Linking persistent negative symptoms to amygdala-hippocampus structure in first-episode psychosis.

Early persistent negative symptoms (PNS) following a first episode of psychosis (FEP) are linked to poor functional outcome. Reports of reduced amygdalar and hippocampal volumes in early psychosis have not accounted for heterogeneity of symptoms. Age is also seldom considered in this population, a factor that has the potential to uncover symptom-specific maturational biomarkers pertaining to volume and shape changes within the hippocampus and amygdala. T1-weighted volumes were acquired for early (N=21), secondary (N=30), non-(N=44) PNS patients with a FEP, and controls (N=44). Amygdalar-hippocampal volumes and surface area (SA) metrics were extracted with the Multiple Automatically Generated Templates (MAGeT)-Brain algorithm. Linear mixed models were applied to test for a main effect of group and age × group interactions. Early PNS patients had significantly reduced left amygdalar and right hippocampal volumes, as well as similarly lateralized negative age × group interactions compared to secondary PNS patients (P<0.017, corrected). Morphometry revealed decreased SA in early PNS compared with other patient groups in left central amygdala, and in a posterior region when compared with controls. Early and secondary PNS patients had significantly decreased SA as a function of age compared with patients without such symptoms within the right hippocampal tail (P<0.05, corrected). Significant amygdalar-hippocampal changes with age are linked to PNS after a FEP, with converging results from volumetric and morphometric analyses. Differential age trajectories suggest an aberrant maturational process within FEP patients presenting with PNS, which could represent dynamic endophenotypes setting these patients apart from their non-symptomatic peers. Studies are encouraged to parse apart such symptom constructs when examining neuroanatomical changes emerging after a FEP.

Dissociation of neglect subtypes with transcranial magnetic stimulation.

OBJECTIVE: To identify two forms of hemispatial neglect, attentional and intentional, in healthy volunteers using frontal and parietal repetitive transcranial magnetic stimulation (rTMS). METHODS: Ten healthy volunteers performed line bisection tasks while viewing stimuli on closed circuit TV. Direct view of the exploring hand and the target was precluded and the TV monitor guided performance. In the normal condition, the direction of hand movement on the table (workspace) was congruent with that on the monitor, and in the reversed condition, the lateral movement in the workspace occurred in the opposite direction on the monitor. The line bisections were performed in three conditions: without rTMS (control), with right frontal rTMS, and with right parietal rTMS. RESULTS: In the normal condition, both right frontal and right parietal rTMS caused a significant rightward deviation (left hemispatial neglect). In the reversed condition, right frontal rTMS continued to cause rightward deviation in the workspace corresponding to leftward bias on the monitor, whereas right parietal rTMS caused leftward deviation in the workspace, corresponding to rightward bias on the monitor. CONCLUSIONS: Right frontal repetitive transcranial magnetic stimulation causes motor-intentional neglect, whereas right parietal repetitive transcranial magnetic stimulation causes sensory-attentional neglect. Alternatively, these findings can also be explained based on a dichotomy related to an egocentric-oriented system.

On-line anosognosia: unawareness for chorea in real time but not on videotape delay.

In hemiplegics, anosognosia (unawareness of deficit) rests on a mismatch between expected and actual movement: a feedback hypothesis emphasizes sensory deficits or neglect, a feedforward hypothesis postulates impaired intention to move. Anosognosia for other problems is less studied. The authors report a man without sensory deficits who was unaware of choreiform movements, except on videotape delay. The authors believe that a feed-forward mechanism underlies his "on-line" unawareness.

fMri studies of Stroop tasks reveal unique roles of anterior and posterior brain systems in attentional selection.

The brain's attentional system identifies and selects information that is task-relevant while ignoring information that is task-irrelevant. In two experiments using functional magnetic resonance imaging, we examined the effects of varying task-relevant information compared to task-irrelevant information. In the first experiment, we compared patterns of activation as attentional demands were increased for two Stroop tasks that differed in the task-relevant information, but not the task-irrelevant information: a color-word task and a spatial-word task. Distinct subdivisions of dorsolateral prefrontal cortex and the precuneus became activated for each task, indicating differential sensitivity of these regions to task-relevant information (e.g., spatial information vs. color). In the second experiment, we compared patterns of activation with increased attentional demands for two Stroop tasks that differed in task-irrelevant information, but not task-relevant information: a color-word task and color-object task. Little differentiation in activation for dorsolateral prefrontal and precuneus regions was observed, indicating a relative insensitivity of these regions to task-irrelevant information. However, we observed a differentiation in the pattern of activity for posterior regions. There were unique areas of activation in parietal regions for the color-word task and in occipitotemporal regions for the color-object task. No increase in activation was observed in regions responsible for processing the perceptual attribute of color. The results of this second experiment indicate that attentional selection in tasks such as the Stroop task, which contain multiple potential sources of relevant information (e.g., the word vs. its ink color), acts more by modulating the processing of task-irrelevant information than by modulating processing of task-relevant information.

The teratogenic effects of methylmercury on early development of the zebrafish, Danio rerio.

Chronic bioassays were used to evaluate the concentration and exposure duration of methylmercury that resulted in specific teratogenic defects in Danio rerio embryos exposed at different developmental stages. Embryos in different stages of development (cleavage, blastula, gastrula, or segmentation) were exposed to 20 or 30 µg/l of methylmercuric chloride (CH(3)HgCl) for various exposure durations (8, 16, 32 h, or continuously to hatching). These exposures frequently caused two morphological defects, tissue abnormality in the median finfold and a flexure of the posterior tail region. The critical period of exposure for the production of both effects begins around 18-20 h after fertilization, with increased exposure resulting in more severe effects. These critical periods coincide with both tail and median finfold formation.

Mamillothalamic tract transection blocks anterior thalamic training-induced neuronal plasticity and impairs discriminative offidance behavior in rabbits.

Rabbits with bilateral transecting lesions of the mamillothalamic tract, control (tract-sparing and sham) lesions, or no lesions, and chronic, fixed-position anterior ventral (AV) and medial dorsal (MD) thalamic and posterodorsal subicular complex unit recording electrodes were trained to step in an activity wheel in response to a 0.5 sec tone (CS+) in order to avoid a brief foot shock. The rabbits also learned to ignore a different tone (CS-) not predictive of shock. Behavioral acquisition was significantly retarded in rabbits with mamillothalamic tract transection compared to controls. When trained, transected rabbits failed to avoid the shock more often than controls. Mamillothalamic tract transection abolished and control lesions attenuated AV thalamic discriminative training-induced activity (i.e., development with training of greater discharges in response to the CS+ than to the CS-). Transection and control lesions attenuated AV thalamic excitatory training-induced activity (greater elicited activity during training than during unpaired tone-shock presentations before training) as well as AV thalamic "spontaneous" baseline unit activity. CS-elicited discharge magnitude was reduced by control lesions and it was further reduced by tract transecting lesions. Significant lesion-related changes were not found in the subicular or MD thalamic neuronal receptor. Mamillothalamic tract afferent information flow is thus essential for AV thalamic discriminative training-induced activity, excitatory training-induced activity, tone-elicited discharges and maintenance of conditioned avoidance responses. The effects of the control lesions suggested that afferents which course in parallel with and near the mamillothalamic tract may contribute to AV thalamic spontaneous activity and excitatory training-induced activity.

Dissociations in memory for item identity and item frequency: evidence from hemispheric interactions.

Evidence for a dissociation between memory for the identity of an item and memory for its frequency of occurrence was provided by two tachistoscopic studies employing lateralized abstract designs as stimuli. In both experiments, subjects viewed a random series of presentation trials, in which certain designs appeared only once, others 5 times, and still others 9 times. Then in a series of probe trials, subjects decided, on each trial, if a design was familiar or novel, either by an old/new decision (Experiment 1) or a forced-choice decision (Experiment 2), after which they estimated the frequency of item occurrence. Presentation and probe trials were either displayed in the same visual field (within-hemisphere trials) or opposite visual fields (across-hemisphere trials). Both experiments revealed that the pattern of interhemispheric processing as well as lateralized processing differed for item identity as compared to item frequency, providing further evidence for a dissociation between these two memory processes.

[Prenatal diagnosis of albinism].

Prenatal diagnosis of oculocutaneous albinism (OCA) was made in 1 of 6 pregnancies at risk examined during the 20th week of gestation. A skin biopsy was taken from the fetal scalp under ultrasonic screening. Light and electron microscopy studies were performed in each case to demonstrate melanin pigment and melanosomal development in the melanocytes of the hair bulbs and the epidermis. In 1 fetus albinism was diagnosed by the absence of melanin pigment and by the demonstration that melanosomes were only present in stages I and II. In the other 5 fetuses melanin pigment and mature melanosomes (up to stage IV) were demonstrated. The pregnancy with the albino fetus was interrupted and the diagnosis of OCA was confirmed at autopsy.

Toxicity of zinc and bleached kraft mill effluent to larval english sole (Parophrys vetulus) and topsmelt (Atherinops affinis).

Toxicity test protocols were developed for larvae of two species of marine fishes of the Pacific coast of the United States. During winter months, larvae were obtained from adult English sole (Parophrys vetulus) spawned in the laboratory. Newly-hatched, nonfeeding larvae were used in 96-hr experiments to determine their acute sensitivity to inorganic and organic toxicants. Exposure to ZnSO(4) produced a 96-hr LC(50) of 14.5 mg Zn/L. A complex and variable organic effluent (untreated bleached kraft mill effluent; BKME) yielded 96-hr LC(50)s ranging from 1.2-9.3% BKME.Larvae were obtained from eggs collected from wild and laboratory populations of the spring and summer-spawning topsmelt (Atherinops affinis). Both acute (96-hr) mortality and longer-term (7-14 days) growth responses of topsmelt larvae to BKME were determined. Acute toxicity levels (96-hr LC(50)s) ranged from 6.2-9.7% BKME. No Observed Effect Levels (NOELs) for 7 and 14 day exposures ranged from 1.0-3.0% BKME.

Follicular fluid contents as predictors of success of in-vitro fertilization-embryo transfer.

In order to establish criteria for selection of the best ova in in-vitro fertilization-embryo transfer (IVF-ET) programes we have examined the follicular fluid (FF) levels of plasminogen activator (PA), collagenolytic activity, progesterone (P) and alpha 2 macroglobulin (alpha 2M) and related them to the success of pregnancy. PA activity was similar in FF of pregnant and nonpregnant cycles, 13.8 +/- 3.9 mU/ml versus 14.6 +/- 2.9 (mean +/- SEM) respectively. By contrast, FF from pregnant cycles exhibited lower collagenolytic activity (49.6 +/- 3.9% versus 67.9 +/- 3.0; P less than 0.001). Likewise, in a semi-quantitative assay of alpha 2M, only 18.4% of the aspirates from pregnant cycles showed a precipitation line, whereas 76.8% of those from non-pregnant cycles were positive. Levels of P in aspirates from pregnant cycles were in the intermediate range, as compared with those from non-pregnant cycles (0.06-5.5 micrograms/ml versus 0.02-12.0 micrograms/ml). All these assays can be completed before ET and performed in IVF-ET programmes. In conclusion, it seems that a combination of follicular alpha 2M levels and collagenolytic activity, and to a lesser extent addition of P assay, may serve as good criteria for selecting the best embryos for establishment of pregnancy.

Effect of clomiphene citrate on preovulatory rat follicles in culture.

The effect of clomiphene citrate was tested on rat preovulatory follicles in culture. Clomiphene inhibited both basal and luteinizing hormone (LH)-stimulated steroid accumulation. The dose-dependent effect of clomiphene was much more pronounced on follicles cultured with LH; while 0.01 mM had no effect, 2 mM clomiphene decreased progesterone accumulation by 97%, estradiol-17 beta by 90% and testosterone by 65% (P less than 0.001). The inhibitory action of the drug was not prevented by addition of 8-Br-cAMP (1 mM) or pregnenolone (1 microgram/ml) to the culture medium. clomiphene (0.01 - 0.5 mM) induced the resumption of meiotic maturation even in LH-free medium in approximately 60% of follicle-enclosed oocytes. At the higher concentrations tested (0.1 - 0.5 mM) degenerative changes were noted in a high proportion of oocytes (30-40%). Follicles incubated for 24 h with clomiphene exhibited dose-dependent atretic-like changes. These effects of clomiphene on preovulatory follicles may account for the discrepancy between ovulation and pregnancy rates observed in women treated with clomiphene.