Speech, voice, and language outcomes following deep brain stimulation: A systematic review.

BACKGROUND: Deep brain stimulation (DBS) reliably ameliorates cardinal motor symptoms in Parkinson's disease (PD) and essential tremor (ET). However, the effects of DBS on speech, voice and language have been inconsistent and have not been examined comprehensively in a single study. OBJECTIVE: We conducted a systematic analysis of literature by reviewing studies that examined the effects of DBS on speech, voice and language in PD and ET. METHODS: A total of 675 publications were retrieved from PubMed, Embase, CINHAL, Web of Science, Cochrane Library and Scopus databases. Based on our selection criteria, 90 papers were included in our analysis. The selected publications were categorized into four subcategories: Fluency, Word production, Articulation and phonology and Voice quality. RESULTS: The results suggested a long-term decline in verbal fluency, with more studies reporting deficits in phonemic fluency than semantic fluency following DBS. Additionally, high frequency stimulation, left-sided and bilateral DBS were associated with worse verbal fluency outcomes. Naming improved in the short-term following DBS-ON compared to DBS-OFF, with no long-term differences between the two conditions. Bilateral and low-frequency DBS demonstrated a relative improvement for phonation and articulation. Nonetheless, long-term DBS exacerbated phonation and articulation deficits. The effect of DBS on voice was highly variable, with both improvements and deterioration in different measures of voice. CONCLUSION: This was the first study that aimed to combine the outcome of speech, voice, and language following DBS in a single systematic review. The findings revealed a heterogeneous pattern of results for speech, voice, and language across DBS studies, and provided directions for future studies.

HD-tDCS over left supplementary motor area differentially modulated neural correlates of motor planning for speech vs. limb movement.

The supplementary motor area (SMA) is implicated in planning, execution, and control of speech production and limb movement. The SMA is among putative generators of pre-movement EEG activity which is thought to be neural markers of motor planning. In neurological conditions such as Parkinson's disease, abnormal pre-movement neural activity within the SMA has been reported during speech production and limb movement. Therefore, this region can be a potential target for non-invasive brain stimulation for both speech and limb movement. The present study took an initial step in examining the application of high-definition transcranial direct current stimulation (HD-tDCS) over the left SMA in 24 neurologically intact adults. Subsequently, event-related potentials (ERPs) were recorded while participants performed speech and limb movement tasks. Participants' data were collected in three counterbalanced sessions: anodal, cathodal and sham HD-tDCS. Relative to sham stimulation, anodal, but not cathodal, HD-tDCS significantly attenuated ERPs prior to the onset of the speech production. In contrast, neither anodal nor cathodal HD-tDCS significantly modulated ERPs prior to the onset of limb movement compared to sham stimulation. These findings showed that neural correlates of motor planning can be modulated using HD-tDCS over the left SMA in neurotypical adults, with translational implications for neurological conditions that impair speech production. The absence of a stimulation effect on ERPs prior to the onset of limb movement was not expected in this study, and future studies are warranted to further explore this effect.

Theta oscillations within right dorsolateral prefrontal cortex contribute differently to speech versus limb inhibition.

Evidence suggests that speech and limb movement inhibition are subserved by common neural mechanisms, particularly within the right prefrontal cortex. In a recent study, we found that cathodal stimulation of right dorsolateral prefrontal cortex (rDLPFC) differentially modulated P3 event-related potentials for speech versus limb inhibition. In the present study, we further analyzed these data to examine the effects of cathodal high-definition transcranial direct current stimulation (HD-tDCS) over rDLPFC on frontal theta - an oscillatory marker of cognitive control - in response to speech and limb inhibition, during a Go/No-Go task in 21 neurotypical adults. Electroencephalography data demonstrated that both speech and limb No-Go elicited prominent theta activity over right prefrontal electrodes, with stronger activity for speech compared to limb. Moreover, we found that cathodal stimulation significantly increased theta power over right prefrontal electrodes for speech versus limb No-Go. Source analysis revealed that cathodal, but not sham, stimulation increased theta activity within rDLPFC and bilateral premotor cortex for speech No-Go compared to limb movement inhibition. These findings complement our previous report and suggest (1) right prefrontal theta activity is an amodal oscillatory mechanism supporting speech and limb inhibition, (2) larger theta activity in prefrontal electrodes for speech versus limb following cathodal stimulation may reflect allocation of additional neural resources for a more complex motor task, such as speech compared to limb movement. These findings have translational implications for conditions such as Parkinson's disease, wherein both speech and limb movement are impaired.

Spatiotemporal characteristics of the neural representation of event concepts.

Events are a fundamentally important part of our understanding of the world. How lexical concepts denoting events are represented in the brain remains controversial. We conducted two experiments using event and object nouns matched on a range of psycholinguistic variables, including concreteness, to examine spatial and temporal characteristics of event concepts. Both experiments used magnitude and valence tasks on event and object nouns. The fMRI experiment revealed a distributed set of regions for events, including the angular gyrus, anterior temporal lobe, and posterior cingulate across tasks. In the EEG experiment, events and objects differed in amplitude within the 300-500 ms window. Together these results shed light into the spatiotemporal characteristics of event concept representation and show that event concepts are represented in the putative hubs of the semantic system. While these hubs are typically associated with object semantics, they also represent events, and have a likely role in temporal integration.

Right frontal HD-tDCS reveals causal involvement of time perception networks in temporal processing of concepts.

Evidence suggests that perceptual and action related features of concepts are grounded in the corresponding sensory-motor networks in the human brain. However, less is known about temporal features of event concepts (e.g., a lecture) and whether they are grounded in time perception networks. We examined this question by stimulating the right dorsolateral prefrontal cortex (rDLPFC)-a part of time perception network-using HD-tDCS and subsequently recording EEG while participants performed semantic and time perception tasks. Semantic tasks were composed of event noun duration judgment (EDur), object noun size judgement (OSize), event (EVal) and object noun valence judgement. In the time perception task, participants judged the durations of pure tones. Results showed that cathodal stimulation accelerated responses for time perception task and decreased the magnitude of global field power (GFP) compared to sham stimulation. Semantic tasks results revealed that cathodal, but not sham, stimulation significantly decreased GFP for EDur relative to OSize, and to EVal. These findings provide first causal evidence that temporal features of event words are grounded in the rDLPFC as part of the temporal cognition network and shed light on the conceptual processing of time.

Deep brain stimulation for substance use disorder: a systematic review and meta-analysis.

Objective: Substance use disorder (SUD) is a significant public health issue with a high mortality rate. Deep brain stimulation (DBS) has shown promising results in treating SUD in certain cases. In this study, we conducted a meta-analysis to evaluate the efficacy of DBS in the treatment of SUD and reduction of relapse rates. Methods: We performed a thorough and methodical search of the existing scientific literature, adhering to the PRISMA guidelines, to identify 16 original studies that fulfilled our inclusion criteria. We used the evidence levels recommended by the Oxford Centre for Evidence-Based Medicine to assess bias. The R version 4.2.3 software was utilized to calculate the mean effect size. We estimated study heterogeneity by employing tau2 and I2 indices and conducting Cochran's Q test. Results: The results showed that DBS treatment resulted in a significant improvement in the clinical SUD scales of patients, with an average improvement of 59.6%. The observed relapse rate was 8%. The meta-analysis estimated a mean effect size of 55.9 [40.4; 71.4]. Heterogeneity analysis showed a large degree of heterogeneity among the included studies. Subgroup and meta-regression analysis based on age and SUD type suggested that DBS may be more effective for patients above 45 years of age, and for alcohol and opioid addiction compared to nicotine addiction. Conclusion: The current literature suggests that DBS has a moderate effect on SUD symptoms. However, the limited number of studies and small sample size indicate that more research is needed to better understand the factors that influence its effectiveness.

Human subthalamic nucleus neurons differentially encode speech and limb movement.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN), which consistently improves limb motor functions, shows mixed effects on speech functions in Parkinson's disease (PD). One possible explanation for this discrepancy is that STN neurons may differentially encode speech and limb movement. However, this hypothesis has not yet been tested. We examined how STN is modulated by limb movement and speech by recording 69 single- and multi-unit neuronal clusters in 12 intraoperative PD patients. Our findings indicated: (1) diverse patterns of modulation in neuronal firing rates in STN for speech and limb movement; (2) a higher number of STN neurons were modulated by speech vs. limb movement; (3) an overall increase in neuronal firing rates for speech vs. limb movement; and (4) participants with longer disease duration had higher firing rates. These data provide new insights into the role of STN neurons in speech and limb movement.

High-definition transcranial direct current stimulation over right dorsolateral prefrontal cortex differentially modulates inhibitory mechanisms for speech vs. limb movement.

Evidence suggests that planning and execution of speech and limb movement are subserved by common neural substrates. However, less is known about whether they are supported by a common inhibitory mechanism. P3 event-related potentials (ERPs) is a neural signature of motor inhibition, which are found to be generated by several brain regions including the right dorsolateral prefrontal cortex (rDLPFC). However, the relative contribution of rDLPFC to the P3 response associated with speech versus limb inhibition remains elusive. We investigated the contribution of rDLPFC to the P3 underlying speech versus limb movement inhibition. Twenty-one neurotypical adults received both cathodal and sham high-definition transcranial direct current stimulation (HD-tDCS) over rDLPFC. ERPs were subsequently recorded while subjects were performing speech and limb Go/No-Go tasks. Cathodal HD-tDCS decreased accuracy for speech versus limb No-Go. Both speech and limb No-Go elicited a similar topographical distribution of P3, with significantly larger amplitudes for speech versus limb at a frontocentral location following cathodal HD-tDCS. Moreover, results showed stronger activation in cingulate cortex and rDLPFC for speech versus limb No-Go following cathodal HD-tDCS. These results indicate (1) P3 is an ERP marker of amodal inhibitory mechanisms that support both speech and limb inhibition, (2) larger P3 for speech versus limb No-Go following cathodal HD-tDCS may reflect the recruitment of additional neural resources-particularly within rDLPFC and cingulate cortex-as compensatory mechanisms to counteract the temporary stimulation-induced decline in speech inhibitory process. These findings have translational implications for neurological conditions that concurrently affect speech and limb movement.

Temporal features of concepts are grounded in time perception neural networks: An EEG study.

Experimental evidence suggests that modality-specific concept features such as action, motion, and sound partially rely on corresponding action/perception neural networks in the human brain.Little is known, however, about time-related features of concepts. We examined whether temporal features of concepts recruit networks that subserve time perception in the brain in an EEG study using event and object nouns. Results showed significantly larger ERPs for event duration vs object size judgments over right parietal electrodes, a region associated with temporal processing. Additionally, alpha/beta (10-15 Hz) neural oscillation showed a stronger desynchronization for event duration compared to object size in the right parietal electrodes. This difference was not seen in control tasks comparing event vs object valence, suggesting that it is not likely to reflect a general difference between event and object nouns. These results indicate that temporal features of words may be subserved by time perception circuits in the human brain.

HD-tDCS of primary and higher-order motor cortex affects action word processing.

The contribution of action-perception systems of the brain to lexical semantics remains controversial. Here, we used high-definition transcranial direct current stimulation (HD-tDCS) in healthy adults to examine the role of primary (left hand motor area; HMA) and higher-order (left anterior inferior parietal lobe; aIPL) action areas in action-related word processing (action verbs and manipulable nouns) compared to non-action-related control words (non-action verbs and non-manipulable nouns). We investigated stimulation-related effects at three levels of semantic processing: subliminal, implicit, and explicit. Broadly, we found that stimulation of HMA and aIPL resulted in relative facilitation of action-related language processing compared to non-action. HMA stimulation facilitated action verb processing in subliminal and implicit task contexts, suggesting that HMA helps represent action verbs even in semantically shallow tasks. HMA stimulation also facilitated manipulable noun comprehension in an explicit semantic task, suggesting that HMA contributes to manipulable noun comprehension when semantic demands are high. aIPL stimulation facilitated both manipulable noun and action verb processing during an implicit task. We suggest that both HMA and aIPL play a functional role in action semantics. HMA plays a general role in the semantics of actions and manipulable objects, while aIPL is important only when visuo-motor coordination is required for the action.

Speech artifact is also present in spike data.

Bush et al. (2022) highlight that brain recordings examining speech production can be significantly affected by microphonic artifact, which would change the interpretation of these kinds of data. While these findings are vital in determining whether data are artifactual or physiological in origin, frequencies were only examined up to 250 Hz (i.e., local field potentials), which would imply that spike-related data (single or multi-neuron recordings) are unaffected. We highlight here that this type of contamination may also be present in unit recordings, with the same aim to understand genuine neural mechanisms rather than mis-interpreting artifactual data.

Speech dysfunction, cognition, and Parkinson's disease.

Communication difficulties are a ubiquitous symptom of Parkinson's disease and include changes to both motor speech and language systems. Communication challenges are a significant driver of lower quality of life. They are associated with decreased communication participation, social withdrawal, and increased risks for social isolation and stigmatization in persons with Parkinson's disease. Recent theoretical advances and experimental evidence underscore the intersection of cognition and motor processes in speech production and their impact on spoken language. This chapter overviews a growing evidence base demonstrating that cognitive impairments interact with motor changes in Parkinson's disease to negatively affect communication abilities in myriad ways, at all stages of the disease, both in the absence and presence of dementia. The chapter highlights common PD interventions (pharmacological, surgical, and non-pharmacological) and how cognitive influences on speech production outcomes are considered in each.

Voice handicap Index in Parkinson's patients: Subthalamic versus globus pallidus deep brain stimulation.

PURPOSE: Subthalamic nucleus (STN) and globus pallidus interna (GPI) are the two most common sites for deep brain stimulation (DBS) in people with Parkinson's disease (PWP). Voice impairments are a common symptom of Parkinson's disease and information about voice outcomes with DBS is limited. Most studies in speech-language pathology have focused on STN-DBS and few have examined the effects of GPI-DBS. This was an initial effort to examine the impact of DBS location on Vocal Handicap Index (VHI) scores, which assess the impact of a voice disorder on an individual. METHOD: Twenty-four gender-matched PWP (12 STN-DBS and 12 GPI-DBS) completed the VHI post-DBS implantation. Two-tailed independent samples t-tests were used to compare each VHI scale score (physical, functional, emotional, total) and patient factors between the two groups. RESULTS: No significant differences in total or subscale VHI scores were identified between the two DBS groups. A trend toward greater impairment in PWP with GPI-DBS was noted. An association between higher VHI scores and DBS settings was found. CONCLUSIONS: Studies directly comparing speech outcomes for different DBS targets are lacking. The current findings provide new insights concerning voice outcomes following DBS by adding to the limited literature directly comparing speech outcomes in multiple DBS targets. Limitations and directions for future research are discussed.

Neural correlates of speech and limb motor timing deficits revealed by aberrant beta band desynchronization in Parkinson's disease.

OBJECTIVE: We used a classical motor reaction time paradigm to examine the effects of Parkinson's disease (PD) on the mechanisms of speech production and upper limb movement. METHODS: Electro-encephalography (EEG) signals were recorded in PD and control groups during speech vowel production and button press tasks in response to temporally predictable and unpredictable visual stimuli. RESULTS: Motor reaction times were slower in PD vs. control group independent of stimulus timing and movement modality. This effect was accompanied by stronger desynchronizations of low beta (13-18 Hz) and high beta (18-25 Hz) band neural oscillations in PD vs. control prior to the onset of speech and hand movement. In addition, pre-movement desynchronization of beta band oscillations were correlated with motor reaction time in control subjects with faster responses associated with weaker beta band desynchronizations during the planning phase of movement. However, no such effect was found in the PD group. CONCLUSIONS: We suggest that the aberrant pattern of beta band desynchronization is a neural correlate of speech and upper limb motor timing deficits as a result of cortico-striatal pathology in PD. SIGNIFICANCE: These findings motivate interventions targeted toward normalizing beta band activities for improving speech and upper limb movement timing in PD.

HD-tDCS over motor cortex facilitates figurative and literal action sentence processing.

The extent to which action and perception systems of the brain are involved in semantic comprehension remains controversial. Whether figurative language, such as metaphors and idioms, is grounded in sensory-motor systems is especially contentious. Here, we used high-definition transcranial direct current stimulation (HD-tDCS) in healthy adults to examine the role of the left-hemisphere motor cortex during the comprehension of action sentences, relative to comprehension of sentences with visual verbs. Action sentences were divided into three types: literal, metaphoric, or idiomatic. This allowed us to ask whether processing of action verbs used in figurative contexts relies on motor cortex. The results revealed that action sentence comprehension response times were facilitated relative to the visual sentence control. Significant interaction relative to visual sentences was observed for literal, metaphoric, and idiomatic action sentences with HD-tDCS of the motor cortex. These results suggest that the left motor cortex is functionally involved in action sentence comprehension. Furthermore, this involvement exists when the action content of the sentences is figurative, for both idiomatic and metaphoric cases. The results provide evidence for functional links between conceptual and action systems of the brain.

Can sex influence the neurocognition of language? Evidence from Parkinson's disease.

Parkinson's disease (PD), which involves basal ganglia degeneration, affects language as well as motor function. However, which aspects of language are impaired in PD and under what circumstances remains unclear. We examined whether lexical and grammatical aspects of language are differentially affected in PD, and whether this dissociation is moderated by sex as well as the degree of basal ganglia degeneration. Our predictions were based on the declarative/procedural model of language. The model posits that grammatical composition, including in regular inflection, depends importantly on left basal ganglia procedural memory circuits, whereas irregular and other lexicalized forms are memorized in declarative memory. Since females tend to show declarative memory advantages as compared to males, the model further posits that females should tend to rely on this system for regulars, which can be stored as lexicalized chunks. We tested non-demented male and female PD patients and healthy control participants on the intensively studied paradigm of English regular and irregular past-tense production. Mixed-effects regression revealed PD deficits only at regular inflection, only in male patients. The degree of left basal ganglia degeneration, as reflected by right-side hypokinesia, predicted only regular inflection, and only in male patients. Left-side hypokinesia did not show this pattern. Past-tense frequency effects suggested that the female patients retrieved regular as well as irregular past-tense forms from declarative memory, whereas the males retrieved only irregulars. Sensitivity analyses showed that the pattern of findings was robust. The results, which are consistent with the declarative/procedural model, suggest a grammatical deficit in PD due to left basal ganglia degeneration, with a relative sparing of lexical retrieval. Female patients appear to compensate for this deficit by relying on chunks stored in declarative memory. More generally, the study elucidates the neurocognition of inflectional morphology and provides evidence that sex can influence how language is computed in the mind and brain.

Slowed Compensation Responses to Altered Auditory Feedback in Post-Stroke Aphasia: Implications for Speech Sensorimotor Integration.

Developing a clearer understanding of impairments that underlie the behavioral characteristics of aphasia is essential for the development of targeted treatments and will help inform theories of speech motor control. Impairments in sensorimotor integration of speech in individuals with conduction aphasia have previously been implicated in their repetition deficits. However, much less is known about the extent to which these integrative deficits occur outside of conduction aphasia and how this manifests behaviorally in areas other than speech repetition. In this study, we aimed to address these issues by examining the behavioral correlates of speech sensorimotor impairment under altered auditory feedback (AAF) and their relationship with the impaired ability to independently correct for online errors during picture naming in people with aphasia. We found that people with aphasia generate slower vocal compensation response to pitch-shift AAF stimuli compared with controls. However, when the timing of responses was controlled for, no significant difference in the magnitude of vocal pitch compensation was observed between aphasia and control groups. Moreover, no relationship was found between self-correction of naming errors and the timing and magnitude of vocal compensation responses to AAF. These findings suggest that slowed compensation is a potential behavioral marker of impaired sensorimotor integration in aphasia.

Event-related desynchronization of alpha and beta band neural oscillations predicts speech and limb motor timing deficits in normal aging.

Normal aging is associated with decline of motor timing mechanisms implicated in planning and execution of movement. Evidence from previous studies has highlighted the relationship between neural oscillatory activities and motor timing processing in neurotypical younger adults; however, it remains unclear how normal aging affects the underlying neural mechanisms of movement in older populations. In the present study, we recorded EEG activities in two groups of younger and older adults while they performed randomized speech and limb motor reaction time tasks cued by temporally predictable and unpredictable sensory stimuli. Our data showed that older adults were significantly slower than their younger counterparts during speech production and limb movement, especially in response to temporally unpredictable sensory stimuli. This behavioral effect was accompanied by significant desynchronization of alpha (7-12 Hz) and beta (13-25 Hz) band neural oscillatory activities in older compared with younger adults, primarily during the preparatory pre-motor phase of responses for speech production and limb movement. In addition, we found that faster motor reaction times in younger adults were significantly correlated with weaker desynchronization of pre-motor alpha and beta band neural activities irrespective of stimulus timing and response modality. However, the pre-motor components of alpha and beta activities were timing-specific in older adults and were more strongly desynchronized in response to temporally predictable sensory stimuli. These findings highlight the role of alpha and beta band neural oscillations in motor timing processing mechanisms and reflect their functional deficits during the planning phase of speech production and limb movement in normal aging.

Modulation of vocal pitch control through high-definition transcranial direct current stimulation of the left ventral motor cortex.

Neural interactions between sensorimotor integration mechanisms play critical roles in voice motor control. We investigated how high-definition transcranial direct current stimulation (HD-tDCS) of the left ventral motor cortex modulates neural mechanisms of sensorimotor integration during voice motor control. HD-tDCS was performed during speech vowel production in an altered auditory feedback (AAF) paradigm in response to upward and downward pitch-shift stimuli. In one experiment, two groups received either anodal or cathodal 2 milliamp (mA) HD-tDCS to the left ventral motor cortex while a third group received sham (placebo) stimulation. In a second experiment, two groups received either 1 mA or 2 mA cathodal HD-tDCS to the left ventral motor cortex. Results of the first experiment indicated that the magnitude of vocal compensation was significantly reduced following anodal and cathodal HD-tDCS only in responses to downward pitch-shift AAF stimuli, with stronger effects associated with cathodal HD-tDCS. However, no such effect was observed following sham stimulation. Results of the second experiment indicate that there is not a differential effect of modulation from 1 mA versus 2 mA. Further, these results replicate the directional finding of the first experiment for vocal compensation in response to downward pitch-shift only. These findings suggest that neurostimulation of the left ventral motor cortex modulates sensorimotor mechanisms underlying voice motor control. We speculate that this effect is associated with the increased contribution of feedforward motor mechanisms, leading to reduced compensatory speech responses to AAF.

A dissociation between syntactic and lexical processing in Parkinson's disease.

Parkinson's disease (PD), which involves the degeneration of dopaminergic neurons in the basal ganglia, has long been associated with motor deficits. Increasing evidence suggests that language can also be impaired, including aspects of syntactic and lexical processing. However, the exact pattern of these impairments remains somewhat unclear, for several reasons. Few studies have examined and compared syntactic and lexical processing within subjects, so their relative deficits remain to be elucidated. Studies have focused on earlier stages of PD, so syntactic and lexical processing in later stages are less well understood. Research has largely probed English and a handful of other European languages, and it is unclear whether findings generalize more broadly. Finally, few studies have examined links between syntactic/lexical impairments and their neurocognitive substrates, such as measures of basal ganglia degeneration or dopaminergic processes. We addressed these gaps by investigating multiple aspects of Farsi syntactic and lexical processing in 40 Farsi native-speaking moderate-to-severe non-demented PD patients, and 40 healthy controls. Analyses revealed equivalent impairments of syntactic comprehension and syntactic judgment, across different syntactic structures. Lexical processing was impaired only for motor function-related objects (e.g., naming 'hammer', but not 'mountain'), in line with findings of PD deficits at naming action verbs as compared to objects, without the verb/noun confound. In direct comparisons between lexical and syntactic tasks, patients were better at naming words like 'mountain' (but not words like 'hammer') than at syntactic comprehension and syntactic judgment. Performance at syntactic comprehension correlated with the last levodopa equivalent dose. No other correlations were found between syntactic/lexical processing measures and either levodopa equivalent dose or hypokinesia, which reflects degeneration of basal ganglia motor-related circuits. All critical significant main effects, interactions, and correlations yielded large effect sizes. The findings elucidate the nature of syntactic and lexical processing impairments in PD.