explain some of the cognitive deficits observed in patients with Korsakoff's syndrome.     

Telencephalic origin of pulvinar neurons in the fetal human brain

Summary Our previous autoradiographic study of fetal human brain fragments exposed supravitally to thymidine-H³ had suggested that the primitive ependyma of the third ventricle ceases neuron production at a time when the pulvinar is only slightly developed. We sought a source of additional pulvinar neurons by examining serial horizontal sections through brains of 5- to 40-week fetuses. In the nearby telencephalon lies the ganglionic eminence, composed of germinal and immature cells coating the fetal corpus striatum and bulging into the lateral ventricle. It contains numerous proliferating cells to the end of gestation. Young cells appear to stream from it, cross beneath the sulcus terminalis to enter the diencephalon, and form a hitherto-undescribed layer, the corpus gangliothalamicus. This structure is found consistently just under the external surface of the developing pulvinar of fetuses from the 18th to the 34th weeks of gestation. A 22-week specimen freshly prepared by the rapid Golgi method shows a progression of cell forms from simple elongate bipolar cells in the part of the corpus gangliothalamicus closest to the telencephalon, through a series of gradations to multipolar young neurons in the most medial and deep parts of the structure, where it merges into the pulvinar proper. We conclude that many of the neurons of the pulvinar, a very large component of the human thalamus, arise in the telencephalon and migrate to the diencephalon during the fifth to eight lunar months of gestation.Supported by research grant 5 RO1-NB07053-02 from the National Institute of Neurological Diseases and Stroke, National Institutes of Health     

Saccadic eye movements following kainic acid lesions of the pulvinar in monkeys

Summary Behavioral and anatomical experiments have suggested that the pulvinar might play a role in the generation of saccadic eye movements to visual targets. To test this idea, we trained monkeys to make visually-guided saccades by requiring them to detect the dimming of a small target. We used three different saccade paradigms. On single-step trials, saccades were made from a central fixation point (FP) to a target at 12, 24 or 36° to the left or right. On overlap trials, the FP remained lit during presentation of a target at 12 or 24°. On double-step trials, the target stepped first to 24°, and then back to 12° on the same side. Animals were trained to criterion, received kainic acid lesions of the pulvinar, and were retested on all three tasks. The lesions were very large, destroying almost all of the visually responsive pulvinar. They also encroached on the lateral geniculate nucleus, thereby producing small foveal scotomas, and this resulted in some behavioral changes, including difficulty in maintaining fixation on the target and in detecting its dimming. Results on the saccade tests suggest that the pulvinar is not crucial for initiation of saccadic eye movements. Saccade latency and amplitude were unimpaired on both single-step and overlap trials. Saccadic performance was also normal on double-step trials. In a second experiment, we measured the average length of fixations during spontaneous viewing of a complex visual scene. Fixation lengths did not differ from those of unoperated control monkeys. We suggest that the neglect, increased saccadic latencies, and prolonged fixations attributed to pulvinar damage in previous studies were probably the result instead of inadvertent damage to tectal afferents. The present results, together with single unit data, point to a role for the pulvinar not in the generation of saccades, but rather in the integration of saccadic eye movements with visual processing.     

Behavioral recovery on a spatial variant of the Konorski test following prefrontal damage in dogs

Two groups of naive dogs were trained on a spatial variant of the Konorski Test, in which pairs of successively presented auditory location cues were differentiated in a conditioning procedure. Instrumental leg flexion to positive stimuli was reinforced by food. Combinations of four different location cues were used as compound conditioned stimuli (CS). In group AA a positive CS involved two identical, successively presented location cues, Sx-Sx, separated by an interval of 5 s, whereas the negative CS was formed by two different successive location, cues, Sx-Sy, with the same intercomponent interval. In group AB positive and negative combinations of location cues were reversed: Sx-Sy combinations were positive, while Sx-Sx were negative. Solving the task required a comparison of the second CS component with the memory trace left by the first component of CS. The two groups did not differ in reaching the preoperative criterion, but the response time was significantly shorter in the AA group. Prefrontal proreal lesion produced a significant but transient impairment of performance in both groups. The third group, trained on a simple differentiation task with single location cues, was completely unimpaired.     

Interdependence of spatial and temporal coding in the auditory midbrain

To date, most physiological studies that investigated binaural auditory processing have addressed the topic rather exclusively in the context of sound localization. However, there is strong psychophysical evidence that binaural processing serves more than only sound localization. This raises the question of how binaural processing of spatial cues interacts with cues important for feature detection. The temporal structure of a sound is one such feature important for sound recognition. As a first approach, we investigated the influence of binaural cues on temporal processing in the mammalian auditory system. Here, we present evidence that binaural cues, namely interaural intensity differences (IIDs), have profound effects on filter properties for stimulus periodicity of auditory midbrain neurons in the echolocating big brown bat, Eptesicus fuscus. Our data indicate that these effects are partially due to changes in strength and timing of binaural inhibitory inputs. We measured filter characteristics for the periodicity (modulation frequency) of sinusoidally frequency modulated sounds (SFM) under different binaural conditions. As criteria, we used 50% filter cutoff frequencies of modulation transfer functions based on discharge rate as well as synchronicity of discharge to the sound envelope. The binaural conditions were contralateral stimulation only, equal stimulation at both ears (IID = 0 dB), and more intense at the ipsilateral ear (IID = -20, -30 dB). In 32% of neurons, the range of modulation frequencies the neurons responded to changed considerably comparing monaural and binaural (IID =0) stimulation. Moreover, in approximately 50% of neurons the range of modulation frequencies was narrower when the ipsilateral ear was favored (IID = -20) compared with equal stimulation at both ears (IID = 0). In approximately 10% of the neurons synchronization differed when comparing different binaural cues. Blockade of the GABAergic or glycinergic inputs to the cells recorded from revealed that inhibitory inputs were at least partially responsible for the observed changes in SFM filtering. In 25% of the neurons, drug application abolished those changes. Experiments using electronically introduced interaural time differences showed that the strength of ipsilaterally evoked inhibition increased with increasing modulation frequencies in one third of the cells tested. Thus glycinergic and GABAergic inhibition is at least one source responsible for the observed interdependence of temporal structure of a sound and spatial cues.     

Deficits in consummatory responses to regulatory challenges following basal ganglia lesions in rats

This study analyzed the responses of rats with electrolytic lesions of the globi pallidi or of three different striatal regions to various regulatory challenges. Pallidal lesions abolished drinking during intracellular dehydration, feeding during glucoprivation (2-DG), and sodium appetite normally induced by desoxycorticosterone. Striatal lesions in the central part of the structure sparing the pallidum impaired feeding during 2-DG and the induction of sodium appetite, but did not alter drinking produced by intracellular dehydration. Rats with anterior or posterior striatal damage were not reliably different from controls on any of these measure. Animals with pallidal, central, and posterior striatal damage had abnormally low water intakes during food deprivation. the number of regulatory impairments found was related to the duration of aphagia initially following surgery. These results suggest that components of the lateral hypothalamic syndrome can be produced by lesions along the nigrostriatal dopamine trajectory which spare hypothalamic tissue, and indicate that anatomical specificity may exist within the striatum for regulating these behavioral responses.     

Deficits in avoidance learning following septal lesions in the albino rat

In the first experiment, rats with large septal lesions (n = 20) and control animals (n = 30) were tested for spontaneous alternation (SA), one way active avoidance (1W-AA), passive avoidance (PA), and two way active avoidance (2W-AA) learning. The acquisition of 1W-AA was tested at three shock levels. Large septal lesions reduced alternation rate in SA test and impaired the acquisition of 1W-AA at all 3 shock levels used. The escape learning was poor and there was no change in freezing behaviour. In the PA test, septal lesion animals showed faster approach to food before shock was introduced, accepted more shocks, were more active and showed less freezing and conflict behavior in the postshock period. Acquisition of 2W-AA was improved by septal lesions, and there was no change in escape learning or freezing behavior. In the 2nd experiment, rats with small lesions in the lateral (n = 6) or medial (n = 4) septum and controls (n = 8) were tested on the same four tasks. Both lateral and medial septal lesions reduced alternation rate and impaired the acquisition of 1W-AA. Only the medial lesions affected escape learning. There was no effect of either lesion in the PA test but both of them enhanced learning of 2W-AA. Selective septal lesions did not change freezing behavior in any task. The behavioral changes following septal lesions seem task dependent. The deficits observed may reflect an impaired ability to use discriminative cues available in the avoidance tasks.     

Characterization of pretectal-nuclear-complex afferents to the pulvinar in the cat

We investigated anatomical and physiological properties of the projection from the pretectal nuclear complex (PNC) to the ipsilateral lateral posterior–pulvinar complex in the cat. After Phaseolus vulgaris leucoagglutinin injections into the PNC, the majority (70%) of anterogradely labeled terminals was localized in the pulvinar proper, the remaining 30% were scattered in the lateral and medial portions of the LP. No PNC neuron retrogradely labeled from the pulvinar was found to also express glutamic acid decarboxylase (GAD) mRNA, although a large number of neurons carrying the GAD label were found in close vicinity. In contrast, 69% of retrogradely labeled PNC cells also displayed glutamate-like immunoreactivity. Twenty-six out of 96 (27%) visually responsive pulvinar neurons were orthodromically activated by electrical stimulation of the ipsilateral PNC at latencies between 1 and 10 ms (median 1.9 ms). All orthodromically activated neurons responded well to the onset and offset of large visual stimuli and to sudden stimulus shifts. Whenever a saccadic eye movement was executed, these neurons were also activated, except during saccades in darkness. The comparison of saccade-evoked response with responses to visual stimuli that elicit similar retinal image shifts revealed that pretectorecipient pulvinar neurons also seem to receive a saccade-related non-visual input. All response properties correspond to those of a specific class of pulvinar neurons that have been termed "SV" neurons because they respond to visual stimulation as well as during saccades. They also closely resemble response properties of PNC neurons that project to the ipsilateral pulvinar. The results support the proposal that PNC cells not only directly activate their postsynaptic target neurons in the pulvinar, but that they also provide a visual input to these neurons that greatly contributes to their response characteristics. Electronic Publication     

Selection and coordination of human locomotor forms following cerebellar damage

We have previously shown that control subjects use two distinct temporal strategies when stepping on an inclined surface during walking: one for level and 10 degrees surfaces and another for 20 and 30 degrees surfaces. These two temporal strategies were characterized by systematic shifts in the timing of muscle activity and peak joint angles. We examined whether cerebellar subjects with mild to moderate gait ataxia were impaired in their ability to select these two temporal strategies, adjust peak joint angle amplitudes, and/or adjust one joint appropriately with respect to movements and constraints at another joint. Subjects walked on a level surface and on different wedges (10, 20, and 30 degrees ) presented in the context of level walking. In a single trial, a subject walked on a level surface in approach to a wedge, took a single step on the wedge, and continued walking on an elevated level surface beyond the wedge. Cerebellar subjects used two temporal strategies, one for the level and 10 degrees surfaces and another for 20 and 30 degrees surfaces. Cerebellar strategies were similar to those used by controls except for the timing of ankle-joint movement on the steeper wedges. Cerebellar subjects adjusted the peak amplitudes of individual joint angles normally, with the exception of peak ankle plantarflexion. However, they exhibited greater trial-to-trial variability of peak hip and knee joint angles that increased as a function of wedge inclination. The most substantial deficit noted in the cerebellar group was in the relative movement of multiple joints. Cerebellar subjects demonstrated multijoint coordination deficits in all conditions, although these deficits were most pronounced during stance on the steeper wedges. On the 30 degrees wedge, cerebellar subjects showed abnormal relative movement of hip, knee, and ankle joints and the most substantial decomposition of movement. We speculate that to simplify multijoint control, cerebellar subjects decomposed their movement by fixing the ankle joint in a dorsiflexed position on the steepest wedges. Our results suggest that the cerebellum may not be critical in selecting the basic motor patterns for the two temporal strategies because cerebellar subjects produced appropriate timing shifts at most joints. Instead, our data suggest that the cerebellum is most critical for adjusting the relative movement of multiple joints, especially to accommodate external constraints.     

Object exploration, habituation, and response to a spatial change in rats following septal or medial frontal cortical damage

Normal rats and rats sustaining septal or medial frontal cortex lesions were compared in experiments dealing with object exploration, habituation, and reaction to novelty (measured by renewed exploration following a spatial change). Normal rats exhibited high levels of initial exploratory activity which decreased over time. Following a spatial change, they reinvestigated both the displaced object and the nondisplaced ones. Frontal animals were similar to normal subjects with respect to their initial exploratory level and habituation pattern. However, frontal rats reexplored only the displaced object and completely neglected the nondisplaced ones. In contrast, the behavioral pattern displayed by septal rats was markedly different from that of normal and frontal animals. Septal rats had lower levels of initial exploratory activity, did not habituate over time, and failed to react to either displaced or nondisplaced objects. These results show that although the septo-hippocampal complex and the medial frontal cortex may share some common function in spatially organized behaviors, both structures have unique roles. Some hypotheses about the possible basic processes subtended by the septal area or the medial frontal cortex are briefly mentioned and discussed.