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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of high-risk offspring (HR) of schizophrenic patients have found abnormalities in attention, working memory and executive functions, suggesting impaired integrity of the prefrontal cortex and related brain regions. The authors conducted a preliminary high-field (3 T) functional magnetic resonance imaging (fMRI) study to assess performance and activation during a memory-guided saccade (MGS) task, which measures spatial working memory. HR subjects showed significant decreases in fMRI-measured activation in the dorsolateral prefrontal cortex (Brodmann's areas 8 and 9/46) and the inferior parietal cortex (Brodmann's area 40) compared to age- and sex-matched healthy controls (HC). Abnormal functional integrity of prefrontal and parietal regions of the heteromodal association cortical (HAC) regions in subjects at genetic risk for schizophrenia is consistent with findings observed in adults with the illness [Callicott et al., Cereb. Cortex 10 (2000) 1078; Manoach et al., Biol. Psychiatry 48 (2000) 99.]. These abnormalities need to be prospectively investigated in nonpsychotic individuals at risk for schizophrenia in order to determine their predictive value for eventual emergence of schizophrenia or related disorders.
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PMID:A preliminary functional magnetic resonance imaging study in offspring of schizophrenic parents. 1245 37

The rat prefrontal cortices participate in cognitive, affective and mnemonic functions. The importance of dopamine innervation for these computations is illustrated in studies showing that both supranormal levels and chemical lesions of prefrontal dopamine induce severe behavioral deficits. Observed hormone effects on some of these same behaviors suggest that the prefrontal cortices are also sensitive to gonadal steroids. These two influences seem to converge in recent evidence of increased dopamine axon density in representative prefrontal but not sensory or motor cortices in gonadectomized adult male rats. The seeming selectivity of these effects was further explored here using immunocytochemistry for tyrosine hydroxylase, dopamine-b-hydroxylase, serotonin and choline acetyltransferase to label neurochemically identified afferents in remaining, unstudied prefrontal fields of rat cortex in animals that were sham-operated or gonadectomized and given placebo, testosterone propionate, estradiol or dihydrotestosterone 28 days before being killed. Group comparisons revealed that across prefrontal zones, gonadectomy produced androgen-sensitive increases in presumed dopamine axon density, but did not affect the other afferents. These findings thus bolster evidence for a targeted gonadal steroid influence involving the prefrontal cortices and a neurotransmitter essential for their normal operations and implicated in their dysfunction in disorders such as schizophrenia as well.
Cereb Cortex 2003 Mar
PMID:Long-term gonadectomy affects the density of tyrosine hydroxylase- but not dopamine-beta-hydroxylase-, choline acetyltransferase- or serotonin-immunoreactive axons in the medial prefrontal cortices of adult male rats. 1257 Nov 18

High density electrical mapping was used to index event-related brain activity in subjects performing parametric variations of the "AX"-type continuous performance task (AX-CPT) that differentially challenge control, and informative control conditions. In the AX-CPT, subjects must use context, created by a cue stimulus, to guide response to a target. Diseases such as schizophrenia and attention deficit hyperactivity disorder (ADHD) are associated with impaired AX-CPT performance. Event-related potentials (ERP) were analyzed as a function of both global and local stimulus context. The topographical analysis revealed that well-defined ERP are elicited under conditions where subjects must override a prepotent response. Activation patterns related to overriding a prepotent response (Go to No-Go) differed markedly from those associated with overriding a prepotent non-response (No-Go to Go). Dipole source mapping suggested that withholding a prepotent response is reflected primarily in anterior cingulate/dorsolateral prefrontal cortex activity during the 350-450 ms latency range following presentation of the No-Go. In contrast, preparing to respond is reflected in parietal (including area BA 40) activity during the same latency range, followed by a prolonged frontal negativity (contingent negative variation; CNV). Similar patterns of activation were observed whether the changes in preparation were triggered by cue or target stimuli, though target-elicited potentials peaked earlier.
Cereb Cortex 2003 Jul
PMID:Changing plans: a high density electrical mapping study of cortical control. 1281 85

Awareness of self-generated movements arises from comparing motor plans, and the accompanying (hypothetical) efference copy, with the visual and proprioceptive consequences of movement. Here we used repetitive transcranial magnetic stimulation (rTMS) to investigate the role of a posterior region in the superior parietal lobule (SPL) in this process. Nine healthy volunteers performed a finger extension actively and passively while wearing a CyberGlove; the glove recorded these (actual) finger movements and used this information in real time to move a virtual hand displayed on a computer screen. To assess the participant's awareness of movement onset, we introduced a delay between the onset of the actual and virtual movement (60-270 ms, 30 ms increments); the task was to judge whether the virtual hand movements were delayed relative to the actual hand movements. Low-frequency rTMS (15 min, 0.6 Hz) was applied either over the left SPL or the left temporal cortex (control site) to decrease excitability of these regions and, in turn, test their role in the awareness of self-generated movement. Following the SPL stimulation, participants' assessments of asynchrony were impaired for active but not passive movements. No significant changes were observed after rTMS applied over the control site. We suggest that these findings are consistent with the role of the SPL in evaluating the temporal congruency of peripheral (visual) and central (efference copy) signals associated with self-generated movements. As such, this region may contribute to the sense of 'agency' and its disturbances in disorders such as apraxia and schizophrenia.
Cereb Cortex 2003 Sep
PMID:The role of parietal cortex in awareness of self-generated movements: a transcranial magnetic stimulation study. 1290 95

Auditory hallucinations are a frequent symptom in schizophrenia. While functional imaging studies have suggested the association of certain patterns of brain activity with sub-syndromes or single symptoms (e.g. positive symptoms such as hallucinations), there has been only limited evidence from structural imaging or post-mortem studies. In this study, we investigated the relation of local brain structural deficits to severity of auditory hallucinations, particularly in perisylvian areas previously reported to be involved in auditory hallucinations. In order to overcome certain limitations of conventional volumetric methods, we used deformation-based morphometry (DBM), a novel automated whole-brain morphometric technique, to assess local gray and white matter deficits in structural magnetic resonance images of 85 schizophrenia patients. We found severity of auditory hallucinations to be significantly correlated (P < 0.001) with volume loss in the left transverse temporal gyrus of Heschl (primary auditory cortex) and left (inferior) supramarginal gyrus, as well as middle/inferior right prefrontal gyri. This demonstrates a pattern of distributed structural abnormalities specific for auditory hallucinations and suggests hallucination-specific alterations in areas of a frontotemporal network for processing auditory information and language.
Cereb Cortex 2004 Jan
PMID:Neuroanatomy of "hearing voices": a frontotemporal brain structural abnormality associated with auditory hallucinations in schizophrenia. 1465 60

The prefrontal cortex plays a key role in the control of higher brain functions and is involved in the pathophysiology and treatment of schizophrenia. Here we report that approximately 60% of the neurons in rat and mouse prefrontal cortex express 5-HT(1A) and/or 5-HT2A receptor mRNAs, which are highly co-localized (approximately 80%). The electrical stimulation of the dorsal and median raphe nuclei elicited 5-HT1A-mediated inhibitions and 5-HT2A-mediated excitations in identified pyramidal neurons recorded extracellularly in rat medial prefrontal cortex (mPFC). Opposite responses in the same pyramidal neuron could be evoked by stimulating the raphe nuclei at different coordinates, suggesting a precise connectivity between 5-HT neuronal subgroups and 5-HT1A and 5-HT2A receptors in pyramidal neurons. Microdialysis experiments showed that the increase in local 5-HT release evoked by the activation of 5-HT2A receptors in mPFC by DOI (5-HT2A/2C receptor agonist) was reversed by co-perfusion of 5-HT1A agonists. This inhibitory effect was antagonized by WAY-100635 and the prior inactivation of 5-HT1A receptors in rats and was absent in mice lacking 5-HT1A receptors. These observations help to clarify the interactions between the mPFC and the raphe nuclei, two key areas in psychiatric illnesses and improve our understanding of the action of atypical antipsychotics, acting through these 5-HT receptors.
Cereb Cortex 2004 Mar
PMID:Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. 1475 68

Serotonin is involved in psychiatric disorders exhibiting abnormal prefrontal cortex (PFC) function (e.g. major depression, schizophrenia). We examined the effect of the stimulation of the dorsal and median raphe nuclei (DR and MnR, respectively) on the activity of PFC neurons. Electrical stimulation of DR/MnR inhibited 66% (115/173) of pyramidal neurons in the medial PFC (mPFC). The rest of the cases exhibited orthodromic excitations, either pure (13%) or preceded by short-latency inhibitions (20%). Excited neurons had a lower pre-stimulus firing rate than those inhibited. Excitations evoked by MnR stimulation had a shorter latency than those evoked by DR stimulation. WAY-100635 [a 5-hydroxytryptamine1A (5-HT1A) antagonist] and the selective gamma aminobutyric acidA (GABAA) antagonist picrotoxinin partially antagonized DR/MnR-evoked inhibitions, suggesting the involvement of 5-HT1A- and GABAA-mediated components. The presence of a direct DR/MnR-mPFC GABAergic component is suggested by the short latency of evoked inhibitions (9 +/- 1 ms), faster than those evoked in the secondary motor area (20 +/- 3 ms), and that of antidromic spikes evoked by DR/MnR stimulation in mPFC pyramidal neurons (15 +/- 1 ms). Stimulation of the DR/MnR with paired pulses enhanced the duration of inhibitions and turned some excitations into inhibitions. Thus, the DR/MnR control the activity of mPFC pyramidal neurons in vivo in a complex manner, involving 5-HT-mediated excitations and GABA- and 5-HT-mediated inhibitions.
Cereb Cortex 2005 Jan
PMID:Modulation of the activity of pyramidal neurons in rat prefrontal cortex by raphe stimulation in vivo: involvement of serotonin and GABA. 1523 48

Phencyclidine (PCP) is a psychotomimetic drug that elicits schizophrenia-like symptoms in healthy persons, and administration of PCP to animals is used as a pharmacological model of schizophrenia. We recently demonstrated that systemic administration of PCP to rats produces long-lasting activation of medial prefrontal cortex (mPFC) neurons with augmentation of locomotor activity, whereas direct application of PCP to mPFC neurons has little effect on their firing activity. These findings suggest that PCP-induced activation of mPFC neurons is elicited mainly via excitatory inputs from regions outside the mPFC. In the present study, we examined effects of local application of PCP to the ventral hippocampus (vHIP) on firing activity of PFC neurons in freely moving rats. PCP locally perfused into the vHIP increased spontaneous discharges of PFC neurons during perfusion with augmentation of locomotor activity. Local application of a more selective NMDA receptor antagonist, MK801, to vHIP neurons under anesthesia increased the spontaneous firing rates of most neurons directly projecting to the mPFC, whereas local application of MK801 to mPFC neurons did not induce excitatory responses in any of those neurons. The present results indicate that tonic excitatory inputs from the vHIP to the PFC may trigger development of behavioral abnormalities.
Cereb Cortex 2005 May
PMID:Activation of medial prefrontal cortex by phencyclidine is mediated via a hippocampo-prefrontal pathway. 1534 31

We mapped regional changes in cortical thickness and intensity-based cortical gray matter concentration in first episode schizophrenia. High-resolution magnetic resonance images were obtained from 72 (51 male, 21 female) first episode patients and 78 (37 male, 41 female) healthy subjects similar in age. Cortical pattern matching methods allowed comparisons of cortical thickness and gray matter concentration at thousands of homologous cortical locations between subjects in three dimensions. Principal components analyses reduced measures obtained across the cortex to identify global differences in cortical thickness/gray matter concentration. First principal component factor scores showed significant effects of diagnosis, sex and age for both cortical measures. Diagnosis and age effects remained significant after brain size correction. Cortical thickness and gray matter concentration values were highly correlated. Statistical maps showed significant regional gray matter thinning in frontal, temporal and parietal heteromodal association cortices bilaterally in first episode patients. Regional reductions in cortical gray matter concentration were similar but pronounced in the superior temporal lobe. Regional reductions in cortical thickness and gray matter concentration are present at disease onset in brain regions linked with functional disturbances in schizophrenia. Cortical thickness and gray matter concentration mapping produce similar results, although the concentration metric may be influenced by diagnostic differences in extra-cortical cerebrospinal fluid and surface curvature/complexity.
Cereb Cortex 2005 Jun
PMID:Mapping cortical thickness and gray matter concentration in first episode schizophrenia. 1537 Dec 91

Evidence is accumulating that patients with schizophrenia exhibit relatively severe deficits in early visual sensory processing within the dorsal stream, while processing within the ventral stream appears to be relatively more intact. Here, illusory contour (IC) processing was investigated in a cohort of schizophrenia patients and age-matched healthy controls using high-density visual evoked potentials (VEPs), spatiotemporal topographic analyses and the Local Auto-Regressive Average distributed linear inverse source estimation. IC processing was assessed because it is now known to be an excellent metric of early processing within regions of the ventral visual stream. Results in the present study show that IC processing (106-194 ms) is spared in patients with schizophrenia, providing strong evidence that early ventral stream processing is essentially normal. This is so despite equally strong evidence that early dorsal stream processing is severely impaired in this population, as indexed by a robust decrement in amplitude of the P1 component in patients and a large topographic difference between groups for this component (54-104 ms). Source analysis confirmed that the flow of activity into the dorsal stream was substantially decreased in patients. As such, these results suggest that some aspects of early ventral processing are not entirely reliant on intact inputs from the dorsal stream. Lastly, we show that later phases of visual processing (240-400 ms) also rely on the activity of different brain networks in controls and patients, with the latter recruiting strong frontal activity perhaps as compensation for impaired ventral stream processing during this period. We interpret the present findings in the context of a two-stage processing model. Under this model, it is suggested that the second stage of ventral stream processing is dependent on the fidelity of inputs from the dorsal visual stream and that impairment of this critical modulatory input may underlie the failure of 'higher-level' ventral stream processes in this population.
Cereb Cortex 2005 Dec
PMID:Filling-in in schizophrenia: a high-density electrical mapping and source-analysis investigation of illusory contour processing. 1577 73


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