The human prefrontal and parietal association cortices are involved in NO-GO performances: an event-related fMRI study

One of the important roles of the prefrontal cortex is inhibition of movement. We applied an event-related functional magnetic resonance imaging (fMRI) technique to observe changes in fMRI signals of the entire brain during a GO/NO-GO task to identify the functional fields activated in relation to the NO-GO decision. Eleven normal subjects participated in the study, which consisted of a random series of 30 GO and 30 NO-GO trials. The subjects were instructed to press a mouse button immediately after the GO signal was presented. However, they were instructed not to move when the NO-GO signal was presented. We detected significant changes in MR signals in relation to the preparation phases, GO responses, and NO-GO responses. The activation fields related to the NO-GO responses were located in the bilateral middle frontal cortices, left dorsal premotor area, left posterior intraparietal cortices, and right occipitotemporal area. The fields of activation in relation to the GO responses were found in the left primary sensorimotor, right cerebellar anterior lobule, bilateral thalamus, and the area from the anterior cingulate to the supplementary motor area (SMA). Brain activations related to the preparation phases were identified in the left dorsal premotor, left lateral occipital, right ventral premotor, right fusiform, and the area from the anterior cingulate to the SMA. The results indicate that brain networks consisting of the bilateral prefrontal, intraparietal, and occipitotemporal cortices may play an important role in executing a NO-GO response.     

Activations related to "mirror" and "canonical" neurones in the human brain: an fMRI study

In the macaque monkey ventral premotor cortex (F5), "canonical neurones" are active when the monkey observes an object and when the monkey grasps that object. In the same area, "mirror neurones" fire both when the monkey observes another monkey grasping an object and when the monkey grasps that object. We used event-related fMRI to investigate where in the human brain activation can be found that reflects both canonical and mirror neuronal activity. There was activation in the intraparietal and ventral limbs of the precentral sulcus when subjects observed objects and when they executed movements in response to the objects (canonical neurones). There was activation in the dorsal premotor cortex, the intraparietal cortex, the parietal operculum (SII), and the superior temporal sulcus when subjects observed gestures (mirror neurones). Finally, activations in the ventral premotor cortex and inferior frontal gyrus (area 44) were found when subjects imitated gestures and executed movements in response to objects. We suggest that in the human brain, the ventral limb of the precentral sulcus may form part of the area designated F5 in the macaque monkey. It is possible that area 44 forms an anterior part of F5, though anatomical studies suggest that it may be a transitional area between the premotor and prefrontal cortices.     

fMRI analysis of active, passive and electrically stimulated ankle dorsiflexion

Ankle dorsiflexion (ADF) is an integral component in gait. The objective of this study was to define, using functional magnetic resonance imaging (fMRI) in healthy volunteers (n=12), the brain regions that are activated during Electrical Stimulation (ES)-induced ADF movements, and compare this to the pattern of activation occurring during active and passive ADF. Concurrent electromyography (EMG) was used to monitor the tibialis anterior muscle activity so as to allow EMG-guided fMRI analysis to be performed. Patterns of cortical and sub-cortical activation in response to active, passive and ES-induced ADF movement were identified. EMG-guided fMRI analysis was shown to improve detection and reduce inter-session variance for active and ES tasks. A significantly greater number of voxels were activated during active and ES-induced ADF compared to passive ADF in contralateral primary motor (M1), primary sensory (SI), and secondary somatosensory (SII) areas, as well as in supplementary motor area (SMA) and cingulate motor areas (CMA); bilateral dorsal and ventral premotor areas and cerebellum VI. The contrast of active greater than ES-induced ADF showed increased activation in SMA, contralateral PMdr; bilateral PMvr, dorsolateral prefrontal cortex and CMA; and ipsilateral cerebellum IV. Active ADF generated greater activation in brain areas responsible for motor planning, execution and visuomotor co-ordination. ES-induced activation was greater in bilateral SII and insula than for active ADF, hypothesised to result from increased sensory integration, but also possibly due to a nociceptive component to ES.     

Orthographic and phonological processing of Chinese characters: an fMRI study

The present study used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms underlying the orthographic and phonological processing of Chinese characters. Four tasks were devised, including one homophone judgment and three physical judgments of characters, pseudo-characters, and Korean-like nonsense figures. While the left occipitotemporal region, left dorsal processing stream, and right middle frontal gyrus constitute a network for orthographic processing, the left premotor gyrus, left middle/inferior frontal gyrus, supplementary motor area (SMA), and the left temporoparietal region work in concert for phonological processing. The ventral part of the left inferior frontal cortex responds specifically to the character stimuli, suggesting a general lexical processing role for this region for linguistic material. The stronger activation of the dorsal visual stream by Chinese homophone judgment pinpoints a tight coupling between phonological representation of Chinese characters and corresponding orthographic percepts. The concomitant engagement of sets of regions for different levels of Chinese orthographic and phonological processing is consistent with the notion of distributed parallel processing.     

Functional topography of working memory for face or voice identity

We used functional magnetic resonance imaging (fMRI) to investigate whether the neural systems for nonspatial visual and auditory working memory exhibits a functional dissociation. The subjects performed a delayed recognition task for previously unfamiliar faces and voices and an audiovisual sensorimotor control task. During the initial sample and subsequent test stimulus presentations, activation was greater for the face than for the voice identity task bilaterally in the occipitotemporal cortex and, conversely, greater for voices than for faces bilaterally in the superior temporal sulcus/gyrus (STS/STG). Ventral prefrontal regions were activated by both memory delays in comparison with the control delays, and there was no significant difference in direct voxelwise comparisons between the tasks. However, further analyses showed that there was a subtle difference in the functional topography for two delay types within the ventral prefrontal cortex. Face delays preferentially activate the dorsal part of the ventral prefrontal cortex (BA 44/45) while voice delays preferentially activate the inferior part (BA 45/47), indicating a ventral/dorsal auditory/visual topography within the ventral prefrontal cortex. The results confirm that there is a modality-specific attentional modulation of activity in visual and auditory sensory areas during stimulus presentation. Moreover, within the nonspatial information-type domain, there is a subtle across-modality dissociation within the ventral prefrontal cortex during working memory maintenance of faces and voices.     

What difference does a year of schooling make? Maturation of brain response and connectivity between 2nd and 3rd grades during arithmetic problem solving

Early elementary schooling in 2nd and 3rd grades (ages 7-9) is an important period for the acquisition and mastery of basic mathematical skills. Yet, we know very little about neurodevelopmental changes that might occur over a year of schooling. Here we examine behavioral and neurodevelopmental changes underlying arithmetic problem solving in a well-matched group of 2nd (n = 45) and 3rd (n = 45) grade children. Although 2nd and 3rd graders did not differ on IQ or grade- and age-normed measures of math, reading and working memory, 3rd graders had higher raw math scores (effect sizes = 1.46-1.49) and were more accurate than 2nd graders in an fMRI task involving verification of simple and complex two-operand addition problems (effect size = 0.43). In both 2nd and 3rd graders, arithmetic complexity was associated with increased responses in right inferior frontal sulcus and anterior insula, regions implicated in domain-general cognitive control, and in left intraparietal sulcus (IPS) and superior parietal lobule (SPL) regions important for numerical and arithmetic processing. Compared to 2nd graders, 3rd graders showed greater activity in dorsal stream parietal areas right SPL, IPS and angular gyrus (AG) as well as ventral visual stream areas bilateral lingual gyrus (LG), right lateral occipital cortex (LOC) and right parahippocampal gyrus (PHG). Significant differences were also observed in the prefrontal cortex (PFC), with 3rd graders showing greater activation in left dorsal lateral PFC (dlPFC) and greater deactivation in the ventral medial PFC (vmPFC). Third graders also showed greater functional connectivity between the left dlPFC and multiple posterior brain areas, with larger differences in dorsal stream parietal areas SPL and AG, compared to ventral stream visual areas LG, LOC and PHG. No such between-grade differences were observed in functional connectivity between the vmPFC and posterior brain regions. These results suggest that even the narrow one-year interval spanning grades 2 and 3 is characterized by significant arithmetic task-related changes in brain response and connectivity, and argue that pooling data across wide age ranges and grades can miss important neurodevelopmental changes. Our findings have important implications for understanding brain mechanisms mediating early maturation of mathematical skills and, more generally, for educational neuroscience.     

Neuroimaging evidence for object model verification theory: Role of prefrontal control in visual object categorization

Although the visual system rapidly categorizes objects seen under optimal viewing conditions, the categorization of objects seen under impoverished viewing conditions not only requires more time but may also depend more on top-down processing, as hypothesized by object model verification theory. Two studies, one with functional magnetic resonance imaging (fMRI) and one behavioral with the same stimuli, tested this hypothesis. FMRI data were acquired while people categorized more impoverished (MI) and less impoverished (LI) line drawings of objects. FMRI results revealed stronger activation during the MI than LI condition in brain regions involved in top-down control (inferior and medial prefrontal cortex, intraparietal sulcus), and in posterior, object-sensitive brain regions (ventral and dorsal occipitotemporal, and occipitoparietal cortex). The behavioral study indicated that taxing visuospatial working memory, a key component of top-down control processes during visual tasks, interferes more with the categorization of MI stimuli (but not LI stimuli) than does taxing verbal working memory. Together, these findings provide evidence for object model verification theory and implicate greater prefrontal cortex involvement in top-down control of posterior visual processes during the categorization of more impoverished images of objects.     

Neural development of selective attention and response inhibition

Brain activation differences between 12 children (9- to 12-year-olds) and 12 adults (20- to 30-year-olds) were examined on two cognitive tasks during functional magnetic resonance imaging (fMRI). Spatial selective attention was measured with the visual search for a conjunction target (red triangle) in a field of distracters and response inhibition was measured with a go no-go task. There were small developmental differences in the selective attention task, with children showing greater activation than adults in the anterior cingulate and thalamus. There were large developmental differences in the response inhibition task, with children showing greater activation than adults in a fronto-striatal network including middle cingulate, medial frontal gyrus, medial aspects of bilateral superior frontal gyrus, and the caudate nucleus on the left. Children also showed greater bilateral activation for the response inhibition task in posterior cingulate, thalamus and the hippocampo-amygdaloid region. The extensive developmental differences on the response inhibition task are consistent with the prolonged maturation of the fronto-striatal network.     

The role of the dorsal stream for gesture production

Skilled gestures require the integrity of the neural networks involved in storage, retrieval, and execution of motor programs. Premotor cortex and/or parietal cortex lesions frequently produce deficits during performance of gestures, transitive more than intransitive. The dorsal stream links object information with object action, suggesting that mechanical knowledge of tool use is stored focally in the brain. Using event-related fMRI, we explored activity during instructed-delay transitive and intransitive hand gestures. The comparison between planning-preparation and execution of gestures demonstrated a temporal rostral to caudal gradient of activation in the ventral premotor cortex (PMv) and inferior to superior gradient of activation in the posterior parietal cortex (PPc). Comparison between transitive and intransitive gestures established a functional specificity within the dorsal stream for mechanical knowledge. Results demonstrate that not only PPc but also the PMv acts in the processing of sensorimotor information during gestures. This might be the substrate underlying selective deficits in ideomotor apraxia patients.     

Neurodevelopmental changes in verbal working memory load-dependency: an fMRI investigation

Development of working memory (WM) aptitude parallels structural changes in the frontal–parietal association cortices important for performance within this cognitive domain. The cerebellum has been proposed to function in support of the postulated phonological loop component of verbal WM, and along with frontal and parietal cortices, has been shown to exhibit linear WM load-dependent activation in adults. It is not known if these kinds of WM load-dependent relationships exist for cerebro-cerebellar networks in developmental populations, and whether there are age-related changes in the nature of load-dependency between childhood, adolescence, and adulthood. The present study used fMRI and a verbal Sternberg WM task with three load levels to investigate developmental changes in WM load-dependent cerebro-cerebellar activation in a sample of 30 children, adolescents, and young adults between the ages of 7 and 28. The neural substrates of linear load-dependency were found to change with age. Among adolescents and adults, frontal, parietal and cerebellar regions showed linear load-dependency, or increasing activation under conditions of increasing WM load. In contrast, children recruited only left ventral prefrontal cortex in response to increasing WM load. These results demonstrate that, while children, adolescents, and young adults activate similar cerebro-cerebellar verbal working memory networks, the extent to which they rely on parietal and cerebellar regions in response to increasing task difficulty changes significantly between childhood and adolescence.     

An fMRI Investigation of Cortical Contributions to Spatial and Nonspatial Visual Working Memory

The experiments presented in this report were designed to test the hypothesis that visual working memory for spatial stimuli and for object stimuli recruits separate neuronal networks in prefrontal cortex. We acquired BOLD fMRI data from subjects while they compared each serially presented stimulus to the one that had appeared two or three stimuli previously. Three experiments failed to reject the null hypothesis that prefrontal cortical activity associated with spatial working memory performance cannot be dissociated from prefrontal cortical activity associated with nonspatial working memory performance. Polymodal regions of parietal cortex (inferior and superior parietal lobules), as well as cortex surrounding the superior frontal sulcus (and encompassing the frontal eye fields), also demonstrated equivalent levels of activation in the spatial and object conditions. Posterior cortical regions associated with the ventral visual processing stream (portions of lingual, fusiform, and inferior temporal gyri), however, demonstrated greater object than spatial working memory-related activity, particularly when stimuli varied only along spatial or featural dimensions. These experiments, representing fMRI studies of spatial and object working memory in which the testing procedure and the stimuli were identical in the two conditions, suggest that domain-specific visual working memory processing may be mediated by posterior regions associated with domain-specific sensory processing.     

A role of the basal ganglia and midbrain nuclei for initiation of motor sequences

The mesial premotor cortex is crucial for planning sequential procedures and movement initiation. With event-related (ER) functional magnetic resonance imaging (fMRI) it has been possible to separate mesial premotor activation before, during, and after self-initiated movements and, thereby, to distinguish advance planning from execution. The mesial premotor cortex is part of distributed cortico-basal ganglia-thalamo-cortical networks but, to date, the subcortical contributions to self-initiated movements are far less well understood. Using ER fMRI at 3T in 12 right-handed male volunteers, we studied the subcortical activation preceding an automated four-digit finger sequence that was either self-initiated or triggered externally by a visual cue. Beyond typical cortical activation increases in fronto-parietal regions, both initiation modes induced consistent subcortical activation in basal ganglia, midbrain (substantia nigra), and ipsilateral cerebellum. The planning phase of the internally initiated condition, when contrasted with the externally triggered condition, was associated with enhanced activity in frontal regions (mesial premotor cortex/rostral cingulate zone, dorsolateral prefrontal cortex), parietal regions (precuneus, inferior parietal cortex, encroaching onto V5/MT), insula, contralateral anterior putamen and midbrain (bilateral red nucleus/subthalamic nucleus). These data demonstrate the impact of initiation mode on planning-related activity in the ventral basal ganglia and interconnected midbrain nuclei, thereby stressing the crucial role of distributed cortico-basal ganglia-thalamo-cortical networks for self-initiated automated motor repertoires. Involvement of the substantia nigra during planning, as shown here, indicates dopaminergic gating of motor sequences.     

Neuroanatomic overlap of working memory and spatial attention networks: a functional MRI comparison within subjects

Frontal and posterior parietal activations have been reported in numerous studies of working memory and visuospatial attention. To directly compare the brain regions engaged by these two cognitive functions, the same set of subjects consecutively participated in tasks of working memory and spatial attention while undergoing functional MRI (fMRI). The working memory task required the subject to maintain an on-line representation of foveally displayed letters against a background of distracters. The spatial attention task required the subject to shift visual attention covertly in response to a centrally presented directional cue. The spatial attention task had no working memory requirement, and the working memory task had no covert spatial attention requirement. Subjects' ability to maintain central fixation was confirmed outside the MRI scanner using infrared oculography. According to cognitive conjunction analysis, the set of activations common to both tasks included the intraparietal sulcus, ventral precentral sulcus, supplementary motor area, frontal eye fields, thalamus, cerebellum, left temporal neocortex, and right insula. Double-subtraction analyses yielded additional activations attributable to verbal working memory in premotor cortex, left inferior prefrontal cortex, right inferior parietal lobule, precuneus, and right cerebellum. Additional activations attributable to covert spatial attention included the occipitotemporal junction and extrastriate cortex. The use of two different tasks in the same set of subjects allowed us to provide an unequivocal demonstration that the neural networks subserving spatial attention and working memory intersect at several frontoparietal sites. These findings support the view that major cognitive domains are represented by partially overlapping large-scale neural networks. The presence of this overlap also suggests that spatial attention and working memory share common cognitive features related to the dynamic shifting of attentional resources.     

Differentiation between external and internal cuing: an fMRI study comparing tracing with drawing

Externally cued movement is thought to preferentially involve cerebellar and premotor circuits whereas internally generated movement recruits basal ganglia, pre-supplementary motor cortex (pre-SMA) and dorsolateral prefrontal cortex (DLPFC). Tracing and drawing are exemplar externally and internally guided actions and Parkinson's patients and cerebellar patients show deficits in tracking and drawing, respectively. In this study we aimed to examine this external/internal distinction in healthy subjects using functional imaging. Ten healthy subjects performed tracing and drawing of simple geometric shapes using pencil and paper while in a 3-T fMRI scanner. Results indicated that compared to tracing, drawing generated greater activation in the right cerebellar crus I, bilateral pre-SMA, right dorsal premotor cortex and right frontal eye field. Tracing did not recruit any additional activation compared to drawing except in striate and extrastriate visual areas. Therefore, drawing recruited areas more frequently associated with cognitively challenging tasks, attention and memory, but basal ganglia and cerebellar activity did not differentiate tracing from drawing in the hypothesised manner. As our paradigm was of a simple, repetitive and static design, these results suggest that the task familiarity and the temporal nature of visual feedback in tracking tasks, compared to tracing, may be important contributing factors towards the degree of cerebellar involvement. Future studies comparing dynamic with static external cues and visual feedback may clarify the role of the cerebellum and basal ganglia in the visual guidance of drawing actions.     

Atypical neural substrates of Embedded Figures Task performance in children with Autism Spectrum Disorder

Superior performance on the Embedded Figures Task (EFT) has been attributed to weak central coherence in perceptual processing in Autism Spectrum Disorder (ASD). The present study used functional magnetic resonance imaging to examine the neural basis of EFT performance in 7- to 12-year-old ASD children and age- and IQ-matched controls. ASD children activated only a subset of the distributed network of regions activated in controls. In frontal cortex, control children activated left dorsolateral, medial and dorsal premotor regions whereas ASD children only activated the dorsal premotor region. In parietal and occipital cortices, activation was bilateral in control children but unilateral (left superior parietal and right occipital) in ASD children. Further, extensive bilateral ventral temporal activation was observed in control, but not ASD children. ASD children performed the EFT at the same level as controls but with reduced cortical involvement, suggesting that disembedded visual processing is accomplished parsimoniously by ASD relative to typically developing brains.     

Dorsal and ventral stream activation and object recognition performance in school-age children

We explored how developing neural artifact and animal representations in the dorsal and ventral stream play a role in children's increasingly more proficient interactions with objects. In thirty-three 6- to 10-year-old children and 11 adults, we used fMRI to track the development of (1) the cortical category preference for tools compared to animals and (2) the response to complex objects (as compared to scrambled objects) during a passive viewing task. In addition, we related a cognitive skill that improved substantially from age 6 to 10, namely the ability to recognize tools from unusual viewpoints, to the development of cortical object processing. In multiple complementary analyses we showed that those children who were better at recognizing tools from unusual viewpoints outside the scanner showed a reduced cortical response to tools and animals when viewed inside the scanner, bilaterally in intraparietal and inferotemporal cortex. In contrast, the cortical preference for tools in the dorsal and ventral visual stream did not predict object recognition performance, and was organized in an adult-like manner at six. While cortical tool preference did not change with age, the findings suggest that animal-preferring regions in the ventral visual stream may develop later, concordant with previous reports of a protracted development in similar regions for faces. We thus conclude that intraparietal and inferotemporal cortical networks that support aspects of object processing irrespective of tool or animal category, continue to develop during the school-age years and contribute to the development of object recognition skills during this period.     

An fMRI investigation of short-term source memory in young and older adults

Using functional magnetic resonance imaging (fMRI) and a working memory procedure, we compared source memory judgments (format and location) with old-new judgments in young and older adults. Consistent with previous fMRI findings, for young adults, an area of left dorsolateral prefrontal cortex showed greater activity during format than old-new judgments made immediately, as well as those made after a brief, filled delay. In contrast, for older adults, activity in this area was not greater during format than old-new judgments at either retention interval. These data provide additional evidence that left lateral prefrontal cortex is important in monitoring specific source information and new evidence that older adults' source memory deficits may be related, in part, to reduced function of this brain area.     

应用基于体素的形态测量学分析工作记忆老化的脑灰质萎缩基础

目的利用基于体素的形态测量学(VBM)方法探讨老年人工作记忆能力衰退与脑灰质萎缩间的关系。方法在30名老年人(老年组)和38名青壮年人(对照组)中分别进行keep-track任务和2-back任务两种工作记忆任务检测。对所有受试者进行高分辨力MR扫描,并使用统计参数图(SPM)8软件进行VBM分析,比较老年组与对照组的脑灰质体积差异,并在老年组内利用多元回归分析寻找与工作记忆任务能力下降相关的责任萎缩脑区。结果与对照组相比,老年组工作记忆能力显著衰退,且出现广泛的脑灰质萎缩。老年组中,与keep-track任务能力相关的萎缩脑区主要位于双侧前额叶中下部、运动前区、顶叶后下部和小脑;与2-back任务相关的萎缩脑区主要位于左侧的前额叶下部、运动前区和颞叶。左腹侧运动前区(BA6)皮层的灰质体积与两个任务的行为学数据均存在显著相关性。结论老年人工作记忆能力下降与工作记忆神经网络的灰质萎缩有关。     

Age-Related Changes in Regional Cerebral Blood Flow during Working Memory for Faces

Young and old adults underwent positron emission tomography during the performance of a working memory task for faces (delayed match-to-sample), in which the delay between the sample and choice faces was varied from 1 to 21 s. Reaction time was slower and accuracy lower in the old group, but not markedly so. Values of regional cerebral blood flow (rCBF) were analyzed for sustained activity across delay conditions, as well as for changes as delay increased. Many brain regions showed similar activity during these tasks in both young and old adults, including left anterior prefrontal cortex, which had increased rCBF with delay, and ventral extrastriate cortex, which showed decreased rCBF with delay. However, old adults had less activation overall and less modulation of rCBF across delay in right ventrolateral prefrontal cortex than did the young adults. Old adults also showed greater rCBF activation in left dorsolateral prefrontal cortex across all WM delays and increased rCBF at short delays in left occipitoparietal cortex compared to young adults. Activity in many of these regions was differentially related to performance in that it was associated with decreasing response times in the young group and increasing response times in the older individuals. Thus despite the finding that performance on these memory tasks and associated activity in a number of brain areas are relatively preserved in old adults, differences elsewhere in the brain suggest that different strategies or cognitive processes are used by the elderly to maintain memory representations over short periods of time.     

Being right is its own reward: load and performance related ventral striatum activation to correct responses during a working memory task in youth

The ventral striatum (VS) is a critical brain region for reinforcement learning and motivation. Intrinsically motivated subjects performing challenging cognitive tasks engage reinforcement circuitry including VS even in the absence of external feedback or incentives. However, little is known about how such VS responses develop with age, relate to task performance, and are influenced by task difficulty. Here we used fMRI to examine VS activation to correct and incorrect responses during a standard n-back working memory task in a large sample (n=304) of healthy children, adolescents and young adults aged 8-22. We found that bilateral VS activates more strongly to correct than incorrect responses, and that the VS response scales with the difficulty of the working memory task. Furthermore, VS response was correlated with discrimination performance during the task, and the magnitude of VS response peaked in mid-adolescence. These findings provide evidence for scalable intrinsic reinforcement signals during standard cognitive tasks, and suggest a novel link between motivation and cognition during adolescent development.