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Introduction: Dysphagia commonly occurs after stroke, yet the mechanisms of post-stroke corticobulbar plasticity are not well understood. While cortical activity associated with swallowing actions is bihemispheric, prior research has suggested that plasticity of the intact cortex may drive recovery of swallowing after unilateral stroke. Age may be an important factor as it is an independent predictor of dysphagia after stroke and neuroplasticity may be reduced with age. Based on previous clinical studies, we hypothesized that cranial muscle activating volumes may be expanded in the intact hemisphere and would contribute to swallowing function. We also hypothesized that older age would be associated with limited map expansion and reduced function. As such, our goal was to determine the impact of stroke and age on corticobulbar plasticity by examining the jaw and tongue muscle activating volumes within the bilateral sensorimotor cortices. Methods: Using the middle cerebral artery occlusion rat stroke model, intracortical microstimulation (ICMS) was used to map regions of sensorimotor cortex that activate tongue and jaw muscles in both hemispheres. Young adult (7 months) and aged (30 months) male F344 x BN rats underwent a stroke or sham-control surgery, followed by ICMS mapping 8 weeks later. Videofluoroscopy was used to assess oral-motor functions. Results: Increased activating volume of the sensorimotor cortex within the intact hemisphere was found only for jaw muscles, whereas significant stroke-related differences in tongue activating cortical volume were limited to the infarcted hemisphere. These stroke-related differences were correlated with infarct size, such that larger infarcts were associated with increased jaw representation in the intact hemisphere and decreased tongue representation in the infarcted hemisphere. We found that both age and stroke were independently associated with swallowing differences, weight loss, and increased corticomotor thresholds. Laterality of tongue and jaw representations in the sham-control group revealed variability between individuals and between muscles within individuals. Conclusion: Our findings suggest the role of the intact and infarcted hemispheres in the recovery of oral motor function may differ between the tongue and jaw muscles, which may have important implications for rehabilitation, especially hemisphere-specific neuromodulatory approaches. This study addressed the natural course of recovery after stroke; future work should expand to focus on rehabilitation. [ABSTRACT FROM AUTHOR]

Forelimb-related areas of the motor cortex communicate directly to downstream areas in the brainstem and spinal cord via axons that project to and through the pyramidal tract (PT). To better understand the diversity of the brainstem branching patterns of these pyramidal tract projections, we used MAPseq, a molecular barcode technique for population-scale sampling with single-axon resolution. In experiments using mice of both sexes, we first confirmed prior results demonstrating the basic efficacy of axonal barcode identification of primary motor cortex (M1) PT-type axons, including corticobulbar (CBULB) and corticospinal (CSPI) subclasses. We then used multiplexed MAPseq to analyze projections from M1 and M2 (caudal and rostral forelimb areas). The four basic axon subclasses comprising these projections (M1-CSPI, M1-CBULB, M2-CSPI, M2- CBULB) showed a complex mix of differences and similarities in their brainstem projection profiles. This included relatively abundant branching by all classes in the dorsal midbrain, by M2 subclasses in the pons, and by CSPI subclasses in the dorsal medulla. Cluster analysis showed graded distributions of the basic subclasses within the PT class. Clusters were of diversely mixed subclass composition and showed distinct rostrocaudal and/or dorsomedial projection biases. Exemplifying these patterns was a subcluster likely enriched in corticocuneate branches. Overall, the results indicate high yet systematic PT axon diversity at the level of brainstem branching patterns; projections of M1 and M2 appear qualitatively similar, yet with quantitative differences in subclasses and clusters. [ABSTRACT FROM AUTHOR]

Objective: Dysphagia is a significant complication in fourth ventricle surgery. Corticobulbar motor evoked potentials (CB-MEPs) of the lower cranial nerves may provide real-time information possibly correlating with postoperative swallowing dysfunction, and the vagus nerves may prove ideal for this purpose. However, the literature is heterogeneous, non-systematic, and inconclusive on this topic. The object of this retrospective study was to evaluate the correlation between CB-MEPs of the vagus nerve and postoperative worsening or new-onset swallowing deficits in intraaxial fourth ventricle surgery., Methods: In 21 consecutive patients undergoing surgery for fourth ventricle intraaxial tumors between February 2018 and October 2022, endotracheal tubes with two applied electrodes contacting the vocal cords were used to record vagus nerve MEPs including values at baseline, the end of surgery, and the minimum value during the operation. From the mean value of right and left vagus nerve MEP amplitudes, the minimum-to-baseline amplitude ratio (MBR) and final-to-baseline amplitude ratio (FBR) were calculated. These indexes were correlated with postoperative swallowing function., Results: Given their clinical significance, receiver operating characteristic curves were obtained to evaluate the performance of these indexes in predicting postoperative swallowing function. The area under the curve (AUC) was 0.850 (p < 0.001) and the best cutoff for FBR was 67.55% for the worsening of swallowing in the postoperative period. The AUC was 0.750 (p = 0.026) and the best cutoff was 46.37% in MBR for the absence of a swallowing disorder at the late follow-up., Conclusions: This study confirmed that vagus nerve MEPs are reliable predictors of postoperative swallowing function in fourth ventricle surgery and can be feasibly used as an intraoperative monitoring technique.

Lateral medullary syndrome is a common brainstem stroke associated with a classical triad of Horner's Syndrome, ipsilateral ataxia and hypalgesia and thermoanasthesia of ipsilateral face. We report a case of a 49-year-old diabetic, non-hypertensive, postmenopausal female who presented with symptoms involving the left dorsal medulla along with right sided hemiparesis and left UMN-type facial palsy. Contralateral hemiparesis was explained by caudal extension of infarct involving the pyramids before decussation at the medulla, known as Babinski–Nageotte Syndrome. UMN-type facial palsy was attributed to involvement of hypothetical supranuclear aberrant corticobulbar fibres of facial nerve which descend down in the contralateral ventromedial medulla, decussate at level of upper medulla and then ascend in the dorsolateral medulla to reach the facial nerve nucleus. Association of these two entities with Wallenberg's Syndrome have been reported separately in literature, but not together as in this case. [ABSTRACT FROM AUTHOR]

There are multiple descending neural pathways, including the corticospinal pathway (CS) and the corticobulbar pathway (CB). The corticospinal pathway has been shown to exhibit within-pathway (CS-to-CS) motor transfer. However, motor transfer across each pathway (CS-to-CB or CB-to-CS) has yet to be studied in depth. The aim of the present study was to examine the effects of cross-pathway motor transfer between the ankle (CS) and tongue (CB) after training with a ballistic goal-directed motor task. Twelve healthy participants were recruited for this two-day experimental study. Six participants performed a ballistic goal-directed task with their ankle on Day 1 (ankle dorsiflexion), then tongue on Day 2 (elevate tongue against IOPI). The other 6 participants performed the same task with their tongue on Day 1, then ankle on Day 2. Both the ankle and tongue tasks (50 trials each) required matching force and time to a visual target. Our findings indicate that participants who underwent ankle training on Day 1 exhibited decreased tongue force error on Day 2 compared with participants who completed the tongue training on Day 1, with no prior ankle training (p = 0.02) (i.e. greater accuracy). This finding suggests that cross-pathway transfer from the corticospinal pathway to the corticobulbar pathway occurred with respect to force error. In other words, training of the ankle (CS) translated to improved training performance of the tongue (CB) through a reduction in force error. However, the reverse was not true – training the tongue did not elicit improved performance of the ankle. Nonetheless, if training with the corticospinal pathway can lead to improved corticobulbar pathway functioning, incorporating multi-pathway rehabilitation techniques might be valuable for clinicians across medical disciplines. [ABSTRACT FROM AUTHOR]

Subcortical white matter injury is often accompanied by orofacial motor dysfunction, but little is known about the structural substrates accounting for these common neurological deficits. We studied the trajectory of the corticobulbar projection from the orofacial region of the primary (M1), ventrolateral (LPMCv), supplementary (M2), rostral cingulate (M3) and caudal cingulate (M4) motor regions through the corona radiata (CR), internal capsule (IC) and crus cerebri of the cerebral peduncle (ccCP). In the CR each pathway was segregated. Medial motor area fibers (M2/M3/M4) arched over the caudate and lateral motor area fibers (M1/LPMCv) curved over the putamen. At superior IC levels, the pathways were widespread, involving the anterior limb, genu and posterior limb with the M3 projection located anteriorly, followed posteriorly by projections from M2, LPMCv, M4 and M1, respectively. Inferiorly, all pathways maintained this orientation but shifted posteriorly, with adjacent fiber bundles overlapping minimally. In the ccCP, M3 fibers were located medially and M1 fibers centromedially, with M2, LPMCv, and M4 pathways overlapping in between. Finally, at inferior ccCP levels, all pathways overlapped. Following CR and superior IC lesions, the dispersed pathway distribution may correlate with acute orofacial dysfunction with spared pathways contributing to orofacial motor recovery. In contrast, the gradually commixed nature of pathway representation inferiorly may enhance fiber vulnerability and correlate with severe, prolonged deficits following lower subcortical and midbrain injury. Additionally, in humans these findings may assist in interpreting orofacial movements evoked during deep brain stimulation, and neuroimaging tractography efforts to localize descending orofacial motor pathways. [ABSTRACT FROM AUTHOR]

Although the modified balloon dilatation therapy has been demonstrated to improve pharyngeal swallowing function post stroke, the underlying neural mechanisms of improvement are unknown. Our aims are (1) to investigate the effect of modified balloon dilatation on the excitability of corticobulbar projections to the submental muscle in dysphagic patients with brainstem stroke and (2) the relation between changes in excitability and pharyngeal kinematic modifications. Thirty patients with upper esophageal sphincter (UES) dysfunction due to unilateral brainstem stroke were recruited into two groups. The patients in dilatation group received modified balloon dilatation and conventional therapies, and those in control were only treated by conventional therapies (twice per day). The amplitudes of bilateral submental motor evoked potentials (MEPs) induced by transcranial magnetic stimulations over bilateral motor cortex, diameters of UES opening (UOD) and maximal displacement of hyoid (HD) were all assessed at baseline and the endpoint of treatments. Repeated ANOVA analysis revealed significant main effect of group, time and MEP laterality on MEP amplitudes (p = 0.02). There were no differences in the pretreatment measures between groups (all p > 0.05). After treatment, the amplitudes of affected submental MEP evoked by ipsilateral cortical pulse as well as UOD and HD were significantly different in dilatation group compared to control (amplitude: p = 0.02, UOD: p < 0.001, HD: p = 0.03). The differences of pre- and post-treatment amplitudes of the affected MEP evoked by ipsilateral stimulation showed a positive correlation with the improvement of HD (dilatation: R 2 = 0.51, p = 0.03; control: R 2 = 0.39, p = 0.01), rather than UOD in both groups (all p > 0.05). In conclusion, modified balloon dilatation therapy can increase the excitability of affected projection in patients with unilateral brainstem stroke. [ABSTRACT FROM AUTHOR]

Primary motor networks are known to be involved in the control of voluntary oral movements as well as the modulation of pharyngeal movements during experimentally controlled single swallows performed on command. The role of these networks in the more typical task of sequential swallowing remains unexplored. This study evaluated the hypothesis that experimental disruption of motor cortical activation would reduce the rate and regularity of repeatedly performed volitional or volitionally initiated motor tasks controlled by corticospinal (finger tapping) and corticobulbar (eyebrow movement, jaw opening, volitional sequential swallowing) motor systems, but would not influence a more reflexive corticobulbar task (reflexive sequential swallowing to pharyngeal water infusion). This premise was investigated in 24 healthy participants using two techniques: a dual task paradigm and a transcranial magnetic stimulation paradigm. Disruption effects were quantified by changes in rate and regularity of performance for each tested motor task. In summary, volitional motor tasks controlled by corticospinal motor networks (finger tapping) are more susceptible to behavioural and neurophysiological disruption than tasks controlled by cortiobulbar motor networks containing a reflexive component (both volitional and experimentally initiated consecutive swallowing). Purely volitional motor tasks controlled by the corticobulbar motor system (eyebrow raising or jaw opening) were affected in similar ways as the volitional corticospinal motor tasks. In summary, tasks involving sequential pharyngeal swallowing - whether volitionally or experimentally initiated - are largely robust against disruption of primary cortical motor networks, supporting a key role of medullary CPGs in the motor control of sequential pharyngeal swallowing. [ABSTRACT FROM AUTHOR]

Objective: The palmomental reflex (PMR) is a primitive reflex, which may appear when cortical inhibitory pathways are disrupted by disease. In this study, we examined whether the PMR is associated with corticobulbar involvement in people with ALS (PALS). Methods: PMR was routinely tested for each patient attending the ALS clinic. Three hundred and eighteen consecutive PALS were included, of whom 271 were PMR positive (PMR+). Clinical evaluation defined the presence of upper motor neuron (UMN) and lower motor neuron (LMN) signs in the bulbar, cervical and lumbosacral segments. Results: The PMR + group had a higher rate of both UMN and LMN bulbar involvement (BI) as well as more UMN upper-limb involvement and UMN involvement of any type, the strongest association being between PMR + and UMN BI. In patients without BI at presentation, UMN BI developed roughly 15 months early in the PMR + group compared to the PMR- group. Conclusion: We found that the PMR is strongly associated with UMN signs within the bulbar region and to a lesser extent with upper-limb UMN involvement. We propose the PMR be considered a harbinger of corticobulbar involvement in PALS. [ABSTRACT FROM AUTHOR]

Both limb and cranial motor functions are adversely impacted by Parkinson's disease (PD). While current pharmacological and surgical interventions are effective in alleviating general limb motor symptoms of PD, they have failed to provide significant benefit for cranial motor functions. This suggests that the neuropathologies mediating limb and cranial motor impairments in PD may differ. Animal models provide a mechanism by which the potential neural dysfunctions underlying these different motor impairments may be characterized. Central goals to our laboratory have been to (a) determine the differential responses of cranial motor and limb motor function to striatal dopamine depletion and (b) determine the differential effects of striatal dopamine depletion on the integrity of cranial motor and limb motor neural circuits. This paper details the use of a comprehensive battery of limb and cranial motor behavioral tasks and the application of intracortical microstimulation to assess corticospinal and corticobulbar circuits in a rodent model of PD. Our work suggests that striatal dopamine depletion does differentially affect cranial and limb motor function and corticospinal and corticobulbar circuits. Further, we propose that cranial motor impairments in PD may be mediated by pathology both within and outside nigrostriatal dopamine system. Learning outcomes: Readers will be able to (a) describe a set of motor tests used to assess limb motor and cranial motor function in an animal model of Parkinson's disease, (b) understand the application of intracortical microstimulation to assess corticospinal and corticobulbar circuits, (c) describe the differential effects of dopamine depletion on limb motor and cranial motor function in a rodent model of PD, and (d) understand the potential role of dysfunction outside the nigrostriatal system mediating cranial motor impairments in Parkinson's disease. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the time-course of changes in masseter motoneuron pool excitability following transcranial magnetic stimulation of motor cortex, and relate this to the duration of the masseter cortical silent period (CSP). Methods: Surface EMG was recorded bilaterally from masseter and digastric muscles in 13 subjects. Focal TMS was applied at 1.3× active motor threshold (AMT) to motor cortex of one hemisphere to elicit a muscle evoked potential (MEP) and silent period bilaterally in masseter as subjects maintained an isometric bite at ∼10% maximum. With jaw muscles relaxed, a servo-controlled stretcher evoked a stretch reflex in masseter which was conditioned by TMS (1.3× AMT) at 14 different conditioning–testing intervals. There were 20 trials at each interval, in random order. TMS evoked no MEP in resting masseter, but often produced a small MEP in digastric. Results: Mean (±SE) masseter CSP was 67±3ms. The masseter stretch reflex was facilitated when stretch preceded TMS by 8 and 10ms, which we attribute to spatial summation of corticobulbar and Ia-afferent excitatory inputs to masseter. Masseter stretch reflex amplitude was reduced when TMS was given up to 75ms before stretch, and for up to 2ms afterwards. Conclusions: We conclude that descending corticobulbar activity evoked by TMS acts bilaterally on brainstem interneurons that either inhibit masseter motoneurons or increase pre-synaptic inhibition of Ia-afferent terminals for up to 75ms after TMS. The reduction of masseter motoneuron pool excitability following TMS has a similar time-course to the CSP. Significance: In contrast to the situation for spinal and facial (CN VII) muscles, the masseter CSP appears to have no component that can be attributed exclusively to cortical mechanisms. Abnormalities in the masseter cortical silent period observed in neurological conditions may be due to pathophysiological changes at cortical and/or sub-cortical levels. [Copyright &y& Elsevier]

Abstract: Objective: To determine whether a single hemisphere exerts distinct inhibitory influences over masseter muscles on each side, and to compare features of the masseter cortical silent period (CSP) evoked by transcranial magnetic stimulation (TMS) with previous reports from limb and other cranial muscles. Methods: Focal TMS was applied over the motor cortex jaw area in 14 normal subjects. In one experiment, TMS intensity was constant (1.1 or 1.3× active motor threshold, T) and masseter muscle activation varied from 10% to 100% of maximal. In another experiment, muscle activation was constant (20% maximal) and TMS intensity varied from 0.7 to 1.3T. Results: In all subjects, TMS evoked a silent period of similar duration in masseter muscles on both sides. Masseter CSP duration increased at higher TMS intensities, but was not affected by muscle activation level or the size of the excitatory response evoked by TMS. Weak TMS produced a bilateral CSP without short-latency excitation. The masseter CSP was short (∼100ms at 1.3T), yet this was not due to maintenance of excitatory drive from the unstimulated hemisphere, as the masseter CSP was not prolonged with dual-hemisphere TMS. Conclusions: Intracortical inhibitory circuits activated by TMS have a relatively weak effect on corticotrigeminal neurons supplying masseter, and effects are equivalent for corticobulbar efferents directed to contralateral and ipsilateral masseter motoneuron pools. Significance: Trigeminally innervated masseter muscles exhibit weak, bilaterally symmetric inhibition following focal TMS. This method can be used to investigate abnormalities of intracortical inhibition in movement disorders or focal lesions affecting the masticatory muscles in humans. [Copyright &y& Elsevier]

A long-latency stretch reflex (LLSR) has been described in the human masseter muscle, but its pathway remains uncertain. To investigate this, the excitability of corticomotoneuronal (CM) cells projecting to masseter motoneurons during the LLSR was assessed with transcranial magnetic stimulation (TMS). A facilitated response to TMS would be evidence of a LLSR pathway that traverses the motor cortex. Surface electromyogram electrodes were placed over the left or right masseter, and subjects (n=10) bit on bars with their incisor teeth at 10% of maximal electromyographic activity (EMG). Servo-controlled displacements were imposed on the lower jaw to evoke a short- and long-latency stretch reflex in masseter. TMS intensity was just suprathreshold for a response in contralateral masseter. Trials consisted of: (1) stretch alone, (2) TMS alone, and (3) TMS with a preceding conditioning stretch at varied conditioning-testing (C-T) intervals chosen to combine TMS with the short-latency stretch reflex (3 ms, 5 ms) and the LLSR (23–41 ms). Masseter EMG was rectified and averaged. With TMS alone, mean (± SE) MEP area above baseline was 56±9%. The area of masseter MEPs above baseline in the C-T trials was calculated from each EMG average following subtraction of the response to stretch alone. Conditioning muscle stretch had no significant effect on masseter MEPs evoked by TMS with any C-T interval (ANOVA; P=0.90). In addition, subjects were unable to modify the SLSR or LLSR by voluntary command. It is concluded that the long-latency stretch reflex in the masseter does not involve the motor cortex and is not influenced by "motor set". [ABSTRACT FROM AUTHOR]

Abstract: The Miller Fisher syndrome, Guillain–Barre syndrome and Bickerstaff''s brainstem encephalitis are related conditions in which anti-GQ1b antibody positivity occur in varied frequencies. This report demonstrates the presence of corticobulbar and corticospinal dysfunction in BBE, by means of a novel transcranial magnetic stimulation technique. It further supports the presence of protean manifestations in anti-GQ1b IgG antibody-positive spectrum of disorders. [Copyright &y& Elsevier]

Objective: To characterize the organization of speech- and language-related white matter tracts in children with developmental speech and/or language disorders.Study Design: We collected magnetic resonance diffusion-weighted imaging data from 41 children, ages 9-11 years, with developmental speech and/or language disorders, and compared them with 45 typically developing controls with the same age range. We used probabilistic tractography of diffusion-weighted imaging to map language (3 segments of arcuate fasciculus, extreme capsule system) and speech motor (corticobulbar) tracts bilaterally. The corticospinal and callosal tracts were used as control regions. We compared the mean fractional anisotropy and diffusivity values between atypical and control groups, covarying for nonverbal IQ. We then examined differences between atypical subgroups: developmental speech disorder (DSD), developmental language disorder, and co-occurring developmental speech and language disorder.Results: Fractional anisotropy in the left corticobulbar tract was lower in the DSD than in the control group. Radial and mean diffusivity were higher in the DSD than the developmental language disorder, co-occurring developmental speech and language disorder, or control groups. There were no group differences for any metrics in the language or control tracts.Conclusions: Atypical development of the left corticobulbar tract may be a neural marker for DSD. This finding is in line with reports of speech disorder after left corticobulbar damage in children and adults with brain injury. By contrast, we found no association between diffusion metrics in language-related tracts in developmental language disorder, and changes for language disorders are likely more complex. [ABSTRACT FROM AUTHOR]

Object: The human ventral sensorimotor cortex (vSMC) is involved in facial expression, mastication, and swallowing, as well as the dynamic and highly coordinated movements of human speech production. However, vSMC organization remains poorly understood, and previously published population-driven maps of its somatotopy do not accurately reflect the variability across individuals in a quantitative, probabilistic fashion. The goal of this study was to describe the responses to electrical stimulation of the vSMC, generate probabilistic maps of function in the vSMC, and quantify the variability across individuals., Methods: Photographic, video, and stereotactic MRI data of intraoperative electrical stimulation of the vSMC were collected for 33 patients undergoing awake craniotomy. Stimulation sites were converted to a 2D coordinate system based on anatomical landmarks. Motor, sensory, and speech stimulation responses were reviewed and classified. Probabilistic maps of stimulation responses were generated, and spatial variance was quantified., Results: In 33 patients, the authors identified 194 motor, 212 sensory, 61 speech-arrest, and 27 mixed responses. Responses were complex, stereotyped, and mostly nonphysiological movements, involving hand, orofacial, and laryngeal musculature. Within individuals, the presence of oral movement representations varied; however, the dorsal-ventral order was always preserved. The most robust motor responses were jaw (probability 0.85), tongue (0.64), lips (0.58), and throat (0.52). Vocalizations were seen in 6 patients (0.18), more dorsally near lip and dorsal throat areas. Sensory responses were spatially dispersed; however, patients' subjective reports were highly precise in localization within the mouth. The most robust responses included tongue (0.82) and lips (0.42). The probability of speech arrest was 0.85, highest 15-20 mm anterior to the central sulcus and just dorsal to the sylvian fissure, in the anterior precentral gyrus or pars opercularis., Conclusions: The authors report probabilistic maps of function in the human vSMC based on intraoperative cortical electrical stimulation. These results define the expected range of mapping outcomes in the vSMC of a single individual and shed light on the functional organization of the vSMC supporting speech motor control and nonspeech functions.

Background: Recent evidence suggests that motor training may be beneficial for slowing the onset of motor impairments in Parkinson's disease (PD)., Objective: To examine the impact of targeted rehabilitation on limb motor and cranial motor function and the corresponding corticospinal and corticobulbar circuits in a rodent model of PD., Methods: Baseline performance of limb (reaching) and cranial (licking) motor function were established prior to and 6 weeks following unilateral intrastriatal 6-hydroxydopamine (6-OHDA) infusions. Animals then received 6 weeks of limb motor rehabilitation (LMR) or cranial motor rehabilitation (CMR), after which motor performance was reassessed. Intracortical microstimulation (ICMS) was used to generate motor maps of corresponding corticospinal (forelimb) and corticobulbar (tongue) movement representations within the motor cortex ipsilateral to the 6-OHDA infusion. Quantitative tyrosine hydroxylase (TH) immunohistochemistry was performed to determine levels of striatal TH depletion in 6-OHDA animals using near infrared densitometry., Results: (1) unilateral intrastriatal dopamine depletion impaired both reaching accuracy and lick force; (2) targeted LMR ameliorated impairments in reaching performance; however, CMR did not improve lick force impairments; (3) unilateral dopamine depletion significantly reduced forelimb but not tongue motor map topography; (4) LMR partially restored forelimb motor maps, whereas CMR did not alter tongue motor maps; and (5) significant correlations were observed between skilled reaching accuracy, forelimb motor map area, and TH depletion, but no relationships were revealed for cranial motor function, motor maps, or TH depletion., Conclusions: These data demonstrate dissociation between striatal dopamine depletion, limb versus cranial motor function, and targeted motor rehabilitation in a rodent model of PD.