The representation of blinking movement in cingulate motor areas: a functional magnetic resonance imaging study

Recent anatomical evidence from nonhuman primates indicates that cingulate motor areas (CMAs) play a substantial role in the cortical control of upper facial movement. Using event-related functional magnetic resonance imaging in 10 healthy subjects, we examined brain activity associated with volitional eye closure involving primarily the bilateral orbicularis oculi. The findings were compared with those from bimanual tapping, which should identify medial frontal areas nonsomatotopically or somatotopically related to bilateral movements. In a group-level analysis, the blinking task was associated with rostral cingulate activity more strongly than the bimanual tapping task. By contrast, the bimanual task activated the caudal cingulate zone plus supplementary motor areas. An individual-level analysis indicated that 2 foci of blinking-specific activity were situated in the cingulate or paracingulate sulcus: one close to the genu of the corpus callosum (anterior part of rostral cingulate zone) and the posterior part of rostral cingulate zone. The present data support the notion that direct cortical innervation of the facial subnuclei from the CMAs might control upper face movement in humans, as previously implied in nonhuman primates. The CMAs may contribute to the sparing of upper facial muscles after a stroke involving the lateral precentral motor regions.     

The neural basis of visual skill learning: an fMRI study of mirror reading

The learning of perceptual skills is thought to rely upon multiple regions in the cerebral cortex, but imaging studies have not yet provided evidence about the changes in neural activity that accompany visual skill learning. Functional magnetic resonance imaging (fMRI) was used to examine changes in activation of posterior brain regions associated with the acquisition of mirror-reading skill for novel and practiced stimuli. Multiple regions in the occipital lobe, inferior temporal cortex, superior parietal cortex and cerebellum were involved in the reading of mirror-reversed compared to normally oriented text. For novel stimuli, skilled mirror-reading was associated with decreased activation in the right superior parietal cortex and posterior occipital regions and increased activation in the left inferior temporal lobe. These results suggest that learning to read mirror- reversed text involves a progression from visuospatial transformation to direct recognition of transformed letters. Reading practiced, relative to unpracticed, stimuli was associated with decreased activation in occipital visual cortices, inferior temporal cortex and superior parietal cortex and increased activation in occipito-parietal and lateral temporal regions. By examining skill learning and item- specific repetition priming in the same task, this study demonstrates that both of these forms of learning exhibit shifts in the set of neural structures that contribute to performance.      

Enhanced cortical activation in the contralesional hemisphere of chronic stroke patients in response to motor skill challenge

The brain processes involved in the restoration of motor skill after hemiparetic stroke are not fully understood. The current study compared cortical activity in chronic stroke patients who successfully recovered hand motor skill and normal control subjects during performance of kinematically matched unskilled and skilled hand movements using functional magnetic resonance imaging. We found that cortical activation during performance of the unskilled movement was increased in the patients relative to controls in the contralesional primary sensorimotor cortex. Performance of the skilled movement elicited increased activation in the patients relative to controls in the contralesional primary sensorimotor cortex, ventral premotor cortex, supplementary motor area/cingulate, and occipitoparietal cortex. Further, the activation change in the contralesional occipitoparietal cortex was greater in the patients relative to controls with the increase in motor skill challenge. Kinematic differences, mirror movements, and residual motor deficits did not account for the enhanced activation in the contralesional cortices in the patients. These results suggest that activation in the contralesional cortical network was enhanced as a function of motor skill challenge in stroke patients with good motor recovery. The findings of the current study suggest that successful recovery of motor skill after hemiparetic stroke involves participation of the contralesional cortical network.     

Could variations in technical skills acquisition in surgery be explained by differences in cortical plasticity?

SUMMARY/BACKGROUND: Variations in technical performance in surgery are known to exist but are poorly understood. Gaining an appreciation of these differences may have implications for technical skills training, assessment, and selection. Investigators attempting to correlate technical skill with visuospatial or perceptual tests have failed to identify surrogate markers of surgical aptitude. Evidence from unrelated fields suggests that studying brain function may advance our understanding of disparate technical performance in surgery. METHODS: A literature search was conducted to identify relevant studies assessing both motor skills learning and changes in brain function. RESULTS: The brain is dynamic and patterns of activation vary with experience and training, a property referred to as "neuroplasticity." Functional neuroimaging studies of complex nonsurgical skills have demonstrated smaller, more refined neuronal networks in experts compared with novices. Novel unrefined performance places a significant burden on generic areas of attention and control such as the anterior cingulate cortex and the prefrontal cortex (PFC). These regions are recruited less as skills are performed with increasing automaticity. Persistent PFC activation has been shown to herald poor bimanual coordination learning in studies involving nonsurgical tasks. CONCLUDING HYPOTHESIS: It is suspected that alterations in brain activation foci accompany a transition through phases of surgical skills learning and that those patterns of activation may vary according to technical ability. Validating this hypothesis is challenging because it requires studying brain function in ambulant subjects performing complex motor skills. In a surgical knot-tying study involving over 60 subjects of varying expertise, PFC activation was identified in novices but not in trained surgeons. Further work should aim to determine whether PFC activation attenuates in the context of learning success in surgery.     

Motor planning, imagery, and execution in the distributed motor network: a time-course study with functional MRI

Activation of motor-related areas has consistently been found during various motor imagery tasks and is regarded as the central mechanism generating motor imagery. However, the extent to which motor execution and imagery share neural substrates remains controversial. We examined brain activity during preparation for and execution of physical or mental finger tapping. During a functional magnetic resonance imaging at 3 T, 13 healthy volunteers performed an instructed delay finger-tapping task either in a physical mode or mental mode. Number stimuli instructed subjects about a finger-tapping sequence. After an instructed delay period, cue stimuli prompted them either to execute the tapping movement or to imagine it. Two types of planning/preparatory activity common for movement and imagery were found: instruction stimulus-related activity represented widely in multiple motor-related areas and delay period activity in the medial frontal areas. Although brain activity during movement execution and imagery was largely shared in the distributed motor network, imagery-related activity was in general more closely related to instruction-related activity than to the motor execution-related activity. Specifically, activity in the medial superior frontal gyrus, anterior cingulate cortex, precentral sulcus, supramarginal gyrus, fusiform gyrus, and posterolateral cerebellum likely reflects willed generation of virtual motor commands and analysis of virtual sensory signals.     

Evidence for impaired long-term potentiation in schizophrenia and its relationship to motor skill learning

Several lines of evidence suggest that schizophrenia (SCZ) is associated with disrupted plasticity in the cortex. However, there is little direct neurophysiological evidence of aberrant long-term potentiation (LTP)-like plasticity in SCZ and little human evidence to establish a link between LTP to learning and memory. LTP was evaluated using a neurophysiological paradigm referred to as paired associative stimulation (PAS). PAS involves pairing of median nerve electric stimulation with transcranial magnetic stimulation (TMS) over the contralateral motor cortex (for abductor pollicis brevis muscle activation) delivered at 25-ms interstimulus interval. This pairing was delivered at a frequency of 0.1 Hz for 30 min. LTP was reflected by the change in motor evoked potentials (MEPs) before and after PAS. In addition, motor skill learning was assessed using the rotary pursuit task. Compared with healthy subjects, patients with SCZ demonstrated significant MEP facilitation deficits following PAS and impaired rotary-pursuit motor learning. Across all subjects there was a significant association between LTP and motor skill learning. These data provide evidence for disrupted LTP in SCZ, whereas the association between LTP with motor skill learning suggests that the deficits in learning and memory in SCZ may be mediated through disordered LTP.     

Functional magnetic resonance imaging for the evaluation of the motor system: primary and secondary brain areas in different motor tasks

Functional magnetic resonance imaging was used to characterize the primary and secondary motor system in subjects performing different motor tasks. Nine right-handed subjects performed simple motor tasks using hand, foot, knee, tongue, lips, eyes and the diaphragm-pelvis. All tasks revealed significant activation in primary and secondary motor areas. In the average across subjects, only the activity in the precentral gyrus was statistically distinctive for each motor task and followed the distribution of the motor homunculus. We consider these results as a possible basis of presurgical planning, extending the currently used procedures over a broader spectrum of motor tasks and brain structures leading to a more precise evaluation of functional areas for intracerebral interventions.     

Ongoing brain activity fluctuations directly account for intertrial and indirectly for intersubject variability in Stroop task performance

Recent studies have established a relation between ongoing brain activity fluctuations and intertrial variability in evoked neural responses, perception, and motor performance. Here, we extended these investigations into the domain of cognitive control. Using functional neuroimaging and a sparse event-related design (with long and unpredictable intervals), we measured ongoing activity fluctuations and evoked responses in volunteers performing a Stroop task with color-word interference. Across trials, prestimulus activity of several regions predicted subsequent response speed and across subjects this effect scaled with the Stroop effect size, being significant only in subjects manifesting behavioral interference. These effects occurred only in task relevant as the dorsal anterior cingulate and dorsolateral prefrontal cortex as well as ventral visual areas sensitive to color and visual words. Crucially, in subjects showing a Stroop effect, reaction times were faster when prestimulus activity was higher in task-relevant (color) regions and slower when activity was higher in irrelevant (word form) regions. These findings suggest that intrinsic brain activity fluctuations modulate neural mechanisms underpinning selective voluntary attention and cognitive control. Rephrased in terms of predictive coding models, ongoing activity can hence be considered a proxy of the precision (gain) with which prediction error signals are transmitted upon sensory stimulation.     

Practice and difficulty evoke anatomically and pharmacologically dissociable brain activation dynamics

Brain activation is adaptive to task difficulty and practice. We used functional MRI to map brain systems activated by an object-location learning task in 24 healthy elderly volunteers each scanned following placebo and two of four active drugs studied. We distinguished a fronto-striatal system adaptive to difficulty from a posterior system adaptive to practice. Fronto-striatal response to increased cognitive load was significantly attenuated by scopolamine, sulpiride and methylphenidate; practice effects were not modulated by these drugs but were enhanced by diazepam. We also found enhancement by methylphenidate, and attenuation by sulpiride, of load response in premotor, cingulate and parietal regions comprising a spatial attention network. Difficulty and practice evoke anatomically and pharmacologically dissociable brain activation dynamics, which are probably mediated by different neurotransmitter systems in humans.     

Functional connectivity of cortical networks involved in bimanual motor sequence learning

Motor skill learning requires the involvement and integration of several cortical and subcortical regions. In this study, we focus on how the functional connectivity of cortical networks changes with the acquisition of a novel motor skill. Using functional magnetic resonance imaging, we measured the localized blood oxygenation level-dependent (BOLD) signal in cortical regions while subjects performed a bimanual serial reaction time task under 2 conditions: 1) explicitly learning a novel sequence (NOVEL) and 2) playing a previously learned sequence (LEARNED). To investigate stages of learning, each condition was further divided into nonoverlapping early and late conditions. Functional connectivity was measured using a task-specific low-frequency coherence analysis of the data. We show that within the cortical motor network, the sensorimotor cortex, premotor cortex, and supplementary motor area have significantly greater inter- and intrahemispheric coupling during the early NOVEL condition compared with the late NOVEL condition. Additionally, we observed greater connectivity between frontal regions and cortical motor regions in the early versus late NOVEL contrast. No changes in functional connectivity were observed in the LEARNED condition. These results demonstrate that the functional connectivity of the cortical motor network is modulated with practice and suggest that early skill learning is mediated by enhanced interregional coupling.     

A study of pyramidal cell structure in the cingulate cortex of the macaque monkey with comparative notes on inferotemporal and primary visual cortex

Recent studies have revealed a marked degree of variation in the pyramidal cell phenotype in visual, somatosensory, motor and prefrontal cortical areas in the brain of different primates, which are believed to subserve specialized cortical function. In the present study we carried out comparisons of dendritic structure of layer III pyramidal cells in the anterior and posterior cingulate cortex and compared their structure with those sampled from inferotemporal cortex (IT) and the primary visual area (V1) in macaque monkeys. Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors was determined, and somal areas measured. We found that pyramidal cells in anterior cingulate cortex were more branched and more spinous than those in posterior cingulate cortex, and cells in both anterior and posterior cingulate were considerably larger, more branched, and more spinous than those in area V1. These data show that pyramidal cell structure differs between posterior dysgranular and anterior granular cingulate cortex, and that pyramidal neurons in cingulate cortex have different structure to those in many other cortical areas. These results provide further evidence for a parallel between structural and functional specialization in cortex.     

White matter microstructural correlates of superior long-term skill gained implicitly under randomized practice

We value skills we have learned intentionally, but equally important are skills acquired incidentally without ability to describe how or what is learned, referred to as implicit. Randomized practice schedules are superior to grouped schedules for long-term skill gained intentionally, but its relevance for implicit learning is not known. In a parallel design, we studied healthy subjects who learned a motor sequence implicitly under randomized or grouped practice schedule and obtained diffusion-weighted images to identify white matter microstructural correlates of long-term skill. Randomized practice led to superior long-term skill compared with grouped practice. Whole-brain analyses relating interindividual variability in fractional anisotropy (FA) to long-term skill demonstrated that 1) skill in randomized learners correlated with FA within the corticostriatal tract connecting left sensorimotor cortex to posterior putamen, while 2) skill in grouped learners correlated with FA within the right forceps minor connecting homologous regions of the prefrontal cortex (PFC) and the corticostriatal tract connecting lateral PFC to anterior putamen. These results demonstrate first that randomized practice schedules improve long-term implicit skill more than grouped practice schedules and, second, that the superior skill acquired through randomized practice can be related to white matter microstructure in the sensorimotor corticostriatal network.     

Distribution of cortical activation during visuospatial n-back tasks as revealed by functional magnetic resonance imaging

Human neuroimaging studies conducted during visuospatial working memory tasks have inconsistently detected activation in the prefrontal cortical areas depending presumably on the type of memory and control tasks employed. We used functional magnetic resonance imaging to study brain activation related to the performance of a visuospatial n-back task with different memory loads (0-back, 1-back and 2-back tasks). Comparison of the 2-back versus 0-back tasks revealed consistent, bilateral activation in the medial frontal gyrus (MFG), superior frontal sulcus and adjacent cortical tissue (SFS/SFG) in all subjects and in six out of seven subjects in the intraparietal sulcus (IPS). Activation was also detected in the inferior frontal gyrus, medially in the superior frontal gyrus, precentral gyrus, superior and inferior parietal lobuli, occipital visual association areas, anterior and posterior cingulate areas and in the insula. Comparison between the 1- back versus 0-back tasks revealed activation only in a few brain areas. Activation in the MFG, SFS/SFG and IPS appeared dependent on memory load. The results suggest that the performance of a visuospatial working memory task engages a network of distributed brain areas and that areas in the dorsal visual pathway are engaged in mnemonic processing of visuospatial information.      

Focal Hand Dystonia: Effectiveness of a Home Program of Fitness and Learning-based Sensorimotor and Memory Training

Study DesignThis was a pre post test design.IntroductionRetraining the brain is one approach to remediate movement dysfunction resulting from task specific focal hand dystonia (FHD_TSP).PurposeDocument change in task specific performance (TSP) for patients with FHD_TSP after 8 weeks of comprehensive home training (fitness activities, task practice, learning based memory and sensorimotor training).MethodsThirteen subjects were admitted and evaluated at baseline, immediately and 6 months post treatment for task specific performance, functional independence, sensory discrimination, fine motor speed and strength. In Phase I, 10 subjects were randomly assigned to home training alone or supervised practice prior to initiating the home training. In phase II, 2 subjects crossed over and 3 new subjects were added (18 hands). The intent to treat model was followed. Outcomes were summarized by median, effect size, and proportion improving with nonparametric analysis for significance.ResultsImmediately post-intervention, TSP, sensory discrimination, and fine motor speed improved 60-80% (p<0.00l respectively). Functional independence and strength improved by 50%. Eleven subjects (16 hands) were re-evaluated at 6 months; all but one subject reported a return to work. Task-specific performance was scored 84-90%. Supervised practice was associated with greater compliance and greater gains in performance.ConclusionsProgressive task practice plus learning based memory and sensorimotor training can improve TSP in patients with FHD_TSP. Compliance with home training is enhanced when initiated with supervised practice.Level of Evidence4.     

Disruption of functional connectivity of the default-mode network in alcoholism

The default mode network (DMN) comprises brain structures maximally active at rest. Disturbance of network nodes or their connections occurs with some neuropsychiatric conditions and may underlie associated dysfunction. DMN connectivity has not been examined in alcoholism, which is marked by compromised DMN nodes and impaired spatial working memory. To test whether performance would be related to DMN integrity, we examined DMN functional connectivity using functional magnetic resonance imaging (fMRI) data and graph theory analysis. We assumed that disruption of short paths between network nodes would attenuate processing efficiency. Alcoholics and controls were scanned at rest and during a spatial working memory task. At rest, the spontaneous slow fluctuations of fMRI signals in the posterior cingulate and cerebellar regions in alcoholics were less synchronized than in controls, indicative of compromised functional connectivity. Graph theory analysis indicated that during rest, alcoholics had significantly lower efficiency indices than controls between the posterior cingulate seed and multiple cerebellar sites. Greater efficiency in several connections correlated with longer sobriety in alcoholics. During the task, on which alcoholics performed on par with controls, connectivity between the left posterior cingulate seed and left cerebellar regions was more robust in alcoholics than controls and suggests compensatory networking to achieve normal performance.     

Functional Anatomy of Reaching and Visuomotor Learning: A Positron Emission Tomography Study

The purpose of this study was to identify the functional corticalfields involved in reaching for targets in extrapersonal space,and to identify the specific fields representing visual targetinformation in long-term memory. Ten healthy subjects were askedto learn the positions of seven circular targets that were repeatedlyprojected on a screen. The regional cerebral blood flow wasmeasured with positron emission tomography during a rest state,at an early learning stage, at a later learning stage, and finallyat 30 min after the course of learning had been completed. MeanrCBF change images for each task minus rest were calculatedand fields of significant rCBF changes were identified. In all three task states, cortical fields were consistentlyactivated in the left motor and premotor areas, the posteriorpart of the superior parietal lobule, and the right angulargyrus. When learning of the target positions had been achieved,additional fields appeared bilaterally in the posterior partof the superior parietal lobule, the right superior occipitalgyrus, the left motor and premotor areas, the medial aspectof the superior frontal gyrus, the postcentral gyrus, the superiorpart of the cuneus, the inferior part of the angular gyrus,and the anterior part of the insula. The results indicate thatthere are at least two different types of functional fieldsin the posterior part of the superior parietal lobule; one isactive during reaching for the targets when guided by internalrepresentations of target positions; the other likely representsthe storage sites of visual target information that is addressedin long-term memory.     

Cerebral plasticity in crossed C7 grafts of the brachial plexus: an fMRI study

In order to rescue elbow flexion after complete accidental avulsion of one brachial plexus, seven patients underwent a neurotization of the biceps with fibers from the contralateral C7 root. The C7 fibers used for the graft belonged to the pyramidal pathway, which descends from the cerebral hemisphere ipsilateral to the damaged plexus, and which controls extension and abduction of the contralateral arm. After several months of reeducation, a functional magentic resonance imaging study was performed with a 1.5 tesla clinical magnetic resonance scan system, in order to investigate the central neural networks involved in the recovery of elbow flexion. Functional brain images were acquired under four conditions: flexion of each of the two elbows, and imagined flexion of each elbow. Results show that flexion of the neurotized arm is associated with a bilateral network activity. The contralateral cortex originally involved in control of the rescued arm still participates in the elaboration and control of the task through the bilateral premotor and primary motor cortex. The location of the ipsilateral clusters in the primary motor, premotor, supplementary motor area, and posterior parietal areas is similar among patients. The location of contralateral activations within the same areas differs across patients.     

Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions.

The cingulate gyrus is a major part of the "anatomical limbic system" and, according to classic accounts, is involved in emotion. This view is oversimplified in light of recent clinical and experimental findings that cingulate cortex participates not only in emotion but also in sensory, motor, and cognitive processes. Anterior cingulate cortex, consisting of areas 25 and 24, has been implicated in visceromotor, skeletomotor, and endocrine outflow. These processes include responses to painful stimuli, maternal behavior, vocalization, and attention to action. Since all of these activities have an affective component, it is likely that connections with the amygdala are critical for them. In contrast, posterior cingulate cortex, consisting of areas 29, 30, 23, and 31, contains neurons that monitor eye movements and respond to sensory stimuli. Ablation studies suggest that this region is involved in spatial orientation and memory. It is likely that connections between posterior cingulate and parahippocampal cortices contribute to these processes. We conclude that there is a fundamental dichotomy between the functions of anterior and posterior cingulate cortices. The anterior cortex subserves primarily executive functions related to the emotional control of visceral, skeletal, and endocrine outflow. The posterior cortex subserves evaluative functions such as monitoring sensory events and the organism's own behavior in the service of spatial orientation and memory.     

The functional integration of the anterior cingulate cortex during conflict processing

Although functional activation of the anterior cingulate cortex(ACC) related to conflict processing has been studied extensively,the functional integration of the subdivisions of the ACC andother brain regions during conditions of conflict is still unclear.In this study, participants performed a task designed to elicitconflict processing by using flanker interference on targetresponse while they were scanned using event-related functionalmagnetic resonance imaging. The physiological response of severalbrain regions in terms of an interaction between conflict processingand activity of the anterior rostral cingulate zone (RCZa) ofthe ACC, and the effective connectivity between this zone andother regions were examined using psychophysiological interactionanalysis and dynamic causal modeling, respectively. There wassignificant integration of the RCZa with the caudal cingulatezone (CCZ) of the ACC and other brain regions such as the lateralprefrontal, primary, and supplementary motor areas above andbeyond the main effect of conflict and baseline connectivity.The intrinsic connectivity from the RCZa to the CCZ was modulatedby the context of conflict. These findings suggest that conflictprocessing is associated with the effective contribution ofthe RCZa to the neuronal activity of CCZ, as well as other corticalregions.     

High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice

Changes in cortical activity during working memory tasks were examined with electroencephalograms (EEGs) sampled from 115 channels and spatially sharpened with magnetic resonance imaging (MRI)-based finite element deblurring. Eight subjects performed tasks requiring comparison of each stimulus to a preceding one on verbal or spatial attributes. A frontal midline theta rhythm increased in magnitude with increased memory load. Dipole models localized this signal to the region of the anterior cingulate cortex. A slow (low-frequency), parietocentral, alpha signal decreased with increased working memory load. These signals were insensitive to the type of stimulus attribute being processed. A faster (higher-frequency), occipitoparietal, alpha signal was relatively attenuated in the spatial version of the task, especially over the posterior right hemisphere. Theta and alpha signals increased, and overt performance improved, after practice on the tasks. Increases in theta with both increased task difficulty and with practice suggests that focusing attention required more effort after an extended test session. Decreased alpha in the difficult tasks indicates that this signal is inversely related to the amount of cortical resources allocated to task performance. Practice-related increases in alpha suggest that fewer cortical resources are required after skill development. These results serve: (i) to dissociate the effects of task difficulty and practice; (ii) to differentiate the involvement of posterior cortex in spatial versus verbal tasks; (iii) to localize frontal midline theta to the anteromedial cortex; and (iv) to demonstrate the feasibility of using anatomical MRIs to remove the blurring effect of the skull and scalp from the ongoing EEG. The results are discussed with respect to those obtained in a prior study of transient evoked potentials during working memory.