Articulatory Gain Predicts Motor Cortex and Subthalamic Nucleus Activity During Speech.

Speaking precisely is important for effective verbal communication, and articulatory gain is one component of speech motor control that contributes to achieving this goal. Given that the basal ganglia have been proposed to regulate the speed and size of limb movement, that is, movement gain, we explored the basal ganglia contribution to articulatory gain, through local field potentials (LFP) recorded simultaneously from the subthalamic nucleus (STN), precentral gyrus, and postcentral gyrus. During STN deep brain stimulation implantation for Parkinson's disease, participants read aloud consonant-vowel-consonant syllables. Articulatory gain was indirectly assessed using the F2 Ratio, an acoustic measurement of the second formant frequency of/i/vowels divided by/u/vowels. Mixed effects models demonstrated that the F2 Ratio correlated with alpha and theta activity in the precentral gyrus and STN. No correlations were observed for the postcentral gyrus. Functional connectivity analysis revealed that higher phase locking values for beta activity between the STN and precentral gyrus were correlated with lower F2 Ratios, suggesting that higher beta synchrony impairs articulatory precision. Effects were not related to disease severity. These data suggest that articulatory gain is encoded within the basal ganglia-cortical loop.

Simultaneously recorded subthalamic and cortical LFPs reveal different lexicality effects during reading aloud.

Many language functions are traditionally assigned to cortical brain areas, leaving the contributions of subcortical structures to language processing largely unspecified. The present study examines a potential role of the subthalamic nucleus (STN) in lexical processing, specifically, reading aloud of words (e.g., 'fate') and pseudowords (e.g., 'fape'). We recorded local field potentials simultaneously from the STN and the cortex (precentral, postcentral, and superior temporal gyri) of 13 people with Parkinson's disease undergoing awake deep brain stimulation and compared STN's lexicality-related neural activity with that of the cortex. Both STN and cortical activity demonstrated significant task-related modulations, but the lexicality effects were different in the two brain structures. In the STN, an increase in gamma band activity (31-70 Hz) was present in pseudoword trials compared to word trials during subjects' spoken response. In the cortex, a greater decrease in beta band activity (12-30 Hz) was observed for pseudowords in the precentral gyrus. Additionally, 11 individual cortical sites showed lexicality effects with varying temporal and topographic characteristics in the alpha and beta frequency bands. These findings suggest that the STN and the sampled cortical regions are involved differently in the processing of lexical distinctions.

Motivation-dependent responses in the human caudate nucleus.

Motivation is a complex process that leads to completion or avoidance of a behavior. Past research strongly implicates the basal ganglia in a circuit integral for the control of motivation. Specifically, the human striatum has been shown to process reward information, differentiating between monetary rewards and punishments in recent neuroimaging experiments. It is unclear, however, how the dorsal striatum, particularly the caudate nucleus, responds to changes in the motivational context of a task. Using an event-related design, where participants were given positive and negative feedback upon guessing the value of an unknown card, we manipulated the motivational context of the task by dividing trials into periods of high incentive (where visual feedback indicated monetary rewards and punishments) and low incentive (where visual feedback indicated only accuracy). We found that activity in the caudate nucleus was strongly influenced by the different incentive periods. The hemodynamic response was characterized by a larger rise at the onset of trials and larger differences between positive and negative feedback during periods of high incentive. These results suggest that changes in motivation are capable of modulating basal ganglia activity, and further support an important role for the caudate nucleus in affective processing.

Dorsal striatum responses to reward and punishment: effects of valence and magnitude manipulations.

The goal of this research was to further our understanding of how the striatum responds to the delivery of affective feedback. Previously, we had found that the striatum showed a pattern of sustained activation after presentation of a monetary reward, in contrast to a decrease in the hemodynamic response after a punishment. In this study, we tested whether the activity of the striatum could be modulated by parametric variations in the amount of financial reward or punishment. We used an event-related fMRI design in which participants received large or small monetary rewards or punishments after performance in a gambling task. A parametric ordering of conditions was observed in the dorsal striatum according to both magnitude and valence. In addition, an early response to the presentation of feedback was observed and replicated in a second experiment with increased temporal resolution. This study further implicates the dorsal striatum as an integral component of a reward circuitry responsible for the control of motivated behavior, serving to code for such feedback properties as valence and magnitude.

Functional heterogeneity within Broca's area during verbal working memory.

In previous fMRI research, we found that two subregions of the left inferior frontal cortex showed distinct patterns of activity during a verbal working memory task. Specifically, a more dorsal region tracked with performance, while a more ventral region was sensitive to lexical status. To test the veracity of this finding, we developed a new method for meta-analysis of neuroimaging results. In this method, Gaussian probability distributions are formed around stereotaxic coordinates obtained from published neuroimaging studies. These probability distributions are then combined to identify regions of convergence across studies. When this method was applied to prior studies of working memory, the results largely paralleled those from earlier reviews of the literature on working memory, but also confirmed our empirical findings showing distinct foci within Broca's area. Further application of this meta-analytic technique substantiated the dissociation in these regions for performance and sublexical processing. These results help to validate a novel approach for meta-analysis of neuroimaging findings that avoids many of the subjective assumptions involved in alternative approaches.

Neuroimaging studies of speech an overview of techniques and methodological approaches.

UNLABELLED: Over the past two decades, there has been an explosion in the use of imaging technology to study the structure and function of the human brain. The purpose of this article is to explore how functional neuroimaging has been applied to the study of speech production. This article begins with a brief review of neuroimaging methods and limitations. Then, two approaches that can be used to study the brain areas that support speech production are illustrated. The first approach is based upon comparisons across different types of language production tasks; the second approach is based upon comparing the effects of different types of stimuli within a single task. Results obtained using these approaches will be used to dissociate the contributions of different brain regions involved in speech production. For example, evidence will be presented that Broca's area contributes to phonological encoding, whereas motor cortex, the supplementary motor area (SMA), and the cerebellum support phonetic encoding and articulation. LEARNING OUTCOMES: As a result of this activity, the participant will be able to describe basic methods for conducting a positron emission tomography study and a functional magnetic resonance imaging study. The participant will also be introduced to two approaches for fractionating the brain regions involved in speech production: (1) comparisons between tasks, and (2) manipulations of stimulus materials. Finally, the participant will be able to summarize a cognitive model of the components of speech production that will be introduced, and potential mappings between these components and particular brain regions will be discussed.

Dissociation of verbal working memory system components using a delayed serial recall task.

Functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of component processes in verbal working memory. Based on behavioral research using manipulations of verbal stimulus type to dissociate storage, rehearsal, and executive components of verbal working memory, we designed a delayed serial recall task requiring subjects to encode, maintain, and overtly recall sets of verbal items for which phonological similarity, articulatory length, and lexical status were manipulated. By using a task with temporally extended trials, we were able to exploit the temporal resolution afforded by fMRI to partially isolate neural contributions to encoding, maintenance, and retrieval stages of task performance. Several regions commonly associated with maintenance, including supplementary motor, premotor, and inferior frontal areas, were found to be active across all three trial stages. Additionally, we found that left inferior frontal and supplementary motor regions showed patterns of stimulus and temporal sensitivity implicating them in distinct aspects of articulatory rehearsal, while no regions showed a pattern of sensitivity consistent with a role in phonological storage. Regional modulation by task difficulty was further investigated as a measure of executive processing. We interpret our findings as they relate to notions about the cognitive architecture underlying verbal working memory performance.

Task-dependent modulation of regions in the left inferior frontal cortex during semantic processing.

To distinguish areas involved in the processing of word meaning (semantics) from other regions involved in lexical processing more generally, subjects were scanned with positron emission tomography (PET) while performing lexical tasks, three of which required varying degrees of semantic analysis and one that required phonological analysis. Three closely apposed regions in the left inferior frontal cortex and one in the right cerebellum were significantly active above baseline in the semantic tasks, but not in the nonsemantic task. The activity in two of the frontal regions was modulated by the difficulty of the semantic judgment. Other regions, including some in the left temporal cortex and the cerebellum, were active across all four language tasks. Thus, in addition to a number of regions known to be active during language processing, regions in the left inferior frontal cortex were specifically recruited during semantic processing in a task-dependent manner. A region in the right cerebellum may be functionally related to those in the left inferior frontal cortex. Discussion focuses on the implications of these results for current views regarding neural substrates of semantic processing.

Bridging the gap between neuroimaging and neuropsychology: using working memory as a case-study.

Neuropsychology and neuroimaging both provide information about the relationship between brain structure and function, and thus attempt to understand if the neural basis of cognition should benefit from converging results obtained across the two methods. However, serious attempts to integrate the two methodologies face several challenges, such as differences in basic paradigm designs. To illustrate these points, this article will review neuropsychological and neuroimaging research in the area of working memory. Points of discussion will include discrepancies between neuropsychological and neuroimaging evidence for domain-specific rehearsal systems, the role of left inferior parietal cortex in phonological storage, and the contributions of Brocas area and the cerebellum to articulatory rehearsal. Methodological factors and assumptions that may account for these discrepancies, and the steps that could be taken to overcome them, will be evaluated. The overall objective of this "case study" is to encourage neuroimagers and neuropsychologists to evaluate seriously the results obtained in both methodologies when formulating interpretations of their data and when designing new studies.

Tracking the hemodynamic responses to reward and punishment in the striatum.

Research suggests that the basal ganglia complex is a major component of the neural circuitry that mediates reward-related processing. However, human studies have not yet characterized the response of the basal ganglia to an isolated reward, as has been done in animals. We developed an event-related functional magnetic resonance imaging paradigm to identify brain areas that are activated after presentation of a reward. Subjects guessed whether the value of a card was higher or lower than the number 5, with monetary rewards as an incentive for correct guesses. They received reward, punishment, or neutral feedback on different trials. Regions in the dorsal and ventral striatum were activated by the paradigm, showing differential responses to reward and punishment. Activation was sustained following a reward feedback, but decreased below baseline following a punishment feedback.

Lesion segmentation and manual warping to a reference brain: intra- and interobserver reliability.

The study of subjects with acquired brain damage has been an invaluable tool for exploring human brain function, and the description of lesion locations within and across subjects is an important component of this method. Such descriptions usually involve the separation of lesioned from nonlesioned tissue (lesion segmentation) and the description of the lesion location in terms of a standard anatomical reference space (lesion warping). The objectives of this study were to determine the sources and magnitude of variability involved in lesion segmentation and warping using the MAP-3 approach. Each of two observers segmented the lesion volume in ten brain-damaged subjects twice, so as to permit pairwise comparisons of both intra- and interobserver agreement. The segmented volumes were then warped to a reference brain using both a manual (MAP-3) and an automated (AIR-3) technique. Observer agreement between segmented and warped volumes was analyzed using four measures: volume size, distance between the volume surfaces, percentage of nonoverlapping voxels, and percentage of highly discrepant voxels. The techniques for segmentation and warping produced high agreement within and between observers. For example, in most instances, the warped volume surfaces created by different observers were separated by less than 3 mm. The performance of the automated warping technique compared favorably to the manual technique in most subjects, although important exceptions were found. Overall, these results establish benchmark parameters for expert and automated lesion transfer, and indicate that a high degree of confidence can be placed in the detailed anatomical interpretation of focal brain damage based upon the MAP-3 technique.

Sound and meaning: how native language affects reading strategies.

In the Italian language, spelling is consistently related to pronunciation, whereas English words that are spelled similarly are often pronounced differently. An imaging study now shows that native language affects the brain regions activated by reading aloud.

Neural correlates of recovery from aphasia after damage to left inferior frontal cortex.

OBJECTIVE: To determine neural correlates of recovery from aphasia after left frontal injury. METHODS: The authors studied the verbal performance of patients with infarcts centered in the left inferior frontal gyrus (IFG), using a battery of attention-demanding lexical tasks that normally activate the left IFG and a simpler reading task that does not normally recruit the left IFG. The authors used positron emission tomography (PET) and functional MRI (fMRI) to record neural activity in the same group of patients during word-stem completion, one of the attention-demanding lexical tasks. To identify potential neural correlates of compensation/recovery, they analyzed the resulting data for the group as a whole (PET, fMRI) and also for each participant (fMRI). RESULTS: Patients with damage to the left IFG were impaired on all attention-demanding lexical tasks, but they completed the word-reading tasks normally. The imaging studies demonstrated a stronger-than-normal response in the right IFG, a region homologous to the damaged left IFG. The level of activation in the right IFG did not correlate with verbal performance, however. In addition, a perilesional response within the damaged left IFG was localized in the two patients who gave the best performance in the word-stem completion task and showed the most complete recovery from aphasia. CONCLUSIONS: Right-IFG activity may represent either the recruitment of a preexisting neural pathway through alternative behavioral strategies or an anomalous response caused by removal of the left IFG. Perilesional activity in the left IFG may represent sparing or restoration of normal function in peri-infarctual tissue that was inactive early on after injury. This activity may be of greater functional significance than right IFG activity because it was associated with more normal verbal performance.

A comment on the functional localization of the phonological storage subsystem of working memory.

Working memory, as defined by Baddeley and Hitch, is an interactive set of cognitive processes responsible for holding information online and available for analysis. Part of that system is a specialized subsystem devoted to maintaining verbal information; the verbal "slave" subsystem has as a core component a phonological store. For many years, the anatomical locus of the phonological store has been thought to be in the supramarginal and angular gyri of the speech dominant hemisphere, and functional neuroimaging studies provide broad support for this localization. However, a finer grained analysis of published experiments reveals two possible foci for the phonological store within the parietal lobe, neither of which has a pattern of functional activation that is fully consistent with the Baddeley and Hitch model. The purpose of the present paper is to review several studies relevant to the question of the localization of the phonological store and to suggest possible reasons the results are discrepant.

Effects of lexicality, frequency, and spelling-to-sound consistency on the functional anatomy of reading.

Functional neuroimaging was used to investigate three factors that affect reading performance: first, whether a stimulus is a word or pronounceable non-word (lexicality), second, how often a word is encountered (frequency), and third, whether the pronunciation has a predictable spelling-to-sound correspondence (consistency). Comparisons between word naming (reading) and visual fixation scans revealed stimulus-related activation differences in seven regions. A left frontal region showed effects of consistency and lexicality, indicating a role in orthographic to phonological transformation. Motor cortex showed an effect of consistency bilaterally, suggesting that motoric processes beyond high-level representations of word phonology influence reading performance. Implications for the integration of these results into theoretical models of word reading are discussed.

The effects of practice on the functional anatomy of task performance.

The effects of practice on the functional anatomy observed in two different tasks, a verbal and a motor task, are reviewed in this paper. In the first, people practiced a verbal production task, generating an appropriate verb in response to a visually presented noun. Both practiced and unpracticed conditions utilized common regions such as visual and motor cortex. However, there was a set of regions that was affected by practice. Practice produced a shift in activity from left frontal, anterior cingulate, and right cerebellar hemisphere to activity in Sylvian-insular cortex. Similar changes were also observed in the second task, a task in a very different domain, namely the tracing of a maze. Some areas were significantly more activated during initial unskilled performance (right premotor and parietal cortex and left cerebellar hemisphere); a different region (medial frontal cortex, "supplementary motor area") showed greater activity during skilled performance conditions. Activations were also found in regions that most likely control movement execution irrespective of skill level (e.g., primary motor cortex was related to velocity of movement). One way of interpreting these results is in a "scaffolding-storage" framework. For unskilled, effortful performance, a scaffolding set of regions is used to cope with novel task demands. Following practice, a different set of regions is used, possibly representing storage of particular associations or capabilities that allow for skilled performance. The specific regions used for scaffolding and storage appear to be task dependent.

Neuroimaging studies of word reading.

This review discusses how neuroimaging can contribute to our understanding of a fundamental aspect of skilled reading: the ability to pronounce a visually presented word. One contribution of neuroimaging is that it provides a tool for localizing brain regions that are active during word reading. To assess the extent to which similar results are obtained across studies, a quantitative review of nine neuroimaging investigations of word reading was conducted. Across these studies, the results converge to reveal a set of areas active during word reading, including left-lateralized regions in occipital and occipitotemporal cortex, the left frontal operculum, bilateral regions within the cerebellum, primary motor cortex, and the superior and middle temporal cortex, and medial regions in the supplementary motor area and anterior cingulate. Beyond localization, the challenge is to use neuroimaging as a tool for understanding how reading is accomplished. Central to this challenge will be the integration of neuroimaging results with information from other methodologies. To illustrate this point, this review will highlight the importance of spelling-to-sound consistency in the transformation from orthographic (word form) to phonological (word sound) representations, and then explore results from three neuroimaging studies in which the spelling-to-sound consistency of the stimuli was deliberately varied. Emphasis is placed on the pattern of activation observed within the left frontal cortex, because the results provide an example of the issues and benefits involved in relating neuroimaging results to behavioral results in normal and brain damaged subjects, and to theoretical models of reading.

Neuroimaging studies of the cerebellum: language, learning and memory.

During the decade following a functional neuroimaging study of language that showed cerebellar involvement in a cognitive task, PET and fMRI studies have continued to provide evidence that the role of the cerebellum extends beyond that of motor control and that this structure contributes in some way to cognitive operations. In this review, we describe neuroimaging evidence for cerebellar involvement in working memory, implicit and explicit learning and memory, and language, and we discuss some of the problems and limitations faced by researchers who use neuroimaging to investigate cerebellar function. We also raise a set of outstanding questions that need to be addressed through further neuroimaging and behavioral experiments before differing functional accounts of cerebellar involvement in cognition can be resolved.