Social phobics do not see eye to eye: a visual scanpath study of emotional expression processing

Clinical observation suggests that social phobia is characterised by eye avoidance in social interaction, reflecting an exaggerated social sensitivity. These reports are consistent with cognitive models of social phobia that emphasize the role of interpersonal processing biases. Yet, these observations have not been verified empirically, nor has the psychophysiological basis of eye avoidance been examined. This is the first study to use an objective psychophysiological marker of visual attention (the visual scanpath) to examine directly how social phobia subjects process interpersonal (facial expression) stimuli. An infra-red corneal reflection technique was used to record visual scanpaths in response to neutral, happy and sad face stimuli in 15 subjects with social phobia, and 15 age and sex-matched normal controls. The social phobia subjects showed an avoidance of facial features, particularly the eyes, but extensive scanning of non-features, compared with the controls. These findings suggest that attentional strategies for the active avoidance of salient facial features are an important marker of interpersonal cues in social phobia. Visual scanpath evidence may, therefore, have important implications for clinical intervention.     

Intrauterine enucleation of normal mice mimics a structural compensatory response in the geniculate of eyeless mutant mice

Identification of a compensatory structural pathway for the retinal terminals in the glomerular configuration of the dorsal lateral geniculate nucleus (dLGN) of the adult anophthalamic mutant mouse (ZRDCT-An) led to an experimental analysis of the effect of surgical enucleation on the dLGN of normal embryonic and postnatal C57 mice². Young C57 adults were prenatally enucleated (embryonic days 14–19) or during the early postnatal period (birth to 5 days old). Light and electron microscopic observations on the dLGN of these enucleated mice were compared with the dLGN of two types of mutant mice, the bilaterally eyeless anophtalmic and the unilaterally eyeless naked splotch (NSP). A structural compensatory response, similar to that occurring naturally in these two mutant mice, is cativated by prenatal experimental enucleation as shown by the appearance of large replacement terminals (LRTs) for the retinal afferents. The glomeruli in the ipsi-and/or contralateral dLGN in these 3 conditions contain extensive synaptic areas covered by compensatory large axons. This pattern of synaptic thalamic reorganization occurs after experimental prenatal and postnatal enucleation of normal mice. This structural reorganization in experimentally and genetically enucleated mice suggests a common mechanism for replacement of retinal terminals. The precise origin and function of this tracts remains to be determined. This evidence demonstrates that the anopthalmic mutant mouse is a valid model system for analysis of thalamic reorganization that occurs in normal mice after perinatal enucleation.     

Cell body response to injury in motoneurons and primary sensory neurons of a mutant mouse,ola (Wld), in which wallerian degeneration is delayed

We examined the response to axon injury in the facial motoneurons and dorsal root ganglion (DRG) neurons of C57BL/Ola (Wld) mice, compared with the responses of C57BL/6J mice. The peripheral nerves of Ola mutants undergo remarkably slowed and muted Wallerian degeneration after injury. The increase in GAP-43 mRNA levels in facial motoneurons and DRG neurons was similar in both strains of mice, as was the initial decrease in medium-weight neurofilament (NFM) mRNA in facial motoneurons, and the increase in JUN immunoreactivity in both types of neurons. However, the subsequent recovery to normal low levels of JUN and GAP-43 mRNA expression and high levels of NFM mRNA was delayed in Ola motoneurons. We ascribe this delay to the slow regeneration and target reinnervation of facial axons in the Ola mice. These results show that absence of rapid Wallerian degeneration does not affect the initial cell body response to axonal injury. They also provide further evidence that restoration of normal levels of expression of GAP-43 and NFM mRNAs is dependent on target reinnervation and/or trophic factors provided by the distal nerve, Impaired regeneration in the Ola mouse does not seem to be a consequence of a defective cell body response to injury, and our results illustrate the general principle that, even if there is a vigorous cell body response to injury, normal axonal regeneration requires the additional provision of a favorable environment for growth. © 1995 Wiley-Liss, Inc.     

Brain metastases in patients with pelvic or abdominal malignancy do not prevail in the posterior fossa: a retrospective study

Pelvic and gastrointestinal tumors are generally considered to have a predilection to metastasize to the posterior fossa rather than to the supratentorial brain. Review of imaging of 100 patients with brain metastases from pelvic and gastrointestinal primary tumors and of 100 patients with brain metastases from other primary tumors did not reveal a difference in distribution of brain metastases between the two groups of patients. So, there is no evidence that pelvic and gastrointestinal tumors metastasize preferentially to the posterior fossa.     

Vestibulo-ocular reflex (VOR) induced by passive head rotation and goal-directed saccadic eye movements do not simply add in man

Additivity between vestibulo-ocular reflex (VOR) and saccadic eye movements was quantified in man by passively rotating the subject's head as he tracked a stepping target. A systematically increased gaze (i.e. eye + head) saccadic velocity was observed when the head was rotated toward the target, as compared to a head-fixed condition, indicating that VOR and saccades do not fully add. Moreover, although VOR was assumed to be inhibited during ocular saccades, mean gaze saccadic amplitude remained unchanged. This would suggest an on-line computation of gaze position to be fed back to the saccadic system in order to stop the saccade once gaze reaches its goal.     

Structural MRI-Based Measures of Accelerated Brain Aging do not Moderate the Acute Antidepressant Response in Late-Life Depression

ObjectiveLate-life depression (LLD) is characterized by accelerated biological aging. Accelerated brain aging, estimated from structural magnetic resonance imaging (sMRI) data by a machine learning algorithm, is associated with LLD diagnosis, poorer cognitive performance, and disability. We hypothesized that accelerated brain aging moderates the antidepressant response.Design and InterventionsFollowing MRI, participants entered an 8-week randomized, controlled trial of escitalopram. Nonremitting participants then entered an open-label 8-week trial of bupropion.ParticipantsNinety-five individuals with LLD.MeasurementsA machine learning algorithm estimated each participant's brain age from sMRI data. This was used to calculate the brain-age gap (BAG), or how estimated age differed from chronological age. Secondary sMRI measures of aging pathology included white matter hyperintensity (WMH) volumes and hippocampal volumes. Mixed models examined the relationship between sMRI measures and change in depression severity. Initial analyses tested for a moderating effect of MRI measures on change in depression severity with escitalopram. Subsequent analyses tested for the effect of MRI measures on change in depression severity over time across trials.ResultsIn the blinded initial phase, BAG was not significantly associated with a differential response to escitalopram over time. BAG was also not associated with a change in depression severity over time across both arms in the blinded phase or in the subsequent open-label bupropion phase. We similarly did not observe effects of WMH volume or hippocampal volume on change in depression severity over time.ConclusionsMRI markers of accelerated brain aging were not associated with treatment response in this sequential antidepressant trial.     

Brain serotonin depletion by lesions of the median raphe nucleus enhances the psychotomimetic action of phencyclidine, but not dizocilpine (MK-801), in rats

We have previously shown that brain serotonin depletion by lesions of the median raphe nucleus (MRN) causes enhancement of phencyclidine-induced locomotor hyperactivity [S. Kusljic, D.L. Copolov, M. van den Buuse, Differential role of serotonergic projections arising from the dorsal and median raphe nuclei in locomotor hyperactivity and prepulse inhibition, Neuropsychopharmacology 28 (2003) 2138-2147]. In this study, we extend our previous work by (1) comparing the effect of phencyclidine with that of another NMDA receptor antagonist, dizocilpine (MK-801); (2) investigate behavioral changes in more detail; (3) assess in detail the effect of raphe lesions on regional serotonin levels in the brain. Male Sprague-Dawley rats received microinjection of the serotonergic neurotoxin 5,7-dihydroxytryptamine into the MRN or dorsal raphe nucleus (DRN). The effects of treatment with saline, phencyclidine and MK-801 on locomotor activity were determined 2 weeks after the surgery. MRN lesions caused serotonin depletion in the dorsal hippocampus, whereas DRN lesions caused serotonin depletion in the frontal cortex, striatum and ventral hippocampus. There was a significant increase in phencyclidine-induced locomotor hyperactivity in the MRN-lesioned group compared to sham-operated controls. Further analysis of behavior showed that phencyclidine-induced hyperambulation, but not stereotypy or rearing, was significantly higher in MRN-lesioned rats compared to controls. In contrast, there was no significant effect of the lesions on the psychotomimetic effect of MK-801. These results indicate that a hyposerotonergic state induced by destruction of projections from the MRN leads to altered brain circuitry that is responsible for the regulation of phencyclidine-but not MK-801-induced locomotor hyperactivity. Thus, MRN projections may play an inhibitory role in mechanisms involved in symptoms of schizophrenia.     

Post-session injections of a protein synthesis inhibitor,cycloheximide do not alter saccharin self-administration

A large body of evidence indicates that reactivation of aversive memories leads to protein synthesis-dependent memory reconsolidation which can be disrupted by cycloheximide (CHX) and other protein synthesis inhibitors. The aim of the present study was to investigate whether CHX would alter maintenance of well-trained instrumental responding for 0.1% saccharin. Male Wistar rats were trained to lever press for saccharin. When lever pressing stabilized, experimental self-administration sessions with CHX (3 mg/kg, s.c.) started. The animals received four experimental sessions, with each session separated by 5 days. The protein synthesis inhibitor was injected immediately after the experimental sessions 1–3. Repeated post-session injections of CHX did not alter saccharin self-administration. A two-bottle choice test conducted after the last experimental session revealed that CHX had not induced any conditioned taste aversion to 0.1% saccharin. The present results suggest that well-consolidated long-term memory of an appetitive instrumental task does not depend on de novo protein synthesis.     

More to ADHD than meets the eye: Observable abnormalities in search behaviour do not account for performance deficits on a discrimination task

Children with Attention Deficit/Hyperactivity Disorder (ADHD) often perform poorly on tasks requiring sustained and systematic attention to stimuli for extended periods of time. The current paper tested the hypothesis that such deficits are the result of observable abnormalities in search behaviour (e.g., attention-onset, -duration and -sequencing), and therefore can be explained without reference to deficits in non-observable (i.e., cognitive) processes. Forty boys (20 ADHD and 20 controls) performed a computer-based complex discrimination task adapted from the Matching Familiar Figures Task with four different fixed search interval lengths (5-, 10-, 15- and 20-s). Children with ADHD identified fewer targets than controls (p < 0.001), initiated searches later, spent less time attending to stimuli, and searched in a less intensive and less systematic way (p's < 0.05). There were significant univariate associations between ADHD, task performance and search behaviour. However, there was no support for the hypothesis that abnormalities in search carried the effect of ADHD on performance. The pattern of results in fact suggested that abnormal attending during testing is a statistical marker, rather than a mediator, of ADHD performance deficits. The results confirm the importance of examining covert processes, as well as behavioural abnormalities when trying to understand the psychopathophyiology of ADHD.     

Modifications of the retina neuronal populations of the heterozygous mutant small eye mouse, the Sey(Dey)

We analyzed the modifications of the retinal neurons in a heterozygous mutant small eye mouse, the Sey(Dey). This mouse presents a mutation in chromosome 2 which affects the gene Pax6 and other nearby genes, such as the Wt1 gene and the gene of the Reticulocalbin. The eyes of these animals do not have lenses and their retinas present important morphological alterations: in the anterior portion they are joined to the cornea, they are found detached from the pigment epithelium, they present folds that form rosettes in some zones and alteration of the lamination can be observed. The partial loss of the genes affected does not prevent the formation of the different layers of the retina, but does affect its thickness, principally of the plexiform layers; moreover, the internal limiting membrane is found disorganized. All the neuronal populations are present in the retina of these animals and express the same neurochemical markers as the control animals, but the number of Pax6(+) cells is notably reduced. In these retinas a marked disorganization of the distribution of the dendrites and axons is observed and a notable reduction in the axons of ganglion cells. These results suggest that, although it does not appear determinant in the differentiation of the distinct neuronal types of the retina, the partial lack of genes of the heterozygotes +/Sey(Dey) provokes important morphological and neurochemical modifications in the cytoarchitecture of the retina.     

Specific monoclonal antibodies against normal microtubule-associated protein-2 (MAP2) epitopes present in Alzheimer pathological structures do not recognize paired helical filaments

Summary We have developed monoclonal antibodies that detect normal microtubule-associated protein-2 (MAP2) epitopes in routinely fixed, paraffin-embedded tissue. The somatodendritic distribution of MAP2 in bovine and human nervous tissue was confirmed with several of these antibodies. Furthermore, some of these antibodies immunohistochemically labeled certain pathological structures in Alzheimer brain, especially neurites in senile plaques. Electron microscopic observations, however, indicate that these MAP2 epitopes are not located in the Alzheimer paired helical filaments themselves, but in amorphous granular structures coexistent with them. While the pathological nature of these structures is undetermined, they may represent artefactual modifications of normal cytoskeletal components.     

Retrohippocampal, hippocampal and related structures of the forebrain in the reeler mutant mouse

Retrohippocampal, hippocampal and some related forebrain regions of the reeler mutant mouse were examined in cresyl violet and myelin stained preparations. All cortical structures are abnormal. The entorhinal cortex, parasubiculum, presubiculum, subiculum, and anterior hippocampal cortex share an anomaly of common quality. All lack an external plexiform layer and their neurons are not arranged in the usual laminae. The positions of neurons are not random, however. Cells of smaller average size and of polymorphic shape are grouped in an outer relatively narrow zone external to a broad zone of larger cells. The histological features of these two cell zones in the mutant are similar to the deep polymorphic cell stratum and the superjacent pyramidal field respectively in the normal animal, but their relative depths in the cortex are reversed. The histological pattern of the mutant hippocampus is less disturbed. Its external plexiform layer is well developed and, although the positions of some neurons are abnormal, there is an explicit laminar pattern and the cytological features of the individual hippocampal cytoarchitectonic fields are readily recognized. It appears from these observations that in a variety of cortical structures, even those which are most disturbed, the positions of neurons are systematically regulated, yet are controlled according to some rule that differs in normal and mutant. The basic developmental event which dictates eventual neuron position probably occurs early and its effects may depend on critical timing or precise location of interacting cells as influenced by the reeler locus.     

The elevated plasma lipoprotein(a) concentrations in preeclampsia do not precede the development of the disorder

We sought to determine whether maternal plasma lipoprotein(a) [Lp(a)] levels are elevated in the second trimester, before the development of preeclampsia and other obstetrical complications, in women at risk. In the first part of the study (cross-sectional), plasma concentrations of Lp(a) were compared among 16 women with preeclampsia, 35 normotensive pregnant women and 18 healthy nonpregnant women. In the second part (nested case-control), blood samples were collected prospectively from 82 women at risk of preeclampsia, at 14-24 weeks of gestation, and Lp(a) levels were compared between those in whom preeclampsia or other obstetrical complications developed and those in whom they did not. In the cross-sectional study, plasma concentrations of Lp(a) were significantly higher in women with preeclampsia than in normotensive pregnant and healthy nonpregnant women (41 +/- 31 vs. 24 +/- 16 and 15 +/- 10 mg/dl, respectively; P=.001). Of the 82 women in the second part of the study, 9 (11%) developed preeclampsia and 19 (23%) had complications such as intrauterine growth restriction, preterm delivery and fetal or neonatal loss. There were no differences in plasma Lp(a) concentrations between the women with preeclampsia and those without complications, though Lp(a) levels were significantly higher in women with other complications than in those with either preeclampsia or uncomplicated pregnancies (40 +/- 29 vs. 17 +/- 13 or 28 +/- 18 mg/dl, respectively; P=.05). In conclusion, elevated plasma levels of Lp(a), associated with clinically established preeclampsia, are not detected before the appearance of the disorder in pregnant women at risk.     

Auditory evoked potentials of adults who do or do not show a significant right ear advantage in dichotic listening

The Halwes Fused Dichotic Words Test was used to divide a sample of university students into a group having a statistically significant right ear advantage (REA) and a group having either a significant left ear advantage or a non-significant ear asymmetry (NREA). Of these participants, 30 (14 REA, 16 NREA) had electrical potentials measured from temporal, central, and frontal sites as series of brief tones were presented monaurally. No behavioural response was required. Group differences were found in the latency but not the amplitude of the averaged event-related responses. The REA group showed faster conduction to the right hemisphere than to the left hemisphere. In both groups the amplitude of left hemisphere responses was greater for right ear stimulation than for left ear stimulation. The results for amplitude indicate that the crossed auditory pathway is a superior conductor of information to the left hemisphere but not to the right hemisphere. Group differences, however, are related only to the speed with which information reaches the right hemisphere.     

Soluble, cross-linked fibrin(ogen) hybrid oligomers do not stimulate t-PA conversion of plasminogen.

Cross-linked hybrid oligomers of fibrinogen and fibrin are found in plasma from fibrinaemic patients and normal individuals as well as in preparations of purified human fibrinogen. The present study was undertaken to see if such hybrid oligomers have the same stimulatory effect on tissue plasminogen activator (t-PA) conversion of plasminogen as do polymeric and monomeric fibrin. Hybrid oligomeric fibrin(ogen) material was provided by subjecting purified human fibrinogen to gel filtration in urea-containing buffer at pH 5.6. Well separated fractions of hybrid oligomeric material and monomeric fibrinogen were thus obtained. Some of this material was converted to soluble polymeric or monomeric fibrin using insolubilized thrombin. Hybrid polymeric fibrin, polymeric fibrin or monomeric fibrin were then added to citrated, normal plasma to 2.5 or 5 per cent of the plasma fibrinogen concentration. The added material was kept in solution by plasma fibrinogen. The "COA-SET Fibrin Monomer Test" (Kabi,Stocholm,Sweden), based on the ability of fibrin monomers to enhance t-PA mediated plasminogen-plasmin conversion, was used to compare the potential stimulatory effect of the preparations above. The results led to the following conclusions: 1) Cross-linked, soluble fibrin(ogen) hybrid polymers in a concentration of 5 per cent of plasma fibrinogen concentration (w/w) do not stimulate t-PA. 2) Thrombin conversion of the fibrin-fibrinogen hybrid material resulted in an increase in the rate of t-PA mediated plasminogen conversion, corresponding to the one observed with equivalent (w/w) amounts of fibrin monomers. Compared on a mole to mole basis, fibrin oligomers are more powerful than fibrin monomers as stimulators of t-PA activity.     

Neural cell adhesion molecule (NCAM) null mice do not show a deficit in odour discrimination learning

Polysialylated neural cell adhesion molecule (PSA-NCAM) is predominantly expressed during development where it regulates biological functions including axon targeting and neuronal precursor cell migration. Although dramatically down regulated after birth in most regions of the nervous system, PSA-NCAM remains highly expressed into adulthood in areas that have ongoing regeneration and plasticity such as in the olfactory bulb and hippocampus. Consequently, lack of PSA-NCAM in NCAM null mice results in distinct morphological changes to these areas. The functional correlates of these changes are not well defined although there have been reports that learning is impaired in NCAM null mice. In the present study, we assessed the ability of old and young NCAM null mice to learn an odour discrimination task. We tested male and female experimental and control animals of two different ages: 30-60 days and 12-15 months. During 4 days of training, NCAM null and C57BL/6J received trials where one odour (CS+) was paired with sugar while another odour (CS-) was not. In a subsequent preference test, conducted in the absence of sugar, all animals, regardless of strain or age, spent significantly more time digging in the CS+ odour than in the CS- odour. In addition, there was no significant difference in digging behaviour in the CS+ between the NCAM null and the control animals. These data indicate that deletion of the NCAM gene may change the morphology of the olfactory bulb but does not interfere with the ability to learn an odour discrimination task.