Distinct Neural Regions Research Articles

Memory consolidation of sequence learning and dynamic adaptation during wakefulness.

Motor learning involves acquiring new movement sequences and adapting motor commands to novel conditions. Labile motor memories, acquired through sequence learning and dynamic adaptation, undergo a consolidation process during wakefulness after initial training. This process stabilizes the new memories, leading to long-term memory formation. However, it remains unclear if the consolidation processes underlying sequence learning and dynamic adaptation are independent and if distinct neural regions underpin memory consolidation associated with sequence learning and dynamic adaptation. Here, we first demonstrated that the initially labile memories formed during sequence learning and dynamic adaptation were stabilized against interference through time-dependent consolidation processes occurring during wakefulness. Furthermore, we found that sequence learning memory was not disrupted when immediately followed by dynamic adaptation and vice versa, indicating distinct mechanisms for sequence learning and dynamic adaptation consolidation. Finally, by applying patterned transcranial magnetic stimulation to selectively disrupt the activity in the primary motor (M1) or sensory (S1) cortices immediately after sequence learning or dynamic adaptation, we found that sequence learning consolidation depended on M1 but not S1, while dynamic adaptation consolidation relied on S1 but not M1. For the first time in a single experimental framework, this study revealed distinct neural underpinnings for sequence learning and dynamic adaptation consolidation during wakefulness, with significant implications for motor skill enhancement and rehabilitation.

The neural correlates for spatial language: Perspective-dependent and -independent relationships in American Sign Language and spoken English

In American Sign Language (ASL) spatial relationships are conveyed by the location of the hands in space, whereas English employs prepositional phrases. Using event-related fMRI, we examined comprehension of perspective-dependent (PD) (left, right) and perspective-independent (PI) (in, on) sentences in ASL and audiovisual English (sentence-picture matching task). In contrast to non-spatial control sentences, PD sentences engaged the superior parietal lobule (SPL) bilaterally for ASL and English, consistent with a previous study with written English. The ASL-English conjunction analysis revealed bilateral SPL activation for PD sentences, but left-lateralized activation for PI sentences. The direct contrast between PD and PI expressions revealed greater SPL activation for PD expressions only for ASL. Increased SPL activation for ASL PD expressions may reflect the mental transformation required to interpret locations in signing space from the signer’s viewpoint. Overall, the results suggest both overlapping and distinct neural regions support spatial language comprehension in ASL and English.

Cognitive brakes in interference resolution: A mouse-tracking and EEG co-registration study

Cognitive control is particularly challenged when it is necessary to resolve interference and correct our behavior on-the-fly. To do this, it is necessary to inhibit the ongoing wrong action and reprogram a new motor plan as appropriate for the current task. This ability requires a complex interaction between cognitive and motor control. Here, we aimed at shedding light on this interplay. To do this, we administered a spatial version of the Stroop task comprising blocks with different Proportion Congruency (PC) manipulations (i.e., manipulating the percentage of congruent trials at 25%, 50% or 75%), to elicit different cognitive control demands. Moreover, we used two techniques with high-temporal resolution, as we simultaneously recorded EEG and mouse trajectories, that can be considered the real-time kinematic correlates of the ongoing cognitive processing. Specifically, we analyzed the Event Related Potentials (ERPs) locked to the peak deceleration time, which marks the suppression of ongoing erroneous trajectories, and we estimated their neural sources. We found three PC-dependent ERP components engaging distinct neural regions, which showed a reduction of the Stroop effect for low-PC blocks. By using a novel co-registration of mouse-trajectories and EEG, we suggest that the observed components may reflect different mechanisms engaged by reactive cognitive control to resolve the interference, including the suppression of an ongoing but no longer appropriate response, the selection of the new motor plan and its actual updating.

Goal-oriented and habitual decisions: Neural signatures of model-based and model-free learning

Human decision-making is mainly driven by two fundamental learning processes: a slow, deliberative, goal-directed model-based process that maps out the potential outcomes of all options and a rapid habitual model-free process that enables reflexive repetition of previously successful choices. Although many model-informed neuroimaging studies have examined the neural correlates of model-based and model-free learning, the concordant activity among these two processes remains unclear. We used quantitative meta-analyses of functional magnetic resonance imaging experiments to identify the concordant activity pertaining to model-based and model-free learning over a range of reward-related paradigms. We found that: 1) both processes yielded concordant ventral striatum activity, 2) model-based learning activated the medial prefrontal cortex and orbital frontal cortex, and 3) model-free learning specifically activated the left globus pallidus and right caudate head. Our findings suggest that model-free and model-based decision making engage overlapping yet distinct neural regions. These stereotaxic maps improve our understanding of how deliberative goal-directed and reflexive habitual learning are implemented in the brain.

Moving in time: Simulating how neural circuits enable rhythmic enactment of planned sequences

Many complex actions are mentally pre-composed as plans that specify orderings of simpler actions. To be executed accurately, planned orderings must become active in working memory, and then enacted one-by-one until the sequence is complete. Examples include writing, typing, and speaking. In cases where the planned complex action is musical in nature (e.g. a choreographed dance or a piano melody), it appears to be possible to deploy two learned sequences at the same time, one composed from actions and a second composed from the time intervals between actions. Despite this added complexity, humans readily learn and perform rhythm-based action sequences. Notably, people can learn action sequences and rhythmic sequences separately, and then combine them with little trouble (Ullén & Bengtsson 2003). Related functional MRI data suggest that there are distinct neural regions responsible for the two different sequence types (Bengtsson et al. 2004). Although research on musical rhythm is extensive, few computational models exist to extend and inform our understanding of its neural bases. To that end, this article introduces the TAMSIN (Timing And Motor System Integration Network) model, a systems-level neural network model capable of performing arbitrary item sequences in accord with any rhythmic pattern that can be represented as a sequence of integer multiples of a base interval. In TAMSIN, two Competitive Queuing (CQ) modules operate in parallel. One represents and controls item order (the ORD module) and the second represents and controls the sequence of inter-onset-intervals (IOIs) that define a rhythmic pattern (RHY module). Further circuitry helps these modules coordinate their signal processing to enable performative output consistent with a desired beat and tempo.

Use of Synaptic Zinc Histochemistry to Reveal Different Regions and Laminae in the Developing and Adult Brain.

Characterization of anatomical and functional brain organization and development requires accurate identification of distinct neural circuits and regions in the immature and adult brain. Here we describe a zinc histochemical staining procedure that reveals differences in staining patterns among different layers and brain regions. Others have utilized this procedure not only to reveal the distribution of zinc-containing neurons and circuits in the brain, but also to successfully delineate areal and laminar boundaries in the developing and adult brain in several species. Here we illustrate this staining procedure with images from developing and adult ferret brains. We reveal a zinc-staining pattern that serves as an anatomical marker of areas and layers, and can be reliably used to distinguish visual cortical areas in the developing and adult visual cortex. The main goal of this protocol is to present a histochemical method that allows the accurate identification of layers and regions in the developing and adult brain where other methods fail to do so. Secondarily, in conjunction with densitometric image analysis, this method allows one to assess the distribution of synaptic zinc to reveal potential changes throughout development. This protocol describes in detail the reagents, tools, and steps necessary to successively stain frozen brain sections. Although this protocol is described using ferret brain tissue, it can easily be adapted for use in rodents, cats, or monkeys as well as in other brain regions.

Use of Synaptic Zinc Histochemistry to Reveal Different Regions and Laminae in the Developing and Adult Brain

Characterization of anatomical and functional brain organization and development requires accurate identification of distinct neural circuits and regions in the immature and adult brain. Here we describe a zinc histochemical staining procedure that reveals differences in staining patterns among different layers and brain regions. Others have utilized this procedure not only to reveal the distribution of zinc-containing neurons and circuits in the brain, but also to successfully delineate areal and laminar boundaries in the developing and adult brain in several species. Here we illustrate this staining procedure with images from developing and adult ferret brains. We reveal a zinc-staining pattern that serves as an anatomical marker of areas and layers, and can be reliably used to distinguish visual cortical areas in the developing and adult visual cortex. The main goal of this protocol is to present a histochemical method that allows the accurate identification of layers and regions in the developing and adult brain where other methods fail to do so. Secondarily, in conjunction with densitometric image analysis, this method allows one to assess the distribution of synaptic zinc to reveal potential changes throughout development. This protocol describes in detail the reagents, tools, and steps necessary to successively stain frozen brain sections. Although this protocol is described using ferret brain tissue, it can easily be adapted for use in rodents, cats, or monkeys as well as in other brain regions.

Overlapping and distinct neural correlates of imitating and opposing facial movements

Previous studies have demonstrated that imitating a face can be relatively automatic and reflexive. In contrast, opposing facial expressions may require engaging flexible, cognitive control. However, few studies have examined the degree to which imitation and opposition of facial movements recruit overlapping and distinct neural regions. Furthermore, little work has examined whether opposition and imitation of facial movements differ between emotional and averted eye gaze facial expressions. This study utilized a novel task with 40 participants to compare passive viewing, imitation and opposition of emotional faces looking forward and neutral faces with averted eye gaze [(3: Look, Imitate, Oppose) x (2: Emotion, Averted Eye)]. Imitation and opposition of both types of facial movements elicited overlapping activation in frontal, premotor, superior temporal and anterior intraparietal regions. These regions are recruited during cognitive control, face processing and mirroring tasks. For both emotional and averted eye gaze photos, opposition engaged the superior frontal gyrus, superior temporal sulcus and the anterior intraparietal sulcus to a greater extent compared to imitation. Finally, stimulus type and instruction interacted, such that for the eye gaze condition only, greater activation was observed in the dorsal anterior cingulate (dACC) during opposition compared to imitation, while no significant dACC differences were observed for the emotional expression conditions, which instead showed significantly greater activation in the middle and frontal pole. Overall these results showed significant overlap between imitation and opposition, as well as increased activation of these regions to generate an opposing facial movement relative to imitating.

Neural correlates of fingerspelling, text, and sign processing in deaf American Sign Language–English bilinguals

We used functional magnetic resonance imaging to identify the neural regions that support comprehension of fingerspelled words, printed words, and American Sign Language (ASL) signs in deaf ASL–English bilinguals. Participants made semantic judgements (concrete–abstract?) to each lexical type, and hearing non-signers served as controls. All three lexical types engaged a left frontotemporal circuit associated with lexical semantic processing. Both printed and fingerspelled words activated the visual word form area for deaf signers only. Fingerspelled words were more left lateralised than signs, paralleling the difference between reading and listening for spoken language. Greater activation in left supramarginal gyrus was observed for signs compared to fingerspelled words, supporting its role in processing sign-specific phonology. Fingerspelling ability was negatively correlated with activation in left occipital cortex, while ASL ability was negatively correlated with activation in right angular gyrus. Overall, the results reveal both overlapping and distinct neural regions for comprehension of signs, text, and fingerspelling.

Decoding the Neuroanatomical Basis of Reading Ability: A Multivoxel Morphometric Study

As a relatively recent cultural invention in human evolution, reading is an important gateway to personal development and socioeconomic success. Despite the well documented individual differences in reading ability, its neuroanatomical correlates have not been well understood, largely due to the fact that reading is a complex skill that consists of multiple components. Using a large sample of 416 college students and 7 reading tasks, the present study successfully identified three uncorrelated components of reading ability: phonological decoding, form-sound association, and naming speed. We then tried to predict individuals' scores in these components from their gray matter volume (GMV) on a subset of participants (N = 253) with high-quality structural images, adopting a multivariate support vector regression analysis with tenfold cross-validation. Our results revealed distinct neural regions that supported different aspects of reading ability: whereas phonological decoding was associated with the GMV in the left superior parietal lobe extending to the supramarginal gyrus, form-sound association was predicted by the GMV in the hippocampus and cerebellum. Naming speed was associated with GMV in distributed brain regions in the occipital, temporal, parietal, and frontal cortices. Phonological decoding and form-sound association were uncorrelated with general cognitive abilities. However, naming speed was correlated with intelligence and processing speed, and some of the regions that were predictive of naming speed also predicted these general cognitive abilities. These results provide further insights on the cognitive and neural architecture of reading and the structural basis of individual differences in reading abilities.

The neuropsychology of face perception: beyond simple dissociations and functional selectivity

Face processing relies on a distributed, patchy network of cortical regions in the temporal and frontal lobes that respond disproportionately to face stimuli, other cortical regions that are not even primarily visual (such as somatosensory cortex), and subcortical structures such as the amygdala. Higher-level face perception abilities, such as judging identity, emotion and trustworthiness, appear to rely on an intact face-processing network that includes the occipital face area (OFA), whereas lower-level face categorization abilities, such as discriminating faces from objects, can be achieved without OFA, perhaps via the direct connections to the fusiform face area (FFA) from several extrastriate cortical areas. Some lesion, transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) findings argue against a strict feed-forward hierarchical model of face perception, in which the OFA is the principal and common source of input for other visual and non-visual cortical regions involved in face perception, including the FFA, face-selective superior temporal sulcus and somatosensory cortex. Instead, these findings point to a more interactive model in which higher-level face perception abilities depend on the interplay between several functionally and anatomically distinct neural regions. Furthermore, the nature of these interactions may depend on the particular demands of the task. We review the lesion and TMS literature on this topic and highlight the dynamic and distributed nature of face processing.

Common and distinct neural regions for the guidance of selection by visuoverbal information held in memory: Converging evidence from fMRI and rTMS

Recent research indicates that working memory (WM) and attention interact, with attention automatically biased to stimuli that match the contents of WM. Though there is behavioral evidence for verbal guidance (written words) as well as guidance by more visual cues in WM, we have limited understanding of how these two representational formats influence the guidance of visual selection at a neural level. Here, we present converging evidence from functional MRI and transcranial magnetic stimulation (TMS), which indicates that both common and distinct neural regions mediate the influence of visuoverbal representations on WM. Colored shapes, but not words, in WM activated the superior frontal gyrus (SFG) and recognition memory areas in the temporal lobe when the contents of WM matched a stimulus in a subsequent search display. rTMS to the SFG disrupted WM effects from colored shapes. The lateral occipital cortex, however, tended to be more activated with written word cues, and rTMS to the lateral occipital complex tended to disrupt effects from written words more than from colored shapes in WM. There was also evidence for cue validity effects from colored shapes and written stimuli operating through different subthalamic nuclei. We discuss the evidence for understanding the neural systems mediating attention effects from WM.

Decomposing the neural mechanisms of visual search through model-based analysis of fMRI: Top-down excitation, active ignoring and the use of saliency by the right TPJ

Despite being studied intensively over the past 30 years, the neural processes underlying visual search are not yet fully understood. In the current study we extend prior work using model-based analysis to decompose fMRI data. fMRI data on human search were assessed using activation functions predicted from the spiking Search over Time and Space model (sSoTS; Mavritsaki et al., 2006). Going beyond previous work, we show for the first time that activity in a central location map in the model, which computes the saliency of a target relative to distractors, correlated with the BOLD response in the right temporo-parietal junction (TPJ) – a key region implicated in clinical studies of unilateral neglect. This is consistent with the right TPJ responding to the relative saliency of visual stimuli. In addition, a re-analysis of search performance, with a larger participant set and a psychologically plausible response rule, showed distinct neural regions in parietal and occipital cortices linked to top-down excitation and the to active ignoring of distractors. The results indicate that excitatory and inhibitory circuits for visual selection can be separated, and that the right TPJ may be critical for responding to salient targets. The value of using a model-based approach is discussed.

Getting mixed messages: The impact of conflicting social signals on the brain's target emotional response

Amidst a barrage of sensory information in the environment, the impact that individual stimuli have on our behaviour is thought to depend on the outcome of competition that occurs within and between multiple brain regions. Although biased competition models of attention have been tested in visual cortices and to a lesser extent in auditory cortex, little is known about the nature of stimulus competition outside of sensory areas. Given the hypothesized role of multiple pathways (cortical and subcortical) and specialized brain regions for processing valence information, studies involving conflicting basic emotional stimuli provide a unique opportunity to examine whether the principles of biased competition apply outside of sensory cortex. We used fMRI to examine the neural representation and resolution of emotional conflict in a sample of healthy individuals. Participants made explicit judgments about the valence of happy or fearful target facial expressions in the context of emotionally congruent, neutral, or incongruent distracters. The results suggest that emotional conflict is reflected in a dissociable manner across distinct neural regions. Posterior areas of visual cortex showed enhanced responding to congruent relative to neutral or incongruent stimuli. Orbitofrontal cortex remained sensitive to positive affect in the context of conflicting emotional stimuli. In contrast, within the amygdala, activity associated with identifying positive target expressions declined with the introduction of neutral and incongruent expressions; however, activity associated with fearful target expressions was less susceptible to the influence of emotional context. Enhanced functional connectivity was observed between medial prefrontal cortex and the amygdala during incongruent trials; the degree of connectivity was correlated with reaction time costs incurred during incongruent trials. The results are interpreted with reference to current models of emotional attention and regulation.

Spatio-temporal Brain Dynamics Underlying Saccade Execution, Suppression, and Error-related Feedback

Human and nonhuman animal research has outlined the neural regions that support saccadic eye movements. The aim of the current work was to outline the sequence by which distinct neural regions come on-line to support goal-directed saccade execution and error-related feedback. To achieve this, we obtained behavioral responses via eye movement recordings and neural responses via magnetoencephalography (MEG), concurrently, while participants performed an antisaccade task. Neural responses were examined with respect to the onset of the saccadic eye movements. Frontal eye field and visual cortex activity distinguished subsequently successful goal-directed saccades from (correct and erroneous) reflexive saccades prior to the deployment of the eye movement. Activity in the same neural regions following the saccadic movement distinguished correct from incorrect saccadic responses. Error-related activity in the frontal eye fields preceded that from visual regions, suggesting a potential feedback network that may drive corrective eye movements. This work provides the first empirical demonstration of simultaneous remote eyetracking and MEG recording. The coupling of behavioral and neuroimaging technologies, used here to characterize dynamic brain networks underlying saccade execution and error-related feedback, demonstrates a novel within-paradigm converging evidence approach by which to outline the neural underpinnings of cognition.

Age-related Changes in Object Processing and Contextual Binding Revealed Using fMR Adaptation

Using fMR adaptation, we studied the effects of aging on the neural processing of passively viewed naturalistic pictures composed of a prominent object against a background scene. Spatially distinct neural regions showing specific patterns of adaptation to objects, background scenes, and contextual integration (binding) were identified in young adults. Older adults did not show adaptation responses corresponding to binding in the medial-temporal areas. They also showed an adaptation deficit for objects whereby their lateral occipital complex (LOC) did not adapt to repeated objects in the context of a changing background. The LOC could be activated, however, when objects were presented without a background. Moreover, the adaptation deficit for objects viewed against backgrounds was reversed when elderly subjects were asked to attend to objects while viewing these complex pictures. These findings suggest that the elderly have difficulty with simultaneous processing of objects and backgrounds that, in turn, could contribute to deficient contextual binding.

Long-Term Storage of an Associative Memory Trace in the Cerebellum.

Distinct neural regions may be engaged during acquisition and maintenance of some memories. In delay classical conditioning of the eyeblink response, the cerebellum is necessary for acquisition and expression of the conditioned response (CR), but loci of long-term memory storage are not known. Rabbits (Oryctolagus cuniculus) were trained, overtrained, and given either 30 additional days of training or 30 days of rest. Half the subjects in the rest group were given a reminder training session. Subjects then received either reversible inactivation of the cerebellar interpositus nucleus (muscimol) or permanent electrolytic lesions. In all cases, inactivation and lesions of the interpositus completely abolished the CR. The site of memory formation in the interpositus nucleus also appears to be the site of long-term memory storage.

Objects and their actions: evidence for a neurally distributed semantic system

An influential model of conceptual knowledge claims that objects are represented in a distributed network of cortical areas that store information about different types of attributes, such as form, colour, and motion (A. Martin et al., 2000, in: The Cognitive Neurosciences, 2nd ed., MIT Press, Cambridge). Two specific claims of this account are that (a) the motions and actions associated with objects (along with other attributes) are automatically activated whenever the object concept is evoked and (b) topographically distinct neural regions are responsible for motion/action attributes pertaining to objects in the categories of tools and animals. We used fMRI to examine the neural activation associated with conceptual processing of nouns referring to animals and tools and for verbs referring to tool-associated actions (e.g., drilling, painting) and biological actions (e.g., walking, jumping). We found that object names and their associated actions activated the same set of neural regions (left fusiform gyrus, superior and middle temporal cortex) consistent with the claim that word tool and animal concepts implicitly activate the actions associated with them. However, there was no evidence of category specificity for either objects or actions, with essentially the same activations for the form and motion attributes of both living and nonliving categories.

Regions of neural dysfunction associated with impaired naming of actions and objects in acute stroke

The proposal that there are distinct neural regions devoted to the representation or processing of names of objects versus actions has received support from a variety of sources. However, there have been conflicting results regarding the localisation of the postulated mechanisms that are more crucial for one category or the other. There is also controversy as to whether the separation of mechanisms devoted to object versus action naming arises at the level of lexical-semantics or at the level of accessing lexical representations for output. We addressed these issues by testing oral naming and word comprehension of object and action names in 33 right-handed patients with acute left-hemisphere stroke, and by obtaining magnetic resonance (MR) perfusion-weighted and diffusion-weighted imaging of each patient at the same time. We identified regions of abnormal blood flow or infarction associated with impaired naming (with and without impaired word comprehension) of objects, of actions, or of both, using Fisher Exact tests. We found both neural regions shared by networks underlying naming of actions and networks underlying naming of objects, and other neural regions that were crucial to only one network or the other. One of the shared components (in the left superior temporal gyrus) was also essential to comprehension of action and object names (as tested by word/picture verification). These results converge with evidence from chronic lesion studies and functional imaging studies, indicating that some components of the neural networks for accessing lexical representations for output are more important for object names (e.g., left temporal cortex) and others more important for action names (e.g., left posterior frontal cortex).

126. Working memory impairment in schizophrenia patients and their first-degree relatives

There is accumulating evidence for the involvement of the prefrontal cortex in the genetic diathesis for schizophrenia. One of the primary functions supported by the prefrontal cortex is working memory. Findings from neuroimaging studies increasingly suggest that working memory task characteristics, including the modality of stimuli presentation (e.g., verbal, spatial, or object), as well as the processing demands (e.g., storage, rehearsal/maintenance or executive processes such as task management) activate distinct neural regions thought to mediate performance. Given these findings, we evaluated the performance of schizophrenia patients, their first-degree relatives and nonpsychiatric controls on a battery of working memory tasks that varied in the modality of stimuli presentation and processing demands (digit span, letter-number sequencing, delayed response and self-ordered pointing tasks). Whereas schizophrenia patients consistently demonstrated impaired performance across working memory measures, their first-degree nonpsychotic relatives appeared to demonstrate impairment only on a selective subset of measures. It may be that working memory impairment in these relatives is directly related to the degree to which executive processes are evoked, such that only tasks that require substantial manipulation of material within working memory or its protection from interference reveal impaired performance. These findings may begin to suggest which components of working memory are most effective at identifying individuals with genetic risk for schizophrenia and the corresponding candidate sites of neuropathology.