Journal ofNeurology, Neurosurgery, and Psychiatry 1996;60:41-50 41

Jaw movement dysfunction related to Parkinson's J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.41 on 1 January 1996. Downloaded from disease and partially modified by levodopa

Lee T Robertson, John P Hammerstad

Abstract also have difficulties in the production of clear Objectives-To test the hypotheses that speech5 and with the automatic clearing of the Parkinson's disease can differentially throat or swallowing.3 Although the same produce deficits in voluntary and rhyth- peripheral structures are involved in various mic movements, which involve differ- oral motor acts, such as speaking, swallowing, ent neuronal circuits, and that levodopa or chewing, distinct basal ganglia circuits may treatment improves specific components be used to generate the various motor pat- of the motor deficit. terns.6 The neural circuits involved in volun- Methods-Patients with idiopathic tary movement of the may be Parkinson's disease and control subjects different from those used for force production were tested on a series of jaw motor tasks whereas those circuits regulating chewing may that included simple voluntary move- include portions of circuits for voluntary ment, isometric clenching, and natural movement and force as well as additional cir- and paced rhythmic movements. Jaw cuits to process specific sensory input. A major movements were measured by changes in basal ganglia circuit is the projection from the electromagnetic fields and EMG activity. globus pallidus and substantia nigra reticulata, Patients with Parkinson's disease with via the thalamus, to the primary motor cortex, fluctuations in motor responses to lev- the supplementary motor cortex, and the pre- odopa were tested while off and on. motor area. Animal studies suggest that these Results-During the off state, patients cortical areas help to control the initiation, with Parkinson's disease were signifi- direction, force, and internal guidance of vol- cantly worse than the control subjects on untary movements.68 A circuit that may influ- most tasks. The deficits included a ence rhythmic jaw movements is a small direct decrease in amplitude and velocity during projection from the substantia nigra reticulata jaw opening and closing, aberrant pat- to brain stem neurons, which have connec- terns and low amplitude of EMG activity tions with the trigeminal motor complex.9 10 during clenching, and low vertical ampli- Little information is available on how tude and prolonged durations of Parkinson's disease affects the motor control during rhythmic movements. No decre- of the jaw. Connor and Abbs" showed that ments were found in the amplitude of patients with Parkinson's disease had http://jnnp.bmj.com/ voluntary lateral jaw movements or the decreased peak velocities and increased dura- frequency of rhythmic movements. tions in a visually guided vertical jaw move- During the on state, improvements ment task. Abbs and associates3 reported that occurred in the patterns and level ofEMG patients with Parkinson's disease were unable activity during clenching and in the verti- to sustain a steady four to five second isometric cal amplitude and duration of occlusion force using jaw closing muscles. However, the during rhythmic movements, although a changes in velocity and force occurred in Department of significant decrement occurred in the lat- patients receiving dopamine replacement, on October 2, 2021 by guest. Protected copyright. Biological Structure eral excursion ofthe jaw. which may have produced a motor deficit and Function, School Conclusions-Parkinson's disease affects of Dentistry, Oregon because of dyskinesia.4 Karlsson and cowork- Health Sciences the central programming of functionally ers'2 studied patients both on and off levodopa University, Pordand, related muscles involved in voluntary and treatment and showed that levodopa increased OR, USA rhythmic jaw movements and levodopa the duration of the chewing cycle and the L T Robertson replacement influences only certain opening and closing velocities during Department of peanut Neurology, School of aspects of jaw movement, most likely chewing. Medicine, Oregon those requiring sensory feedback. The present study examines the effects of Health Sciences Parkinson's disease and the effect of dopamine University, Portland, CT Neurol Neurosurg OR, USA Psychiatry 1996;60:41-50) replacement on voluntary jaw movements, jaw J P Hammerstad clenching, and rhythmic jaw movements. A Correspondence to: battery of jaw motor tasks was used to discern Dr Lee Robertson, Keywords: mastication; Parkinson's disease; levodopa Department of Biological possible involvement of different neural cir- Structure and Function, cuits (for example, voluntary jaw movements Oregon Health Sciences Orofacial motor abnormalities have long been that likely involve University, 611 S W Campus connections with the motor Drive, Portland, OR 97201, recognised in Parkinson's disease. -3 Included cortical areas versus rhythmic movements that USA. in most textbook descriptions of Parkinson's may include connections with brain stem neu- Received 30 March 1995 disease is hypokinesia of the muscles of facial rons), differences and in revised form among various variables of 28 June 1995 expression and a reduced eye blink rate, movement (for example, velocity, amplitude, Accepted 7 September 1995 resulting in a mask-like face.4 Many patients or force), and differences between internal and 42 Robertson, Hammerstad

external signals to organise rhythmic jaw small magnet was glued to a point below the J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.41 on 1 January 1996. Downloaded from movements. By testing patients with lower central and changes in the elec- Parkinson's disease with major fluctuations in tromagnetic fields were detected by magne- their motor response to levodopa (the on-off tometers mounted on a lightweight set of phenomenon), we could determine whether eyeglass frames worn by the subject. The kine- Parkinson's disease, as manifested during the siograph was interfaced with a microcomputer off state, affects particular types of jaw motor for data display and analyses. control and whether acute levodopa treat- Recordings of the EMG activity of the right ment, during the on state, is useful for all types and left temporalis and masseter muscles were or only specific classes of jaw motor deficits. obtained with bipolar, silver-silver chloride EMG electrodes placed in standardised posi- tions on the skin over each pair of muscles. Subjects and methods For the jaw clenching task, the EMG activity SUBJECTS was differentially amplified, bandpass filtered We tested eight patients (six men and two (30 to 500 Hz), and full wave rectified. women with a mean age of 53-7 years) with idiopathic Parkinson's disease (average dura- EXPERIMENTAL DESIGN AND PROCEDURES tion nine years) and 11 control subjects (nine Patients with Parkinson's disease were evalu- men and two women with a mean age of 54-4 ated in two one-hour test sessions. The first years) who were free of signs of neurological test session was done while the patients were disease. Routine examinations of the orofacial in the off state and the second test session region were made and included an examina- began one hour after the patients took their tion of intraoral structures; palpation of the usual oral dose of carbidopa-levodopa (the on temporomandibular joints, muscles of mastica- state). A single test session was used for most tion, and associated muscles and tissues; and control subjects because no difference was an assessment of the range of movement of the found between the first and second test session mandible and any accompanying pain or joint for three subjects who were tested in two one- sounds. All subjects had most of their normal hour sessions with an hour of rest between ses- dentition and no signs of . Two sions and because the performance of the controls and two patients with Parkinson's dis- control subjects was not significantly different ease had condyle displacement during the from the results of a pilot study, which showed opening phase of the movement, but no evi- no difference between two separate one-hour dence of pain and tenderness in the region of sessions. the jaw muscles and joints. All patients with The jaw motor tasks were performed while Parkinson's disease showed some reduction in the subject sat upright on a chair. Three types the range of normal jaw movement. of jaw motor tasks were given simple volun- Patients were specifically selected because tary jaw movements, brief isometric they displayed an on-off oscillating clinical clenching, and natural and paced rhythmic response to levodopa and did not show signs of movements and were done in the same oral-buccal-lingual dyskinesia. For the data col- sequence for all subjects. All tasks began and lection, the patients with Parkinson's disease ended with intercuspal contact. The subjects had refrained from all medication for 10 to 12 were given simple verbal instructions and hours and showed posture and locomotion dis- allowed to practice the tasks two to three http://jnnp.bmj.com/ turbances when they entered the laboratory. times. Each task involved several trials with During their off state, the patients with about 30 to 60 seconds of rest between trials; Parkinson's disease reported that they had con- no information was given to the subject siderable difficulty with activities of daily living, regarding their performance. were unable or barely able to walk, and several The voluntary jaw movements included reported having difficulty chewing or an normal vertical opening and closing of the

entire meal. Their motor disability during the mouth, opening the mouth as wide as possible, on October 2, 2021 by guest. Protected copyright. off state ranged from stage 2 5 to 5 0 on the vertically opening and closing the mouth as Hoehn and Yahr scale.'3 After being tested in fast as possible, and right to left horizontal jaw the off state, the patients took their usual morn- movements. Changing the conditions of the ing oral dose of carbidopa-levodopa (Sinemet). task for example, from normal opening to Within one hour, they were independent in opening wide or fast differentially activates ambulation and most other activities; their dis- various muscle groups.'4 Measurements were ability according to the Hoehn and Yahr scale made on the amplitude, velocity, and variability ranged from stage 2 0 to 2 5, with an average of the jaw trajectory. For the isometric jaw improvement of 1 4 from the off state. At the clenching task, the subjects were required to end of the test session, the patients took their bite on a piece of gauze using their molar routine doses of other medications (including teeth. Due to the wide range in age and clinical Sinemet-CR, selegiline hydrochloride, per- status of the patients with Parkinson's disease, golide mesylate, and bromocriptine mesylate). the level of force during clenching was not All subjects gave informed consent for the pro- specified. Each subject performed a series of cedures used in this study. three two second maximal effort jaw clenches, with one second of rest between each clench. JAW POSITION AND MUSCLE ACTIVITY The series was repeated three times with one Three dimensional measurement of mandibu- minute of rest between each series. Measure- lar movement was achieved with a model K6 ments were made of the pattern, sequence, Kinesiograph (MyoTronics, Seattle, WA). A and amplitude of muscle activity. J7aw movement dysfunction related to Parkinson's disease and partially modified by levodopa 43

The natural and paced rhythmic jaw move- were collected and another set of data was col- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.41 on 1 January 1996. Downloaded from ments were evaluated by unilateral gum chew- lected during the last 10 seconds of each one ing. The cadence of the natural versus the minute trial for both the natural and paced paced chewing provided information on inter- chewing tasks. A comparison between the first nal timing regulation versus the ability of the and last 10 seconds of data provided another subject to follow a rhythmic external signal. measure of fatigue. Data were collected on the For the natural chewing, the subjects were rate and variability of the rhythmic move- instructed to first soften a piece of gum by ments, the vertical amplitude, and the dura- chewing and then to chew the gum in their tion of occlusion, although accurate habitual manner on the right side for 60 sec- measurements of occlusion could not be made onds and, after a one minute rest, to repeat the for the 2/s and 3/s paced conditions. task for another minute. Paced rhythmic jaw movements at various frequencies were STATISTICAL ANALYSIS included to disclose differences in jaw kine- Statistical analyses were performed separately matics and velocity.'5 The paced rhythmic jaw for the results from each task. Student's t test movement task involved making vertical jaw was used to the compare the differences movements with contact in time with a between the control subjects and patients with one, two, or three second auditory signal. Parkinson's disease. Differences in the perfor- Increasing the frequency of the paced move- mance between the off state (non-drug condi- ment also provided an indication of fatigue, as tion) and the on state (dopamine replacement more work was done at the higher frequencies condition) for each task were analysed using a than at 1/s. The paced rhythmic movements repeated measures analysis of variance were done for one minute and then repeated (ANOVA), followed by post hoc Student's t after a one minute rest. About 10 seconds after tests. The criterion for significance was set at the subject began chewing, 10 seconds of data P < 0 05.

Figure 1 Kinematics of three normal opening and closingjaw movements for a control subject (A) and two patients with Parkinson's disease (B). The control subject's traces were from ._ & two test sessions separated by one hour of rest; the data .A for the patients with * Parkinson's disease were collected during the off and -,. on states. The vertical plane represents the maximal vertical opening between the start position and the change between opening and closing phases the of cycle; the horizontal http://jnnp.bmj.com/ plane represents velocity during opening (traces on 7~~~~~~~~.- the right side) and closing (left side) of the cycle. The closing phase begins when the opening velocity returns to zero. During both off and on states, the patients had lower vertical

amplitude and decreased on October 2, 2021 by guest. Protected copyright. velocity than the controls. During the on state, the opening amplitude increasedfor one patient (P03) and the opening velocities increasedfor both patients (P03 and P05). A A The midline is indicated by the small vertical arrow.

.'-- ,f ' ."_

A ~~~~~~~~~~A 44 Robertson, Hammnerstad

Figure 2 Means (SD) J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.41 on 1 January 1996. Downloaded from (error bars) of vertical amplitude (A) during niornal opening and zwide opening, anid of the velocity (B) dur'ng nominal andfast openinlg and closing. During off and onl states, the patienits zvith Parkinson 's disease had a reduced vertical amplitude for both normnal opening and wide opening tasks and slozver velocities dur'ng normnal anzdfast opening anid closing than the controls. *P < 0Q05; **P < o.oJ; ***P < 0*001 v controls.

Results worse than the control's performance. The During the off state, patients with Parkinson's other patient (P05) slightly reduced his maxi- disease experienced some difficulty doing mal vertical opening and closing velocity, but most of the jaw motor tasks, including one slightly increased his opening velocity. patient who was unable to move his jaw later- Patients with Parkinson's disease were sig- ally and two who were unable or declined to nificantly worse than the control subjects for do the paced chewing at 3/s In the on state, maximum vertical amplitudes and velocities the degree of improvement or decrement var- for normal opening and closing, opening wide, ied among the patients and the tasks. Six of and opening fast tasks (fig 2). During the off the eight patients with Parkinson's disease state, the maximal vertical amplitude during improved their performance on rhythmic jaw normal opening by patients was about 30% movements and improved or showed no lower than the amplitude of the control sub- change in jaw clenching, and two of these jects. During the on state, four patients had a patients also improved their vertical voluntary 5% to 15% increase in vertical amplitude jaw movements. However, one of the eight compared with the off state but three had a patients only improved his voluntary vertical 30% to 61% decrease in amplitude. The aver- jaw movements and one had performance age vertical amplitude during the on state was deficits on all the behavioural tasks. significantly (P < 0-001) lower than the con- Unexpectedly, most patients reduced their trol condition but was not significantly differ- ability to move the jaw laterally during the on ent from the off state. For the opening wide http://jnnp.bmj.com/ state. In this section, we describe for each task task, there was little change between the off the differences between the patients with and on states, with the vertical amplitudes for Parkinson's disease during the off state and both off and on states being significantly less the control subjects and then the differences (P < 0 01) than the controls. between the off and on states. The maximum velocities during normal opening and closing were significantly

VOLUNTARY JAW MOVEMENTS (P < 0-05) slower for patients with Parkinson's on October 2, 2021 by guest. Protected copyright. Even for the simplest voluntary movement of disease during the off state than for the control opening and closing the mouth, patients with subjects (fig 2B). The average opening and clos- Parkinson's disease had restricted movement, ing velocities did not change during the on state both in amplitude and opening and closing compared with the off state. When making fast velocities, although the amplitudes and veloci- vertical jaw movements, the control subjects ties were generally consistent from trial to increased their opening and closing velocities by trial. Figure 1 shows examples of the ampli- about 50% in comparison with the normal situa- tudes and velocities of three normal opening tion. The patients with Parkinson's disease also and closing cycles for a representative control increased their velocity by about 42% but they and two representative patients with were still significantly (P < 0 001) slower than Parkinson's disease. During the off state, the the control subjects for both the opening and patients showed a reduced maximal vertical closing phases. No significant differences were amplitude and opening velocity in comparison found between the off and on states for the with the control subjects, one patient (P03) opening and closing velocities or for the normal also had a slow closing velocity, and one (P05) versus the fast conditions. had some trial to trial variability in his closing The lateral movement of the jaw was velocities (fig iB). Comparing the on state included in the test battery because it was a with the off state, one patient (P03) increased movement that the subject did not make rou- his maximal vertical opening and the opening tinely, so it required conscious control. The and closing velocities, although they were still task required several practice trials by both J7aw mnovemnent dysfunction related to Parkinson 's di'sease anzd partially, miodified by, levodopa 445

Figure 3 Fronital plane Off On Off On J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.41 on 1 January 1996. Downloaded from vi'ew of the ki'nemtati.cs Of lateralljaw movements Of ------seveni pati'ents wi'th Parkinson's di'sease (onie ------was unable to mtove hi's jaw co laterally during the off state) and two representative conitrol P07- P05 subjects. For the pati'ents, ------the first and seconid trials are shown for both off and ------on states; for the controls, the and second trials Co first ------are shown for each subject. CN4

Although the ki'nemiatics ------between trials were simtilar, considerable variability occurred between patients. Five patients with. ------Parkinison's di'sease (P07, P01, P06, P03, and P05) ------had less total right to left lateral excursion during the on state than during the off state. Some subj'ects ------requi'red a final lateral ------mnovemtent to achi'eve i.ntercuspal occlusion ...... (arrow). ------P02, -P-0-1 ------

------

------

------6 -P-0 -P-0-8 ------

Controls

------http://jnnp.bmj.com/

------

------

E E on October 2, 2021 by guest. Protected copyright. P03 0

5 mm 2nd trial

groups and one patient was unable to make resulted in a significant (P < 0-05) difference

lateral jaw movements during the off state between off and on states. Six patients with

(this patient's data were not included in the Parkinson's disease were worse during the on statistical computations). Variability in the state than during the off state, including two

vertical and the right to left horizontal ampli- with reduced total lateral excursions of more tudes of the movement was evident among the than 70% (for example, the average for patient

controls and patients with Parkinson's disease P07 went from 15 mm to 6-6 mm total excur- (fig 3). However, all except one patient (P06) sions). For several patients, the kinematics of

had consistent trial to trial kinematics, and all the lateral movement during the on state were except two patients (P06 and P08) had sym- also more complex than during the off state metric right to left movements, The right to and often included difficulties in achieving left distances averaged 18-7 mm for the con- final intercuspal occlusion (fig 3: P01, P06, trols and 15S4 mm for patients and were not P03, and P02). significantly different.

During the on state, the total right to left ISOMETRIC JAW CLENCHING

excursions decreased by about 6 1 mm, which During the off state, none of the patients with 46 Robertson, Hammerstad

Figurc 4 Rectified EMG

A Control J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.41 on 1 January 1996. Downloaded from activity of the left temnporalis (LT) and iniasseter (LM) muscles during three isomzetric jaw cleniches for a representative conitrol subject (A) and three patienits with LT Parkinson 's disease during the off (B) and On (C) states. In the representative LM conitrol subject (A), the left C09 mnasseter muscle had greater activity than the left temporalis muscle, which B was similarfor half of the Off state C On state control subjects whereas the reverse was true for the rest of the controls. During the off state, none of the patients had a nornal LT pattern ofEMG activity Y: (subject P01 had an EMG ------I---- pattern that zwas m1ost si7nilar to the control LM - patteni, zwhereas P06 was P01 the least simnilar). During the on state, an imnproved pattern ofEMG activity is represented by patients P01 and P06, whereas subject P05 represents little change. LT r~~~~~~------*------r------t--g A------r------o------t------<\ r---mJ----t------LM P05 ------J ---t-----W ------X ------l-- L

LT ------i------~~~~~~~~~~~~~~~~~~~~~~~~~~~~..i1i. Li_

LM P06 1 s

Parkinson's disease had a pattern of EMG mination of activity (fig 4C, P06). The activity to clenching that completely resembled absence of EMG activity during the rest phase the EMG pattern of control subjects, although corresponds with the absence of involuntary two patientsLS_had activity in one of the four movements jaw (mandibular dyskinesia) dur- muscles recorded that resembled the control ing the on state. The average peak amplitude condition (fig 4B, P01). The pattern of EMG of EMG activity (120 (SD 34) ,V) of the jaw http://jnnp.bmj.com/ activity for each two second episode of clench- closing muscles during clenching for patients ing by the control subjects consisted of a sharp with Parkinson's disease while in the off state onset of activity for each muscle that quickly was lower than the average (215 (SD 102) pV) reached peak amplitude and then gradually for control subjects, but they were not signifi- decayed until the verbal signal to relax, after cantly different. During the on state, the aver- which there was sharp, synchronous termina- age peak EMG activity increased by about tion of activity, followed an absence by of 28% but was not significantly different from on October 2, 2021 by guest. Protected copyright. activity during the rest phase (fig 4A). During the off state. the off state, patients with Parkinson's disease exhibited a variety of patterns of EMG activity RHYTHMIC JAW MOVEMENTS to clenching (fig 4B). The abnormal EMG pat- All subjects were easily able to chew the gum terns included no clear onset or offset of activ- for one minute and to make the paced move- ity, very low amplitude of activity in one or ments at 1/s and 2/s. Several controls and more of the muscles, a slow rise to peak ampli- patients with Parkinson's disease reported that tude, a rapid decay of activity, brief (< 1 s) sus- the movements at 3/s were fatiguing and that tained activity, and failure to return to baseline they had problems maintaining the frequency; during the rest period. two patients declined to preform the 3/s paced During the on state, five of the eight movement. However, no significant differ- patients showed improvements in the pattern ences were found in the cycle frequency or the of EMG activity, two had minimal change, vertical amplitude of the opening cycles and one was worse. Although no consistent between the first and last 10 seconds of the pattern of improvement was evident among one minute trial of normal chewing or for any the patients with Parkinson's disease, of the paced movements. Consequently, the improvements included an absence of inap- first and last 10 seconds of data were com- propriate activity during the rest phase (fig 4C, bined for the present analysis. P01), an increased duration of activity (fig 4C, The mean vertical amplitude of the opening P05), and a more well defined onset and ter- phase was significantly less (P < 0-05) for J7aw movement dysfunction related to Parkinson's disease and partially modified by levodopa 47

Figure 5 Mean (SD) of J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.41 on 1 January 1996. Downloaded from the vertical amplitude (A) and the duration of occlusion (B) during normal chewing and paced jaw movements (no measurements of occlusion were made for the 2 and 3/s paced tasks). During the offstate, the vertical amplitude was significantly reduced during normal chewing and the 1/s paced condition and the duration ofocclusion were significantly increased during the 1/s paced task. *P< 0-05.

Patients with Parkinson's disease during the off cant (P < 0 05) difference between the off and state than for the control subjects for normal on states but no significant difference between chewing and the 1/s paced movement (fig 5A). the on state and the controls (fig 5A). The The average vertical amplitudes during the 2/s duration of occlusion for the 1/s paced move- and 3/s paced movement were also lower than ment during the on state was also similar to the controls but were not significantly differ- the control condition. In addition, the two ent. During the off state, the duration of the patients who were unable to do the 3/s paced occlusal phase during normal chewing was movement during the off state, had an appro- similar to the control subjects, but was signifi- priate frequency and vertical amplitudes dur- cantly (P < 0 05) longer than the control ing the on state. condition during the 1/s paced movement (fig 5B). The vertical amplitude during the normal Discussion chewing and the 1/s paced movement The present study shows that Parkinson's dis- increased slightly more than 4 mm between ease affects more variables of motor control of the off and on states. This resulted in a signifi- the jaw than indicated by previous reports3 11 12

Figure 6 Percentage difference between the Voluntirv jawaN vemen'etS control subjects and the patients with Parkinson's disease during the offstate http://jnnp.bmj.com/ and between the off and on states for variables of the jaw motor tasks. Parkinson's disease was associated with deficits in all categories except the frequency of rhythmical jaw movements. Levodopa treatment (on state) produced improvement in on October 2, 2021 by guest. Protected copyright. the amplitude ofEMG activity during clenching and in the opening Clench .X119 amplitude and duration of occlusion during the rhythmicaljaw movements, but caused a decrease in the amplitude of the lateraljaw Rhythm-iic jaw movements movement and, in a few patients, a decrease of vertical amplitude during normal opening. 48 Robertson, Hammerstad

and that dopamine replacement seems to tar- formance decrements.4 Because the patients J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.41 on 1 January 1996. Downloaded from get only specific jaw motor deficits (fig 6). with Parkinson's disease were specifically During the off state, Parkinson's disease is selected to be free of cranial-cervical dyskine- associated with large deficits in several vari- siae, they did not show any oral-buccal-lingual ables of voluntary jaw control, jaw clenching, dyskinesia during the on state. Further, during and rhythmic jaw movements. Most of the vol- the on state of isometric jaw clenching, the untary jaw movements were of low amplitude absence of masseter and temporalis EMG and slowly executed, similar to the characteris- activity during the rest phase corresponds with tic bradykinesia of voluntary limb move- the absence of involuntary jaw movements. ments,4 the EMG activity was abnormal in all Even the patient with decrements on all the patients with Parkinson's disease during iso- jaw motor tasks had no obvious dyskinesia. In metric jaw clenching, and the vertical ampli- this patient, levodopa resulted in considerable tude during chewing was low. However, improvement in posture and locomotion, but Parkinson's disease had little influence on hindered her fine hand movements, such as cycle frequency during either normal chewing writing, which may correspond to her deficits or paced movements during the off state and in jaw motor control. In this discussion, we only a few patients had difficulties making lat- evaluate the influence of Parkinson's disease eral jaw movements or had prolonged occlusal and levodopa on the various jaw motor tasks durations during rhythmic jaw movements. An and then consider how levodopa treatment oral dose of levodopa (the on state) produced may affect jaw motor control, while acknowl- improvements, in comparison with the off edging that for a few patients other unknown state, in the jaw clenching and in the vertical mechanisms may be operating. amplitude and duration of occlusion during Disease or drug induced alterations of spe- rhythmic movements. A few patients also cific neural circuits may account for perfor- improved the velocity of their fast voluntary mance decrements during the off state or jaw movements. However, levodopa treatment between off and on states. The voluntary jaw also resulted in a decreased amplitude of lat- movement tasks used in the present study eral jaw movements and, in a few patients, the were designed to test the pallidothalamocortical vertical amplitude during normal jaw opening. connections with different cortical motor A limitation of the present study was the areas,(-) which then project to interneurons of variability between patients of the motor the gigantocellar reticular formation near the impairments, which was most likely related to trigeminal motor nucleus.'8I'9 In the present the unique features of the disease process and study, Parkinson's disease resulted in deficits the variability of the therapeutic benefits of in the velocity and vertical amplitude of volun- dopamine replacement. Patients with tary jaw movements made on command, Parkinson's disease displayed a wide range of movements that are likely regulated by motor performance on each task during both the off areas of the cortex. Connor and Abbs" also and on states. For example, most patients had have noted that Parkinson's disease results in normal lateral jaw movements during the off decrements in the velocity:amplitude ratios of state but one patient was completely unable to visually guided jaw movements, but not for move his jaw laterally. The changes in perfor- similar movements made during speech. mance related to levodopa ranged from one These investigators" suggested that the decre- patient who achieved improvements on all ment during the visually controlled task was http://jnnp.bmj.com/ tasks to another who was worse on all tasks. because the task was unfamiliar or unnatural, The individual differences were not correlated whereas the jaw movements made during with the severity or duration of the disease, the speech were embedded in a natural sequence. degree of improvement of the Hoehn and The simple task of voluntary opening and clos- Yahr scores between the off and on states, or ing of the mouth, used in the present study, the patients' age. was obviously a familiar task, which suggests

Some performance deficits of the patients that the deficit was probably in the cortical on October 2, 2021 by guest. Protected copyright. with Parkinson's disease may be related to control of voluntary movement. This idea is temporomandibular disorders (TMDs) supported by the similar deficits for normal because of their limited range of vertical and opening versus wide opening and for normal lateral movements and the abnormal pattern versus fast opening and closing, though the of EMG activity. Miller4 described neuromus- different tasks activated different combina- cular changes of TMD, including decreased tions of muscles and sensory feedback.'4 EMG activity during clenching, increased Although patients with Parkinson's disease duration of the masticatory discharge, and could increase their amplitude and velocity of spastic discharges. Although the EMG activity jaw opening, their level was consistently below of the patients with Parkinson's disease that achieved by control subjects. These included some EMG characteristics of TMD, results are consistent with the recent findings none of the patients showed symptoms of ten- for arm movements2' and postural adjust- derness and pain to palpation of their ments21 of an inability of patients with mandibular and cervical muscles, which is Parkinson's disease to scale up the magnitude most often the initial symptom of the TMD.'6 of a movement when increased speed or force is Further, there is little evidence to support the required. idea that variables of jaw movement and EMG Not all voluntary jaw movements were activity are good predictors of TMDs in affected by Parkinson's disease or unaffected asymptomatic subjects.7 by levodopa. The amplitudes of the lateral jaw Peak dose dyskinesia can account for per- movements during the off state were not dif- Jaw movement dysfunvction related to Parkinson 's disease anid partially modified by levodopa 49

ferent from control subjects, but during the on imised by comparing the same patient during J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.41 on 1 January 1996. Downloaded from state, were significantly reduced. This was just the off and on states, which showed that the opposite of the levodopa effects on vertical Parkinson's disease influenced both the pat- jaw movements. We initially expected that all tern and amplitude of EMG activity during voluntary jaw movements would have reduced clenching. Levodopa treatment produced amplitudes and that less practiced movements mixed effects, including improved onset and would have a greater deficit than the familiar offset of EMG activity and large increases in movements. The lateral jaw movement task EMG amplitude, although a few patients had was initially not easy for the patients to exe- decreases in amplitude. Although single unit cute, as they all required several practice trials. activity of neurons in the basal ganglia is Consequently, the lateral jaw movement task poorly correlated with EMG activity, ' a may have involved learning whereas the verti- reduction in thalamocortical activation may cal movement tasks were already well learned prevent the motor cortex from generating motor patterns. If the basal ganglia provide a appropriate commands. mechanism to suppress unwanted movements Rhythmic jaw movements that occur during during the acquisition of a movement," then mastication are mainly controlled by brain performance of the lateral movement should stem neurons. The basal ganglia can influence have been worse during the off state than that rhythmic jaw movements through direct pro- of the control subjects, which was not the case. jections from the substantia nigra reticulata to Another possible explanation is that the lateral parvicellular reticular neurons of the brain and vertical jaw movements involve different stem,"3" which form direct connections with neural circuits. For example, lateral jaw move- neurons controlling the jaw closing muscles.' ments have a different cortical representation Parkinson's disease influenced the vertical than the jaw closing representation in the amplitude and the durations of occlusion of motor cortex,2324 which may also occur for the internally (self induced) and externally paced other motor cortical areas. rhythmic movements, suggesting either that The negative effects of levodopa were also the tasks involved similar circuits for internal not expected. During the on state, patients and external control or that Parkinson's dis- with Parkinson's disease showed mild to severe ease does not influence the internal versus the reductions in the amplitude of the lateral jaw external control of a movement. Although movements, even though levodopa was associ- internal control versus synchronisation with an ated in these patients with improvements in external signal may involve separate neuronal various aspects of rhythmic movements and circuits,8 there is also evidence from animal jaw clenching. The negative effect of levodopa experiments that parts of the striatum, outside on a specific task is consistent with negative the motor region, are activated by both inter- effects of levodopa for lateral head move- nal and external stimuli before a motor ments23 and postural adjustments.2' Further response.3' 32 investigation will be required to decide Levodopa increased the vertical amplitude whether the deficit induced by levodopa in lat- and decreased the occlusion duration enough eral jaw movements is related to variables in that there was no significant difference the acquisition of the motor task, particularities between the on state and the control subjects. of the neuronal circuits, or other reasons. Karlsson et al ' noted similar findings for The isometric jaw clenching task was peanut chewing during off and on states. The http://jnnp.bmj.com/ included as another task involving the pallido- similarity of the results between gum chewing, thalamocortical circuit, particularly those con- vertical paced movements, and chewing nections with the primary motor cortex, which peanuts is remarkable, as the size, shape, and animal studies have shown to be important in hardness of the are known to influence regulating force.26 A deficit in force production the pattern of chewing movements, the and maintenance is suggested by the low level accompanying EMG activity, and the force-

of EMG activity during isometric jaw clench- time curves."33 4 on October 2, 2021 by guest. Protected copyright. ing by patients with Parkinson's disease, as the Because both the jaw clenching and the EMG activity during isometric clenching is rhythmic movements tasks benefited from lev- linearly related to the total tension force devel- odopa, they may share important common oped by the muscles.2 Reduced force produc- features, such as access to sensory stimuli. tion by patients with Parkinson's disease has Achieving appropriate force levels during been noted in tasks involving the upper clenching or chewing depends on feedback extremities28 and the orofacial muscles of the from receptors in the periodontal region of the lip, , and jaw.3 In the present study, all dentition, the temporal-mandibular joint, and patients showed some abnormal EMG activity the muscles and ligaments,"1 although animal during isometric clenching, although the peak studies have shown that muscle spindles or amplitude of EMG activity in patients with temporal-mandibular joint receptor afferents Parkinson's disease was not significantly dif- do not influence the frequency of rhythmic jaw ferent from the controls due to the high vari- movements.35 The dopaminergic circuits may ability between patients. Some of this participate in the processing of sensory infor- variability may have occurred because the mation or in the regulation of access of sensory instructions did not specify the amount of input to appropriate motor centres.2 Patients force to be reached, slight differences in the with Parkinson's disease show deficits in tests EMG electrode placement, and variations in of orofacial sensory function and sensorimotor facial dimensions and size of the jaw closing integration,2 although they also exhibit hyper- muscles.4 However, these factors were min- sensitivity to cutaneous stimuli as part of a 50 Robertson, Hammerstad

perioral reflex3' and alterations of various 15 Plesh 0, Bishop B, McCall W. Mandibular movements J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.41 on 1 January 1996. Downloaded from and jaw muscles' activity while voluntarily chewing at dif- trigemotrigeminal or trigemofacial reflexes.37 ferent rates. Exp Neuirol 1987;98:285-300. Thus the dopamine induced improvements of 16 Mohl ND, Dixon DC. Current status of diagnostic proce- dures for temporomandibular disorders. 7 Am Denit Assoc clenching may result from better processing of 1994;125:56-64. somatosensory stimuli within the brain stem 17 Lund JP, Widmer CG, Feine JS. Validity of diagnostic and reticular formation. monitoring tests used for temporomandibular disorders. .7 Dent Res 1995;74:1133-43. The results of this study support the idea 18 Olsson KA, Landgren S, Westberg KG. Location of, and peripheral convergence on, the interneurone in the disy- that Parkinsonism does not alter just one type naptic path from the coronal gyrus of the cerebral cortex to of jaw movement but affects several variables the trigeminal motoneurons in the cat. Exp Brain Res 1986;65:83-97. of voluntary and automatic movement, con- 19 Nakamura S, Muramatsu S, Yoshida M. Role of the basal firming the conclusions of animal studies.sx ganglia in manifestation of rhythmical jaw movement in rats. Braint Res 1990;S35:335-8. Parkinson's disease seems to affect behaviours 20 Montgomery EB, Nuessen J, Gorman DS. Reaction time that are probably controlled by ascending con- and movement velocity abnormalities in Parkinson's dis- ease under different task conditions. Ncurology 1991;41: nections with various cortical areas and 1476-81. descending projections to the brain stem. 21 Horak FB, Frank J, Nutt J, Shupert C. Reactive and pre- dictive scaling of postural responses in Parkinsonian However, the present data support a limited patients. Soc Neurosci Abstr 1991;17:1034. role for dopamine replacement in motor con- 22 Marsden CD, Obeso JA. The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson's dis- trol of the jaw. The dopaminergic system may ease. Brain 1994;117:877-97. impact the general motor control of the limbs 23 Hoffman DS, Luschei ES. Responses of monkey precentral cortical cells during a controlled jaw bite task. 7 and posture in various ways but, for jaw motor Neiurophysiol 1980;44:333-48. tasks, the dopaminergic influence seems 24 Murray GM, Lin L-D, Moustafa EM, Sessle BJ. Effects of reversible inactivation by cooling of the primate face restricted to a few tasks, possibly those involv- motor cortex on the performance of a trained tongue- ing a particular type of sensory feedback. protrusion task and a trained task. 7 Neuraphysiol 1991;65:511-30. 25 Weinrich M, Koch K, Garcia F, Angel RW. Axial versus We thank Dr Hiroshi Ueno for assistance with the oral exami- distal motor impairment in Parkinson's disease. nation and the use of the kinesiograph. We also appreciate the Neuralogy 1988;38:540-5. excellent technical assistance of Mary Dennis and Charell 26 Evarts EV, Fromm C, Kroller J, Jennings VA. Motor cortex Melfi. This work was supported by NIDR grant DE10395. control of finely graded forces. _7 NAurophysiol 1983;49: 1199-215. 27 Haraldson T, Carlsson GE, Dahlstrom L, Jansson T. 1 Hunker CJ, Abbs JH, Barlow SM. The relationship Relationship between myoelectric activity on masticatory between parkinsonism rigidity and hypokinesia in the muscles and bite force. Scand .7 Denit Res 1985;93: orofacial system: A quantitative analysis. Neurology 1982; 539-45. 32:755-61. 28 Stelmach GE, Teasdale N, Phillips J, Worringham CJ. 2 Schneider JS, Diamond SG, Markham CH. Deficits in oro- Force production characteristics in Parkinson's disease. facial sensorimotor function in Parkinson's disease. Ann Exp Brain Res 1989;76:165-72. Neuirol 1986;19:275-82. 29 DeLong MR, Georgopoulos AP. Motor functions of the 3 Abbs JH, Hartman DE, Vishwanat B. Orofacial motor con- basal ganglia as revealed by studies of single cell activity trol impairment in Parkinson's disease. Neurology 1987; in behaving primate. Adv Neurol 1979;23:137-53. 37:394-8. 30 Chandler SH, Goldberg LJ. Effects of pontomedullary 4 McDowell F, Cedarbaum JM. The extrapyramidal system reticular formation stimulation on the neuronal networks and disorders of movement. In: Joynt RJ, ed. Clinical neu- responsible for rhythmical jaw movements in the guinea -ology. Vol 3. Philadelphia: J B Lippincott, 1991: pig. _f Neurophysiol 1988;S9:819-32. 1-121. 31 Gardiner TW, Nelson RJ. Striatal neuronal activity during 5 Robbins JA, Logemann JA, Kirshner HS. Swallowing and the initiation and execution of hand movements made in speech production in Parkinson's disease. Ann Neurol response to visual and vibratory cues. Exp Brainl Res 1986;19:28-37. 1992;92: 15-26. 6 Hoover JE, Strick PL. Multiple output channels in the 32 Schultz W, Romo R. Role of primate basal ganglia and basal ganglia. Science 1993;259:819-21. frontal cortex in the internal generation of movements. I. 7 Alexander GE, Crutcher MD. Functional architecture of Preparatory activity in the anterior striatum. Exp Brain basal ganglia circuits: Neural substrates of parallel pro- Res 1992;91:363-84. cessing. TINS 1990;13:266-72. 33 Luschei ES, Goldberg LJ. Neural mechanisms of mandibu- http://jnnp.bmj.com/ 8 Mushiake H, Inase M, Tanji J. Neuronal activity in the pri- lar control: mastication and voluntary biting. In: mate premotor, supplementary, and precentral motor Brookhart JM, Mountcastle VB, Brooks VB, Geiger SR, cortex during visually guided and internally determined eds. Handbook of physiology, section 1, the nervous systemii. sequential movements. _7 Neurophysiol 1991 ;66:705-1 8. Volume ii. Motor control. Bethesda, MD: American 9 von Krosigk M, Smith AD. Descending projection from the Physiology Society, 1981:1237-74. substantia nigra and retrorubral field to the medullary 34 Wang J-S, Stohler CS. Textural properties of food used in and pontomedullary reticular formation. Eur _7 Neurosci studies of mastication. .7 Dent Res 1990,69: 1546-50. 1991 ;3:260-73. 35 Goodwin GM, Luschei ES. Effects of destroying spindle 10 Mogoseanu D, Smith AD, Bolam JP. Monosynaptic inner- afferents from jaw muscles on mastication in monkeys.. vation of trigeminal motor neurones involved in mastica- Neurophysiol 1974;37:967 -81. tion by neurones of the parvicellular reticular formation. 7 36 Caligiuri MP, Abbs JH. Response properties of the perioral on October 2, 2021 by guest. Protected copyright. Coanp Neurol 1993;336:53-65. reflex in Parkinson's disease. Exp Neurol 1987;98: 11 Connor NP, Abbs JH. Task-dependent variations in 563-72. parkinsonian motor impairments. Brain 1991; 114: 37 Cruccu G, Pauletti G, Agostino R, Berardelli A, Manfredi 321-32. M. Masseter inhibitory reflex in movement disorders. 12 Karlsson S, Persson M, Johnels B. Levodopa induced ON- Huntington's chorea, Parkinson's disease, dystonia, and OFF motor fluctuations in Parkinson's disease related to unilateral masticatory spasm. Electroencephalogr Clin rhythmical masticatory jaw movements. _7 Neurol Neurophysiol 1991;81:24-30. Neurosurg Psychiatry 1992;55:304-7. 38 DeLong MR, Crutcher MD, Georgopoulos AP. Primate 13 MacDonald JWC, Hannam AG. Relationship between globus pallidus and subthalamic nucleus: functional occlusal contacts and jaw-closing muscle activity during organization. .7 Neurophysiol 1985,53:530-53. tooth clenching: Part I. Prosthet Dent 1984;52:718-28. 39 Mink JW, Thach WT. Basal ganglia motor control. I. 14 Miller AJ. Craniomandibular muscles: their role in function and Nonexclusive relation of pallidal discharge to five move- form. Boca Raton: CRC Press, 1991:1-277. ment modes. _7 Neurophysiol 1991;65:273-300.