"Bottom-up" and "top-down" effects on reading saccades: a case study

OBJECTIVE: To investigate the role right foveal/parafoveal sparing plays in reading single words, word arrays, and eye movement patterns in a single case with an incongruous hemianopia. METHODS: The patient, a 48-year-old right handed male with a macular sparing hemianopia in his left eye and a macular splitting hemianopia in his right eye, performed various reading tasks. Single word reading speeds were monitored using a "voice-trigger" system. Eye movements were recorded while reading three passages of text, and PET data were gathered while the subject performed a variety of reading tasks in the camera. RESULTS: The patient was faster at reading single words and text with his left eye compared with his right. A small word length effect was present in his right eye but not his left. His eye movement patterns were more orderly when reading text with his left eye, making fewer saccades. The PET data provided evidence of "top-down" processes involved in reading. Binocular single word reading produced activity in the representation of foveal V1 bilaterally; however, text reading with the left eye only was associated with activation in left but not right parafoveal V1, despite there being visual stimuli in both visual fields. CONCLUSIONS: The presence of a word length effect (typically associated with pure alexia) can be caused by a macular splitting hemianopia. Right parafoveal vision is not critically involved in single word identification, but is when planning left to right reading saccades. The influence of top-down attentional processes during text reading can be visualised in parafoveal V1 using PET.     

Side effects and the "blindability" of clinical drug trials.

A novel, simple approach to retrospective assessment of "blindability" was applied to data on outpatients in a controlled, double-blind clinical comparison of a putative antidepressant, etoperidone, and placebo. A "blind" evaluator proved capable of discriminating between the active drug and placebo on the basis of reported side effects alone, raising questions about the true blindness of the study.     

More "mapping" in brain mapping: statistical comparison of effects

The term "mapping" in the context of brain imaging conveys to most the concept of localization; that is, a brain map is meant to reveal a relationship between some condition or parameter and specific sites within the brain. However, in reality, conventional voxel-based maps of brain function, or for that matter of brain structure, are generally constructed using analyses that yield no basis for inferences regarding the spatial nonuniformity of the effects. In the normal analysis path for functional images, for example, there is nowhere a statistical comparison of the observed effect in any voxel relative to that in any other voxel. Under these circumstances, strictly speaking, the presence of significant activation serves as a legitimate basis only for inferences about the brain as a unit. In their discussion of results, investigators rarely are content to confirm the brain's role, and instead generally prefer to interpret the spatial patterns they have observed. Since "pattern" implies nonuniform effects over the map, this is equivalent to interpreting results without bothering to test their significance, a practice most of the experimentally-trained would eschew in other contexts. In this review, we appeal to investigators to adopt a new standard of data presentation that facilitates comparison of effects across the map. Evidence for sufficient effect size difference between the effects in structures of interest should be a prerequisite to the interpretation of spatial patterns of activation.     

Internuclear ophthalmoplegia and "optic neuritis": paraneoplastic effects of bronchial carcinoma

A 56-year-old man developed bilateral internuclear ophthalmoplegia and "optic neuritis" as remote effects of a bronchial carcinoma. These clinical findings correlated pathologically with secondary demyelination of the medial longitudinal fasciculus and with round cell infiltration and adhesive arachnoiditis of the optic nerve. There was no evidence of CNS metastasis. "Optic neuritis" and internuclear ophthalmoplegia may be paraneoplastic effects of systemic cancer.     

Positive effects of L-dopa on a "marginal" symptomatology observed in parkinsonians]

In some patients with parkinsonism, we have found and, often, cured by L-DOPA: 1) An unfrequent symptomatology (oculomotor, sensory, syncinesias, "Babinski" sign), not included in the classic rating scales. 2) A symptomatology "attributable to frontal lesion": grasping; inability to reproduce a serie of three gestures; inability to react to an audio-visual stimulus by a definited opposite gesture. In such patients, the improvement is in total contrast with the lack of effect of L-DOPA in several patients with frontal lesions, but without parkinsonism. It is possible that the last constatation may contribute: a) to localize more exactly the topography of dopaminergic pathways, b) to approach the respective parts of the cortical and subcortical structures in the programming of the movement.     

"Dopamine-dependent" side effects of selective serotonin reuptake inhibitors: a clinical review

OBJECTIVE: Neurophysiologic findings indicate an inhibition of dopaminergic neurotransmission by selective serotonin reuptake inhibitors (SSRIs). This article highlights the relationships between changes in dopaminergic neurotrans-mission induced by SSRIs and the occurrence of certain side effects such as hyperprolactinemia, extrapyramidal symptoms, sexual and cognitive dysfunction, galactorrhea, mammary hypertrophy, and, more rarely, gynecomastia. DATA SOURCES AND SELECTION: A systematic search of the literature in English, French, and German from 1980 to 2004 was performed in MEDLINE, EMBASE, and the Cochrane Library using the keywords SSRI, dopamine, serotonin, side effects, antidepressants, citalopram, escitalopram, sertraline, paroxetine, fluoxetine, fluvoxamine, and nefazodone. References cited in all trials were searched iteratively to identify missing studies. All studies concerning inhibition of dopaminergic neurotransmission by SSRIs and SSRI-related side effects were considered. We retained 62 significant articles debating the subject. DATA EXTRACTION AND SYNTHESIS: We critically reviewed the studies, depending on the methodologies (case reports, clinical reports, randomized studies), and assessed the pertinence of "dopamine-dependent" SSRI-related side effects. The analytic review of these articles suggests that some specific SSRI-related side effects be classified as dopamine-dependent. CONCLUSIONS: At a clinical level, it could be useful to underline dopamine-dependent characteristics of some SSRI-related side effects. This approach would allow clinicians the opportunity to search other dopamine-dependent side effects systematically. At a pharmacologic level, this approach could stimulate the development of molecules with a "corrective" function on dopamine-dependent side effects of SSRIs by facilitating dopaminergic neurotransmission.     

Long lasting behavioral effects of dimethyl sulfoxide and the "peripheral" toxicant p-bromophenylacetylurea

Behavioral toxic effects caused by a relatively small dose of the "peripheral" neurotoxin, p-bromophenylacetylurea (BPAU), and of its vehicle, dimethyl sulfoxide (DMSO) were investigated. BPAU induces, in rats, a central-peripheral distal axonopathy similar to that produced in humans by toxic organophosphorus-containing compounds, and has been proposed as a model to study this type of toxicity in a convenient experimental mammal. Rats were injected with BPAU (50 or 100 mg/kg) in DMSO (1 ml/kg), with DMSO alone, or with saline. 100 mg BPAU/kg produced permanent weight loss and hind limb paresis; the low dose did not. Behavioral testing, 2 days to 4 mo post-treatment, indicated that DMSO and/or 50 mg/kg of BPAU retarded habituation of spontaneous exploratory activity, impaired acquisition of conditioned (auto-shaped) behavior, and changed the dose-response relationship ford-amphetamine-induced suppression of operant (fixed ratio 32) responding. BPAU-treated animals were also impaired in initial performance of operant behavior maintained by a fixed ratio schedule of reinforcement, at high (greater than or equal to FR 16) ratio values. Thus, neurobehavioral toxicity may occur at doses too low to induce organophosphorus-type sensorimotor impairment or pathology. Further, DMSO may also exert effects on neurobehavioral function, suggesting it too may be potentially toxic within this domain.     

The "benefits" of distractibility: mechanisms underlying increased Stroop effects in schizophrenia

Recent studies of selective attention in schizophrenia patients suggest a particular pattern of single-trial Stroop performance: increased facilitation but not interference in reaction times (RTs), combined with increased error interference. Our Stroop task analysis suggests that this pattern can be explained by a selective attention deficit if one accounts for (1) performance in the congruent condition; (2) the nature of the neutral stimulus; (3) the relationship between accuracy and RT; and (4) response set effects. To test these hypotheses, we examined Stroop performance in 40 DSM-IV schizophrenia patients and 20 healthy control subjects, using a range of neutral stimuli (color patches, noncolor words, color words not in the response set). The findings confirmed several of our predictions and the results were consistent with the hypothesis that abnormal Stroop performance in schizophrenia reflects a failure to adequately attend to the task-appropriate stimulus dimension (color). This inattention affects both the congruent and incongruent conditions and multiple points in the information processing pathway.     

An alternative perspective on "semantic P600" effects in language comprehension

The literature on the electrophysiology of language comprehension has recently seen a very prominent discussion of "semantic P600" effects, which have been observed, for example, in sentences involving an implausible thematic role assignment to an argument that would be a highly plausible filler for a different thematic role of the same verb. These findings have sparked a discussion about underlying properties of the language comprehension architecture, as they have generally been viewed as a challenge to established models of language processing and specifically to the notion that syntax precedes semantics in the comprehension process. In this paper, we review the literature on semantic P600 effects and discuss a number of challenges--both conceptual and empirical--to existing approaches in this domain. We then provide a new perspective on these effects by showing how they can be derived within an independently motivated, hierarchically organised neurocognitive model of language comprehension in which syntactic structuring precedes argument interpretation (the extended Argument Dependency Model, eADM; Bornkessel and Schlesewsky, 2006). In addition to straightforwardly deriving the phenomenon of a "semantic P600," the basic architectural properties of the eADM account for existing empirical puzzles within the semantic P600 literature.     

Clinical and electroencephalographic signs of side effects in patients after myelography using "amipaque"

The authors present the results of own investigations on the occurrence of side effects following myelography with the contrast medium Amipaque administered usually by the lumbar route. Sixty patients aged 21-65 years with various diseases of the spinal cord and cauda equina were studied. Clinical and myelographic investigations were performed before and after myelography. In 6 out of 60 cases (10%) transient neurological disturbances developed including epileptic seizures, speech disturbances of the type of aphasia and dysartria, visual disturbances and twitching of lower extremities. Other symptoms and signs included: headaches, vomiting, collapse. One patient with cardiorespiratory failure died hours after myelography with evidence of increased symptoms of cardiorespiratory failure. EEG changes appeared after myelography in 2/3 of cases and persisted for up to 12 days. The authors call attention to the high proportion of neurological complications and EEG changes which must be taken into account when indications to myelography are considered. Particular caution is necessary in cases with coexistent cardiorespiratory failure.     

A prospective study of the psychological effects of "person under train" incidents on drivers

Previous studies have shown that person under train (PUT) accidents cause psychological distress to drivers during the first year following the incident. Our aims were to assess the psychological consequences of PUT accidents on drivers prospectively, and to identify risk factors for psychological effects. In this prospective, one-year, follow-up study, a consecutive series of PUT drivers (n = 202) were compared with a group of matched control drivers (n = 186). Psychological state was assessed 15 days, 3 months and 1 year after the event, using the GHQ-28 questionnaire and a standardised diagnostic interview (the v4.4 MINI). Fifteen days after the event, PUT drivers had significantly higher GHQ-28 scores (p < 0.0001) and more acute stress disorder (p = 0.008) than control drivers. No significant differences were found 3 months and 1 year after the accident. Significant explicative variables were the presence of acute and chronic psychosocial stressors (OR = 3.30 and 3.68) and the availability of immediate help (OR = 0.46). We thus confirm previous findings that train drivers who have experienced a PUT accident experience acute psychological disturbances. Our results also highlight the utility of the systematic prevention programme provided.