What is the cause of stuttering? -> According to Chang & Guenther (PhD researchers) + tips (that I extracted from the research)

What is the cause of stuttering? -> According to Chang & Guenther (PhD researchers) + tips (that I extracted from the research) The curious PWS (person who stutters) in me read [this](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997432/) research ([pdf](https://osf.io/2qhtp/download)) ([video](https://www.youtube.com/watch?v=UD-_YHq3GE0&ab_channel=OxfordDysfluencyConference)). After finishing the 33 pages, I summed up the key points. **Goal** * In this review, we utilize the Directions Into Velocities of Articulators (DIVA) neurocomputational modeling framework to mechanistically interpret relevant findings from the behavioral and neurological literatures on developmental stuttering. We propose that the primary impairment underlying stuttering behavior is malfunction in the cortico-basal ganglia-thalamocortical (hereafter, cortico-BG) loop that is responsible for **initiating speech motor programs** **Intro** * The DIVA model divides speech into feedforward and sensory feedback-based control processes. The feedforward control system is further sub-divided into an **articulation circuit**, which is responsible for generating the finely timed and coordinated muscle activation patterns (motor programs) for producing speech sounds, and an **initiation circuit**, which is responsible for turning the appropriate motor programs on and off at the appropriate instants in time * A **(speech) motor program** is the execution of coordinated movement commands of units (such as, the syllable "you") stored in memory. Each program contains parameters, such as, how the jaw, lips, tongue, larynx, etc should be moved (watch above YT video for a detailed explanation) * **Phonemes** are the smallest units of sound that correspond to a specific set of articulatory gestures, involving the coordinated movement of the tongue, lips, etc **The Cortico-Basal Ganglia-Thalamocortical Loop** * The core deficit in **persistent developmental stuttering (PDS)** is an impaired ability (1) to initiate, sustain, or terminate **motor programs** for phonemic/gestural units within a speech sequence, and (2) sequencing of learned speech sequences, due to impairment of the left hemisphere cortico-BG loop * In the DIVA model, the initiation circuit is responsible for sequentially initiating phonemic gestures within a (typically syllabic) motor program by activating nodes for each phoneme in an initiation map in the **supplementary motor area (SMA)** * Early in development pre-SMA involvement is required to sequentially activate nodes in SMA for initiating each phoneme. Later in development, the basal ganglia motor loop has taken over sequential activation of the SMA nodes, thus making production more “automatic” and freeing up higher-level cortical areas such as pre-SMA * Potential impairments of the basal ganglia motor loop: * Basal ganglia impairment * Impairment of axonal projections between cerebral cortex, basal ganglia, and thalamus * Impairment in cortical processing * Prolonging, blocks and repetitions: * Failure to recognize the sensory, motor, and cognitive context for terminating the current phoneme > prolongation stutter * Failure to recognize the context for initiating the next phoneme > block stutter * Initiation signal “drops out” > repetition stutter * Alm: * Initiation and termination signals for speech movements are timing signals * External timing cues (such as, choral reading, singing) > perceived by sensory cortical areas > relaying signals to SMA > reducing dependence on the basal ganglia motor loop for generating initiation/termination signals (cf. internal timing cues to initiate propositional speech) **Impairment in the Basal Ganglia** * Levodopa treatment aimed at increasing dopamine levels in the striatum can exacerbate stuttering * Pathways within the basal ganglia: * direct pathway to excite cerebral cortex (activate the correct motor program) * indirect pathway to inhibit cerebral cortex (suppress competing motor programs) * Two subtypes of speech blocks: * underactive indirect pathway: excessive motor activity due to reduced inhibition of movement * underactive direct pathway: reduced level of motor activity due to reduced excitation of movement **Impairments in Projections Between Cerebral Cortex, the Basal Ganglia, and Thalamus** * **Root cause** of stuttering: Impaired left hemisphere corticostriatal connectivity can result in poor detection of the cognitive and sensorimotor context for **initiating** the next sound by the basal ganglia motor loop, thereby impairing the generation of **initiation/termination** signals to SMA **Impairments in the Network of Cortical Regions That Process Cognitive and Sensorimotor Aspects** * White matter structural changes correlate with learning/training * There is a very low rate of stuttering in congenitally deaf individuals # Discussion **Primary Deficits & Secondary Effects in Stuttering** * **Primary deficits**: Anatomical and functional anomalies involving the left hemisphere premotor cortex, IFG, SMA, and putamen * **Secondary effects**: (1) auditory cortex deactivation, and (2) decreased compensation to auditory perturbations **Network Connectivity of the Cortico-BG Loop: Deficits** * Stuttering is likely a system-level problem rather than the result of impairment in a particular neural region or pathway # Neural substrates: **Cerebral cortices** * **Somatosensory cortex**: detect sensory information from the body regarding temperature, proprioception, touch, texture, and pain * **Premotor cortex**: planning and organizing movements * **Motor cortex**: generate signals to direct movements * **Supplementary motor area** (SMA): planning of complex movements that are internally generated rather than triggered by sensory events * posterior auditory cortex (pAC) * ventral motor cortex (vMC): vMC contains representations of the speech articulators * ventral premotor cortex (vPMC) * ventral somatosensory cortex (vSC) * posterior inferior frontal sulcus (pIFS) **Inferior frontal cortical regions and Rolandic cortical regions** * inferior frontal gyrus pars opercularis (IFo) * inferior frontal gyrus pars triangularis (IFt) * postcentral gyrus (PoCG) * precentral gyrus (PrCG) **Basal Ganglia:** * **Description**: It performs a pattern matching operation in which it monitors the current cognitive context as represented by activity in prefrontal cortical areas including pre-SMA and the posterior inferior frontal sulcus (pIFS); motor context represented in ventral premotor cortex (vPMC), SMA, and ventral primary motor cortex (vMC); and sensory context represented in posterior auditory cortex (pAC) and ventral somatosensory cortex (vSC). When the proper context is detected, the basal ganglia signals to SMA that means it is time to terminate the ongoing phoneme (termination signal) and initiate the next phoneme of the speech sequence (initiation signal) * **Striatum:** utilization of sensory cues to guide behavior - to modulate cortical auditory-motor interaction relevant to motor control. It may detect a mismatch between the current sensorimotor context and the context needed for initiating the next motor program, thus reducing its competitive advantage over competing motor programs, which in turn may lead to impaired generation of initiation signals by the basal ganglia and a concomitant stutter * **(1) Putamen**: learning and motor control, including speech articulation, language functions, reward, cognitive functioning. Automatic responses; Doing things without thinking; Poor connectivity to pre-frontal cortex * **(2) Caudete**: * **(3) Nucleus Accumbens**: * **Internal Globus Pallidus** (GPi): integrating information including movement activity from the striatum, GPe, and subthalamic nucleus (STN) * **Substantia nigra** pars reticulata (SNr) (inside BG): integrating information. * **SNr and GPi**: selectively exciting the correct motor program in the current context while inhibiting the competing motor programs * **Subthalamic nucleus** (STN): * **Anterior thalamic radiation**: sequence learning, rule-based categorization, attention-switching, working memory **Thalamus** * **VL thalamus**: integrating information from the cerebellum, striatum, and cortex and projecting to the primary motor cortex * ventral anterior thalamic nucleus (VA) * ventral lateral thalamic nucleus (VL) # Tips: * Increase the efficacy of the indirect pathway by increasing the inhibition of competing actions * Improve the ability to maintain the chosen action over competing actions in the indirect pathway - to address the impaired initiation through sequences in the presence of competing tasks * Develop interventions involving better synchronizing and in turn inducing better communication across the basal ganglia, motor, and auditory regions to help achieve more fluent speech * Achieve normalized segregation among networks to resolve aberrant cues from the basal ganglia, and don't engage in auditory and motor areas * Address the malfunction in the cortico-basal ganglia-thalamocortical loop that is responsible for **initiating speech motor programs** * Prioritize **feedforward** over and **sensory feedback** control processes * Address the disruptions (e.g., heightened demands around triggers, physical arousal, not instructing to send motor commands, etc) when activating the **initiation circuit**, which is responsible for turning the appropriate motor programs on and off at the appropriate instants in time * Don't perceive a **speech motor program** as an anticipated (or feared) word - when executing speech movement commands stored in memory. And thus, don't link such motor programs with inhibiting/initiating motor programs * Don't perceive a **phoneme** (which is the smallest units of sound) as an anticipated (or feared) letter. And thus, don't link such phonemes with inhibiting/initiating motor programs * Address the impaired ability (1) to initiate, sustain, or terminate **motor programs**, and (2) to sequence learned speech sequences * Learn to initiate phonemes by involving pre-SMA to sequentially activate nodes in SMA, and with reduced involvement of the basal ganglia motor loop - to prevent speaking/stuttering on auto-pilot, and instead induce motor-learning - even if this leads to speaking less automatic, and overloading higher-level cortical areas such as pre-SMA * Address the impairment of axonal projections between cerebral cortex, basal ganglia, and thalamus - to improve your ability to initiate motor programs * Address the impairment in cortical processing - to improve your ability to initiate motor programs * Learn to recognize the sensory, motor, and cognitive context for terminating the current phoneme or initiating the next phoneme * Implement internal timing cues for initiating/terminating speech movements (over external speech motor timing cues) e.g., by not relying anymore on excessive sensory cortical areas - to reduce dependence on the basal ganglia motor loop for generating initiation/termination signals to initiate propositional speech * Address the impairment of not exciting cerebral cortex (not activating the correct motor program) in the **direct pathway** \- to increase competitive advantage of motor programs, resulting in less stuttering. So, address the reduced level of motor activity due to reduced excitation of movement * Address the impairment of not inhibiting cerebral cortex (not suppressing competing motor programs) in the **indirect pathway** \- to increase inhibition to suppress competing motor programs, making it easier for the correct motor program to be chosen over incorrect alternatives, resulting in less stuttering. So, address the excessive motor activity due to reduced inhibition of movement * Address the impaired left hemisphere corticostriatal connectivity that result in poor detection of the cognitive and sensorimotor context for **initiating** the next sound by the basal ganglia motor loop, thereby impairing the generation of **initiation/termination** signals to SMA * Address the impairments in the Network of Cortical Regions That Process Cognitive and Sensorimotor Aspects * Engage in speech motor learning/training, such as suggested in this list of tips, to improve white matter structural changes. So, don't give up on developing clinical interventions to target neural impairments, and thus, don't give up for the reason that "it's genetic", because it's still unclear how mutations in genes affect (1) stuttering, or (2) the proposed basal ganglia circuitry * A compensatory mechanism involving left medial premotor cortex may contribute to **recovery** * Reduce the detection of errors in articulation that would otherwise reduce the match between expected and actual sensorimotor context for the next motor program in **striatum** * Develop clinical interventions associated with a shift toward more normal, left-lateralized frontal activation To compensate for the primary deficits (such as, impaired basal ganglia function, left hemisphere premotor cortex, IFG, SMA, and putamen), avoid these maladaptive compensatory interventions: * forcing reliance on the right hemisphere, leading to increased right hemisphere white matter tract strengths due to additional use * correcting **sensory errors** by the right-lateralized **auditory** and **somatosensory** feedback control systems * correcting **errors** in auditory feedback of one’s own speech (i.e., when it does not match the expected pattern for the current sound) (e.g., due to subtle errors in articulation) * engaging in cerebellum-related mechanisms * auditory cortex deactivation * decreased compensation to auditory perturbations * excessively focusing on the **articulation circuit** (aka production system) to attempt to initiate speech programs Employ clinical interventions to target neural regions: * the neural activity in the **caudate nucleus** \- to reduce stuttering severity * increased gray matter volume in the **left putamen** * the deficit in the ability to perceive temporally structured sound sequences (in the atypical processing in **corticostriatal circuits**): the relationship between rhythm perception and timing-related brain network activity. Rhythm processing implies rhythm perception and speech perception and production * the anomalous functional connectivity including pathways between auditory cortical areas and putamen and thalamus, between thalamus and pre-SMA, and between thalamus and putamen * the less structural connectivity between **left putamen** and left hemisphere **cortical regions** (IFo, SMA) * decreased growth rate in white matter in the **anterior thalamic radiation** * the anomalies in the connections between prefrontal areas and the basal ganglia - to address the affected higher-order cognitive functions (e.g., attention), which help develop speech control automaticity via the cortico-BG loop * the lower white matter in the **anterior and superior thalamic radiations** (tracts) - which helps interface speech motor control and other cognitive functions * normalize structural connectivity among **left premotor**, **motor**, and **auditory cortical** areas which may play a role in natural **recovery** from stuttering * the deactivation of **auditory cortex** involving inhibition of auditory feedback of one’s own speech to avoid detection of minor errors in production - which is a compensatory mechanism developed after years of stuttering rather than a **root cause** of the disorder * structural differences in the **left inferior frontal and premotor cortex** regions * anomalous diffusivity of white matter in the **left frontal aslant tract (FAT)** (connecting SMA and pre-SMA with posterior inferior frontal cortical areas) - which is correlated with stuttering severity * intra-hemispheric tracts between **inferior frontal cortical ROIs** and **sensorimotor (Rolandic) cortical ROIs**, which is correlated with stuttering severity * anomalous functioning in **left hemisphere inferior frontal cortex** * suppression of right-dominant **motor rhythms** (over left dominant in fluent speakers) * hyperactivity in right hemisphere **cerebral cortex** * decreased cortical thickness in **left ventral motor cortex (vMC)** and **ventral premotor cortex (vPMC)** areas. **Recovered children** showed increased thickness, and decreased gyrification in the **SMA** and **pre-SMA** which may indicate better long-range connectivity with regions such as **left IFG** * decreased white matter affecting the **frontal motor areas** * reduced neural activity in **left auditory cortex** of the posterior superior temporal gyrus * deactivation in the **left inferior frontal** and **premotor cortices** * deficit in betweenness centrality of **left vPMC** * aberrant connectivity patterns involving the **somatomotor network** and its connectivity with **frontoparietal** and **attention networks** \- to improve how attention mediates corticocortical and corticostriatal connectivities * aberrant connectivity involving the **default mode network (DMN)** \[task-negative aka resting state\] and its connections to **attention** and **frontoparietal networks** \[task-positive aka during activities\]. These results suggest that cognitive and higher-order functions could be involved in mediating **recovery.** Better segregation from task-negative networks to enable efficient functioning of the somatomotor, executive control, and attention networks could allow once-vulnerable children to **recover** from stuttering