Neuroimaging insights into the pathophysiology of sleep disorders

Neuroimaging methods can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. However, it is still unclear how these new data might improve our understanding of the pathophysiology underlying adult sleep disorders. Here we review functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). The studies reviewed include neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy), metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging), and ligand marker measurements. Based on the current state of the research, we suggest that brain imaging is a useful approach to assess the structural and functional correlates of sleep impairments as well as better understand the cerebral consequences of various therapeutic approaches. Modem neuroimaging techniques therefore provide a valuable tool to gain insight into possible pathophysiological mechanisms of sleep disorders in adult humans.     

Functional neuroimaging findings in healthy middle-aged adults at risk of Alzheimer’s disease

It is well established that the neurodegenerative process of Alzheimer's disease (AD) begins many years before symptom onset. This preclinical phase provides a crucial time-window for therapeutic intervention, though this requires biomarkers that could evaluate the efficacy of future disease-modification treatments in asymptomatic individuals. The last decade has witnessed a proliferation of studies characterizing the temporal sequence of the earliest functional and structural brain imaging changes in AD. These efforts have focused on studying individuals who are highly vulnerable to develop AD, such as those with familial genetic mutations, susceptibility genes (i.e. apolipoprotein epsilon-4 allele), and/or a positive family history of AD. In this paper, we review the rapidly growing literature of functional imaging changes in cognitively intact individuals who are middle-aged: positron emission tomography (PET) studies of amyloid deposition, glucose metabolism, as well as arterial spin labeling (ASL), task-dependent, resting-state functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) studies. The prevailing evidence points to early brain functional changes in the relative absence of cognitive impairment and structural atrophy, although there is marked variability in the directionality of the changes, which could, in turn, be related to antagonistic pleiotropy early in life. A common theme across studies relates to the spatial extent of these changes, most of which overlap with brain regions that are implicated in established AD. Notwithstanding several methodological caveats, functional imaging techniques could be preferentially sensitive to the earliest events of AD pathology prior to macroscopic grey matter loss and clinical manifestations of AD. We conclude that while these techniques have great potential to serve as biomarkers to identify at-risk individuals, more longitudinal studies with greater sample size and robust correction for multiple comparisons are still warranted to establish their utility.     

Effect of finger tracking combined with electrical stimulation on brain reorganization and hand function in subjects with stroke

Synergism of rehabilitative interventions could maximize recovery following stroke. We examined whether the combination of peripherally initiated electrical stimulation of finger extensors and centrally operating finger tracking training could accentuate brain reorganization and its relationship to recovery, beyond the effects of either treatment alone. Twenty subjects with stroke were randomly assigned to an electrical stimulation (ES), tracking training (TR) or combination (CM) group. Each group was trained for ten 1-h sessions over 2–3 weeks. Pretest and posttest measurements consisted of the Box and Block and Jebsen Taylor tests of manual dexterity and a finger tracking test that was performed during functional magnetic resonance imaging (fMRI). fMRI variables included laterality index and BOLD signal intensity of primary motor (M1), primary sensory (S1), sensorimotor (SMC) and premotor (PMC) cortices as well as, supplementary motor area (SMA). ES and CM groups improved on dexterity, whereas the TR group did not. Improvement in the CM group was not greater than the other two groups. Subjects who had an intact M1 showed greater functional improvement than those who had direct involvement of M1. fMRI analysis did not yield significant changes from pretest to posttest. In the CM group only, functional improvement was positively correlated with laterality index change in M1, S1, SMC and PMC, indicating greater ipsilesional control and was negatively correlated with BOLD Signal Intensity change in ipsilesional S1 and SMA, indicating neurophysiological trimming of irrelevant neurons. The correlational results suggest that the combined intervention may be more influential on brain reorganization than either treatment alone but a larger sample size, longer duration of training, or a restricted inclusion of stroke location and volume may be needed to demonstrate a difference in efficacy for producing behavioral changes.     

Sleep-dependent motor memory plasticity in the human brain

Growing evidence indicates a role for sleep in off-line memory processing, specifically in post-training consolidation. In humans, sleep has been shown to trigger overnight learning on a motor-sequence memory task, while equivalent waking periods produce no such improvement. But while the behavioral characteristics of sleep-dependent motor learning become increasingly well characterized, the underlying neural basis remains unknown. Here we present functional magnetic resonance imaging data demonstrating a change in the representation of a motor memory after a night of sleep. Subjects trained on a motor-skill memory and 12 hours later, after either sleep or wake, were retested during functional magnetic resonance imaging. Following sleep relative to wake, regions of increased activation were expressed in the right primary motor cortex, medial prefrontal lobe, hippocampus and left cerebellum; changes that can support faster motor output and more precise mapping of key-press movements. In contrast, signal decreases were identified in parietal cortices, the left insular cortex, temporal pole and fronto-polar region, reflecting a reduced need for conscious spatial monitoring and a decreased emotional task burden. This evidence of an overnight, systems-level change in the representation of a motor memory holds important implications for acquiring real-life skills and in clinical rehabilitation following brain trauma, such as stroke.     

Plastic changes of motor network after constraint-induced movement therapy

The effects of short-term constraint-induced movement (CIM) therapy on the activation of the motor network were investigated with functional magnetic resonance imaging (fMRI). Movement of the less-affected arms of five patients was restricted and intensive training of the affected upper limb was performed. Functional MRI was acquired before and after two-weeks of CIM therapy. All patients showed significant improvement of motor function in their paretic limbs after CIM therapy. For three patients, new activation in the contralateral motor/premotor cortices was observed after CIM therapy. Increased activation of the ipsilateral motor cortex and SMA was observed in the other patient. Our results demonstrated that plastic changes of the motor network occurred as a neural basis of the improvement subsequent to CIM therapy following brain injury.     

Compensatory mechanisms in the aging motor system

Motor functions decline with age due to a number of factors. There is interest in whether these changes are reflected in the organisation of the cerebral motor system in older subjects and whether such changes might be in some way compensatory. Most studies in humans have used functional brain imaging techniques to compare motor system activation in younger and older subjects. Interpretation of these results is made more difficult by potential neurovascular changes in older subjects. However, in general, there appears to be greater motor task-related brain activity in a wider network of brain regions in older compared to younger subjects. The evidence that these changes are compensatory in nature is less clear. Incorporation of behavioural and anatomical data will be required in order to fully interpret the functional imaging results.     

Mapping genetic influences on the corticospinal motor system in humans

It is becoming increasingly clear that genetic variations account for a certain amount of variance in the acquisition and maintenance of different skills. Until now, several levels of genetic influences were examined, ranging from global heritability estimates down to the analysis of the contribution of single nucleotide polymorphisms (SNP) and variable number tandem repeats. In humans, the corticospinal motor system is essential to the acquisition of fine manual motor skills which require a finely tuned coordination of activity in distal forelimb muscles. Here we review recent brain mapping studies that have begun to explore the influence of functional genetic variation as well as mutations on function and structure of the human corticospinal motor system, and also the clinical implications of these studies. Transcranial magnetic stimulation of the primary motor hand area revealed a modulatory role of the common val66met polymorphism in the BDNF gene on corticospinal plasticity. Diffusion-sensitive magnetic resonance imaging has been employed to pinpoint subtle structural changes in corticospinal motor projections in individuals carrying a mutation in genes associated with motor neuron degeneration. These studies underscore the potential of non-invasive brain mapping techniques to characterize the genetic influence on the human corticospinal motor system.     

Age-dependent changes in the neural correlates of force modulation: an fMRI study

Functional imaging studies in humans have demonstrated widespread age-related changes in cortical motor networks. However, the relative contribution of cortical regions during motor performance varies not only with age but with task parameters. In this study, we investigated whether motor system activity during a task involving increasingly forceful hand grips was influenced by age. Forty right-handed volunteers underwent functional magnetic brain imaging whilst performing repetitive isometric hand grips with either hand in separate sessions. We found no age-related changes in the average size and shape of the task-related blood oxygen level dependent (BOLD) signal in contralateral primary motor cortex (M1), but did observe reduced ipsilateral M1 deactivation in older subjects (both hands). Furthermore, task-related activity co-varied positively with force output in a number of brain regions, but was less prominent with advancing age in contralateral M1, cingulate sulcus (both hands), sensory and premotor cortices (right hand). These results indicate that a reduced ability to modulate activity in appropriate motor networks when required may contribute to age-related decline in motor performance.     

Magnetic resonance imaging in multiple sclerosis

The contribution of magnetic resonance imaging techniques to the clinical prognosis of multiple sclerosis. Magnetic resonance imaging (MRI) is a diagnostic technique with a high sensitivity for the detection of lesions, but with a poor pathological specificity. In the case of multiple sclerosis (MS), the improvement of diagnostic efficacy depends on a careful analysis of the clinical presentation and the use of increasingly stringent MRI criteria aimed at improving the specificity of the conventional MRI T2 sequences. New sequences such as fast spin-echo (also called turbo spin-echo) and FLAIR (fluid attenuated inversion recovery, a method derived from inversion recovery) have improved the visualization of lesions. MRI can under certain conditions be used to monitor the evolution of MS. Acute-phase monitoring is focused on observed changes in disease activity such as the appearance, recurrence or extension of lesions after i.v. injection of contrast medium, i.e., gadolinium (Gd)-enhanced MRI. In the chronic phase, the lesions is the aspect used as the monitoring criterion. However, MRI is still only a secondary criterion in phase III therapeutic trials due to its insufficient correlation with the disability. In neurological daily practice, conventional MRI is only of limited interest at the individual level in patient follow-up, as its prognostic value is poor. Moreover, the difficulty in determining the lesion load can only be excluded in the context of clinical trials, in which certain methodological precautions are taken. This is why techniques other than MRI are being investigated to obtain a better correlation with the clinical course of the disease, for instance the quantification of 'black holes' on T1 weighted images, and the measurement of cerebral and spinal atrophy. Adapted MRI techniques allow a weighted signal to be obtained via the movement (diffusion imaging), by the complexity of the molecular structure (magnetization transfer imaging), by chemical shift (spectroscopic imaging), or by local oxygenation (functional MRI). These new MRI techniques allow a more precise assessment of the pathological mechanisms involved in MS, such as edema, blood brain barrier break-down, demyelinisation, gliosis, cellular infiltration and axonal loss; they provide a better means of establishing the correlation between clinical impact and the destructive nature of the MS lesion. The importance of axonal loss has recently been confirmed in MS by analyzing MRI spectroscopic and neuropathological findings. In addition to magnetization transfer imaging, MR diffusion imaging and functional MRI are being intensively studied in order to assess their contribution to the study of reversibility of the degenerative process.     

Pain and emotion in the insular cortex: evidence for functional reorganization in major depression

Huntington's Disease (HD) is a neurodegenerative disease caused by a CAG triplet-repeat expansion-mutation in the Huntingtin gene. Subjects at risk for HD can be identified by genetic testing in the prodromal phase. Structural changes of basal-ganglia nuclei such as the caudate nucleus are well-replicated findings observable early in prodromal-HD subjects and may be preceded by distinct functional alterations of cortico-striatal circuits. This study aims to assess functional integrity of the motor system as a cortico-striatal circuit with particular clinical relevance in HD. Ten subjects in the prodromal phase of HD and ten matched controls were administered blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at rest (3T). Functional connectivity was measured as synchrony of BOLD activity between the caudate nucleus and thirteen cortical brain regions (seeds). Basal-ganglia volumes were assessed as established markers of disease progression in prodromal-HD. Linear regression analysis was performed to test for a relationship between structural changes and group differences in functional connectivity. Prodromal-HD subjects showed reduced BOLD synchrony between two seeds in the premotor cortex (BA6) and the caudate nucleus. While similar effect sizes could be observed for reduced basal-ganglia volumes and differences in functional connectivity, coefficients of determination indicate a moderate relationship between functional connectivity and striatal atrophy. Our data show reduced cortico-striatal functional connectivity at rest in prodromal-HD and suggest a relation to early structural brain changes. Additional longitudinal studies are necessary to elucidate the temporal relationship between functional alterations and earliest structural brain changes in prodromal-HD.     

Sentence processing in the cerebral cortex

Human language is a unique faculty of the mind. It has been the ultimate mystery throughout the history of neuroscience. Despite many aphasia and functional imaging studies, the exact correlation between cortical language areas and subcomponents of the linguistic system has not been established. One notable drawback is that most functional imaging studies have tested language tasks at the word level, such as lexical decision and word generation tasks, thereby neglecting the syntactic aspects of the language faculty. As proposed by Chomsky, the critical knowledge of language involves universal grammar (UG), which governs the syntactic structure of sentences. In this article, we will review recent advances made by functional neuroimaging studies of language, focusing especially on sentence processing in the cerebral cortex. We also present the recent results of our functional magnetic resonance imaging (fMRI) study intended to identify cortical areas specifically involved in syntactic processing. A study of sentence processing that employs a newly developed technique, optical topography (OT), is also presented. Based on these findings, we propose a modular specialization of Broca's area, Wernicke's area, and the angular gyrus/supramarginal gyrus. The current direction of research in neuroscience is beginning to establish the existence of distinct modules responsible for our knowledge of language.     

Neural activities during affective processing in people with Alzheimer's disease

This study examined brain activities in people with Alzheimer's disease when viewing happy, sad, and fearful facial expressions of others. A functional magnetic resonance imaging and a voxel-based morphometry methodology together with a passive viewing of emotional faces paradigm were employed to compare the affective processing in 12 people with mild Alzheimer's disease and 12 matched controls. The main finding was that the clinical participants showed reduced activations in regions associated with the motor simulation system (the ventral premotor cortex) and in regions associated with emotional simulation—empathy (the anterior insula and adjacent frontal operculum). This regional decline in blood oxygen level-dependent signals appeared to be lateralized in the left hemisphere and was not related to any structural degeneration in the clinical participants. Furthermore, the regions that showed changes in neural activity differed for the 3 emotional facial expressions studied. Findings of our study indicate that neural changes in regions associated with the motor and emotional simulation systems might play an important role in the development of Alzheimer's disease.     

硬膜外植入式皮质刺激脑卒中患者提高神经网络功能

背景：硬膜外植入式皮质刺激兼顾了经颅磁刺激、经颅直流电刺激、硬膜下皮质刺激和深部脑刺激的优点,可显著改善脑卒中后的肢体运动与语言功能。 目的：综述近年来有关硬膜外植入式皮质刺激在脑卒中康复中的研究及其临床应用。 方法：由第一作者应用计算机检索1995年1月至2014年4月PubMed 数据库及中国期刊全文数据库文献,检索关键词为“cortical stimulation,extradural motor cortex stimulation,extradural cortical implants,extradural cortical stimulation,stroke,rehabilitation;皮质刺激,硬膜外电刺激,硬膜外皮质植入,硬膜外皮质刺激,脑卒中,康复”。纳入有关硬膜外植入式皮质刺激在脑卒中后运动与言语障碍中应用的文章。 结果与结论：硬膜外皮质刺激是植入式皮质刺激,其优势是侵入性小、高度精确性和经硬膜与大脑密切接触,对缺乏有效治疗的脑卒中慢性期运动和语言障碍患者来说,这有可能是一种新的治疗方法。硬膜外皮质刺激通过促进神经可塑性、促进病灶周围结构与功能改变、提高神经网络功能、促进大脑半球间功能平衡及增加感觉输入来改善脑卒中后的肢体运动功能与语言功能。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

Differential relationships between transcallosal structural and functional connectivity in young and older adults

Numerous studies have identified age differences in brain structure and function that correlate with declines in motor performance. While these investigations have typically focused on activity in isolated regions of the brain, resting state functional connectivity magnetic resonance imaging (MRI) and diffusion tensor imaging allow for more integrative assessments of spatially disparate neural networks. The novel contribution of the current study is to combine both resting state functional connectivity and diffusion tensor imaging to examine motor corticocortical circuits in young and older adults. We find that relatively greater functional connectivity between the primary motor cortices was strongly associated with decreased structural connectivity and poorer motor performance solely in older adults. We suggest that greater functional connectivity in older adults may be reflective of a release from the normally predominantly inhibitory interhemispheric communication associated with the primary motor cortices.     

Wavelet Analysis as a Tool for Investigating Movement-Related Cortical Oscillations in EEG-fMRI Coregistration

Electroencephalography combined with functional magnetic resonance imaging (EEG-fMRI) identifies blood oxygenation level dependent (BOLD) signal changes associated with physiological and pathological EEG events. In this study we used EEG-fMRI to determine the possible correlation between topographical movement-related EEG changes in brain oscillatory activity recorded from EEG electrodes over the scalp and fMRI cortical responses in motor areas during finger movement. Thirty-two channels of EEG were recorded in 12 subjects during eyes-closed condition inside a three T magnetic resonance (MR) scanner using an MR-compatible EEG recording system. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during fMRI acquisition. For EEG data analysis we used a time–frequency approach to measure time by varying the energy in a signal at a given frequency band by the convolution of the EEG signal with a wavelet family in the alpha and beta bands. The correlation between the BOLD signal associated with the EEG regressor provides that sensory motor region is a source of the EEG. We conclude that combined EEG-fMRI can be used to investigate movement-related oscillations of the human brain inside an MRI scanner and wavelet analysis adds further details on the EEG changes. The movement-related changes in the EEG signals are useful to identify the brain activation sources responsible for BOLD-signal changes.     

Changing brain networks for visuomotor control with increased movement automaticity

Learning a motor skill is associated with changes in patterns of brain activation with movement. Here we have further characterized these dynamics during fast (short-term) learning of a visuomotor skill using functional magnetic resonance imaging. Subjects (n = 15) were studied as they learned to visually track a moving target by varying the isometric force applied to a pressure plate held in the right hand. Learning was confirmed by demonstration of improved performance and automaticity (the relative lack of need for conscious attention during task execution). We identified two distinct, time-dependent patterns of functional changes in the brain associated with these behavioral changes. An initial, more attentionally demanding stage of learning was associated with the greatest relative activity in widely distributed, predominantly cortical regions including prefrontal, bilateral sensorimotor, and parietal cortices. The caudate nucleus and ipsilateral cerebellar hemisphere also showed significant activity. Over time, as performance improved, activity in these regions progressively decreased. There was an increase in activity in subcortical motor regions including that of the cerebellar dentate and the thalamus and putamen. Short-term motor-skill learning thus is associated with a progressive reduction of widely distributed activations in cortical regions responsible for executive functions, processing somatosensory feedback and motor planning. The results suggest that early performance gains rely strongly on prefrontal-caudate interactions with later increased activity in a subcortical circuit involving the cerebellum and basal ganglia as the task becomes more automatic. Characterization of these changes provides a potential tool for functional "dissection" of pathologies of movement and motor learning.     

Renewal of the neurophysiology of language: functional neuroimaging

Functional neuroimaging methods have reached maturity. It is now possible to start to build the foundations of a physiology of language. The remarkable number of neuroimaging studies performed so far illustrates the potential of this approach, which complements the classical knowledge accumulated on aphasia. Here we attempt to characterize the impact of the functional neuroimaging revolution on our understanding of language. Although today considered as neuroimaging techniques, we refer less to electroencephalography and magnetoencephalography studies than to positron emission tomography and functional magnetic resonance imaging studies, which deal more directly with the question of localization and functional neuroanatomy. This review is structured in three parts. 1) Because of their rapid evolution, we address technical and methodological issues to provide an overview of current procedures and sketch out future perspectives. 2) We review a set of significant results acquired in normal adults (the core of functional imaging studies) to provide an overview of language mechanisms in the "standard" brain. Single-word processing is considered in relation to input modalities (visual and auditory input), output modalities (speech and written output), and the involvement of "central" semantic processes before sentence processing and nonstandard language (illiteracy, multilingualism, and sensory deficits) are addressed. 3) We address the influence of plasticity on physiological functions in relation to its main contexts of appearance, i.e., development and brain lesions, to show how functional imaging can allow fine-grained approaches to adaptation, the fundamental property of the brain. In closing, we consider future developments for language research using functional imaging.     

To move or not to move: imperatives modulate action-related verb processing in the motor system

It has been suggested that the processing of action-related words involves activation of the motor circuitry. Using fMRI (functional magnetic resonance imaging), the current study further explored the interaction between action and language by investigating whether the linguistic context, in which an action word occurs, modulates motor circuitry activity related to the processing of action words. To this end, we examined whether the presentation of hand action-related verbs as positive or negative imperatives, for example, “Do grasp” or “Don't write,” modulates neural activity in the hand area of primary motor cortex (M1) or premotor cortex (Pm). Subjects (n = 19) were asked to read silently the imperative phrases, in which both meaningful action verbs and meaningless pseudo-verbs were presented, and to decide whether they made sense (lexical decision task). At the behavioral level, response times in the lexical decision task were significantly longer for negative, compared to positive, imperatives. At the neural level, activity was differentially decreased by action verbs presented as negative imperatives for the premotor and the primary motor cortex of both hemispheres. The data suggest that context (here: positive vs. negative imperatives), in which an action verb is encountered, modulates the neural activity within key areas of the motor system. The finding implies that motor simulation (or motor planning) rather than semantic processing per se may underlie previously observed motor system activation related to action verb processing. Furthermore, the current data suggest that negative imperatives may inhibit motor simulation or motor planning processes.     

额颞叶肿瘤患者手术前后大脑网络特性研究

脑肿瘤患者大脑的损伤及手术对大脑认知的影响是目前临床最为关注的问题。基于静息态fMRI脑功能分析技术及小世界网络分析方法,研究9例脑额颞叶肿瘤患者的大脑肿瘤对大脑默认模式网络和感觉运动网络的影响,以及肿瘤切除对大脑功能网络特性的改变。首先基于ICA方法,研究肿瘤及手术切除对患者大脑默认网络和感觉运动网络的影响;接着构建肿瘤患者术前术后和正常对照组的小世界网络,对网络的拓扑特性和网络参数进行分析;然后运用介数中心度,求出各组的脑功能网络核心节点,并比较分析患者和正常人、患者术前术后核心节点的变化;最后比较分析患者术前、术后默认模式网络和感觉运动网络中脑区的具体变化。研究结果发现,默认模式网络和感觉运动网络神经活动活跃程度降低,证明肿瘤病灶对大脑内源性网络的两个模块造成了明显的损害;患者术后的小世界属性(σ=γ/λ)显著降低(术前:3.591±0.302,术后:3.263±0.174),簇系数显著降低(术前:0.482±0.007,术后:0.454±0.011),并且脑肿瘤使核心节点向肿瘤对侧偏移。默认网络中手术后肿瘤的切除使得右侧脑区(原肿瘤侧)活动变得强烈,右脑介数中心度值明显上升(术前:0.012 5±0.000 5,术后:0.018 4±0.001 0);左脑活动有所缓和,左侧介数中心度值显著下降(术前:0.018 0±0.001 1,术后:0.012 2±0.000 6)。术后部分被抑制的节点又重新激活。通过对病人的默认模式网络和感觉运动网络的研究,发现肿瘤对患者大脑功能网络有一定的破坏,术后会有所改善。研究结果表明,由于大脑高级神经皮层的重组性和代偿机制,脑肿瘤患者术后可能出现功能恢复。     

Aberrant brain activation following motor skill learning in schizophrenic patients as shown by functional magnetic resonance imaging

BACKGROUND: Motor skill learning may be impaired in schizophrenia. While functional brain imaging studies have shown reduced activation during motor task performance in schizophrenic patients, brain activity changes with motor skill learning in these patients have not been studied by functional imaging. METHODS: A sequential complex motor task involving the right hand was performed by nine medicated schizophrenic patients and 10 age-matched healthy controls. Functional magnetic resonance images were obtained using a gradient echo, echoplanar imaging (EPI) pulse sequence before and after 1 week of training in performing the task. RESULTS: Bilaterally, patients showed significantly less blood oxygenation level-dependent (BOLD) signal response in the premotor area (PMA) before beginning motor training than controls. BOLD signal response increased in the left PMA of schizophrenic patients after 1 week of motor training; in contrast, the signal decreased in the left PMA of control subjects. Training effects concerning the number of finger movement sequences achieved did not differ between groups. Daily neuroleptic dose did not significantly affect changes with training in BOLD signal response in the PMA. CONCLUSIONS: These preliminary results suggest that schizophrenic patients have dysfunction of neural networks in areas including the PMA that are involved in executing a complex motor task. In terms of brain activity, motor learning may be less efficient or slower in the patients than in healthy subjects.