Oxytocinergic modulation of speech production-a double-blind placebo-controlled fMRI study.

Many socio-affective behaviors, such as speech, are modulated by oxytocin. While oxytocin modulates speech perception, it is not known whether it also affects speech production. Here, we investigated effects of oxytocin administration and interactions with the functional rs53576 oxytocin receptor (OXTR) polymorphism on produced speech and its underlying brain activity. During functional magnetic resonance imaging, 52 healthy male participants read sentences out loud with either neutral or happy intonation, a covert reading condition served as a common baseline. Participants were studied once under the influence of intranasal oxytocin and in another session under placebo. Oxytocin administration increased the second formant of produced vowels. This acoustic feature has previously been associated with speech valence; however, the acoustic differences were not perceptually distinguishable in our experimental setting. When preparing to speak, oxytocin enhanced brain activity in sensorimotor cortices and regions of both dorsal and right ventral speech processing streams, as well as subcortical and cortical limbic and executive control regions. In some of these regions, the rs53576 OXTR polymorphism modulated oxytocin administration-related brain activity. Oxytocin also gated cortical-basal ganglia circuits involved in the generation of happy prosody. Our findings suggest that several neural processes underlying speech production are modulated by oxytocin, including control of not only affective intonation but also sensorimotor aspects during emotionally neutral speech.

How the conception of control influences our understanding of actions.

Wilful movement requires neural control. Commonly, neural computations are thought to generate motor commands that bring the musculoskeletal system - that is, the plant - from its current physical state into a desired physical state. The current state can be estimated from past motor commands and from sensory information. Modelling movement on the basis of this concept of plant control strives to explain behaviour by identifying the computational principles for control signals that can reproduce the observed features of movements. From an alternative perspective, movements emerge in a dynamically coupled agent-environment system from the pursuit of subjective perceptual goals. Modelling movement on the basis of this concept of perceptual control aims to identify the controlled percepts and their coupling rules that can give rise to the observed characteristics of behaviour. In this Perspective, we discuss a broad spectrum of approaches to modelling human motor control and their notions of control signals, internal models, handling of sensory feedback delays and learning. We focus on the influence that the plant control and the perceptual control perspective may have on decisions when modelling empirical data, which may in turn shape our understanding of actions.

Aberrant sensorimotor coupling and movement planning in complex regional pain syndrome.

ABSTRACT: Complex regional pain syndrome (CRPS) is characterized by inflammation and a failure of multimodal signal integration in the central nervous system (CNS). Central nervous system reorganization might account for sensory deficits, pain, and motor symptoms in CRPS, but it is not clear how motor control is affected by CNS mechanisms. The present study characterized the motor performance and related cortical activity of 16 CRPS patients and 16 control participants during the planning of visually guided unimanual grips, in patients with either the unaffected left or the affected right hand, and investigated resting-state sensorimotor coupling in MRI. Patients started isometric movements further in advance of the "go" cue and earlier than control participants. Even when accounting for this different timing, results showed side-independent overactivation in planning-related sensorimotor regions in CRPS during manual grips and increased functional coupling between those regions at rest. Fear of movement or individual pain scores contributed only marginally to the observed effects. The study suggests that changes in planning-related sensorimotor CNS regions may explain difficulties with force exertion and motor control in CRPS.Perspective : Functional changes in motor planning-related brain regions might indicate that feedback-enhanced functional motor training may be effective for CRPS rehabilitation.

Neurocognitive deficits in patients suffering from glioma in speech-relevant areas of the left hemisphere.

OBJECTIVE: Patients with brain tumors frequently present neurocognitive deficits. Aiming at better understanding the impact of tumor localization on neurocognitive processes, we evaluated neurocognitive function prior to glioma surgery within one of four specific regions in the left speech-dominant hemisphere. METHODS: Between 04/2011 and 12/2019, 43 patients undergoing neurocognitive evaluation prior to awake surgery for gliomas (WHO grade I: 2; II: 6; III: 23; IV: 11) in the inferior frontal gyrus (IFG; n = 20), the anterior temporal lobe (ATL; n = 6), the posterior superior temporal region/supramarginal gyrus (pST/SMG; n = 7) or the posterior middle temporal gyrus (pMTG; n = 10) of the language dominant left hemisphere were prospectively included in the study. Cognitive performances were analyzed regarding an influence of patient characteristics and tumor localization. RESULTS: Severe impairment in at least one neurocognitive domain was found in 36 (83.7%) patients. Anxiety and depression were observed most frequently, followed by verbal memory impairments. Verbal memory was more strongly affected in patients with ATL or pST/SMG tumors compared to IFG tumors (p = 0.004 and p = 0.013, resp.). Overall, patients suffering from tumors in the ATL were most frequently and severely impaired. CONCLUSION: Patients suffering from gliomas involving different regions within the language dominant hemisphere frequently present impairments in neurocognitive domains also other than language. Considering individual functions at risk may help in better advising patients prior to treatment and in tailoring the individual therapeutic strategy to preserve patients' quality of life.

[Aphasia associated with lacunar infarctions]. / Aphasien bei lakunären Hirninfarkten.

BACKGROUND: Typical lacunar syndromes do not include aphasia but aphasia has been reported in rare atypical lacunar syndromes. OBJECTIVE: Description of the phenomenology and of affected fiber tracts. MATERIAL AND METHODS: Case series of three patients with lacunar stroke as evidenced by magnetic resonance imaging. Identification of affected fiber tracts via fiber tracking from coregistered lesion sites in brains of two healthy participants. RESULTS: The lacunar strokes that produced aphasia were located in the very lateral territory of perforating branches of the middle cerebral artery and extended along the external capsule into its most rostrodorsal aspect. Even though the cortex, thalamus and most parts of the basal ganglia were unaffected, patients exhibited a mild to moderate nonfluent aphasia with syntactic deficits. Fiber tracking revealed that in contrast to the nonaphasic control patient with a neighboring lacunar stroke, the aphasic patient strokes involved particularly fibers of the left arcuate fascicle as well as fibers of the frontostriatal and frontal aslant tracts. CONCLUSION: Left lateral lacunar stroke can cause clinically relevant aphasia through disruption of speech-relevant fiber tracts.

Differential contributions of the two cerebral hemispheres to temporal and spectral speech feedback control.

Proper speech production requires auditory speech feedback control. Models of speech production associate this function with the right cerebral hemisphere while the left hemisphere is proposed to host speech motor programs. However, previous studies have investigated only spectral perturbations of the auditory speech feedback. Since auditory perception is known to be lateralized, with right-lateralized analysis of spectral features and left-lateralized processing of temporal features, it is unclear whether the observed right-lateralization of auditory speech feedback processing reflects a preference for speech feedback control or for spectral processing in general. Here we use a behavioral speech adaptation experiment with dichotically presented altered auditory feedback and an analogous fMRI experiment with binaurally presented altered feedback to confirm a right hemisphere preference for spectral feedback control and to reveal a left hemisphere preference for temporal feedback control during speaking. These results indicate that auditory feedback control involves both hemispheres with differential contributions along the spectro-temporal axis.

"Spontaneous" late recovery from stuttering: Dimensions of reported techniques and causal attributions.

PURPOSE: (1) To survey the employed techniques and the reasons/occasions which adults who had recovered from stuttering after age 11 without previous treatment reported as causal to overcome stuttering, (2) to investigate whether the techniques and causal attributions can be reduced to coherent (inherently consistent) dimensions, and (3) whether these dimensions reflect common therapy components. METHODS: 124 recovered persons from 8 countries responded by SurveyMonkey or paper-and-pencil to rating scale questions about 49 possible techniques and 15 causal attributions. RESULTS: A Principal Component Analysis of 110 questionnaires identified 6 components (dimensions) for self-assisted techniques (Speech Restructuring; Relaxed/Monitored Speech; Elocution; Stage Performance; Sought Speech Demands; Reassurance; 63.7% variance explained), and 3 components of perceived causal attributions of recovery (Life Change, Attitude Change, Social Support; 58.0% variance explained). DISCUSSION: Two components for self-assisted techniques (Speech Restructuring; Elocution) reflect treatment methods. Another component (Relaxed/Monitored Speech) consists mainly of items that reflect a common, non-professional understanding of effective management of stuttering. The components of the various perceived reasons for recovery reflect differing implicit theories of causes for recovery from stuttering. These theories are considered susceptible to various biases. This identification of components of reported techniques and of causal attributions is novel compared to previous studies who just list techniques and attributions. CONCLUSION: The identified dimensions of self-assisted techniques and causal attributions to reduce stuttering as extracted from self-reports of a large, international sample of recovered formerly stuttering adults may guide the application of behavioral stuttering therapies.

Low-Frequency Oscillations Code Speech during Verbal Working Memory.

The way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time. During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired knowledge on the temporal structure of language influences speech perception-related brain activity. This suggests that speech could be represented in the temporal domain, a form of representation that the brain also uses to encode autobiographic memories. Empirical evidence for such a memory code is lacking. We investigated the nature of speech memory representations using direct cortical recordings in the left perisylvian cortex during delayed sentence reproduction in female and male patients undergoing awake tumor surgery. Our results reveal that the brain endogenously represents speech in the temporal domain. Temporal pattern similarity analyses revealed that the phase of frontotemporal low-frequency oscillations, primarily in the beta range, represents sentence identity in working memory. The positive relationship between beta power during working memory and task performance suggests that working memory representations benefit from increased phase separation.SIGNIFICANCE STATEMENT Memory is an endogenous source of information based on experience. While neural oscillations encode autobiographic memories in the temporal domain, little is known on their contribution to memory representations of human speech. Our electrocortical recordings in participants who maintain sentences in memory identify the phase of left frontotemporal beta oscillations as the most prominent information carrier of sentence identity. These observations provide evidence for a theoretical model on speech memory representations and explain why interfering with beta oscillations in the left inferior frontal cortex diminishes verbal working memory capacity. The lack of sentence identity coding at the syllabic rate suggests that sentences are represented in memory in a more abstract form compared with speech coding during speech perception and production.

Cognitive effects of rhythmic auditory stimulation in Parkinson's disease: A P300 study.

Rhythmic auditory stimulation (RAS) may compensate dysfunctions of the basal ganglia (BG), involved with intrinsic evaluation of temporal intervals and action initiation or continuation. In the cognitive domain, RAS containing periodically presented tones facilitates young healthy participants' attention allocation to anticipated time points, indicated by better performance and larger P300 amplitudes to periodic compared to random stimuli. Additionally, active auditory-motor synchronization (AMS) leads to a more precise temporal encoding of stimuli via embodied timing encoding than stimulus presentation adapted to the participants' actual movements. Here we investigated the effect of RAS and AMS in Parkinson's disease (PD). 23 PD patients and 23 healthy age-matched controls underwent an auditory oddball task. We manipulated the timing (periodic/random/adaptive) and setting (pedaling/sitting still) of stimulation. While patients elicited a general timing effect, i.e., larger P300 amplitudes for periodic versus random tones for both, sitting and pedaling conditions, controls showed a timing effect only for the sitting but not for the pedaling condition. However, a correlation between P300 amplitudes and motor variability in the periodic pedaling condition was obtained in control participants only. We conclude that RAS facilitates attentional processing of temporally predictable external events in PD patients as well as healthy controls, but embodied timing encoding via body movement does not affect stimulus processing due to BG impairment in patients. Moreover, even with intact embodied timing encoding, such as healthy elderly, the effect of AMS depends on the degree of movement synchronization performance, which is very low in the current study.

Endogenous modulation of human visual cortex activity improves perception at twilight.

Perception, particularly in the visual domain, is drastically influenced by rhythmic changes in ambient lighting conditions. Anticipation of daylight changes by the circadian system is critical for survival. However, the neural bases of time-of-day-dependent modulation in human perception are not yet understood. We used fMRI to study brain dynamics during resting-state and close-to-threshold visual perception repeatedly at six times of the day. Here we report that resting-state signal variance drops endogenously at times coinciding with dawn and dusk, notably in sensory cortices only. In parallel, perception-related signal variance in visual cortices decreases and correlates negatively with detection performance, identifying an anticipatory mechanism that compensates for the deteriorated visual signal quality at dawn and dusk. Generally, our findings imply that decreases in spontaneous neural activity improve close-to-threshold perception.

Speaking-related changes in cortical functional connectivity associated with assisted and spontaneous recovery from developmental stuttering.

We previously reported speaking-related activity changes associated with assisted recovery induced by a fluency shaping therapy program and unassisted recovery from developmental stuttering (Kell et al., Brain 2009). While assisted recovery re-lateralized activity to the left hemisphere, unassisted recovery was specifically associated with the activation of the left BA 47/12 in the lateral orbitofrontal cortex. These findings suggested plastic changes in speaking-related functional connectivity between left hemispheric speech network nodes. We reanalyzed these data involving 13 stuttering men before and after fluency shaping, 13 men who recovered spontaneously from their stuttering, and 13 male control participants, and examined functional connectivity during overt vs. covert reading by means of psychophysiological interactions computed across left cortical regions involved in articulation control. Persistent stuttering was associated with reduced auditory-motor coupling and enhanced integration of somatosensory feedback between the supramarginal gyrus and the prefrontal cortex. Assisted recovery reduced this hyper-connectivity and increased functional connectivity between the articulatory motor cortex and the auditory feedback processing anterior superior temporal gyrus. In spontaneous recovery, both auditory-motor coupling and integration of somatosensory feedback were normalized. In addition, activity in the left orbitofrontal cortex and superior cerebellum appeared uncoupled from the rest of the speech production network. These data suggest that therapy and spontaneous recovery normalizes the left hemispheric speaking-related activity via an improvement of auditory-motor mapping. By contrast, long-lasting unassisted recovery from stuttering is additionally supported by a functional isolation of the superior cerebellum from the rest of the speech production network, through the pivotal left BA 47/12.

Assisted and unassisted recession of functional anomalies associated with dysprosody in adults who stutter.

PURPOSE: Speech in persons who stutter (PWS) is associated with disturbed prosody (speech melody and intonation), which may impact communication. The neural correlates of PWS' altered prosody during speaking are not known, neither is how a speech-restructuring therapy affects prosody at both a behavioral and a cerebral level. METHODS: In this fMRI study, we explored group differences in brain activation associated with the production of different kinds of prosody in 13 male adults who stutter (AWS) before, directly after, and at least 1 year after an effective intensive fluency-shaping treatment, in 13 typically fluent-speaking control participants (CP), and in 13 males who had spontaneously recovered from stuttering during adulthood (RAWS), while sentences were read aloud with 'neutral', instructed emotional (happy), and linguistically driven (questioning) prosody. These activations were related to speech production acoustics. RESULTS: During pre-treatment prosody generation, the pars orbitalis of the left inferior frontal gyrus and the left anterior insula were activated less in AWS than in CP. The degree of hypo-activation correlated with acoustic measures of dysprosody. Paralleling the near-normalization of free speech melody following fluency-shaping therapy, AWS normalized the inferior frontal hypo-activation, sooner after treatment for generating emotional than linguistic prosody. Unassisted recovery was associated with an additional recruitment of cerebellar resources. CONCLUSIONS: Fluency shaping therapy may restructure prosody, which approaches that of typically fluent-speaking people. Such a process may benefit from additional training of instructed emotional and linguistic prosody by inducing plasticity in the inferior frontal region which has developed abnormally during childhood in PWS.

Non-linear Relationship between BOLD Activation and Amplitude of Beta Oscillations in the Supplementary Motor Area during Rhythmic Finger Tapping and Internal Timing.

Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region.

Phonetic detail and lateralization of reading-related inner speech and of auditory and somatosensory feedback processing during overt reading.

Phonetic detail and lateralization of inner speech during covert sentence reading as well as overt reading in 32 right-handed healthy participants undergoing 3T fMRI were investigated. The number of voiceless and voiced consonants in the processed sentences was systematically varied. Participants listened to sentences, read them covertly, silently mouthed them while reading, and read them overtly. Condition comparisons allowed for the study of effects of externally versus self-generated auditory input and of somatosensory feedback related to or independent of voicing. In every condition, increased voicing modulated bilateral voice-selective regions in the superior temporal sulcus without any lateralization. The enhanced temporal modulation and/or higher spectral frequencies of sentences rich in voiceless consonants induced left-lateralized activation of phonological regions in the posterior temporal lobe, regardless of condition. These results provide evidence that inner speech during reading codes detail as fine as consonant voicing. Our findings suggest that the fronto-temporal internal loops underlying inner speech target different temporal regions. These regions differ in their sensitivity to inner or overt acoustic speech features. More slowly varying acoustic parameters are represented more anteriorly and bilaterally in the temporal lobe while quickly changing acoustic features are processed in more posterior left temporal cortices. Furthermore, processing of external auditory feedback during overt sentence reading was sensitive to consonant voicing only in the left superior temporal cortex. Voicing did not modulate left-lateralized processing of somatosensory feedback during articulation or bilateral motor processing. This suggests voicing is primarily monitored in the auditory rather than in the somatosensory feedback channel. Hum Brain Mapp 38:493-508, 2017. © 2016 Wiley Periodicals, Inc.

Actively but not passively synchronized motor activity amplifies predictive timing.

Previous studies have shown that the effect of temporal predictability of presented stimuli on attention allocation is enhanced by auditory-motor synchronization (AMS). The present P300 event-related potential study (N=20) investigated whether this enhancement depends on the process of actively synchronizing one's motor output with the acoustic input or whether a passive state of auditory-motor synchrony elicits the same effect. Participants silently counted frequency deviants in sequences of pure tones either during a physically inactive control condition or while pedaling on a cycling ergometer. Tones were presented either at fixed or variable intervals. In addition to the pedaling conditions with fixed or variable stimulation, there was a third condition in which stimuli were adaptively presented in sync with the participants' spontaneous pedaling. We replicated the P300 enhancement for fixed versus variable stimulation and the amplification of this effect by AMS. Synchronization performance correlated positively with P300 amplitude in the fixed stimulation condition. Most interestingly, P300 amplitude was significantly reduced for the passive synchronization condition by adaptive stimulus presentation as compared to the fixed stimulation condition. For the first time we thus provide evidence that it is not the passive state of (even perfect) auditory-motor synchrony that facilitates attention allocation during AMS but rather the active process of synchronizing one's movements with external stimuli.

Asymmetric intra- and interhemispheric interactions during covert and overt sentence reading.

Covert and overt sentence reading evoke lateralized activations in overall bihemispheric networks. We assumed that the study of functional connectivity may reveal underlying principles of functional lateralization. Left-lateralized activations could relate to stronger reading-related modulation of intrahemispheric functional connectivity in the left than the right hemisphere. Alternatively, left-lateralization could result from suppression of contralateral processing and thus reflect asymmetric interhemispheric interactions. To address this issue, this functional MRI study investigated the regional lateralization of covert and overt German sentence reading in 39 healthy participants. Further, it revealed the modulation of the lateralized brain regions' functional connectivity and their contralateral homotopes by covert and overt reading (psychophysiological interactions). Left-lateralization during covert reading was associated with stronger intrahemispheric coupling particularly in the left dorsal stream rather than with suppression of contralateral processing. Lateralization during overt sentence reading instead went along with additional recruitment of right perisylvian cortices involved in articulation by asymmetric positive heterotopic interhemispheric interactions. Given the paucity of interhemispheric anti-correlations with homotopic regions, functional lateralization is likely a consequence of a task-dependent interplay between asymmetric positive intra- and interhemispheric coupling.

Dopaminergic Modulation of Cognitive Preparation for Overt Reading: Evidence from the Study of Genetic Polymorphisms.

Choosing and implementing the rules for contextually adequate behavior depends on frontostriatal interactions. Observations in Parkinson's disease and pharmacological manipulations of dopamine transmission suggest that these corticobasal loops are modulated by dopamine. To determine, therefore, the physiological contributions of dopamine to task-rule-related processing, we performed a cue-target fMRI reading paradigm in 71 healthy participants and investigated the effects of COMT Val158Met, DAT1 VNTR 9/10, and DRD2/ANKK1 polymorphisms. The DRD2/ANKK1 polymorphism did not affect results. Intermediate prefrontal dopamine concentrations in COMT Val158Met heterozygotes facilitated preparatory interactions between the mesial prefrontal cortex and the left striatum during preparation for overt reading. To our knowledge, this is the first report of an inverted U-shaped curve modulation of cognition-related brain activity by prefrontal dopamine levels. In contrast, a linear effect of COMT Val158Met and DAT1 VNTR 9/10 polymorphisms on preparatory activity in the left inferior frontal gyrus pointed to a negative interaction between tonic lateral prefrontal and phasic subcortical dopamine. The COMT Val158Met polymorphism affected also feedforward and feedback processing in the sensorimotor speech system. Our results suggest that dopamine modulates corticobasal interactions on both the cortical and subcortical level but differently depending on the specific cognitive subprocesses involved.

Brain Mapping-Based Model of Δ(9)-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix.

Cannabinoids receive increasing interest as analgesic treatments. However, the clinical use of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) has progressed with justified caution, which also owes to the incomplete mechanistic understanding of its analgesic effects, in particular its interference with the processing of sensory or affective components of pain. The present placebo-controlled crossover study therefore focused on the effects of 20 mg oral THC on the connectivity between brain areas of the pain matrix following experimental stimulation of trigeminal nocisensors in 15 non-addicted healthy volunteers. A general linear model (GLM) analysis identified reduced activations in the hippocampus and the anterior insula following THC administration. However, assessment of psychophysiological interaction (PPI) revealed that the effects of THC first consisted in a weakening of the interaction between the thalamus and the secondary somatosensory cortex (S2). From there, dynamic causal modeling (DCM) was employed to infer that THC attenuated the connections to the hippocampus and to the anterior insula, suggesting that the reduced activations in these regions are secondary to a reduction of the connectivity from somatosensory regions by THC. These findings may have consequences for the way THC effects are currently interpreted: as cannabinoids are increasingly considered in pain treatment, present results provide relevant information about how THC interferes with the affective component of pain. Specifically, the present experiment suggests that THC does not selectively affect limbic regions, but rather interferes with sensory processing which in turn reduces sensory-limbic connectivity, leading to deactivation of affective regions.

Left dorsal speech stream components and their contribution to phonological processing.

Models propose an auditory-motor mapping via a left-hemispheric dorsal speech-processing stream, yet its detailed contributions to speech perception and production are unclear. Using fMRI-navigated repetitive transcranial magnetic stimulation (rTMS), we virtually lesioned left dorsal stream components in healthy human subjects and probed the consequences on speech-related facilitation of articulatory motor cortex (M1) excitability, as indexed by increases in motor-evoked potential (MEP) amplitude of a lip muscle, and on speech processing performance in phonological tests. Speech-related MEP facilitation was disrupted by rTMS of the posterior superior temporal sulcus (pSTS), the sylvian parieto-temporal region (SPT), and by double-knock-out but not individual lesioning of pars opercularis of the inferior frontal gyrus (pIFG) and the dorsal premotor cortex (dPMC), and not by rTMS of the ventral speech-processing stream or an occipital control site. RTMS of the dorsal stream but not of the ventral stream or the occipital control site caused deficits specifically in the processing of fast transients of the acoustic speech signal. Performance of syllable and pseudoword repetition correlated with speech-related MEP facilitation, and this relation was abolished with rTMS of pSTS, SPT, and pIFG. Findings provide direct evidence that auditory-motor mapping in the left dorsal stream causes reliable and specific speech-related MEP facilitation in left articulatory M1. The left dorsal stream targets the articulatory M1 through pSTS and SPT constituting essential posterior input regions and parallel via frontal pathways through pIFG and dPMC. Finally, engagement of the left dorsal stream is necessary for processing of fast transients in the auditory signal.

Pathomechanisms and compensatory efforts related to Parkinsonian speech.

Voice and speech in Parkinson's disease (PD) patients are classically affected by a hypophonia, dysprosody, and dysarthria. The underlying pathomechanisms of these disabling symptoms are not well understood. To identify functional anomalies related to pathophysiology and compensation we compared speech-related brain activity and effective connectivity in early PD patients who did not yet develop voice or speech symptoms and matched controls. During fMRI 20 PD patients ON and OFF levodopa and 20 control participants read 75 sentences covertly, overtly with neutral, or with happy intonation. A cue-target reading paradigm allowed for dissociating task preparation from execution. We found pathologically reduced striato-prefrontal preparatory effective connectivity in early PD patients associated with subcortical (OFF state) or cortical (ON state) compensatory networks. While speaking, PD patients showed signs of diminished monitoring of external auditory feedback. During generation of affective prosody, a reduced functional coupling between the ventral and dorsal striatum was observed. Our results suggest three pathomechanisms affecting speech in PD: While diminished energization on the basis of striato-prefrontal hypo-connectivity together with dysfunctional self-monitoring mechanisms could underlie hypophonia, dysarthria may result from fading speech motor representations given that they are not sufficiently well updated by external auditory feedback. A pathological interplay between the limbic and sensorimotor striatum could interfere with affective modulation of speech routines, which affects emotional prosody generation. However, early PD patients show compensatory mechanisms that could help improve future speech therapies.