Uncovering a Role for the Dorsal Hippocampal Commissure in Recognition Memory.

The dorsal hippocampal commissure (DHC) is a white matter tract that provides interhemispheric connections between temporal lobe brain regions. Despite the importance of these regions for learning and memory, there is scant evidence of a role for the DHC in successful memory performance. We used diffusion-weighted magnetic resonance imaging (DW-MRI) and white matter tractography to reconstruct the DHC in both humans (in vivo) and nonhuman primates (ex vivo). Across species, our findings demonstrate a close consistency between the known anatomy and tract reconstructions of the DHC. Anterograde tract-tracer techniques also highlighted the parahippocampal origins of DHC fibers in nonhuman primates. Finally, we derived diffusion tensor MRI metrics from the DHC in a large sample of human subjects to investigate whether interindividual variation in DHC microstructure is predictive of memory performance. The mean diffusivity of the DHC correlated with performance in a standardized recognition memory task, an effect that was not reproduced in a comparison commissure tract-the anterior commissure. These findings highlight a potential role for the DHC in recognition memory, and our tract reconstruction approach has the potential to generate further novel insights into the role of this previously understudied white matter tract in both health and disease.

Thalamocortical Connectivity and Microstructural Changes in Congenital and Late Blindness.

There is ample evidence that the occipital cortex of congenitally blind individuals processes nonvisual information. It remains a debate whether the cross-modal activation of the occipital cortex is mediated through the modulation of preexisting corticocortical projections or the reorganisation of thalamocortical connectivity. Current knowledge on this topic largely stems from anatomical studies in animal models. The aim of this study was to test whether purported changes in thalamocortical connectivity in blindness can be revealed by tractography based on diffusion-weighted magnetic resonance imaging. To assess the thalamocortical network, we used a clustering method based on the thalamic white matter projections towards predefined cortical regions. Five thalamic clusters were obtained in each group representing their cortical projections. Although we did not find differences in the thalamocortical network between congenitally blind individuals, late blind individuals, and normal sighted controls, diffusion tensor imaging (DTI) indices revealed significant microstructural changes within thalamic clusters of both blind groups. Furthermore, we find a significant decrease in fractional anisotropy (FA) in occipital and temporal thalamocortical projections in both blind groups that were not captured at the network level. This suggests that plastic microstructural changes have taken place, but not in a degree to be reflected in the tractography-based thalamocortical network.

Distribution and Morphology of Cortical Terminals in the Cat Thalamus from the Anterior Ectosylvian Sulcus.

Two main types of cortical terminals have been identified in the cat thalamus. Large (type II) have been proposed to drive the response properties of thalamic cells while smaller (type I) are believed to modulate those properties. Among the cat's visual cortical areas, the anterior ectosylvian visual area (AEV) is considered as one of the highest areas in the hierarchical organization of the visual system. Whereas the connections from the AEV to the thalamus have been recognized, their nature (type I or II) is presently not known. In this study, we assessed and compared the relative contribution of type I and type II inputs to thalamic nuclei originating from the AEV. The anterograde tracer BDA was injected in the AEV of five animals. Results show that (1) both type I and II terminals from AEV are present in the Lateral Posterior- Pulvinar complex, the lateral median suprageniculate complex and the medial and dorsal geniculate nuclei (2) type I terminals significantly outnumber the type II terminals in almost all nuclei studied. Our results indicate that neurons in the AEV are more likely to modulate response properties in the thalamus rather than to determine basic organization of receptive fields of thalamic cells.

Complex motion sensitivity of neurons, in the visual part of the anterior ectosylvian cortex in cats.

In cats, it is generally believed that the visual part of the anterior ectosylvian cortex (AEV) is involved in motion integration. It receives a substantial proportion of its afferents from cortical (e.g. lateral suprasylvian cortex) and subcortical (e.g. lateral posterior-pulvinar complex) areas known to participate in complex motion analysis. It has been established that a subset of AEV neurons can code the veridical motion of a moving plaid pattern (pattern-motion selectivity). In our study, we have further investigated the possibility that AEV neurons may play a role in higher-order motion processing by studying their responses to complex stimuli which necessitate higher order spatial and temporal integration. Experiments were performed in anesthetized adult cats. Classical receptive fields were stimulated with (1) complex random-dot kinematograms (RDKs), where the individual elements of the pattern do not provide coherent motion cues; (2) optic flow fields which require global spatial integration. We report that a large proportion of AEV neurons were selective to the direction and speed of RDKs. Close to two-thirds of the cells were selective to the direction of optic flow fields with about equal proportions being selective to contraction and expansion. The complex RDK and optic flow responsive units could not be systematically characterized based on their responses to plaid patterns; they were either pattern- or component-motion selective. These findings support the proposal that AEV is involved in higher-order motion processing. Our data suggest that the AEV may be more involved in the analysis of motion of visual patterns in relation to the animal's behavior rather than the analysis of the constituents of the patterns.

TMS of the occipital cortex induces tactile sensations in the fingers of blind Braille readers.

Various non-visual inputs produce cross-modal responses in the visual cortex of early blind subjects. In order to determine the qualitative experience associated with these occipital activations, we systematically stimulated the entire occipital cortex using single pulse transcranial magnetic stimulation (TMS) in early blind subjects and in blindfolded seeing controls. Whereas blindfolded seeing controls reported only phosphenes following occipital cortex stimulation, some of the blind subjects reported tactile sensations in the fingers that were somatotopically organized onto the visual cortex. The number of cortical sites inducing tactile sensations appeared to be related to the number of hours of Braille reading per day, Braille reading speed and dexterity. These data, taken in conjunction with previous anatomical, behavioural and functional imaging results, suggest the presence of a polysynaptic cortical pathway between the somatosensory cortex and the visual cortex in early blind subjects. These results also add new evidence that the activity of the occipital lobe in the blind takes its qualitative expression from the character of its new input source, therefore supporting the cortical deference hypothesis.

Uncertainty about the intensity of impending pain increases ensuing pain responses in congenital blindness.

We have shown that congenitally blind individuals are more sensitive to painful heat compared to their sighted counterparts. This hypersensitivity might be at least partly mediated by psychological and cognitive factors, such as pain expectation and anxiety. Here we investigate whether uncertainty about the intensity of a pending painful stimulus affects pain differently in congenitally blind and sighted control subjects. We measured pain and anxiety in a group of 11 congenitally blind and 11 age- and sex-matched normal sighted control participants. Painful stimuli were delivered under two psychological conditions, whereby participants were either certain or uncertain about the intensity of a pending noxious stimuli. Although both blind and sighted participants had increased anxiety ratings in the uncertain condition, pain ratings increased only in the congenitally blind participants. Our data therefore indicate that increased anxiety levels have a stronger influence on the perceived pain intensity in blind individuals, possibly because they allocate greater attention to signals of external threat.

Melatonin and cortisol profiles in the absence of light perception.

As light plays an important role in the synchronisation of the internal biological clock to the environmental day/night schedule, we compared the 24-h profiles of biological circadian markers in blind and normal sighted individuals. Salivary melatonin and cortisol concentrations were collected every two hours in eleven blind subjects, reporting no conscious light perception, and eleven age- and sex-matched normal sighted controls. Timing of melatonin onset and associated cortisol quiescence period confirm an increased incidence of abnormal circadian patterns in blindness. Additionally, blind subjects showed a greater overall melatonin concentration throughout the 24-h period. Cortisol profiles, including concentration and morning cortisol peaks, on the other hand, did not differ between blind and sighted individuals. These findings support previous reports of an increase in abnormal circadian rhythms and the absence of the entrainment properties of light in blindness.

Distribution, morphology, and synaptic targets of corticothalamic terminals in the cat lateral posterior-pulvinar complex that originate from the posteromedial lateral suprasylvian cortex.

The lateral posterior (LP) nucleus is a higher order thalamic nucleus that is believed to play a key role in the transmission of visual information between cortical areas. Two types of cortical terminals have been identified in higher order nuclei, large (type II) and smaller (type I), which have been proposed to drive and modulate, respectively, the response properties of thalamic cells (Sherman and Guillery [1998] Proc. Natl. Acad. Sci. U. S. A. 95:7121-7126). The aim of this study was to assess and compare the relative contribution of driver and modulator inputs to the LP nucleus that originate from the posteromedial part of the lateral suprasylvian cortex (PMLS) and area 17. To achieve this goal, the anterograde tracers biotinylated dextran amine (BDA) or Phaseolus vulgaris leucoagglutinin (PHAL) were injected into area 17 or PMLS. Results indicate that area 17 injections preferentially labelled large terminals, whereas PMLS injections preferentially labelled small terminals. A detailed analysis of PMLS terminal morphology revealed at least four categories of terminals: small type I terminals (57%), medium-sized to large singletons (30%), large terminals in arrangements of intermediate complexity (8%), and large terminals that form arrangements resembling rosettes (5%). Ultrastructural analysis and postembedding immunocytochemical staining for gamma-aminobutyric acid (GABA) distinguished two types of labelled PMLS terminals: small profiles with round vesicles (RS profiles) that contacted mostly non-GABAergic dendrites outside of glomeruli and large profiles with round vesicles (RL profiles) that contacted non-GABAergic dendrites (55%) and GABAergic dendritic terminals (45%) in glomeruli. RL profiles likely include singleton, intermediate, and rosette terminals, although future studies are needed to establish definitively the relationship between light microscopic morphology and ultrastructural features. All terminals types appeared to be involved in reciprocal corticothalamocortical connections as a result of an intermingling of terminals labelled by anterograde transport and cells labelled by retrograde transport. In conclusion, our results indicate that the origin of the driver inputs reaching the LP nucleus is not restricted to the primary visual cortex and that extrastriate visual areas might also contribute to the basic organization of visual receptive fields of neurons in this higher order nucleus.

Pain hypersensitivity in congenital blindness is associated with faster central processing of C-fibre input.

BACKGROUND: We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear. METHODS: To study the contribution of Aδ- and C-fibres in pain perception, we measured thresholds and response times to selective C- and Aδ-fibre activation in congenitally blind, late blind and normally sighted participants. Ultrafast constant-temperature heat pulses were delivered to the hand with a CO2 laser using an interleaved adaptive double staircase procedure. Participants were instructed to respond as quickly as possible when detecting a laser-induced sensation. We used a 650 ms cut-off criterion to distinguish fast Aδ- from slow C-fibre-mediated sensations. RESULTS: Congenitally blind participants showed significantly faster reaction times to C- but not to Aδ-fibre-mediated sensations. In contrast, thresholds for Aδ- and C-fibre stimulation did not differ between groups. Late blind individuals did not differ from sighted controls in any aspect. A follow-up experiment using only suprathreshold stimuli for Aδ- and C-fibre activation confirmed these findings and further showed that congenitally blind individuals detected significantly more C-fibre-mediated stimuli than sighted controls. A decomposition analysis of the reaction times indicated that the faster response times in the congenitally blind are due to more efficient central processing of C-fibre-mediated sensations. CONCLUSION: The increased sensitivity to painful thermal stimulation in congenital blindness may be due to more efficient central processing of C-fibre-mediated input, which may help to avoid impending dangerous encounters with stimuli that threaten the bodily integrity. WHAT DOES THIS STUDY ADD?: Hypersensitivity to heat pain in congenital blindness is associated with faster responses to C-fibre activation, likely caused by more efficient central processing of C-fibre-mediated input.

Altered sleep-wake patterns in blindness: a combined actigraphy and psychometric study.

OBJECTIVE: Light plays an important role in the synchronization of the internal biological clock and the environmental day/night pattern. Thus, absence of vision is often associated with both increases in reported sleep disturbances and incidence of free-running circadian rhythms. In this study we discuss variability in the sleep-wake pattern between blind and normal-sighted individuals. METHODS: Thirty-day actigraphy recordings were collected from 11 blind individuals without residual light perception and 11 age- and sex-matched normal-sighted controls. From these recordings, we extracted parameters of sleep and wake, including episodes of rest, day-time and night-time sleep periods, and the number of awakenings throughout sleep. A measure of sleep efficiency was derived from these measures for each night-time sleep episode. We also examined complementary measures of sleep quality, using the Pittsburgh Sleep Quality Index, and chronotype, using the Morningness-Eveningness Questionnaire. RESULTS: Although no group differences were found when averaging over the entire recording period, we found a greater variability throughout the 30-days in both sleep efficiency and timing of the night-time sleep episode in blind participants as compared to sighted control participants. We also confirm previous reports of reduced sleep quality in blind individuals. Notably, the variability in sleep efficiency and in the timing of sleep correlated with the severity of sleep disturbances. CONCLUSION: The timing and physiology of sleep are strongly dependent on the endogenous circadian phase; therefore, observed findings support the hypothesis of free-running circadian rhythms as a dominant factor for the sleep disturbances experienced in blindness.

Neural correlates of taste perception in congenital blindness.

Sight is undoubtedly important for the perception and the assessment of the palatability of tastants. Although many studies have addressed the consequences of visual impairment on food selection, feeding behavior, eating habits and taste perception, nothing is known about the neural correlates of gustation in blindness. In the current study we examined brain responses during gustation using functional magnetic resonance imaging (fMRI). We scanned nine congenitally blind and 14 age- and sex-matched blindfolded sighted control subjects, matched in age, gender and body mass index (BMI), while they made judgments of either the intensity or the (un)pleasantness of different tastes (sweet, bitter) or artificial saliva that were delivered intra-orally. The fMRI data indicated that during gustation, congenitally blind individuals activate less strongly the primary taste cortex (right posterior insula and overlying Rolandic operculum) and the hypothalamus. In sharp contrast with results of multiple other sensory processing studies in congenitally blind subjects, including touch, audition and smell, the occipital cortex was not recruited during taste processing, suggesting the absence of taste-related compensatory crossmodal responses in the occipital cortex. These results underscore our earlier behavioral demonstration that congenitally blind subjects have a lower gustatory sensitivity compared to normal sighted individuals. We hypothesize that due to an underexposure to a variety of tastants, training-induced crossmodal sensory plasticity to gustatory stimulation does not occur in blind subjects.

The endocannabinoid system within the dorsal lateral geniculate nucleus of the vervet monkey.

The endocannabinoid system mainly consists of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), their endogenous ligands termed endocannabinoids (eCBs), and the enzymes responsible for the synthesis and degradation of eCBs. These cannabinoid receptors have been well characterized in rodent and monkey retinae. Here, we investigated the expression and localization of the eCB system beyond the retina, namely the first thalamic relay, the dorsal lateral geniculate nucleus (dLGN), of vervet monkeys using immunohistochemistry methods. Our results show that CB1R is expressed throughout the dLGN with more prominent labeling in the magnocellular layers. The same pattern is observed for the degradation enzyme, fatty acid amide hydrolase (FAAH). However, the synthesizing enzyme N-acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) is expressed homogenously throughout the dLGN with no preference for any of the layers. These proteins are weakly expressed in the koniocellular layers. These results suggest that the presence of the eCB system throughout the layers of the dLGN may represent a novel site of neuromodulatory action in normal vision. The larger amount of CB1R in the dLGN magnocellular layers may explain some of the behavioral effects of cannabinoids associated with the integrity of the dorsal visual pathway that plays a role in visual-spatial localization and motion perception.

Binocular Interactions in the Lateral Suprasylvian Visual Area of Strabismic Cats Following Section of the Corpus Callosum.

Visually responsive neurons have been recorded in the lateral suprasylvian area (LSA) of cats raised with either a convergent or a divergent strabismus. In contrast to areas 17 and 18, where many studies have documented a profound loss of binocularly activated neurons following early strabismus, in the LSA the majority of cells could still be binocularly driven. Acute or chronic section of the splenium of the corpus callosum reduced but did not abolish binocularity in the LSA. We propose that the widespread callosal connections, the large size of the receptive fields and the peculiar internal circuitry of the LSA all concur in permitting the maintenance of binocular coding in spite of early misalignment of the eyes.

Size and distribution of retinal ganglion cells in the St. Kitts green monkey (Cercopithecus aethiops sabeus).

The topographical distribution of density and the soma size of retinal ganglion cells (RGCs) were studied in the St. Kitts green monkey (Cercopithecus aethiops sabeus). The total number of RGCs, estimated from light microscopic analysis of wholemounted and of transversely sectioned retinae, ranged between 1,183,721 and 1,273,715 (mean 1,228,646). These estimates are comparable to the number of optic nerve fibres (1,220,000) estimated from semithin sections. The topographic distribution of RGCs shows a strong centroperipheral gradient. The soma size distribution of RGCs in Nissl-stained flatmounts falls within a range of between 5.7 microm and 22.9 microm and is comparable to other primate species. Somata of RGCs were found to be generally smaller within the fovea than in peripheral regions. Ganglion cells, as reported for other diurnal primates, are nonuniformly distributed with a slight nasotemporal elongation of isodensity contours, and they exhibit nasotemporal asymmetry in the frequency distribution of soma size. The topography of the RGC distribution of this semiarboreal, ground-dwelling monkey is similar to what has been found in other diurnal Old World species.

Somatosensory receptive field properties of corpus callosum fibres in the raccoon.

Anatomical studies in a number of species have shown that most areas of the somatosensory cortex are callosally interconnected. This is also true for the raccoon, at least for those parts representing proximal and axial body regions. Electrophysiologically, studies carried out in cats and monkeys have demonstrated that all sensory sub-modalities cross in the callosum. Moreover, cells representing the paws and fingers, though occupying a large portion of areas SI and SII, seem to send proportionately fewer axons through the callosum than axial structures. No comparable study has been carried out in the raccoon. The purpose of the present experiment was therefore to investigate the functional organization of the callosal system in this animal by examining the receptive field properties of the somatosensory fibres crossing in the callosum. Axonal activity was recorded directly through tungsten microelectrodes in the corpus callosum of eight raccoons. Results indicated that somatosensory information is transmitted in its rostral portion. Most receptive fields concerned axial and proximal body regions and the head and face. Some receptive fields represented para-axial regions of the body and a few concerned the hands and fingers. Slowly and rapidly adapting fibres were found, as were all the sensory sub-modalities tested. A substantial proportion of the axons had bilateral receptive fields. These results are discussed in relation to those obtained in other species, with particular reference to: (1) the midline fusion hypothesis of callosal function; (2) the representation within this structure of the distal extremities, and (3) the origin of the bilateral receptive fields.

Stereopsis in the cat: behavioral demonstration and underlying mechanisms.

The neural substrates subserving stereopsis were investigated behaviorally and electrophysiologically in the cat. In one set of studies, we examined behaviorally the ability of normal cats to perceive depth on the sole basis of spatial disparity using random-dot stereograms. Results showed that the animals were able to carry out this discrimination. We then evaluated the contribution of the optic chiasm, the corpus callosum and the primary visual cortex to this function. Results indicated that: (1) chiasma transection drastically reduced the ability of the animals to solve the random-dot problem; (2) a callosal split had little or no effect on their ability to relearn the same discrimination; (3) a section of both the corpus callosum and optic chiasm abolished this ability; and (4) bilateral lesions of areas 17-18 also abolished it. In another set of studies, we examined electrophysiologically the properties of neurons in the various visual cortical areas where disparity-based depth discrimination processes are presumed to take place. We recorded from areas 17, 18 and 19 of normal and split-chiasm cats. Results showed that: (1) the primary visual cortex of the normal cat contained cells sensitive to stimulus disparity; (2) these disparity sensitive neurons were also present in area 19 although in a much lower proportion and were more widely tuned than those in areas 17-18; and (3) following the section of the optic chiasm, there was a significant decrease in the number of disparity sensitive cells in areas 17-18, whereas in area 19 they were nearly completely absent. The results obtained from the lesion studies and from the single unit recording experiments indicate that stereoscopic depth perception is highly dependent in the cat upon the integrity of the through-the-chiasm geniculo-striate pathway and its target primary visual cortex.

REM sleep dream mentation in right hemispherectomized patients.

Investigations of dream mentation in brain damaged patients have shed some light on the controversial issue of cerebral lateralization of dreaming. To examine further the relationships between brain function and dreaming, we studied REM sleep dream recall and content in four patients having undergone right functional or anatomical hemispherectomy and eight matched control subjects. Patients were found to have the capacity to report dreams to much the same extent as control subjects. Further, the patients' dream content was overall similar to that of the control subjects. The results provide strong evidence that dreaming is not a right-hemisphere function, and that the left hemisphere may be more critical for the generation of dreams. In addition, some characteristics of hemispherectomized patients' dream content (characters, smells) are consistent with the possibility that a history of epilepsy may influence REM sleep imagery over the long term.

Responses of neurons in the cat posteromedial lateral suprasylvian cortex to moving texture patterns.

The posteromedial lateral suprasylvian cortex represents a point of convergence between the geniculostriate and extrageniculostriate visual pathways. Given its purported role in motion analysis and the conflicting reports regarding the texture sensitivity of this area, we have investigated the response properties of cells in PMLS to moving texture patterns ("visual noise"). In contrast to previous reports, we have found that a large majority of cells (80.1%) responds to the motion of a texture pattern with sustained discharges. In general, responses to noise were more broadly tuned for direction compared to gratings; however, direction selectivity appeared more pronounced in response to noise. The majority of cells was selective for drift velocity of the noise pattern (mean optimal velocity: 26.7 degrees /s). Velocity tuning was comparable to that of its principal thalamic input, the lateral posterior pulvinar nucleus. In general, responsiveness of cells in the posteromedial lateral suprasylvian cortex increased with increasing texture element size, although some units were tuned to smaller element sizes than the largest presented. Finally, the magnitude of these noise responses was dependent on the area of the visual field stimulated. In general, a stimulus corresponding to roughly twice the size of the receptive field was required to elicit an equivalent half-maximal response to that for gratings. The results of this study indicate that the majority of cells in the posteromedial lateral suprasylvian cortex can be driven by the motion of a fine texture field, and highlight the importance of this area in motion analysis.

Development and regulation of alpha adrenoceptors in kitten visual cortex.

Alpha-1 and alpha-2 adrenergic receptors were localized in developing cat visual cortex by using [3H]prazosin and [3H]rauwolscine, respectively as selective ligands. The effects of neuronal input on the development of the two receptor subtypes were also studied in animals with lesions at various sites within the central visual pathways. Binding densities for both ligands increased during the first few postnatal weeks and declined thereafter. For both receptor subtypes, the highest concentration of binding sites was found in the subplate zone of the cortex in neonatal animals. Both ligands showed their highest concentrations in cortical layer IV beginning at postnatal day 30 and in the superficial cortical layers in adulthood. However, the developmental redistribution of alpha-1 receptors began at earlier ages than that of the alpha-2 sites. The alpha-1 sites were still concentrated in the subplate zone up to 60 days postnatal, while the alpha-2 sites in this region disappeared much earlier. Receptor binding densities were also examined in animals with quinolinic acid lesions within cortex, lesions of the lateral geniculate nucleus and lesions of the optic tract. The results indicate that both alpha-adrenoceptor subtypes were mainly located on cortical cells, and that the absence of neuronal activity during development resulted in a reduction of the binding density for both subtypes in the visual cortex. An additional major reduction in alpha-2 but not alpha-1 binding sites was observed following the lateral geniculate nucleus lesion, suggesting that the development of alpha-2 receptors is also dependent on input from the lateral geniculate nucleus. Removal of the lateral geniculate nucleus early in life resulted in a significant increase in alpha-1 receptors in the subplate region, indicating that receptor densities in this zone may be negatively regulated by the lateral geniculate nucleus afferents. These results show that adrenergic receptors reorganize during postnatal cortical development with a strong temporary concentration in the subplate zone. The reorganization process is heavily influenced by cortical inputs.

Topographical distribution of spindles and K-complexes in normal subjects.

To assess the topographical distribution of sleep spindles and K-complexes, four 15-minute samples of stage 2 sleep in a group of eight healthy young adults were analyzed. Results show that a majority of spindles generated are detected over central regions, and that K-complexes are markedly predominant over prefrontal and frontal regions. These findings are consistent with the single-spindle generator hypothesis and raise questions concerning the Rechtschaffen and Kales rules for scoring K-complexes.