Assessment of cerebral blood volume in schizophrenia: A magnetic resonance imaging study

Brain atrophy has consistently been observed in schizophrenia, representing a 'gross' evidence of anatomical abnormalities. Reduced cerebral blood volume (CBV) may accompany brain size decrement in schizophrenia, as suggested by prior small SPECT studies. In this study, we non-invasively investigated the hemisphere CBV in a large sample of patients suffering from schizophrenia with perfusion-weighted imaging (PWI). PWI images were obtained, following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), for 54 DSM-IV patients with schizophrenia (mean age+/-SD=39.19+/-12.20 years; 34 males, 20 females) and 24 normal controls (mean age+/-SD=44.63+/-10.43 years; 9 males, 15 females) with a 1.5T Siemens magnet using an echo-planar sequence (TR=2160 ms, TE=47 ms, slice thickness=5mm). The contrast of enhancement (CE), a semi-quantitative parameter inversely estimating the CBV, were calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/Sox100) for right and left hemisphere on two axial images. Specifically, higher CE values correspond to lower CBV and viceversa Compared to normal controls, patients with schizophrenia had significantly higher bilateral hemisphere CE values (p=0.02) and inverse CE laterality index (p=0.02). This study showed abnormally reduced and inverse hemisphere CBV in a large population of patients with schizophrenia. Hypothetically, chronic low CBV may sustain neural hypoactivation and concomitant increase of free radicals, ultimately resulting in neuronal loss and cognitive impairments. Thus, altered intracranial hemodynamics may accompany brain atrophy and cognitive deficits, being a crucial factor in the pathophysiology of schizophrenia.     

The association of MRI findings and neuropsychological functioning after the first recognized seizure

PURPOSE: To explore relationships between MRI abnormalities of the brain and neuropsychological functioning in children who were evaluated following their first recognized seizure. METHODS: Subjects were children aged 6 to 14 years with a first recognized seizure within the past 3 months who participated in a larger prospective study of child adaptation. The 249 children with neuropsychological testing and neuroimaging were studied. Children underwent neuropsychological examination an average of 2.8 months and MRI examination an average of 1.3 months after the first recognized seizure. On factor analysis four factors were found for neuropsychological function: LANG = Language, PS = Processing Speed, EC = Executive/ Construction, VMEM = Verbal Memory and Learning. For analysis, structural abnormalities found on MRI were classified as significant (yes/no) based on whether they were presumed to be related to the seizure condition. RESULTS: On MRI, 34 (14%) had structural abnormalities that were judged to be significant in that they were possibly related to their seizures. Children with significant abnormalities had significantly lower estimated IQ scores and significantly lower language, processing speed, executive/constructional ability, and verbal memory and learning factor scores than did children without significant abnormalities. CONCLUSIONS: Children who have structural brain abnormalities at onset have slightly lower cognitive functioning overall, and all neuropsychological domains seemed to be affected relatively equally. This pattern was apparent even when we restricted the analysis to children with intellectual functioning in the broadly normal range.     

Dissociable effects of phonetic competition and category typicality in a phonetic categorization task: an fMRI investigation

The current study used fMRI to explore the extent to which neural activation patterns in the processing of speech are driven by the quality of a speech sound as a member of its phonetic category, that is, its category typicality, or by the competition inherent in resolving the category membership of stimuli which are similar to other possible speech sounds. Subjects performed a phonetic categorization task on synthetic stimuli ranging along a voice-onset time continuum from [da] to [ta]. The stimulus set included sounds at the extreme ends of the voicing continuum which were poor phonetic category exemplars, but which were minimally competitive, stimuli near the phonetic category boundary, which were both poor exemplars of their phonetic category and maximally competitive, and stimuli in the middle of the range which were good exemplars of their phonetic category. Results revealed greater activation in bilateral inferior frontal areas for stimuli with the greatest degree of competition, consistent with the view that these areas are involved in selection between competing alternatives. In contrast, greater activation was observed in bilateral superior temporal gyri for the least prototypical phonetic category exemplars, irrespective of competition, consistent with the view that these areas process the acoustic-phonetic details of speech to resolve a token's category membership. Taken together, these results implicate separable neural regions in two different aspects of phonetic categorization.     

The neurocognitive basis of reading single words as seen through early latency ERPs: a model of converging pathways

This paper first provides a brief review of the functional neuroanatomy of reading single words, focusing on the lexical and phonological routes. Next, early (defined as peaking prior to 350 ms) reading event-related potential components are summarized. A comprehensive effort is made to organize existing observations into a coherent scheme and commentary is made on terminology. Proposals are made regarding the cognitive function reflected by each ERP component and the associated generator sites. The overall framework constitutes a neurocognitive model of reading and demonstrates how the high temporal resolution of event-related potentials can provide additional insights into the reading process beyond those available from behavioral and neuroimaging studies, with a special focus on how the two pathways implied in reading are coordinated. The present model suggests that there are two such coordinating operations, convergence processes during an initial information burst and resonance processes during an extended harmonization process that follows.     

Sustained attention in patients receiving and abstinent following methadone maintenance treatment for opiate dependence: Performance and neuroimaging results

Objective

Impairments in the function of attention exacerbate the course of opiate dependence and may play a role in the relapsing nature of the disorder. This study used clinical measures and positron emission tomography (PET) to assess the functioning of sustained attention in subjects with a history of opiate dependence.

Methods

A test of auditory sustained attention was administered to 10 subjects receiving methadone maintenance treatment, 13 formerly opiate-dependent subjects in protracted abstinence, and 14 healthy Comparison subjects. Simultaneous measurement of regional glucose metabolism was made by [¹⁸F] flourodeoxyglucose PET. Subjects groups were compared on the measures of sustained attention and regional cerebral glucose metabolism.

Results

Healthy Comparison subjects scored significantly better than either methadone-maintained or abstinent former opiate addicts on measures of sustained attention. Formerly opiate-dependent subjects in protracted abstinence scored better than methadone-maintained subjects on sustained attention. Methadone-maintained subjects demonstrated a relative reduction in regional cerebral glucose metabolism in the right supramarginal gyrus, and the thalamus bilaterally. The Comparison subjects without a history of opiate dependence demonstrated a relative increase in regional cerebral glucose metabolism in the right anterior cingulate gyrus, the right medial superior frontal gyrus and the thalamus bilaterally.

Conclusions

Subjects with a history of opiate dependence have impairments in the functioning of sustained attention, and abnormalities in brain regions identified as important in attention processing. Impairments in attention performance persist in subjects who enjoy prolonged abstinence from opiates.     

Discovery and development of brain-penetrant 18F-labeled radioligands for neuroimaging of the sigma-2 receptors

We have discovered and synthesized a series of indole-based derivatives as novel sigma-2 (σ₂) receptor ligands. Two ligands with high σ₂ receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities, and evaluated in rodents. In biodistribution studies in male ICR mice, radioligand [¹⁸F]9, or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[¹⁸F]fluoroethoxy)-1H-indole, was found to display high brain uptake and high brain-to-blood ratio. Pretreatment of animals with the selective σ₂ receptor ligand CM398 led to significant reductions in both brain uptake (29%–54%) and brain-to-blood ratio (60%–88%) of the radioligand in a dose-dependent manner, indicating high and saturable specific binding of [¹⁸F]9 to σ₂ receptors in the brain. Further, ex vivo autoradiography in male ICR mice demonstrated regionally heterogeneous specific binding of [¹⁸F]9 in the brain that is consistent with the distribution pattern of σ₂ receptors. Dynamic positron emission tomography imaging confirmed regionally distinct distribution and high levels of specific binding for [¹⁸F]9 in the rat brain, along with appropriate tissue kinetics. Taken together, results from our current study indicated the novel radioligand [¹⁸F]9 as the first highly specific and promising imaging agent for σ₂ receptors in the brain.     

Temporal lobe abnormalities in semantic processing by criminal psychopaths as revealed by functional magnetic resonance imaging

We tested the hypothesis that psychopathy is associated with abnormalities in semantic processing of linguistic information. Functional magnetic resonance imaging (fMRI) was used to elucidate and characterize the neural architecture underlying lexico-semantic processes in criminal psychopathic individuals and in a group of matched control participants. Participants performed a lexical decision task in which blocks of linguistic stimuli alternated with a resting baseline condition. In each lexical decision block, the stimuli were either concrete words and pseudowords or abstract words and pseudowords. Consistent with our hypothesis, psychopathic individuals, relative to controls, showed poorer behavioral performance for processing abstract words. Analysis of the fMRI data for both groups indicated that processing of word stimuli, compared with the resting baseline condition, was associated with neural activation in bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. Analyses confirmed our prediction that psychopathic individuals would fail to show the appropriate neural differentiation between abstract and concrete stimuli in the right anterior temporal gyrus and surrounding cortex. The results are consistent with other studies of semantic processing in psychopathy and support the theory that psychopathy is associated with right hemisphere abnormalities for processing conceptually abstract material.     

轻度认知障碍的神经影像学研究现状及进展

轻度认知障碍（MCI）是介于正常老化与痴呆之间的一种过渡阶段,向阿尔茨海默病转变的风险很高。神经影像学在轻度认知障碍的临床评价、早期诊断、预测病程及监测治疗效果中起着重要的作用。     

Identification and treatment of symptoms associated with inflammation in medically ill patients

Medically ill patients present with a high prevalence of non-specific comorbid symptoms including pain, sleep disorders, fatigue and cognitive and mood alterations that is a leading cause of disability. However, despite major advances in the understanding of the immune-to-brain communication pathways that underlie the pathophysiology of these symptoms in inflammatory conditions, little has been done to translate this newly acquired knowledge to the clinics and to identify appropriate therapies. In a multidisciplinary effort to address this problem, clinicians and basic scientists with expertise in areas of inflammation, psychiatry, neurosciences and psychoneuroimmunology were brought together in a specialized meeting organized in Bordeaux, France, on May 28-29, 2007. These experts considered key questions in the field, in particular those related to identification and quantification of the predominant symptoms associated with inflammation, definition of systemic and central markers of inflammation, possible domains of intervention for controlling inflammation-associated symptoms, and relevance of animal models of inflammation-associated symptoms. This resulted in a number of recommendations that should improve the recognition and management of inflammation-associated symptoms in medically ill patients.