Loss of bone density and bone strength following premenopausal risk-reducing bilateral salpingo-oophorectomy: a prospective controlled study (WHAM Study).

Prophylactic oophorectomy is recommended for women at high risk for ovarian cancer, but the associated impact on bone health is of clinical concern. This prospective, controlled study demonstrated substantial loss of bone density and bone strength following surgical menopause. Postoperative hormone therapy alleviated, but not fully prevented, spinal bone loss. INTRODUCTION: This prospective study investigated bone health in women following premenopausal oophorectomy. METHODS: Dual-energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and pQCT-based finite element analysis (pQCT-FEA) were used to assess bone health between systemic hormone therapy (HT) users and non-users after premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) compared with premenopausal controls over 24-month follow-up. RESULTS: Mean age was 42.4 ± 2.6 years (n = 30) for the surgery group and 40.2 ± 6.3 years for controls (n = 42), and baseline bone measures were similar between groups. Compromised bone variables were observed at 24 months after RRBSO, among which areal bone mineral density (aBMD) at the lumbar spine, tibial volumetric cortical density (Crt vBMD), and tibial bending stiffness (kbend) had decreased by 4.7%, 1.0%, and 12.1%, respectively (all p < 0.01). In non-HT users, significant losses in lumbar spine (5.8%), total hip (5.2%), femoral neck (6.0%) aBMD, tibial Crt vBMD (2.3%), and kbend (14.8%) were observed at 24 months (all p < 0.01). HT prevented losses in kbend, tibial Crt vBMD, and aBMD, except for modest 2.3% loss at the lumbar spine (p = 0.01). CONCLUSION: This prospective, controlled study of bone health following RRBSO or premenopausal oophorectomy demonstrated substantial loss of bone density and bone strength following RRBSO. HT prevented loss of bone density and bone stiffness, although there was still a modest decrease in lumbar spine aBMD in HT users. These findings may inform decision-making about RRBSO and clinical management following premenopausal oophorectomy.

Peripheral quantitative computed tomography (pQCT)-based finite element analysis provides enhanced diagnostic performance in identifying non-vertebral fracture patients compared with dual-energy X-ray absorptiometry.

Due to limitations of the predominant clinical method for diagnosing osteoporosis, an engineering model based on a dedicated CT scanner for bone density and structure was applied in fracture patients and controls. Improved diagnostic performance was observed, which supports its potential use in future research and clinical practice. INTRODUCTION: Dual-energy X-ray absorptiometry (DXA), the predominant clinical method for diagnosing osteoporosis, has limitations in identifying individuals with increased fracture risk. Peripheral quantitative computed tomography (pQCT) provides additional information and can be used to generate finite element (FE) models from which bone strength properties can be estimated. We investigated the ability of pQCT-FE properties to distinguish peripheral low-trauma fracture patients from healthy controls, by comparison with DXA and standard pQCT. METHODS: One hundred and eight fracture patients (77 females aged 67.7 ± 7.9 years, 31 males aged 69.7 ± 8.9 years) were recruited from a hospital fracture liaison service. One hundred and twenty healthy community controls (85 females aged 69.8 ± 8.5 years, 35 males aged 68.9 ± 7.2 years) were recruited. RESULTS: Significant differences between groups were observed in pQCT-FE properties, especially at the 4% tibia site. Fracture odds increased most per standard deviation decrease in pQCT-FE at this location [shear stiffness estimate, kshear, in females, OR = 10.34, 95% CI (1.91, 43.98); bending stiffness estimate, kbend, in males, OR = 8.32, 95% CI (4.15, 33.84)]. Area under the receiver operating characteristics curve (AUROC) was observed to be highest with pQCT-FE properties at 4% the tibia site. In females, this was 0.83 for the pQCT-FE variable kshear, compared with 0.72 for DXA total hip bone density (TH aBMD) and 0.76 for pQCT tibia trabecular density (Trb vBMD); in males, this was 0.81 for the pQCT-FE variable kbend at the 4% tibia site, compared with 0.62 for TH aBMD and 0.71 for Trb vBMD. There were significant differences in AUROC between DXA and pQCT-FE variables in both females (p = 0.02) and males (p = 0.03), while no difference was observed in AUROC between primary pQCT and pQCT-FE variables. CONCLUSIONS: pQCT-FE modeling can provide enhanced diagnostic performance compared with DXA and, given its moderate cost, may be useful in clinical settings.

Visual discrimination of temporal order.

Past research addressed to the minimum temporal separation necessary for the judgment of visual stimulus order has failed to control peripheral adaptation and masking effects. The present study employed pairs of brief stimuli with each member presented to a separate eye; that is, dichoptic presentations. Under these conditions, minimum separations for the correct discrimination of order were found to be far less than those obtained in experiments in which both stimuli were presented to the same eye or to both eyes.

Rapid exercise-induced changes in PGC-1alpha mRNA and protein in human skeletal muscle.

The mRNA of the nuclear coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) increases during prolonged exercise and is influenced by carbohydrate availability. It is unknown if the increases in mRNA reflect the PGC-1alpha protein or if glycogen stores are an important regulator. Seven male subjects [23 +/- 1.3 yr old, maximum oxygen uptake (Vo(2 max)) 48.4 +/- 0.8 ml.kg(-1).min(-1)] exercised to exhaustion ( approximately 2 h) at 65% Vo(2 max) followed by ingestion of either a high-carbohydrate (HC) or low-carbohydrate (LC) diet (7 or 2.9 g.kg(-1).day(-1), respectively) for 52 h of recovery. Glycogen remained depressed in LC (P < 0.05) while returning to resting levels by 24 h in HC. PGC-1alpha mRNA increased both at exhaustion (3-fold) and 2 h later (6.2-fold) (P < 0.05) but returned to rest levels by 24 h. PGC-1alpha protein increased (P < 0.05) 23% at exhaustion and remained elevated for at least 24 h (P < 0.05). While there was no direct treatment effect (HC vs. LC) for PGC-1alpha mRNA or protein, there was a linear relationship between the changes in glycogen and those in PGC-1alpha protein during exercise and recovery (r = -0.68, P < 0.05). In contrast, PGC-1beta did not increase with exercise but rather decreased (P < 0.05) below rest level at 24 and 52 h, and the decrease was greater (P < 0.05) in LC. PGC-1alpha protein content increased in prolonged exercise and remained upregulated for 24 h, but this could not have been predicted by the changes in mRNA. The beta-isoform declined rather than increasing, and this was greater when glycogen was not resynthesized to rest levels.

Bicycle helmet legislation: can we reach a consensus?

Debate continues over bicycle helmet laws. Proponents argue that case-control studies of voluntary wearing show helmets reduce head injuries. Opponents argue, even when legislation substantially increased percent helmet wearing, there was no obvious response in percentages of cyclist hospital admissions with head injury-trends for cyclists were virtually identical to those of other road users. Moreover, enforced laws discourage cycling, increasing the costs to society of obesity and lack of exercise and reducing overall safety of cycling through reduced safety in numbers. Countries with low helmet wearing have more cyclists and lower fatality rates per kilometre. Cost-benefit analyses are a useful tool to determine if interventions are worthwhile. The two published cost-benefit analyses of helmet law data found that the cost of buying helmets to satisfy legislation probably exceeded any savings in reduced head injuries. Analyses of other road safety measures, e.g. reducing speeding and drink-driving or treating accident blackspots, often show that benefits are significantly greater than costs. Assuming all parties agree that helmet laws should not be implemented unless benefits exceed costs, agreement is needed on how to derive monetary values for the consequences of helmet laws, including changes in injury rates, cycle-use and enjoyment of cycling. Suggestions are made concerning the data and methodology needed to help clarify the issue, e.g. relating pre- and post-law surveys of cycle use to numbers with head and other injuries and ensuring that trends are not confused with effects of increased helmet wearing.

The pulvinar and visual salience.

One of the major problems of living in a rich visual environment is deciding which particular object or location should be chosen for complete processing or attention; that is, deciding which object is most salient at any particular time. The pulvinar has enlarged substantially during evolution, although little has previously been known about its function. Recent studies suggest that the pulvinar contains neurons that generate signals related to the salience of visual objects. This evidence includes: (1) anatomical and physiological observations of visual function; (2) augmented responses in the pulvinar for visual stimuli presented in important contexts; (3) suppression of activity for stimuli presented in irrelevant conditions; (4) thalamic modulation producing behavioral changes in cued attention paradigms; and (5) similar changes with visual distracter tasks.

Benefits of including methane measurements in selection strategies.

Estimates of genetic/phenotypic covariances and economic values for slaughter weight, growth, feed intake and efficiency, and three potential methane traits were compiled to explore the effect of incorporating methane measurements in breeding objectives for cattle and meat sheep. The cost of methane emissions was assumed to be zero (scenario A), A$476/t (based on A$14/t CO equivalent and methane's 100-yr global warming potential [GWP] of 34; scenario B), or A$2,580/t (A$30/t CO equivalent combined with methane's 20-yr GWP of 86; scenario C). Methane traits were methane yield (MY; methane production divided by feed intake based on measurements over 1 d in respiration chambers) or short-term measurements of methane production adjusted for live weight (MPadjWt) in grazing animals, e.g., 40-60 min measurements in portable accumulation chambers (PAC) on 1 or 3 occasions, or measurements for 1 wk using a GreenFeed Emissions Monitor (GEM) on 1 or 3 occasions. Feed costs included the cost of maintaining the breeding herd and growth from weaning to slaughter. Sheep were assumed to be grown and finished on pasture (A$50/t DM). Feed costs for cattle included 365 d on pasture for the breeding herd and averages of 200 d postweaning grow-out on pasture and 100 d feedlot finishing. The greatest benefit of including methane in the breeding objective for both sheep and cattle was as a proxy for feed intake. For cattle, 3 GEM measurements were estimated to increase profit from 1 round of selection in scenario A (no payment for methane) by A$6.24/animal (from A$20.69 to A$26.93) because of reduced feed costs relative to gains in slaughter weight and by A$7.16 and A$12.09/animal, respectively, for scenarios B and C, which have payments for reduced methane emissions. For sheep, the improvements were more modest. Returns from 1 round of selection (no methane measurements) were A$5.06 (scenario A), A$4.85 (scenario B), and A$3.89 (scenario C) compared to A$5.26 (scenario A), A$5.12 (scenario B), and A$4.72 (scenario C) for 1 round of selection with 3 PAC measurements. Including MY in the selection index was less profitable because it did not reduce feed costs relative to weight gain. Consequently, for strategies measuring MY but not MPadjWt (and with no estimate of feed intake in the production environment), proportionately greater emphasis was placed on increasing slaughter weight, and as a result, the decreases in methane emissions per animal and per unit of feed intake were smaller than for strategies that measured MPadjWt.

One-hour portable chamber methane measurements are repeatable and provide useful information on feed intake and efficiency.

Feed intake (FI), live weight (LW), and ADG were recorded over 31 d in ninety-six 12-month-old ewes (progeny of 4 sires) given ad libitum access to chaffed lucerne/cereal hay. Methane (CH) and CO emissions of each ewe were measured for 40 to 60 min in portable accumulation chambers (PAC) and in respiration chambers (RC) over 22 h. Testing in RC increased the variability of FI on the test day and depressed the amount eaten from an average of 1,384 to 1,062 g/d; FI depression increased by 0.63 ± 0.24 percentage points for every kilogram of additional LW. Repeatabilities of PAC measurements were 0.76 (CH) and 0.81 (CO). After adjusting for LW and ADG, repeatabilities were 0.47 (PAC CH) and 0.43 (PAC CO). Daily FI measurements had similar repeatability (0.76 before and 0.42 after adjustment for LW and ADG). The PAC measurements were highly correlated with mean 31-d FI ( = 0.81 for both CH and CO). After adjustment for LW and ADG, PAC measurements were moderately correlated with residual feed intake (RFI; = 0.37 for CH, 0.31 for CO). The CH:CO ratio was also significantly correlated with mean 31-d FI ( = 0.52). After most of the ewes had given birth and raised lambs, repeat PAC measurements were available for 91 of the ewes at 2 years of age (with ad libitum access to the same feed). Correlations with the 2012 PAC measurements were 0.64 (CH) and 0.75 (CO). After adjusting 2014 PAC measurements for LW, correlations with RFI in 2012 were 0.34 (CH) and 0.33 (CO), with a clear relationship between sire means for RFI in 2012 and PAC CH adjusted for LW in 2014. These results suggest that PAC tests under similar feeding conditions are repeatable over an extended time period and can provide useful information on FI and feed efficiency as well as methane emissions. Analyses of RC measurements might need to consider FI depression.

Feed intake, growth, and body and carcass attributes of feedlot steers supplemented with two levels of calcium nitrate or urea.

Nitrate supplementation has been shown to be effective in reducing enteric methane emission from ruminants, but there have been few large-scale studies assessing the effects of level of nitrate supplementation on feed intake, animal growth, or carcass and meat quality attributes of beef cattle. A feedlot study was conducted to assess the effects of supplementing 0.25 or 0.45% NPN in dietary DM as either urea (Ur) or calcium nitrate (CaN) on DMI, ADG, G:F, and carcass attributes of feedlot steers ( = 383). The levels of NPN inclusion were selected as those at which nitrate has previously achieved measurable mitigation of enteric methane. The higher level of NPN inclusion reduced ADG as did replacement of Ur with CaN ( < 0.01). A combined analysis of DMI for 139 steers with individual animal intake data and pen-average intakes for 244 bunk-fed steers showed a significant interaction between NPN source and level ( = 0.02) with steers on the high-CaN diet eating less than those on the other 3 diets ( < 0.001). Neither level nor NPN source significantly affected cattle G:F. There was a tendency ( = 0.05) for nitrate-supplemented cattle to have a slower rate of eating (g DMI/min) than Ur-supplemented cattle. When adjusted for BW, neither NPN source nor inclusion level affected cross-sectional area of the LM or fatness measured on the live animal. Similarly, there were no significant main effects of treatments on dressing percentage or fat depth or muscling attributes of the carcass after adjustment for HCW ( > 0.05). Analysis of composited meat samples showed no detectable nitrates or nitrosamines in raw or cooked meat, and the level of nitrate detected in meat from nitrate-supplemented cattle was no higher than for Ur-fed cattle ( > 0.05). We conclude that increasing NPN inclusion from 0.25 to 0.45% NPN in dietary DM and replacing Ur with CaN decreased ADG in feedlot cattle without improving G:F.

Tooth size in patients with supernumerary teeth and a control group measured by image analysis system.

OBJECTIVE: The aim of this study was to compare tooth size measurements between patients with supernumerary teeth and a control group. METHOD: The supernumerary group consisted of 56 subjects (21 females and 35 males) and the control group of 40 subjects (20 females and 20 males). All available permanent teeth on the dental casts were imaged and measured from both buccal and occlusal views using an image analysis system. Mesio-distal, bucco-lingual or occluso-gingival dimensions, area and perimeter were measured from each view. RESULTS: Supernumerary tooth patients tended to have larger tooth size measurements for almost all variables than controls. Significant differences (p<0.05) were found for the mesio-distal dimension of the upper and lower incisors and the bucco-lingual dimensions of the lower first premolars. CONCLUSIONS: The results are compatible with supernumerary teeth being a complex dental anomaly with a multifactorial aetiology in which both genetic and environmental factors are important. There is some evidence of a local effect with greater differences in tooth dimension adjacent to the site of the supernumeraries.

Comparison of repeated measurements of methane production in sheep over 5 years and a range of measurement protocols.

Emissions of 710 ewes at pasture were measured for 1 h (between 09:00-16:30 h) in batches of 15 sheep in portable accumulation chambers (PAC) after an overnight fast continuing until 2 h before measurement, when the sheep had access to baled hay for 1 h. The test was used to identify a group of 104 low emitters (I-Low) and a group of 103 high emitters (I-Hi) for methane emissions adjusted for liveweight (CHawt). The 207 ewes selected at the initial study were remeasured in 5 repeat tests from 2009 through 2014 at another location. The first repeat used the original measurement protocol. Two modified protocols, each used in 2 yr, drafted unfasted sheep on the morning of the test into a yard or holding paddock until measurement. Emissions of the I-Hi sheep were higher (102-112%) than I-Low sheep in all subsequent PAC tests, with statistical significance ( < 0.05) in 3 tests. Tests without overnight fasting were simpler to conduct and had repeatabilities of 51 to 60% compared with 31 and 43% for the initial and first repeat tests, respectively. After habituation to a diet fed at 20 g/kg liveweight, 160 of the 207 sheep were measured in respiration chambers (RC); 10 high (Hi-10) and 10 low (Low-10) sheep were chosen, representing extremes (top and bottom 6.25%) for methane yield (MY; g CH/kg DMI). The Hi-10 group emitted 14% more methane (adjusted for feed intake) in a follow-up RC test, but Low-10 and Hi-10 sheep differed in only 1 of the 5 PAC tests, when Hi-10 sheep emitted less CHawt than Low-10 sheep ( = 0.002) and tended to eat less in the feeding opportunity ( = 0.085). Compared with their weight on good pasture, Low-10 sheep were proportionately lighter than Hi-10 sheep in the relatively poor pasture conditions of the initial test. Sheep identified as low emitters by PAC tests using the initial protocol did not produce less CH (mg/min) when fed a fixed level of intake in RC. Correlations between estimates of an animal's CHawt measured in PAC and CH adjusted for feed intake in RC were quite low ( = 0-19%) and significant ( < 0.05) in only 1 test of unfasted sheep. With moderate repeatability over the 5 yr, PAC tests of CHawt could be a viable way to select for reduced emissions of grazing sheep. As well as exploiting any variation in MY, selecting for reduced CHawt in PAC could result in lower feed intake than expected for the animals' liveweight and might affect the diurnal feeding pattern. Further work is required on these issues.

Single axon analysis of pulvinocortical connections to several visual areas in the macaque.

The pulvinar nucleus is a major source of input to visual cortical areas, but many important facts are still unknown concerning the organization of pulvinocortical (PC) connections and their possible interactions with other connectional systems. In order to address some of these questions, we labeled PC connections by extracellular injections of biotinylated dextran amine into the lateral pulvinar of two monkeys, and analyzed 25 individual axons in several extrastriate areas by serial section reconstruction. This approach yielded four results: (1) in all extrastriate areas examined (V2, V3, V4, and middle temporal area [MT]/V5), PC axons consistently have 2-6 multiple, spatially distributed arbors; (2) in each area, there is a small number of larger caliber axons, possibly originating from a subpopulation of calbindin-positive giant projection neurons in the pulvinar; (3) as previously reported by others, most terminations in extrastriate areas are concentrated in layer 3, but they can occur in other layers (layers 4,5,6, and, occasionally, layer 1) as collaterals of a single axon; in addition, (4) the size of individual arbors and of the terminal field as a whole varies with cortical area. In areas V2 and V3, there is typically a single principal arbor (0.25-0.50 mm in diameter) and several smaller arbors. In area V4, the principal arbor is larger (2.0- to 2.5-mm-wide), but in area MT/V5, the arbors tend to be smaller (0.15 mm in diameter). Size differences might result from specializations of the target areas, or may be more related to the particular injection site and how this projects to individual cortical areas. Feedforward cortical axons, except in area V2, have multiple arbors, but these do not show any obvious size progression. Thus, in areas V2, V3, and especially V4, PC fields are larger than those of cortical axons, but in MT/V5 they are smaller. Terminal specializations of PC connections tend to be larger than those of corticocortical, but the projection foci are less dense. Further work is necessary to determine the differential interactions within and between systems, and how these might result in the complex patterns of suppression and enhancement, postulated as gating mechanisms in cortical attentional effects, or in different states of arousal.

Effects of physostigmine on spatial attention in patients with progressive supranuclear palsy.

We tested patients with progressive supranuclear palsy and control subjects on a task of visuopatial attention. Targets preceded by cues on the same side were termed validly cued; and those on the opposite side, invalidly cued. For all subjects, validly cued targets were responded to faster than those that were invalidly cued. The difference between reaction times for invalidly and validly cued targets, which is hypothesized to measure attentional movement, was significantly increased for the patients. The performance of the controls on certain neuropsychological tests was correlated with their attentional ability. These correlations were altered by progressive supranuclear palsy. Physostigmine treatment of the patients induced a speeding of responses to invalidly cued targets as a function of the duration of the disease. These studies show defects in cognition and attention in patients with progressive supranuclear palsy and demonstrate that physostigmine reduces some of the abnormal visual attentional performance.

Abnormalities in visual spatial attention in men with mirror movements associated with isolated hypogonadotropic hypogonadism.

We studied spatial attentional performance on a visually cued reaction time task in men with isolated hypogonadotropic hypogonadism. A subset of these patients, who displayed mirror movements, have spatial attentional abnormalities. They were slow to respond to targets in the right visual field and especially slow when those targets followed incorrect or diffuse cues. This slowing was present for at least 500 msec after cue onset. They responded equally to targets in the left visual field independent of the spatial cues. The patient population as a whole was significantly faster than controls across all experimental conditions, although the speed of their attentional movement was normal. These data suggest that patients with isolated hypogonadotropic hypogonadism perform reaction time tasks quickly, that faster reaction times do not reflect superior attentional performance, and that a subset of these patients has a spatial attentional abnormality.

Visuospatial attention: effects of age, gender, and spatial reference.

Visual attention is remarkably stable when spatial cuing is used, but non-spatial cues lead to slowing among females and older subjects. Non-spatial cues are associated with poorer performance during the middle stages of the menstrual cycle. Motivation increased overall response speed but not attentional measures, whereas increasing age was associated with generalized slowing and directional asymmetries. Right-eye dominance was correlated with slow responses to downward targets. These data suggest that attentional performance is modified by age, gender, and endocrine status when spatial reference is not present.

Contributions of the pulvinar to visual spatial attention.

Neurons in a subdivision of the pulvinar resemble those in parietal cortex: many respond to visual stimuli, some of these have a spatial selection mechanism, and some have signals about the occurrence of eye movements. These properties suggest a role in visual spatial attention. Injection of GABA-related drugs into this part of the pulvinar alters animals' performance on an attentional task. These data support our hypothesis that the pulvinar contributes to visual spatial attention.

Dopamine dependent reaction time deficits in patients with Parkinson's disease are task specific.

This study tested the hypothesis that patients with Parkinson's disease are impaired when they must rely on internal information to generate a response. Choice reaction times of control subjects and patients with Parkinson's disease, on and off their medication, were measured in tasks in which the motor demands were constant but which varied in the degree to which the stimuli held intrinsic information about the required response. A dopaminergic deficit was observed only in the tasks which employed stimuli compatible with the response and not in a task employing stimuli arbitrarily associated with the response. The data do not support the hypothesis that patients are differentially impaired in using internalized stimulus-response relationships.

A role for presynaptic mechanisms in the actions of nomifensine and haloperidol.

Psychomotor stimulants and neuroleptics exert multiple effects on dopaminergic signaling and produce the dopamine (DA)-related behaviors of motor activation and catalepsy, respectively. However, a clear relationship between dopaminergic activity and behavior has been very difficult to demonstrate in the awake animal, thus challenging existing notions about the mechanism of these drugs. The present study examined whether the drug-induced behaviors are linked to a presynaptic site of action, the DA transporter (DAT) for psychomotor stimulants and the DA autoreceptor for neuroleptics. Doses of nomifensine (7 mg/kg i.p.), a DA uptake inhibitor, and haloperidol (0.5 mg/kg i.p.), a dopaminergic antagonist, were selected to examine characteristic behavioral patterns for each drug: stimulant-induced motor activation in the case of nomifensine and neuroleptic-induced catalepsy in the case of haloperidol. Presynaptic mechanisms were quantified in situ from extracellular DA dynamics evoked by electrical stimulation and recorded by voltammetry in the freely moving animal. In the first experiment, the maximal concentration of electrically evoked DA ([DA](max)) measured in the caudate-putamen was found to reflect the local, instantaneous change in presynaptic DAT or DA autoreceptor activity according to the ascribed action of the drug injected. A positive temporal association was found between [DA](max) and motor activation following nomifensine (r=0.99) and a negative correlation was found between [DA](max) and catalepsy following haloperidol (r=-0.96) in the second experiment. Taken together, the results suggest that a dopaminergic presynaptic site is a target of systemically applied psychomotor stimulants and regulates the postsynaptic action of neuroleptics during behavior. This finding was made possible by a voltammetric microprobe with millisecond temporal resolution and its use in the awake animal to assess release and uptake, two key mechanisms of dopaminergic neurotransmission. Moreover, the results indicate that presynaptic mechanisms may play a more important role in DA-behavior relationships than is currently thought.

Behavioral enhancement of visual responses of prestriate neurons of the rhesus monkey.

Neurons in the superior colliculus, striate cortex, frontal eye fields, and posterior parietal cortex of the monkey respond to visual stimuli. Many of these cells discharge more intensely to a stimulus when it is to be the target for a saccadic eye movement than when fixation is maintained. We have demonstrated that such enhancement of the visual response is also present for cells in prestriate cortex. The prestriate effect is a modulation of the visual response and not a concomitant of oculomotor activity. It is present for eye movements away from as well as into the visual receptive field and is thus similar to that seen in striate cortex and different from that studied in the superior colliculus, frontal eye fields, and posterior parietal cortex. The visual responses of many prestriate cells habituate with repeated stimulation. When the monkey makes saccadic eye movements to a stimulus that is eliciting only a habituated response, the enhancement acts as a dishabituation which persists throughout the eye movement trials.

Functional contributions of the primate pulvinar.

One of the major tasks facing the central nervous system is choosing which sensory events to use for perception and directed behavior. All organisms live in a rich sensory environment, and it is impossible to attend and respond to everything. Certain brain regions and systems must evaluate sensory signals and then determine which are salient. Based on recent data derived from diverse studies of the pulvinar of primates, it is the hypothesis of this paper that a major role of the pulvinar is to participate in the generation of visual salience, those processes which precede perception and action. This process of salience generation makes use of two broad mechanisms, the suppression of noise and the enhancement of significant signals. Outlined above are experiments which show that the visual activity which might be caused by eye movements is filtered from some pulvinar cells. Visual responses associated with certain directions of gaze are removed. Finally the ability to suppress the activity of distracting visual stimuli is dependent on the integrity of the pulvinar. Conversely, there are neurons within the pulvinar which respond best when animals actively select and thus engender certain stimuli with salience. Modulation of pulvinar functioning with transmitter-related drugs changes performance as if salience is being modulated. Humans and monkeys with destruction of the pulvinar behave as if they too cannot create or evaluate salience. Finally, when salience is demanded of humans by making their visual tasks more demanding, there is an increase in PET activity. The hypothesis here is that the pulvinar functions as an early center for the generation of visual salience. This is similar to the view of striate cortex as an early integration stage for the basic elements of visual processing (Hubel and Wiesel, 1968; Zeki, 1976; Allman et al., 1981). Vision does not take place within the complex microstructure of striate neurons, but all of the essential components are present there, and these are distributed to other cortical areas which construct specific aspects of visual perception. Similarly, regions of the pulvinar contain building blocks for visual/behavioral/oculomotor integration which they distribute to various cortical sites for shifts of attention and other types of response specification. When an organism must determine external visual salience, there are neurons within the pulvinar which signal this. Since the major efferents of these thalamic regions are the visual cortices (Benevento and Rezak, 1976; Lin and Kaas, 1979; Kennedy and Bullier, 1985), our present hypothesis is that these signals are used for the construction of visuomotor and visuo-perceptual states.(ABSTRACT TRUNCATED AT 400 WORDS)