Word and letter string processing networks in schizophrenia: evidence for anomalies and compensation

Imaging studies show that in normal language correlated activity between anterior and posterior brain regions increases as the linguistic and semantic content (i.e., from false fonts, letter strings, pseudo words, to words) of stimuli increase. In schizophrenia however, disrupted functional connectivity between frontal and posterior brain regions has been frequently reported and these disruptions may change the nature of language organization. We characterized basic linguistic operations in word and letter string processing in a region-of-interest network using structural equation modeling (SEM). Healthy volunteers and volunteers with schizophrenia performed an fMRI one-back matching task with real words and consonant letter strings. We hypothesized that left hemisphere network dysfunction in schizophrenia would be present during processes dealing with linguistic/semantic content. The modeling results suggest aberrant left hemisphere function in schizophrenia, even in tasks requiring minimal access to language. Alternative mechanisms included increases in right hemisphere involvement and increased top-down influence from frontal to posterior regions.     

Functional Magnetic Resonance Imaging of Language in Epilepsy

Functional magnetic resonance imaging (fMRI) has revolutionized our understanding of functional networks and cerebral organization in both normal and pathological brains. In the present review, we describe the use of fMRI for mapping language in epilepsy patients prior to surgical intervention including a discussion of methodological issues and task design, comparisons between fMRI and the intracarotid sodium amobarbital test, fMRI studies of language reorganization, and the use of fMRI laterality indexes to predict outcome after anterior temporal lobectomy.     

Functional MRI of Language in Aphasia: A Review of the Literature and the Methodological Challenges

Animal analogue studies show that damaged adult brains reorganize to accommodate compromised functions. In the human arena, functional magnetic resonance imaging (fMRI) and other functional neuroimaging techniques have been used to study reorganization of language substrates in aphasia. The resulting controversy regarding whether the right or the left hemisphere supports language recovery and treatment progress must be reframed. A more appropriate question is when left-hemisphere mechanisms and when right-hemisphere mechanisms support recovery of language functions. Small lesions generally lead to good recoveries supported by left-hemisphere mechanisms. However, when too much language eloquent cortex is damaged, right-hemisphere structures may provide the better substrate for recovery of language. Some studies suggest that recovery is particularly supported by homologues of damaged left-hemisphere structures. Evidence also suggests that under some circumstances, activity in both the left and right hemispheres can interfere with recovery of function. Further research will be needed to address these issues. However, daunting methodological problems must be managed to maximize the yield of future fMRI research in aphasia, especially in the area of language production. In this review, we cover six challenges for imaging language functions in aphasia with fMRI, with an emphasis on language production: (1) selection of a baseline task, (2) structure of language production trials, (3) mitigation of motion-related artifacts, (4) the use of stimulus onset versus response onset in fMRI analyses, (5) use of trials with correct responses and errors in analyses, and (6) reliability and stability of fMRI images across sessions. However, this list of methodological challenges is not exhaustive. Once methodology is advanced, knowledge from conceptually driven fMRI studies can be used to develop theoretically driven, mechanism-based treatments that will result in more effective therapy and to identify the best patient candidates for specific treatments. While the promise of fMRI in the study of aphasia is great, there is much work to be done before this technique will be a useful clinical tool.     

Neuroplastic Changes Following Social Cognition Training in Schizophrenia: A Systematic Review

Social cognitive impairment is a key feature of schizophrenia and social cognition training (SCT) is a promising tool to address these deficits. Neurobiological dysfunction in schizophrenia has been widely researched, but neuronal changes induced by SCT have been scarcely explored. This review aims to assess the neuroplastic effects of SCT in patients with schizophrenia spectrum disorders. PubMed and Web of Science databases were searched for clinical trials testing the effects of SCT in functional and structural brain measurements of adult patients with schizophrenia or schizoaffective disorders. A total of 11 studies were included: five used fMRI, two used EEG and ERP, one used ERP only, two used MEG and one study used MRI. Data extracting and processing regarding sociodemographic and clinical variables, intervention characteristics, neuroimaging procedures, neuroplastic findings, effect sizes and study quality criteria was completed by two raters. Results indicate a wide range of structural and functional changes in numerous regions and circuits of the social brain, including early perceptual areas, the limbic system and prefrontal regions. Despite the small number of trials currently available, evidence suggests that SCT is associated with neuroplastic changes in the social brain and concomitant improvements in social cognitive performance. There is a lack of extensive knowledge about the neural mechanisms that underlie social cognitive enhancement after treatment, but the reported findings may shed light on the neural substrates of social cognitive impairment in schizophrenia and how improved treatment procedures can be developed and applied.     

Pre-Surgical Language Mapping with Functional Magnetic Resonance Imaging

Patients with lesions in or near eloquent cortex typically undergo one of several invasive techniques to prevent loss of function following surgery. One of the most promising potential clinical applications of functional magnetic resonance imaging (fMRI) is to map these functions as part of the pre-surgical work-up to identify patients at-risk, guide the surgical entry, or tailor the surgical procedure to prevent deficits. While motor and sensory mapping are relatively straightforward, language mapping is far more complex. The language system is variable in location across individuals and in many cases may reorganize partially or completely to the contralateral hemisphere. In addition, multiple regions of the brain contribute to language functioning including essential regions that must not be removed in surgery, and contributory regions that may result in transient or insignificant impairments post-surgery. Despite these challenges, an increasing number of studies have supported the use of fMRI for pre-surgical language mapping in a variety of disorders. This article reviews the literature from three disorders for which patients benefit from preoperative language mapping: epilepsy, brain tumors, and arteriovenous malformations. Each disorder presents unique challenges to language mapping. Specific case studies are presented highlighting the both the potential benefits of preclinical fMRI for language mapping as well as the potential risks and pitfalls.     

Should Psychology Ignore the Language of the Brain?

ABSTRACT— Claims that neuroscientific data do not contribute to our understanding of psychological functions have been made recently. Here I argue that these criticisms are solely based on an analysis of functional magnetic resonance imaging (fMRI) studies. However, fMRI is only one of the methods in the toolkit of cognitive neuroscience. I provide examples from research on event-related brain potentials (ERPs) that have contributed to our understanding of the cognitive architecture of human language functions. In addition, I provide evidence of (possible) contributions from fMRI measurements to our understanding of the functional architecture of language processing. Finally, I argue that a neurobiology of human language that integrates information about the necessary genetic and neural infrastructures will allow us to answer certain questions that are not answerable if all we have is evidence from behavior.     

运动、语言和学习：小脑的功能磁共振成像研究

对小脑功能的认识在过去的100年里经历了缓慢而稳定的发展。在最近20年,随着活体神经影像技术尤其是功能磁共振成像（fMRI）的出现,这一领域取得了更加显著的进展。文章简要总结了我们最近关于小脑的fMRI研究,考察了该结构在运动、语言和学习任务中的作用;并通过回顾相关文献,讨论了这些研究的理论意义。小脑的功能本质似乎是一般性的而非通道特异的,动态的而非静态的,联系的而非孤立的。作者提出,研究小脑与大脑之间的相互作用和合作机制将是小脑研究领域的新的生长点     

Test-retest reliability of fMRI during nonverbal semantic decisions in moderate-severe nonfluent aphasia patients

Cortical reorganization in poststroke aphasia is not well understood. Few studies have investigated neural mechanisms underlying language recovery in severe aphasia patients, who are typically viewed as having a poor prognosis for language recovery. Although test-retest reliability is routinely demonstrated during collection of language data in single-subject aphasia research, this is rarely examined in fMRI studies investigating the underlying neural mechanisms in aphasia recovery. The purpose of this study was to acquire fMRI test-retest data examining semantic decisions both within and between two aphasia patients. Functional MRI was utilized to image individuals with chronic, moderate-severe nonfluent aphasia during nonverbal, yes/no button-box semantic judgments of iconic sentences presented in the Computer-assisted Visual Communication (C-ViC) program. We investigated the critical issue of intra-subject reliability by exploring similarities and differences in regions of activation during participants' performance of identical tasks twice on the same day. Each participant demonstrated high intra-subject reliability, with response decrements typical of task familiarity. Differences between participants included greater left hemisphere perilesional activation in the individual with better response to C-ViC training. This study provides fMRI reliability in chronic nonfluent aphasia, and adds to evidence supporting differences in individual cortical reorganization in aphasia recovery.     

Structural and functional imaging in children with partial epilepsy

Imaging plays an increasingly important role in the evaluation of children with complex partial seizures. Most partial epilepsy, especially of temporal lobe origin, begins during childhood. Structural imaging with high-resolution MRI can help identify the etiology of partial seizure disorders in many children. MRI studies also show the more widespread effect of seizures on brain structure. Progressive volume loss of the hippocampal formation in some patients with temporal lobe epilepsy provides evidence that continued seizures may be associated with progressive neuronal injury. FDG-PET studies show regional decreases in glucose consumption in the cortical zone from which seizures arise. Functional abnormalities often are more extensive than the seizure focus. Studies in children with recent-onset epilepsy show that metabolic abnormalities are considerably less common than in adults with partial epilepsy, supporting the notion that in some patients there may be progressive metabolic changes that occur with continued seizures. Functional MRI may be used to identify language areas in children with partial epilepsy. fMRI language tasks reliably identify the dominant hemisphere for language dominance when compared to the intracarotid amytal procedure. Tests of verbal fluency and semantic decision identify frontal lobe language areas, while reading text paradigms and auditory passage paradigms are better for identifying temporal language areas. A panel of paradigms is best used to identify language areas in children being considered for epilepsy surgery. fMRI is a valuable tool for elucidating the impact of chronic neurologic disease states on the functional organization of language networks during development.     

Brain network interactions in auditory, visual and linguistic processing

In the paper, we discuss the importance of network interactions between brain regions in mediating performance of sensorimotor and cognitive tasks, including those associated with language processing. Functional neuroimaging, especially PET and fMRI, provide data that are obtained essentially simultaneously from much of the brain, and thus are ideal for enabling one to assess interregional functional interactions. Two ways to use these types of data to assess network interactions are presented. First, using PET, we demonstrate that anterior and posterior perisylvian language areas have stronger functional connectivity during spontaneous narrative production than during other less linguistically demanding production tasks. Second, we show how one can use large-scale neural network modeling to relate neural activity to the hemodynamically-based data generated by fMRI and PET. We review two versions of a model of object processing - one for visual and one for auditory objects. The regions comprising the models include primary and secondary sensory cortex, association cortex in the temporal lobe, and prefrontal cortex. Each model incorporates specific assumptions about how neurons in each of these areas function, and how neurons in the different areas are interconnected with each other. Each model is able to perform a delayed match-to-sample task for simple objects (simple shapes for the visual model; tonal contours for the auditory model). We find that the simulated electrical activities in each region are similar to those observed in nonhuman primates performing analogous tasks, and the absolute values of the simulated integrated synaptic activity in each brain region match human fMRI/PET data. Thus, this type of modeling provides a way to understand the neural bases for the sensorimotor and cognitive tasks of interest.     

Researching the Family Theories of Schizophrenia: An Exercise in Epistemological Confusion

Some, but not all, of the family theories of schizophrenia entail a shift from the Aristotelian/Cartesian/Newtonian epistemology of individual psychology to a systemic epistemology of pattern. Perhaps the most significant (and underappreciated) aspect of this epistemological shift pertains to etiology: The family theories of schizophrenia espoused by Bateson et al. and by Wynne and Singer do not claim that parents or families cause schizophrenia. The persistent failure of researchers to appreciate this has led to many fruitless studies that have sought to discover a causal link between the thought disorder and communication deviance of parents and the schizophrenia of their offspring. This paper reviews from an epistemological viewpoint the empirical literature that has attempted to assess the validity of the family theories of schizophrenia. Particular attention is given to restating and extending the epistemology of pattern within which schizophrenia occurs. The conventional psychiatric approaches to schizophrenia are shown to play an active role within the schizophrenic pattern.     

Magnetic resonance perfusion imaging in the study of language

This paper provides a brief review of various uses of magnetic resonance perfusion imaging in the investigation of brain/language relationships. The reviewed studies illustrate how perfusion imaging can reveal areas of brain where dysfunction due to low blood flow is associated with specific language deficits, and where restoration of blood flow to improve the tissue function results in recovery of those deficits. This sort of evidence helps to reveal areas of the brain that are essential to a particular language task. Other studies have provided clues regarding the mechanisms of early language recovery, or have shown how perfusion imaging can identify patients with chronic hypoperfusion due to cerebrovascular stenosis in whom the BOLD effect in fMRI may be absent or reduced in areas of neural activation.     

Putative sex differences in verbal abilities and language cortex: a critical review

This review brings together evidence from a diverse field of methods for investigating sex differences in language processing. Differences are found in certain language-related deficits, such as stuttering, dyslexia, autism and schizophrenia. Common to these is that language problems may follow from, rather than cause the deficit. Large studies have been conducted on sex differences in verbal abilities within the normal population, and a careful reading of the results suggests that differences in language proficiency do not exist. Early differences in language acquisition show a slight advantage for girls, but this gradually disappears. A difference in language lateralization of brain structure and function in adults has also been suggested, perhaps following size differences in the corpus callosum. Neither of these claims is substantiated by evidence. In addition, overall results from studies on regional grey matter distribution using voxel-based morphometry, indicate no consistent differences between males and females in language-related cortical regions. Language function in Wada tests, aphasia, and in normal ageing also fails to show sex differentiation.     

Functional neuroimaging studies of syntactic processing

This paper reviews studies of the functional neuroanatomy of syntactic processing using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), focusing on interpretability of studies and the model of functional neuroanatomy that emerges from existing work. It is argued that existing studies suggest a specialization for one aspect of syntactic processing in the left inferior frontal cortex in proficient language users, with variability in this localization across the entire population.     

Multichannel fNIRS assessment of overt and covert confrontation naming

Confrontation naming tasks assess cognitive processes involved in the main stage of word production. However, in fMRI, the occurrence of movement artifacts necessitates the use of covert paradigms, which has limited clinical applications. Thus, we explored the feasibility of adopting multichannel functional near-infrared spectroscopy (fNIRS) to assess language function during covert and overt naming tasks. Thirty right-handed, healthy adult volunteers underwent both naming tasks and cortical hemodynamics measurement using fNIRS. The overt naming task recruited the classical left-hemisphere language areas (left inferior frontal, superior and middle temporal, precentral, and postcentral gyri) exemplified by an increase in the oxy-Hb signal. Activations were bilateral in the middle and superior temporal gyri. However, the covert naming task recruited activation only in the left-middle temporal gyrus. The activation patterns reflected a major part of the functional network for overt word production, suggesting the clinical importance of fNIRS in the diagnosis of aphasic patients.     

Lateralized lexical decision in schizophrenia: hemispheric specialization and interhemispheric lexicality priming

Reports of left-hemisphere dysfunction and abnormal interhemispheric transfer in schizophrenia are mixed. The authors used a unified paradigm, the lateralized lexical decision task, to assess hemispheric specialization in word recognition, hemispheric error monitoring, and interhemispheric transfer in male, right-handed participants with schizophrenia (n=34) compared with controls (n=20). Overall, performance and error monitoring were worse in patients. However, patients like controls showed left-hemisphere superiority for lexical processing and right-hemisphere superiority for error monitoring. Only patients showed selective-interhemispheric lexicality priming for accuracy, in which performance improved when the lexical status of target and distractor stimuli presented to each hemifield was congruent. Results suggest that schizophrenia is associated with impaired monitoring and with increased interhemispheric automatic information transfer rather than with changed hemispheric specialization for language or error monitoring.     

文盲与非文盲汉字字形和语音加工的脑机制

利用功能性磁共振成像(fMRI)技术探讨文盲和非文盲汉字字形和语音加工脑机制的差异。实验1使用汉字字形和图形比较了中国人文盲和非文盲字形加工过程脑机制的左侧差异。实验2使用汉字语音和纯音比较了文盲和非文盲语音加工过程脑机制的双侧差异。结果表明文盲与非文盲汉字字形和语音加工脑机制不同,且非文盲的脑活动强。     

fMRI responses to Jung's Word Association Test: implications for theory,treatment and research

Jung's Word Association Test was performed under fMRI conditions by 12 normal subjects. Pooled complexed responses were contrasted against pooled neutral ones. The fMRI activation pattern of this generic ‘complexed response’ was very strong (corrected Z scores ranging from 4.90 to 5.69). The activation pattern in each hemisphere includes mirror neurone areas that track ‘otherness’ (perspectival empathy), anterior insula (both self‐awareness and emotional empathy), and cingulated gyrus (self‐awareness and conflict‐monitoring). These are the sites described by Siegel and colleagues as the ‘resonance circuitry’ in the brain which is central to mindfulness (awareness of self) and empathy (sense of the other), negotiations between self awareness and the ‘internal other’. But there is also an interhemispheric dialogue. Within 3 seconds, the left hemisphere over‐rides the right (at least in our normal subjects). Mindfulness and empathy are central to good psychotherapy, and complexes can be windows of opportunity if left‐brain hegemony is resisted. This study sets foundations for further research: (i) QEEG studies (with their finer temporal resolution) of complexed responses in normal subjects (ii) QEEG and fMRI studies of complexed responses in other conditions, like schizophrenia, PTSD, disorders of self organization.     

Common fronto-parietal activity in attention, memory, and consciousness: shared demands on integration?

Fronto-parietal activity has been frequently observed in fMRI and PET studies of attention, working memory, and episodic memory retrieval. Several recent fMRI studies have also reported fronto-parietal activity during conscious visual perception. A major goal of this review was to assess the degree of anatomical overlap among activation patterns associated with these four functions. A second goal was to shed light on the possible cognitive relationship of processes that relate to common brain activity across functions. For all reviewed functions we observed a consistent and overlapping pattern of brain activity. The overlap was most pronounced for the bilateral parietal cortex (BA 7 and BA 40; close to the intraparietal sulcus), and dorsolateral prefrontal cortex (right BA 9 and left BA 6). The common fronto-parietal activity will be discussed in terms of processes related to integration of distributed representations in the brain.