Dysfunction of early-stage visual processing in schizophrenia: harmonic analysis

Schizophrenia is associated with severe neurocognitive deficits that constitute a core feature of the disorder. Deficits have been most extensively studied in relationship to higher-order processes. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia. Steady-state visual-evoked potentials (ssVEPs) were recorded over the occipital cortex (Oz) in patients with schizophrenia and schizoaffective disorder (N=26) and in age-matched comparison volunteers (N=22). Two stimuli were used: windmill-dartboard and partial-windmill, which are contrast-reversing ( approximately 4 Hz), radial patterns with dominant low spatial-frequency content. Each stimulus was presented for 1 min. Fourier analysis was performed on the ssVEP data to extract the relevant temporal frequency (i.e., harmonic) components. Magnitude-squared coherence (MSC) was computed to estimate the relative signal level for each frequency component. The patients showed reduced amplitude and coherence of second harmonic responses in both conditions, but intact first harmonic responses in the windmill-dartboard condition. This finding of a differential deficit may indicate a significant loss in the magnocellular pathway, which contributes to the generation of the second harmonic component under these conditions. Early sensory deficits may lead to impairments in subsequent stages of processing.     

A topography of executive functions and their interactions revealed by functional magnetic resonance imaging

We used fMRI to study the brain processes involved in the executive control of behavior. The Sustained Attention to Response Task (SART), which allows unpredictable and predictable NOGO events to be contrasted, was imaged using a mixed (block and event-related) fMRI design to examine tonic and phasic processes involved in response inhibition, error detection, conflict monitoring and sustained attention. A network of regions, including right ventral prefrontal cortex (PFC), left dorsolateral PFC (DLPFC) and right inferior parietal cortex, was activated for successful unpredictable inhibitions, while rostral anterior cingulate was implicated in error processing and the pre-SMA in conflict monitoring. Furthermore, the pattern of correlations between left dorsolateral PFC, implicated in task-set maintenance, and the pre-SMA were indicative of a tight coupling between prefrontally mediated control and conflict levels monitored more posteriorly. The results reveal that the executive control of behavior can be separated into distinct functions performed by discrete cortical regions.     

Prefrontal-subcortical dissociations underlying inhibitory control revealed by event-related fMRI

Using event-related fMRI, this study investigated the neural dynamics of response inhibition under fluctuating task demands. Fourteen participants performed a GO/NOGO task requiring inhibition of a prepotent motor response to NOGO events that occurred as part of either a Fast or Slow presentation stream of GO stimuli. We compared functional activations associated with correct withholds (Stops) required during the Fast presentation stream of stimuli to Stops required during the Slow presentation stream. A predominantly right hemispheric network was activated across conditions, consistent with previous studies. Furthermore, a functional dissociation of activations between conditions was observed. Slow Stops elicited additional activation in anterior dorsal and polar prefrontal cortex and left inferior parietal cortex. Fast Stops showed additional activation in a network that included right dorsolateral prefrontal cortex, insula and dorsal striatum. These results are discussed in terms of our understanding of the impact of preparation on the distributed network underlying response inhibition and the contribution of subcortical areas, such as the basal ganglia, to executive control processes.     

Don't think of a white bear: an fMRI investigation of the effects of sequential instructional sets on cortical activity in a task-switching paradigm

Using functional magnetic resonance imaging (fMRI), we investigated processes involved in switching between two ongoing tasks, thought to be paradigmatic of executive control processes. Subjects were considerably slower and less accurate when switching between two tasks than when repeatedly carrying out one task, so-called "switch costs." Switch costs, however, generally occur only when more than one task is associated with each stimulus type. This has led to the surmise that switch costs may be due largely to ongoing interference from previously learned stimulus-response (S-R) associations, which are no longer relevant for the task at hand. We used a paradigm that specifically assessed this hypothesis and investigated three stages. In Stage 1, a single task was carried out with each stimulus type; in Stage 2, a second novel task was introduced for each stimulus type; and in Stage 3, subjects reverted to carrying out solely the original tasks (as in Stage 1). In Stage 1, only one task was associated with each stimulus type, whereas two tasks were associated with each stimulus type in Stages 2 and 3. We compared images obtained during Stage 3 to those obtained during Stage 1 and show that during Stage 3, there was robust activation in the network of areas associated with the Stage 2 tasks, even though these tasks were no longer relevant. Our data strongly suggest that switch costs may derive largely from continued activation of areas associated with carrying out the now-irrelevant task(s). We posit that a large component of executive control processes involves resolution of competition between potentially relevant tasks. Our data also revealed widespread activation of a frontoparietal network of areas, and we discuss how this network might be involved in mediating this competition.     

Hepatic MR imaging with ferumoxides: multicenter study of safety and effectiveness of direct injection protocol

PURPOSE: To compare the safety and effectiveness of an undiluted direct injection of ferumoxides with those of a diluted slow infusion of ferumoxides during 30 minutes in patients with known liver lesions or in those suspected of having them. MATERIALS AND METHODS: Two hundred thirty-three patients at 16 institutions were randomized to receive either an undiluted direct injection of 0.56 mg of iron per kilogram of body weight of ferumoxides administered during 2 minutes (2 mL/min) or a diluted slow infusion administered during 30 minutes. Safety was assessed with monitoring for adverse events and laboratory tests. For sensitivity, specificity, and accuracy analysis, two independent blinded observers identified and classified lesions as benign or malignant with precontrast images and with pre- and postcontrast images combined. RESULTS: There was no statistically significant difference in adverse events in the group with direct injection compared with those in the group with infusion (21 [18%] of 114 patients vs 19 [17%] of 112 patients, respectively). No serious adverse events were observed. The most common adverse events in the group with direct injection versus the group with infusion were headache (five [4%] of 114 vs three [3%] of 112, respectively) and back pain (five [4%] of 114 vs three [3%] of 112, respectively). Overall, in 68 (62%) of 109 patients with direct injection and 71 (66%) of 108 patients with infusion, additional magnetic resonance (MR) imaging information was obtained after ferumoxides administration (P =.67). Sensitivity, specificity, and accuracy for the diagnosis of malignancy were significantly improved by adding images obtained after ferumoxides administration to the images obtained before contrast agent administration (P <.05 for all comparisons). CONCLUSION: Direct injection of ferumoxides has safety and effectiveness profiles similar to those of slow infusion of the agent. Further findings indicate that the addition of ferumoxides increases the sensitivity and specificity of hepatic MR evaluation when compared with unenhanced MR imaging.     

Reversal of phencyclidine-induced prepulse inhibition deficits by clozapine in monkeys

Rationale Prepulse inhibition (PPI) of the acoustic startle reflex is a measure of sensorimotor gating, which occurs across species and is deficient in severe neuropsychiatric disorders such as schizophrenia. In monkeys, as in rodents, phencyclidine (PCP) induces schizophrenia-like deficits in PPI. In rodents, in general, typical antipsychotics (e.g. haloperidol) reverse PPI deficits induced by dopamine (DA) agonists (e.g. apomorphine), but not those induced by N-methyl-d-aspartate (NMDA) receptor antagonists [e.g. phencyclidine (PCP)], whereas atypical antipsychotics (e.g. clozapine) reverse PPI deficits induced by DA agonists and NMDA antagonists. However, some discrepancies exist with some compounds and strains of rodents.Objectives This study investigated whether a typical (haloperidol, 0.035 mg/kg) and an atypical (clozapine, 2.5 mg/kg) antipsychotic could be distinguished in their ability to reverse PCP-induced deficits in PPI in eight monkeys (Cebus apella).Methods First, haloperidol dose was determined by its ability to attenuate apomorphine-induced deficits in PPI. Then, haloperidol and clozapine were tested in eight monkeys with PCP-induced deficits of PPI. Experimental parameters were similar to standard human PPI procedures, with 115 dB white noise startle pulses, either alone or preceded by 120 ms with a prepulse 16 dB above the 70 dB background noise.Results Clozapine reversed PCP-induced PPI deficits. In contrast, haloperidol did not significantly attenuate PCP-induced PPI deficits even at doses that significantly attenuated apomorphine effects.Conclusions In this primate model, clozapine was distinguishable from haloperidol by its ability to attenuate PCP-induced deficits in PPI. The results provide further evidence that PPI in nonhuman primates may provide an important animal model for the development of novel anti-schizophrenia medications.     

Right hemisphere control of visuospatial attention: line-bisection judgments evaluated with high-density electrical mapping and source analysis

The "line-bisection" task has proven an especially useful clinical tool for assessment of spatial neglect syndrome in neurological patients. Here, we investigated the neural processes involved in performing this task by recording high-density event-related potentials from 128 scalp electrodes in normal observers. We characterized a robust net negative potential from 170-400 ms poststimulus presentation that correlates with line-bisection judgments. Topographic mapping shows three distinct phases to this negativity. The first phase (approximately 170-190 ms) has a scalp distribution exclusively over the right parieto-occipital and lateral occipital scalp, consistent with generators in the region of the right temporo-parietal junction and right lateral occipital cortices. The second phase (approximately 190-240 ms) sees the emergence of a second negative focus over the right central parietal scalp, consistent with subsequent involvement of right superior parietal cortices. In the third phase (approximately 240-400 ms), the topography becomes dominated by this right central parietal negativity. Inverse source modeling confirmed that right hemisphere lateral occipital, inferior parietal, and superior parietal regions were the likeliest generators of the bulk of the activity associated with this effect. The line stimuli were also presented at three contrast levels (3, 25, and 100%) in order to manipulate both the latency of stimulus processing and the relative contributions from magnocellular and parvocellular inputs. Through this manipulation, we show that the line-bisection effect systematically tracks/follows the latency of the N1 component, which is considered a temporal marker for object processing in the ventral visual stream. This pattern of effects suggests that this task invokes an allocentric (object-based) form of visuospatial attention. Further, at 3% contrast, the line-bisection effect was equivalent to the effects seen at higher contrast levels, suggesting that parvocellular inputs are not necessary for successful performance of this task.     

Diagnostic value of a psychological test in cases of suspected child abuse

The use of the Bene-Anthony Family Relations Test is described and illustrated by three examples of child abuse. This test should be considered in the investigation of definite or suspected cases of abuse and as part of the preparation of court evidence.     

The physics of FeldenkraisPart 3: stability

In the last article in this series, we briefly examined the Principle of Least Effort and the five forms of strain. Strain, you may recall, in physics, describes a change in the volume of a material when a force is applied. Our treatments are a blend of rotation and translation movements of our hands with a changing mix of strains being applied onto the client's tissues. Harnessing and interweaving the various forms of strain with dexterity may aid us in improving our treatment efficacy.In this tissue, we will consider the importance of anchorage and stability in treatment, We will consider a set of ‘House Rules' for improving treatment. In addition, we will explore Bernstein's concept of degrees of freedom.