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.     

Cognitive impairment and whole brain diffusion in patients with neuromyelitis optica after acute relapse

The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive tests to assess cognitive function. Head diffusion tensor imaging (DTI) of all patients with NMO were collected with a 3-T MR system. Correlations of cognitive test scores and whole brain FA and MD were examined by voxel-based analysis. Region-of-interest analysis was applied to the significantly correlated regions which the most frequently appeared. We found that NMO patients without visible brain lesions had significantly impaired learning and memory, decreased information processing speed, and damaged attention compared with normal control subjects. These impaired cognitive domains were significantly correlated with FA and MD in local regions of corpus callosum, anterior cingulate and medial frontal cortex. In corpus callosum of NMO patients, mean FA was significantly lower and mean MD higher than normal control subjects. Our findings suggest that cognitive impairments in learning and memory, information processing speed and attention occur in NMO patients without visible brain lesions during acute relapse. The impairments in immediate and short-term memory in NMO patients may be due to information encoding deficits in the process of information acquisition. The corpus callosum of such patients may have local microscopic damages that play a role in cognitive impairments during acute relapse.     

The role of the human extrastriate visual cortex in mirror symmetry discrimination: a TMS-adaptation study

The human visual system is able to efficiently extract symmetry information from the visual environment. Prior neuroimaging evidence has revealed symmetry-preferring neuronal representations in the dorsolateral extrastriate visual cortex; the objective of the present study was to investigate the necessity of these representations in symmetry discrimination. This was accomplished by the use of state-dependent transcranial magnetic stimulation, which combines the fine resolution of adaptation paradigms with the assessment of causality. Subjects were presented with adapters and targets consisting of dot configurations that could be symmetric along either the vertical or horizontal axis (or they could be non-symmetric), and they were asked to perform a symmetry discrimination task on the targets while fixating the center of the screen. TMS was applied during the delay between the adapter and the test stimulus over one of four different sites: Left or Right V1/V2, or left or right dorsolateral extrastriate cortex (DLO). TMS over both Left and Right DLO reduced the adaptation effect in detecting vertical and horizontal symmetry, although the Left DLO effect on horizontal symmetry and the Right DLO effect on both vertical and horizontal symmetry were present only when considering subjects who showed a behavioral adaptation effect in the baseline No-TMS condition. Application of TMS over the Left or Right V1/V2 did not modulate the adaptation effect. Overall, these data suggest that both the Left and Right DLO contain neuronal representations tuned to mirror symmetry which play a causal role in symmetry discrimination.     

Impact of motivation on cognitive control in the context of vigilance lowering: an ERP study

We assessed the effects of time-on-task on cognitive control expressed by the CRN/Nc and the extent to which motivation modulates this relationship. We utilized two groups of participants, who were told that their performance would (evaluation condition) or would not (control condition) be evaluated online. Both groups performed a version of the Eriksen Flanker Task for 60 min. We observed classical vigilance lowering, manifested by a progressive performance decline with time-on-task, in the control, but not in the evaluation, condition. In the latter, performance remained stable throughout the task. ERP analysis indicated the same interaction in our main component of interest, the CRN/Nc, whose amplitude decreased from the first to the last period in the control condition but remained stable over time in the evaluation condition. To our knowledge, this study is the first to demonstrate the impact of motivation on monitoring processes as indexed by the correct response negativity, in the context of a prolonged task. Vigilance lowering caused by a repetitive and prolonged flanker task, results in compromised response control and compromised control of correct responses. Our results suggest that alterations in ACC functioning may underlie vigilance decline and can be viewed as evidence that the action monitoring functions of the ACC can be positively affected by motivation.     

Dorsolateral prefrontal cortex mediates working memory processes in motor skill learning

Neuroimaging studies have shown that the dorsolateral prefrontal cortex (DLPFC) is recruited during motor skill learning, which suggests the involvement of the DLPFC in working memory (WM) processes, such as selection and integration of motor representations temporarily stored in WM. However, direct evidence linking activation of the DLPFC to WM storage and manipulation during motor skill learning in real-time is rare. In this study, we conducted two experiments to investigate the causal role of DLPFC activity in WM storage and manipulation during motor skill learning under low and high WM-demand conditions. Participants received continuous theta burst stimulation (cTBS) and sham stimulation (crossover design) over the left DLPFC (experiment 1) or right DLPFC (experiment 2). Before and after stimulation, participants in both experiments performed a sequential finger-tapping (SFT) task containing repeated sequence (low-WM demand) and non-repeated sequence (high-WM demand) conditions which are used to study WM processes. The number of correct sequences (NoCS) and reproduction error rate were analyzed. Learning gains in NoCS improved significantly with the practice for both sequence types in the presence of either stimulation type. Compared to sham stimulation, cTBS over the left DLPFC resulted in significantly reduced learning gains in NoCS for non-repeated sequences. These results suggest that the left DLPFC contributes to WM manipulation during motor skill learning.     

Building phrases in language production: An MEG study of simple composition

Although research on language production has developed detailed maps of the brain basis of single word production in both time and space, little is known about the spatiotemporal dynamics of the processes that combine individual words into larger representations during production. Studying composition in production is challenging due to difficulties both in controlling produced utterances and in measuring the associated brain responses. Here, we circumvent both problems using a minimal composition paradigm combined with the high temporal resolution of magnetoencephalography (MEG). With MEG, we measured the planning stages of simple adjective–noun phrases (‘red tree’), matched list controls (‘red, blue’), and individual nouns (‘tree’) and adjectives (‘red’), with results indicating combinatorial processing in the ventro-medial prefrontal cortex (vmPFC) and left anterior temporal lobe (LATL), two regions previously implicated for the comprehension of similar phrases. These effects began relatively quickly (∼180 ms) after the presentation of a production prompt, suggesting that combination commences with initial lexical access. Further, while in comprehension, vmPFC effects have followed LATL effects, in this production paradigm vmPFC effects occurred mostly in parallel with LATL effects, suggesting that a late process in comprehension is an early process in production. Thus, our results provide a novel neural bridge between psycholinguistic models of comprehension and production that posit functionally similar combinatorial mechanisms operating in reversed order.