There is an urgent need to improve the pharmacotherapy of schizophrenia despite the introduction of important new medications. New treatment insights may come from appreciating the therapeutic ...implications of model psychoses. In particular, basic and clinical studies have employed the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, ketamine, as a probe of NMDA receptor contributions to cognition and behavior. These studies illustrate a translational neuroscience approach for probing mechanistic hypotheses related to the neurobiology and treatment of schizophrenia and other disorders. Two particular pathophysiologic themes associated with schizophrenia, the disturbance of cortical connectivity and the disinhibition of glutamatergic activity may be modeled by the administration of NMDA receptor antagonists. The purpose of this review is to consider the possibility that agents that attenuate these two components of NMDA receptor antagonist response may play complementary roles in the treatment of schizophrenia.
This paper addresses some issues related to the nanomechanical responses of decagonal quasicrystals using nanoindentation techniques. A Hysitron Triboscope with a Berkovich indenter was used to carry ...out the nanoindentation tests on single crystals of Al-Co-Ni decagonal phase. The anisotropy in terms of nanohardness at higher load was observed, whereas it was not possible to establish the same at lower loads. However, the Young's modulus was found to be indistinguishable in all these cases. Discontinuity in load displacement, which is known as a 'pop-in' effect, was observed frequently at various load regime. It was found that this discontinuity was not due to cracking or a phase transformation effect, but to a plastic yielding phenomena and nanodeformation of the material. Significant differences between the nanohardness and microhardness were noticed and are discussed based on various experimental parameters and the consequent mechanical response of materials.
While auditory verbal hallucinations (AH) are a cardinal symptom of schizophrenia, people with a diagnosis of schizophrenia (SZ) may also experience visual hallucinations (VH). In a retrospective ...analysis of a large sample of SZ and healthy controls (HC) studied as part of the functional magnetic resonance imaging (fMRI) Biomedical Informatics Research Network (FBIRN), we asked if SZ who endorsed experiencing VH during clinical interviews had greater connectivity between visual cortex and limbic structures than SZ who did not endorse experiencing VH.
We analyzed resting state fMRI data from 162 SZ and 178 age- and gender-matched HC. SZ were sorted into groups according to clinical ratings on AH and VH: SZ with VH (VH-SZ; n = 45), SZ with AH but no VH (AH-SZ; n = 50), and SZ with neither AH nor VH (NoH-SZ; n = 67). Our primary analysis was seed based, extracting connectivity between visual cortex and the amygdala (because of its role in fear and negative emotion) and visual cortex and the hippocampus (because of its role in memory).
Compared with the other groups, VH-SZ showed hyperconnectivity between the amygdala and visual cortex, specifically BA18, with no differences in connectivity among the other groups. In a voxel-wise, whole brain analysis comparing VH-SZ with AH-SZ, the amygdala was hyperconnected to left temporal pole and inferior frontal gyrus in VH-SZ, likely due to their more severe thought broadcasting.
VH-SZ have hyperconnectivity between subcortical areas subserving emotion and cortical areas subserving higher order visual processing, providing biological support for distressing VH in schizophrenia.
Schizophrenia is commonly considered a neurodevelopmental disorder that is associated with significant morbidity; however, unlike other neurodevelopmental disorders, the symptoms of schizophrenia ...often do not manifest for decades. In most patients, the formal onset of schizophrenia is preceded by prodromal symptoms, including positive symptoms, mood symptoms, cognitive symptoms, and social withdrawal. The proximal events that trigger the formal onset of schizophrenia are not clear but may include developmental biological events and environmental interactions or stressors. Treatment with antipsychotic drugs clearly ameliorates psychotic symptoms, and maintenance therapy may prevent the occurrence of relapse. The use of atypical antipsychotic agents may additionally ameliorate the pathophysiology of schizophrenia and prevent disease progression. Moreover, if treated properly early in the course of illness, many patients can experience a significant remission of their symptoms and are capable of a high level of recovery following the initial episode. Because the clinical deterioration that occurs in schizophrenia may actually begin in the prepsychotic phase, early identification and intervention may favorably alter the course and outcome of schizophrenia.
Fronto-limbic interactions facilitate the generation of task-relevant responses while inhibiting interference from emotionally distracting information. Schizophrenia is associated with deficits in ...both executive attention and affective regulation. This study aims to elucidate the neural correlates of emotion-attention regulation and shifting in schizophrenia.
We employed functional magnetic resonance imaging to probe the fronto-limbic regions in 16 adults with schizophrenia and 13 matched adults with no history of psychiatric illness. Subjects performed a forced-choice visual oddball task where they detected infrequent target circles embedded in a series of infrequent nontarget aversive and neutral pictures and frequent squares.
In control participants, target events activated a dorsal frontoparietal network, whereas these regions were deactivated by aversive stimuli. Conversely, ventral frontolimbic brain regions were activated by aversive stimuli and deactivated by target events. In the patient group, regional hemodynamic timecourses revealed not only reduced activation to target and aversive events in dorsal executive and ventral limbic regions, respectively, but also reduced deactivation to target and aversive stimuli in ventral and dorsal regions, respectively, relative to the control group. Patients further showed reduced spatial extent of activation in the right inferior frontal gyrus during the target and aversive conditions. Activation of the anterior cingulate to aversive images was inversely related to severity of avolition and anhedonia symptoms in the schizophrenia group.
These results suggest both frontal and limbic dysfunction in schizophrenia as well as aberrant reciprocal inhibitions between these regions during attention-emotion modulation in this disorder.
In the previous paper the locations and basic response properties of N200 and other face-specific event-related potentials (ERPs) were described. In this paper responsiveness of N200 and related ERPs ...to the perceptual features of faces and other images was assessed. N200 amplitude did not vary substantially, whether evoked by colored or grayscale faces; normal, blurred or line-drawing faces; or by faces of different sizes. Human hands evoked small N200s at face-specific sites, but evoked hand-specific ERPs at other sites. Cat and dog faces evoked N200s that were 73% as large as to human faces. Hemifield stimulation demonstrated that the right hemisphere is better at processing information about upright faces and transferring it to the left hemisphere, whereas the left hemisphere is better at processing information about inverted faces and transferring it to the right hemisphere. N200 amplitude was largest to full faces and decreased progressively to eyes, face contours, lips and noses viewed in isolation. A region just lateral to face-specific N200 sites was more responsive to internal face parts than to faces, and some sites in ventral occipitotemporal cortex were face-partspecific. Faces with eyes averted or closed evoked larger N200s than those evoked by faces with eyes forward. N200 amplitude and latency were affected by the joint effects of eye and head position in the right but not in the left hemisphere. Full and three-quarter views of faces evoked larger N200s than did profile views. The results are discussed in relation to behavioral studies in humans and single-cell recordings in monkeys.
An event-related functional magnetic resonance imaging study of prefrontal cortex was conducted during which subjects performed a visual "oddball" target detection task. Exemplars of three stimulus ...categories were presented at a rate of one per 1.5 sec for 10 runs, each consisting of 132 trials. Standards were color squares of varying sizes that were presented on approximately 92% of trials. Targets were color circles of varying sizes presented irregularly on approximately 4% of trials. Novels were pictures of everyday objects that were also presented irregularly on approximately 4% of trials. Ten subjects participated in two separate sessions in which they were required to count mentally or to push a button whenever a target appeared. Targets evoked activation within prefrontal cortex, primarily within the middle frontal gyri (MFG). This MFG activation did not differ as a function of the required response. Novels did not evoke significant activity within this region despite evidence from a separate behavioral and event-related potential study demonstrating their strong influence on processing. In additional imaging sessions with two subjects, the rules were reversed to require a button press whenever an object, but not a circle, appeared. These former novels now evoked activation in the MFG, but the former target circles did not. These experiments indicate that MFG activation is reliably evoked by exemplars from arbitrary stimulus categories that are mapped by experimental rules onto an arbitrary covert or overt response.
The (111Zn) surface of single‐crystalline ZnSe was subject to nanoindentations in darkness and under illumination using white light. A positive photoplastic effect was observed in the load range from ...200 μN to 2 mN: a reduction of the penetration depth by about 5%, resulting in a reversible hardness increase by 10% under illumination. The effect was found to saturate already at 30 mW/cm2, comparable to daylight intensity. There is also a photoplastic after‐effect for some seconds, i.e. a reduced hardness increase was found after having turned off the light some seconds before performing the indent.
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