The nature and treatment of stuttering as revealed by fMRI A within- and between-group comparison

This article reviews some of our recent functional magnetic resonance imaging (fMRI) studies of stuttering. Using event-related fMRI experiments, we investigated brain activation during speech production. Results of three studies comparing persons who stutter (PWS) and persons who do not stutter (PWNS) are outlined. Their findings point to a region in the right frontal operculum (RFO) that was consistently implicated in stuttering. During overt reading and before fluency shaping therapy, PWS showed higher and more distributed neuronal activation than PWNS. Immediately after therapy differential activations were even more distributed and left sided. They extended to frontal, temporal, and parietal regions, anterior cingulate, insula, and putamen. These over-activations were slightly reduced and again more right sided two years after therapy. Left frontal deactivations remained stable over two years of observation, and therefore possibly indicate a dysfunction. After therapy, we noted higher activations in persons who stutter moderately than in those who stutter severely. These activations might reflect patterns of compensation. We discuss why these findings suggest that fluency-inducing techniques might synchronize a disturbed signal transmission between auditory, speech motor planning, and motor areas.

Educational objectives: The reader will learn about and be able to: (1) identify regions of brain activations and deactivations specific for PWS; (2) describe brain activation changes induced by fluency shaping therapy; and (3) discuss the correlation between stuttering severity and brain activation.     

Pragmatic communication skills in patients with Parkinson's disease

BACKGROUND: Pragmatic communication abilities may depend on intact frontal lobe systems. Independent evidence suggests that some persons with Parkinson's disease (PD) are impaired on measures of frontal lobe function. HYPOTHESIS: We therefore hypothesized in Study 1 that pragmatic communication skills would be impaired in some persons with PD and would be linked to frontal dysfunction in these patients. In Study 2 we hypothesized that PD patients would be unaware of their pragmatic communication deficits. METHODS: In Study 1 we administered tests of pragmatic abilities and frontal lobe functioning to twenty-two persons with Parkinson's disease (PD) and 10 healthy controls. In Study 2 we obtained self-ratings of pragmatic abilities from 11 PD patients and then checked these self-ratings against ratings of these same abilities by the patient's spouses. RESULTS: We found in Study 1 that patients with PD were: (a) significantly impaired on measures of pragmatic communication abilities, especially in the areas of conversational appropriateness, turn-taking, prosodics and proxemics, and that this impairment was significantly related to measures of frontal lobe function. In study 2 we found that PD patients overestimated their own abilities relative to spousal ratings of those abilities and thus were unaware of the extent of their problems with pragmatic social communication skills. CONCLUSION: We conclude that pragmatic social communication skills are impaired in PD and that this impairment may be related to frontal lobe dysfunction.     

Regulation of glutamate synapses by nicotinic acetylcholine receptors in auditory cortex

Acetylcholine plays an important role in regulating the processing of sensory stimuli, and understanding its specific cellular actions is critical to understanding how sensory cortex develops and functions in different behavioral states. Here we review recent work on the cellular effects of nicotinic receptor activation in auditory cortex and describe how these actions could affect systems-level auditory function. In particular, we describe a novel function of nicotinic acetylcholine receptors to regulate glutamate synapses containing N-methyl-D-aspartate receptors during early postnatal development. The transient regulation of developing glutamate synapses also defines a window of vulnerability during which exposure to exogenous nicotine disrupts synapse development. Thus, it appears that nicotinic regulation of glutamate synapses is a critical feature of auditory cortex development.     

Functional recovery of skilled forelimb use in rats obliged to use the impaired limb after grafting of the frontal cortex lesion with homotopic fetal cortex

The long-term effect of transplanting embryonic frontal cortex into a unilateral frontal cortex lesion has been studied in adult rats. Before surgery, activity in an open field, muscular strength of both forelimbs, and performance in a paw-reaching-for-food task were scored in 26 rats. In 21 animals a unilateral cortex lesion was then made in the forelimb motor area of the hemisphere contralateral to the preferred paw in the paw-reaching-for-food task, while the other 5 animals were sham-operated. On retesting, the lesion animals changed the preferred paw. A solid homotopic transplant of embryonic tissue (embryonic day 17) was then placed in the lesion cavity in 11 of the lesion rats. Three months later neither lesion alone nor lesion plus transplantation affected open field behavior and muscular strength, but the lesion permanently affected performance in the paw-reaching-for-food task, as shown by a change of preferred paw and a functional deficit in the paw contralateral to the lesion. Transplantation ameliorated the deficits caused by the lesion, but this was only evident when animals were forced to reach with the paw contralateral to the lesion plus transplant. The behavioral results were independent of the size of the lesion and graft. Connections between graft and host tissue were studied by means of the fluorescent tracer 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI). A dense array of labeled fibers was found in the host cortex adjacent to the transplant. The results suggest that functional recovery depends on grafting but is only evident when the animal is obliged to use the affected limb.     

A Note on (K)Nots: Response to Robert W. Kentridge''s Commentary

GY, an extensively studied human hemianope, is aware of salient visual events in his cortically blind field but does not call this "vision." To learn whether he has low-level conscious visual sensations or whether instead he has gained conscious knowledge about, or access to, visual information that does not produce a conscious phenomenal sensation, we attempted to image process a stimulus s presented to the impaired field so that when the transformed stimulus T(s) was presented to the normal hemifield it would cause a sensation similar to that caused by s in the impaired field. While degradation of contrast, spatio-temporal filtering, contrast reversal, and addition of smear and random blobs all failed to match the response to a flashed bar s(f), moving textures of low contrast were accepted to match the response to a moving contrast-defined bar, s(m). Orientation and motion direction discrimination of the perceptually matched stimuli [s(m) and T(s(m))] was closely similar. We suggest that the existence of a satisfactory match indicates that GY has phenomenal vision.     

Dopamine regulation of human speech and bird song: a critical review

To understand the neural basis of human speech control, extensive research has been done using a variety of methodologies in a range of experimental models. Nevertheless, several critical questions about learned vocal motor control still remain open. One of them is the mechanism(s) by which neurotransmitters, such as dopamine, modulate speech and song production. In this review, we bring together the two fields of investigations of dopamine action on voice control in humans and songbirds, who share similar behavioral and neural mechanisms for speech and song production. While human studies investigating the role of dopamine in speech control are limited to reports in neurological patients, research on dopaminergic modulation of bird song control has recently expanded our views on how this system might be organized. We discuss the parallels between bird song and human speech from the perspective of dopaminergic control as well as outline important differences between these species.     

Cumulative estrogen exposure and prospective memory in older women

This study looked at cumulative lifetime estrogen exposure, as estimated with a mathematical index (Index of Cumulative Estrogen Exposure (ICEE)) that included variables (length of time on estrogen therapy, age at menarche and menopause, postmenopausal body mass index, time since menopause, nulliparity and duration of breastfeeding) known to influence estrogen levels across the life span, and performance on prospective and retrospective memory measures in a group of 50 postmenopausal women (mean age=69.3years) who, if they were current or former users of estrogen therapy, had started therapy within 5years of menopause. The ICEE was found to be a significant predictor of performance on the Prospective Memory task (F(1)=4.21, p=.046, η(p)(2)=.084). No significant relationship was noted between the ICEE and performance on measures of retrospective memory. The results suggest that the level of cumulative lifetime exposure to estrogen a woman has influences her prospective memory performance later in life and that the influence of reproductive and biological markers of endogenous estrogen exposure are relevant factors to consider when studying the effect of estrogen therapy on cognitive functioning in postmenopausal women. In addition, the finding that performance on a measure of prospective memory, but not performance on measures of retrospective memory, was associated with the ICEE adds further support to the theory that the frontal cortex may be especially sensitive to estrogen.     

Dissociable stages of problem solving (II): first evidence for process-contingent temporal order of activation in dorsolateral prefrontal cortex

In a companion study, eye-movement analyses in the Tower of London task (TOL) revealed independent indicators of functionally separable cognitive processes during problem solving, with processes of building up an internal representation of the problem preceding actual planning processes. These results imply that processes of internalization and planning should also be distinguishable in time and space with respect to concomitant brain activation patterns. To investigate this possibility, here we conducted analyses of fMRI data for left and right dorsolateral prefrontal cortex (dlPFC) during problem solving in the TOL task by accounting for the trial-by-trial variability of onsets and durations of the different cognitive processing stages. Comparisons between stimulus-locked and response-locked modeling approaches affirmed that activation in left dlPFC was elicited particularly during early processes of internalization, comprising the extraction of goal information and the generation of an internal problem representation, whereas activation in right dlPFC was predominantly attributable to later processes of mental transformations on this representation, that is planning proper. Thus, present data corroborate the proposal that often observed bilateral dlPFC activation patterns during complex cognitive tasks such as problem solving may reflect functionally and, to some extent, even temporally separable processes with opposing lateralizations.     

Dissociable stages of problem solving (I): temporal characteristics revealed by eye-movement analyses

Understanding the functional neuroanatomy of planning and problem solving may substantially benefit from better insight into the chronology of the cognitive processes involved. Based on the assumption that regularities in cognitive processing are reflected in overtly observable eye-movement patterns, here we recorded eye movements while participants worked on Tower of London (TOL) problems that comprised an experimental manipulation of different task demands. Single-trial saccade-locked analyses revealed that higher demands on forming an internal problem representation were associated with an increased number of gaze alternations between start state and goal state, but did not show any effect on the durations of these inspections of the states. In contrast, higher demands on actual planning in terms of mental manipulations of working memory contents coincided with a prolonged duration of the very last inspection of the start state (i.e., immediately preceding movement execution) but did not show any effect on the number of gaze alterations. Differential task demands on internalization and planning processes during problem solving hence selectively affect different eye-movement parameters. Moreover, these findings complement previous neuroimaging data on dissociable contributions of left and right dorsolateral prefrontal cortex in problem solving with novel evidence for a corresponding dissociation in the eye-movement patterns reflecting the associated cognitive processes.     

Brain activation during spatial updating and attentive tracking of moving targets

Keeping aware of the locations of objects while one is moving requires the updating of spatial representations. As long as the objects are visible, attentional tracking is sufficient, but knowing where objects out of view went in relation to one's own body involves an updating of spatial working memory. Here, multiple object tracking was employed to study spatial updating and its neural correlates. In a dynamic 3D-scene, targets moved among visually indistinguishable distractors. The targets and distractors either stayed visible during continuous viewpoint changes or they turned invisible. The parametric variation of tracking load revealed load-dependent activations of the intraparietal sulcus, the superior parietal lobule, and the lateral occipital cortex in response to the attentive tracking task. Viewpoint changes with invisible objects that demanded retention and updating produced load-dependent activation only in the precuneus in line with its presumed involvement in updating spatial working memory.