fibres of mammalian and human muscles. Histochemistry 1982;74:27-41. 16. Reichmann H, Hoppeler H, Mathieu-Costello 0, van Bergen F, Pette D. Biochemical and ultrastructural changes of skeletal muscle mitochondria after chronic electrical stimulation in rabbits. Pflugers Arch 1985;404:1-9. 17. Reichmann H, Johnson MA, Turnball DM. Sherratt HSA. The cytochemical determination of enzyme activities in single skeletal muscle fibres from patients with a partial deficiency of cytochrome oxidase. Biochem SOC Trans 1985;13:730. 18. Brooke MH, Kaiser KK. Three “myosin ATPase” systems: the nature of their pH lability and sulfhydryl dependence. J Histochem Cytochem 197018670-672. 19. Ballantyne B, Bright JE. Comparison of kinetic and endpoint microdensitometry for the direct quantitative histochemical assessment of cytochrome oxidase activity. Histochem J 1979;11:173-186. 20. Vetter C, Reichmann H, Pette D. Microphotometric determina-

tion of enzyme activities in type-grouped fibres of reinnervated rat muscle. Histochemistry 1984;80:347-351. 21. Seligman AM, Karnovsky MJ, Wasserkrug HL, Hauker JS. Nondroplet ultrastructural demonstration of cytochrome oxidase activity with a polymerising oamiophilic reagent, diaminobenzidine (DAB). J Cell Biol 1968;38:1-14. 22. Reichmann H, Pette D. Glycerolphosphate oxidase and succinate dehydrogenase activities in type IIA and IIB fibres of mammalian and human muscles. Histochemistry 1984;80:429-433. 23. Reichmann H, Srihari T, Pette D. Ipsi- and contralateral fibre transformations by cross-reinnervation: a principle of symmetry. Pflugers Arch 1983;397:202-208. 24. Wharton DC, Tzagoloff A. Cytochrome oxidase from beef heart mitochondria. Methods Enzymol 1967;10:245-250. 25. Byrne E, Dennett X, Trounce I, Henderson R. Partial cytochrome oxidase (a,) deficiency in chronic progressive external ophthalmoplegia: histochemical and biochemical studies. J Neurol Sci 1985;71:257-271.

Dopaminergic effects on simple and choice reaction time performance in Parkinson’s disease S.L. Pullman, MD; R.L. Watts, MD; J.L. Juncos, MD; T.N. Chase, MD; and J.N. Sanes, PhD

Article abstract-The present study examined whether premovement central neural processing in Parkinson’s disease was related to functional motor disability and plasma L-dopa concentration. Reaction time (RT) performance in simple and choice RT tasks was assessed while plasma L-dopa levels were controlled by continuous IV L-dopa infusion in five parkinsonianpatients. Five age-matched controls performed the same RT tasks for comparison. Simple RT for the patients was longer than the normal control RT at all infusion levels (p 5 0.005). However,choice RT was normal when the patients were “on,”but became prolonged as plasma L-dopa levels decreased (p 5 0.01). The results show that there are abnormalities of premovement central neural processing in Parkinson’s disease, and that simple and choice RTs are differentially affected by L-dopa replacement. This suggests that different neural mechanisms may be involved in the processing of these tasks. NEUROLOGY 1988;38:249-254

Reaction time (RT) studies can be used to analyze objectively premovement abnormalities in Parkinson’s disease and may offer insight into the nature of central neural processing related to motor performance.’ RT studies measure response initiation time in motor tasks and can be separated into simple and choice types, depending on the kind of information given prior to a stimulus to move. Simple RT tasks present a single preparatory cue, providing unambiguous information on the nature of the impending movement prior to the stimulus to move. Choice RT tasks utilize more than one preparatory cue, which results in the need to con-

sider more than one option for the impending movement and to choose the correct one when the stimulus to move is given. While previous studies have shown that parkinsonian patients exhibit prolongation of response initiation in simple RT in the presumably more complex choice RT task, response initiation has been found to be within normal range.ls3These studies have implied that performance in choice RT tasks was paradoxically normal in Parkinson’s disease. However, a problem with these investigations has been that the wide variability among patients’ clinical status and therapies may have precluded finding a meaningful re-

From the Laboratory of Neurophysiology (Drs. Pullman and Watta). National Institute of Mental Health, and the ExperimentalTherapeutics Branch (Drs. Juncos and Chase) and Human Motor Control Section, Medical Neurology Branch (Dr. Sanes), National Institute of Neurologicaland CommunicativeDieorders and Stroke, National Institutes of Health, Bethesda, MD. Presented in part at the thirty-eighth annual meeting of the American Academy of Neurology, New Orleans. LA, April 1986. Received February 24,1987. Accepted for publication in final form April 22, 1987. Address correspondence and reprint requests to Dr. Pullman, The Neurological Institute, Columbia-PresbyterianMedical Center, 710 West 168th Street, New York. NY 10032. February 1988 NEUROLOGY 38 249

A.

Simple reaction time task

Hold perlod

lnltlal porltlon

Movement

Target

B.

Choice reaction time task

Hold period

lnltlal poiltlon

Movement

Target

Target

Figure 1. Schematic diagram of (A) simple and (B) choice RT tasks. The nine-dot matrix represents the hand position cursor. For the simple RT task, when the preparatory outlined target turned solid after a variable “hold period, the subject was instructed to flex or extend the wrist to place the cursor in the target. Only the flexion simple RT task is illustrated. For the choice RT task, the instructions were the same, although two preparatory targets were presented and the final target appeared randomly on either the left or right of center. This required either flexion or extension of the wrist within the same trial. ”

lationship between parkinsonian disability and RT task performance. The present study sought to examine whether there is an abnormality of premovement central neural processing in Parkinson’s disease that is related to functional motor disability and plasma L-dopa levels during the “on” and “off’ states. Simple a n d directionalchoice visual RT tasks were used to evaluate response initiation in patients with predictable response fluctuations to L-dopa (“wearing-off’). A continuous IV infusion pump was used t o regulate plasma L-dopa levels during RT performance. This dose-response evaluation allowed for a more detailed examination of how simple and choice RTs were affected in Parkinson’s disease. Materials and methods. Subjects. Five right-handed patients with Parkinson’s disease (4 men, l woman, aged 29 to 61 years; mean, 49.2) were selected for study according to the following criteria: they exhibited minimal tremor, demonstrated a “wearing-off’ response pattern to L-dopa, were not 260 NEUROLOGY 38 February 1988

clinically depressed, and were capable of following instructions correctly. They were all taking a combination of L-dopa/ carbidopa prior to study, and their disability scores without medication ranged from I1 to IV on the Hoehn and Yahr7 scale. Five age-matched normal controls (3 men, 2 women, aged 31 to 64 years; mean, 47.0) were studied with both tasks for comparison. Patients and normal volunteers participated in accordance with guidelines specified by the NIH Human Subjects Committee. Experimental protocol. Clinical rating of parkinsonian symptoms using a modified Columbia scale8was performed by two neurologists on patients at clinical baseline and after stabilization at each infusion rate, with simultaneous sampling for plasma L-dopa. L-Dopa ( ~ - 3 , 4dihydroxyphenylalanine) was prepared in 0.45% saline to a concentration of 2 mg/ml and given by continuous IV infusion with oral carbidopa 50 mg q3h, starting the day before testing. Infusion rates of L-dopa (mg/kg/hr) were empirically established for each patient based on the corresponding individual clinical response. Three rates (high, middle, and low) were set to achieve three parkinsonian states (optimal or on, mid, and off). Rate adjustments were made 2 hours prior to the administration of each set of trials to allow stabilization of clinical performance and plasma L-dopa level. Plasma samples were stored immediately at - 70 “C and later assayed for L-dopa using high performance liquid chromatography with electrochemical d e t e ~ t i o n .~ Behavioral tasks and recording techniques. Simple and directional-choice visual RT tasks requiring flexion and extension movements about the wrist were performed by all subjects. A subject was seated with the right hand secured to a handle attached to the axle of a DC torque motor with the wrist centered over the motor’s axis of rotation. The forearm was braced to prevent extraneous movements, and the entire arm was hidden from the subject’s view. An electronic transducer recorded wrist angular displacement, and bipolar surface electrodes were used to record EMG activity from wrist flexor and extensor muscles. A video screen was positioned 1 meter in front of the subjects and displayed hand position and target cursors as the visual cues. Target images were displayed as rectangular boxes 1.2 cm high and 2.5 cm wide. A PDP 11/34 minicomputer controlled the tasks and data acquisition. For the simple RT task, a single target appeared in outline form to the left or right of the center window, subtending a visual angle approximately 6 to 7” from the center, as an indication that the subject should prepare for an impending 30” wrist movement. If the hand position cursor was kept within the center window for a variable “hold” period (800 to 1,800 msec), the outlined target changed to solid form and the center window disappeared, signifying the visual “go” stimulus. The subject then hadto move the position cursor into the target by flexing or extending the wrist (figure 1A). For the directional-choice RT task, two outlined preparatory targets were displayed on either side of center. After the same variable hold period, one of the targets changed to solid form as the go stimulus and the other target disappeared. The subject again had to either flex or extend the wrist 30” to move the cursor into the target (figure 1B). Practice sessions were given until subjects became familiar with the apparatus and could perform the tasks as rapidly and accurately as possible. For both types of tasks,a trial consisted of aligning the position cursor in the center starting window and then moving into the target cursor with one continuous movement. After completion of the movement, there was a variable intertrial interval (200 to 600 msec) before the reappearance of the center window and the start of a new hold period. Simple and choice tasks were intermixed in sets of 100 trials in a pseudorandom fashion, such that ultimately there was an equal number of trials for

I

1e-r

I

744

7

8

I

T

I

475T

:f\

0

45a

TI

I

4

425-

400

2

-

0

"on"

mid

"off"

g

a

Infusion Rate I

375.

1

Figure 2. Parkinsonian disability scores compared with plasma L-dopa levels. Steady-state plasma L-dopa concentrations obtained at the high and low infusion rates were significantly different(p 5 0.01).

each RT task. Controls performed two sets of trials and patients performed one set of trials at each of the three infusion rates. Position and the rectified and filtered EMG signals for each trial were coded and digitized at 200 Hz for subsequent analysis. Data analysis. Data were analyzed off-line using an interactive software program that allowed for inspection of each trial. Trials were rejected from the data analysis if the RT was less than 175 msec or greater than 850 msec. RT was measured from the go signal to the onset of movement velocity. Movement time (MT) was measured from movement onset to the first zero crossing of the velocity. To determine whether RT measurements were affected by increasing bradykinesia, the delay interval from EMG onset to the first electronic detection of movement (the electromechanical dissociation) was sampled from controls and patients both on and off. In both RT tasks, the results for flexion and extension movements were comparable and were pooled for statistical analysis. RTs and MTs from accepted trials for controls and patients at each infusion rate and for each task were averaged and compared using paired Student's t tests, analysis of variance with repeated measures, multiple comparison procedures, and simple linear regression methods.

Results. Clinical. Infusion rate and the corresponding plasma L-dopa concentration were significantly correlated (r = 0.88, p I0.001). Plasma L-dopa levels were inversely related to total parkinsonian functional motor disability scores (p I0.05) (figure 2). Kinematic. Simple RT was prolonged in parkinsonian patients at all three infusion rates when compared with controls (p I0.005).Amongpatients, there was no significant change in simple RT as the rate was decreased from high to low (table and figure 3). Directional-choice RT performance changed more dramatically than simple RT performance in relation to L-dopa levels. At optimal treatment levels, choice RT by patients was not significantly different from controls. However, choice RT by patients increased by 24%as the infusion rate decreased 03 5 0.01) (table and figure 3).

350

-

CHOlCE REACTON TIME -#-

Figure 3. Simple and choice RT measurements for controls and patients at three L-dopa infusion rates. This illustrates that the difference between simple and choice RTs more than doubled from the 'bn" to the "off' state.

The temporal difference in response initiation between simple RT and choice RT tasks was calculated. In controls, this RT difference averaged 109.2 msec. In patients, the average extra time was paradoxically shorter than it was for controls at all L-dopa infusion rates, but increasedby 123%from 41.6 msec in the on to 92.8 msec in the off states 03 I0.05). The electromechanical dissociation interval from the onset of muscle activity to the onset of movement for controls was 49.2 k 2.1 msec (mean k SEM) for simple and 46.9 f 2.4 msec for choice RT tasks. These measurements were also taken from three of the five patients. The mean delay was not different from that of controls, nor was it affected by changes in plasma Ldopa. Results from the most severely disabled patient (stage IV) illustrate this point. While optimally treated (on),the delay for this patient was 49.5 f 3.9 msec for simple and 47.3 f 4.4 msec for choice RT tasks. While off, intervals were 49.3 f 3.0 msec for simple and 49.3 f 4.4 msec for choice RT tasks. None of these values February 1988 NEUROLOGY 38 261

SIMPLE REACTION TIMES (25 TRIAL AVGr)

CHOICE REACTION llMES (25 TRIAL AVQ'r)

Figure 5. Sample individual triak. Data from single trials to demonstrate the EMG changes from "on" to "off' more clearly.

Figure 4 . Averaged wrist position and velocity recordings from 25 trials with EMG profiles of the wrist flexors and extensors, from one normal control and one patient at three infusion rates. With decreases in the infusion rate, there was a gradual reduction in the patient's first agonist EMG burst and continued activity throughout the movement.

were significantly different either in comparing the two RT tasks or in comparing the controls and most bradykinetic patient on or off. M T correlated inversely with plasma L-dopa concentration (r = 0.7, p 5 0.005), and was virtually identical for both tasks in patients at a given infusion rate, as it was for both tasks with the controls (table). Optimally treated patient MTs were not significantly different from normal, but became significantlyslower at middle and low dose rates (p 5 0.05). Figures 4 and 5 illustrate the EMG findings as the L-dopa infusion rate was decreased. Discussion. By titrating the level of motor disability using variable rates of an IV L-dopa infusion, we found 252 NEUROLOGY 38 February 1988

abnormalities of both simple and directional-choice RTs in patients with Parkinson's disease. Furthermore, these premovement measurements were differentially affected by L-dopa treatment. While it has been clearly demonstrated that the initiation and execution phases of voluntary movements are abnormal in Parkinson's d i s e a ~ e , l . ~ . ~the . ~ central J ~ J ~ neural mechanisms underlying premovement abnormalities have remained obscure. Evarts et all found a prolongation of simple RT, but did not demonstrate selective impairment in directional-choice RT in Parkinson's disease. Similarly, Bloxham et aP found that parkinsonian patients did not benefit from the preparatory cue in simple RT tasks,but nevertheless performed choice RT tasks almost as well as normal controls. Rafal et a12examined the relationship between clinical state and response initiation time, and found that slowingof premovement (or "cognitive") processes in Parkinson's disease did not always accompany clinical bradykinesia. Though each of these studies investigated central processes in Parkinson's disease,none of them systematicallyexamined RTs in precise relationship to drug or disability level. Consequently, functional changes in these measurements were not obtained. Our results showed that while simple RT was significantly prolonged in parkinsonian patients at all three Ldopa infusion rates, it was not significantly affected by treatment. This is in agreement with other s t ~ d i e s ~ ~ ~ J * that found no improvement in simple RT after L-dopa treatment. We extended those findings using a doseresponse method and demonstrated that patients, even at their clinical best, did not benefit from single preparatory cues to the same extent as normal controls. In comparison, we found that directional-choiceRT was not significantly different from that of controls at the highest L-dopa infusion rate (on), but became significantlyprolonged when the infusionwas decreasedto the middle and lowest rates (off). Choice RT, therefore, was inversely proportional to plasma L-dopa concentration and directly proportional to functional motor disability, particularly to bradykinesia. This finding demonstrated that parkinsonian patients with mild to moderate disease required more time to respond to one of two directional-choice targets when they were at or near their functional worst. Further, we showed that patients were capable of improving prolonged choice RT to normal with L-dopa treatment.

Table. Results

I

I

I II

Simple reaction time

Choice reaction time

Movement time for simple reaction time task

Movement time for choice reaction time task

Norma) controls

251 f 7

360 f 15

261 f 10

255 f 12

Patients “on”

331 f 36

373 f 26

280 f 20

Patients mid-dose

349

25

428 f 21

Patients

371 f 20

464 f 21

?

Plasma L-dopa level

Parkinsonian clinical acore (high = “worse”)

284f 16

6.34 f 1.5

3.0

328 f 18

328 f 13

4.30 2 0.96

6.7

339 k 14

340 f 16

3.06 f 1.1

13.1

“Off’

Reaction and movement times are means (in msec) 2 SEM. Plasma L-dopa levels are means (in pg/ml) 2 SEM.

To alleviate concern that increasing bradykinesia may have artifactually prolonged RT, we calculatedthe electromechanicaldissociation between the onset of the first agonist EMG burst and the earliest detection of movement. Because the sensitivity of movement detection by the torque motor system was equal for all subjects, the low amplitude and slow EMG build-up often seen in bradykinesialO may have resulted in longer electromechanical dissociation intervals in bradykinetic patients. However, our findings indicated that the apparatus accurately detected movement onset even when the ensuing movement was slow. There was no significant difference in electromechanicaldissociation intervals between controls and patients, regardless of the degree of bradykinesia. RT measurements, therefore, were not detectably affected by bradykinesia and were probably an accurate reflection of premovement neural processing times. The term “central delay” has been used to characterize the longer response latency observed in choice compared with simple RT performance. I t has been thought to represent additional processing needed in the selection or formulation of a central motor program in choice RT tasks.lJ1In previous studies, measures of central delay in Parkinson’s disease have been shorter than normal in part because simple RT was prolonged to a greater extent than choice RT. This might have implied normal (or even exceptionallyfast) central neural processing in Parkinson’s disease.1.3 However, when calculating the relative central delay at each dose level, we found that it increased by 123% from the on to off state (figure3). This demonstrated that neural processing of directional-choice tasks slowed as parkinsonian disability increased.Nevertheless,for a given dose level, central delay remained apparently faster in patients than controls. The paradoxically faster than normal central delay in Parkinson’s disease may be explained by the existence of independent neural mechanisms for simple and choice RT tasks. Recently, Alexander et all3 proposed that there may be several parallel basal ganglia-

thalamo-cortical pathways subserving different functions. They reported that, at a fundamental level, these separate pathways can be grouped according to those involved mainly with motor activity and those involved with more complex behavior, including cognition. The main qualitative difference between the simple and choice RT tasks in our study was that the simple task was largely dependent on the subject’s attention and preparation to move (because the target was known in advance), while the directional-choicetask required an additional cognitive factor to select movement in one of two directions. Given the difference between RT tasks, the neural mechanisms underlying RT performance might also be separated along a similar scheme (motor and complex) as that proposed to link the basal ganglia and cortex. Motor connections from sensorimotor cortex project largely to the putamen, while complex pathways from cortical association areas terminate principally in the caudate.13Together with the specific cortical regions to which each pathway ultimately projects, these circuits may comprisetwo completely separate physiologic substrates subserving simple and choice RT tasks. This would allow for independent processing of RT tasks and offer a reason why simple and choice RTs were found unequally affected by L-dopa. The apparently faster than normal central delay in Parkinson’s disease could then be explained as a discrepant value obtained by taking the difference between latencies from two physiologically distinct RT mechanisms. The motor circuit, connecting cortex and putamen, projects almost exclusively back to the supplementary motor area (SMA).“ Using single-cell recording techniques in behaving primates, Tanji et all5 have shown that the SMA contains a significant proportion of neurons exhibiting preparatory-set related activity. The attention and preparation underlying the simple RT task in our study was analogous to motor readiness of preparatory-set behavior. Simple RT performance, therefore, may be associatedwith the SMA. In addition, the SMA and its connections are nondopaminergic.16 February 1988 NEUROLOGY 38 263

Acknowledgment Our finding that simple RT performance was not significantly affected by dopamine replacement further subThis work is dedicated to the late Edward V. Evarta whose unfailing stantiates the possibility that the motor circuit, striving for excellence and accuracy will always be remembered. particularly the SMA, may serve as a substrate for processing simple RT tasks. It follows that simple RT may be at least partially dependent on nondopaminergic physiologic mechanisms. Parkinson’s disease is known to involve several neurotransmitter systems, and it has been suggested17 References that a widespread decrease of norepinephrine (NE) may 1. Evarta EV, Teravainen H, Calne DB. Reaction time in Parkincontribute to clinical deficits such as slowness in reson’s disease. Brain 1981;104:167-186. 2. Rafal RD, Posner MI, Walker JA, Friedrich FJ. Cognition and the sponse initiation. For example, a significant relabasal ganglia. Brain 1984;107:1083-1094. tionship between simple RT and CSF levels of the NE 3. Bloxham CA, Mindel TA, Frith CD. Initiation and execution of metabolite 3-methoxy-4-hydroxyphenylglycol has been predictable and unpredictable movements in Parkinson’s disease. found in parkinsonian patients.18Simple RT also may Brain 1984;107:371-384. be highly dependent on arousal systems to maintain 4. Yokochi F, Nakamura R, Narabayashi H. Reaction time of patients with Parkinson’s disease, with reference to asymmetry of neuroattention and motor readiness. Arousal is thought to be logical signs. J Neurol N e w u r g Psychiatry 1985,48702-705. predominantly mediated by NE19 and acetylcholine,20 5. Heilman KM, Bowers D, Watson RT, Greer M. Reaction times in supporting the participation of additional nonParkinson’s disease. Arch Neurol 1976;33:139-140. dopaminergic mechanisms in the processing of simple 6. Wilson SAK. Some disorders of motility and of muscle tone, with special reference to the corpus striatum. Lancet 1925;2:1-10, RT. 53-62, 169-178,215-219.266-276. Choice RT performance,in contrast, is dependent on 7. Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and cognitiveprocesses more complicated than attention or mortality. Neurology 1967;17:427-444. preparation alone and may be subserved by components 8.Duvoisin RC. The evaluation of extrapyramidal disease. In: de of the complex basal ganglia-thalamo-cortical pathway. Ajuriaguerra J, Gauthier G, eds. Monamines, noyaux gris centraux et syndrome de Parkinson. P a r k Masson, 1971:313-325. This circuit links the caudate with higher association 9. Wagner J, Vitali P, Palfreyman MG, Zraika M, Hunt S. Simulareas, and projects back to regions of the prefrontal taneous determination of L-dopa, 5-HT, dopamine, 4-hydroxy-3~0rtex.l3The circuit is thought to be involved with methoxy-phenylalanine, norepinephrine, DOPAC, HVA, higher cortical processing and complex motor beserotonin, and 5-HIAA in rat cerebrospinal fluid and brain by high havior.?’ We found that choice RT, which was normal performance liquid chromatography with electrochemical detection. J Neurochem 1982;381241-1254. in optimally treated parkinsonian patients, was signifi10. Hallett M, Khoshbin S. A physiological mechanism of bradykinecantly affected by dopamine deficiency. Our results are sia. Brain 1980;103:301-314, consistent with recent experimental findings that also 11.Mareden CD. The mysterious motor function of the basal ganglia. implicate the complex circuit in cognitive processing Neurology 1982;32:514-539. dependent on dopaminergicmechanisms. Taylor et a12? 12. Velasco F, Velasco M. A quantitative evaluation of the effecte of Ldopa on Parkinson’s disease. Neuropharmacology 1973;12:89-99. have shown that cognitive dysfunction specific to Par13. Alexander GE, DeLong MR, Strick PL. Parallel organization of kinson’s disease may be caused by disturbed caudate functionally segregated circuits linking basal ganglia and cortex. outflow and the resulting functional abnormalities in Annu Rev Neurosci 1986;9:357-381. prefrontal cortex. They argue that the prefrontal region 14. Schell GR, Strick PL. The origin of thalamic inputs to the arcuate premotor a n d supplementary motor areas. J Neurosci is particularly vulnerable because it is the cortical target 19@,4539-560. of caudate activity as well as a terminal projection of 15. Tanji J , Taniguchi K, Saga T. Supplementary motor area: neudopaminergic mesocortical fibers from the ventral tegronal response t o motor instructions. J Neurophysiol mental area,23both of which are affected in Parkinson’s 1980;43:60-68. 16. Moore RY, Bloom FE. Central catecholamine neuron system: disease. anatomy and physiology of the norepinephrine and epinephrine Studies by Weinberger et al,24 measuring regional systems. Annu Rev Neurosci 1979;2:113-168. cerebral blood flow (rCBF) over dorsolateral prefrontal 17. Hornykiewicz 0. Brain neurotransmitter changes in Parkinson’s cortex (DLPC), present more evidence to suggest that d i m , chap 4. In: Marsden CD, Fahn S,eds. Movement disorprefrontal dopaminergic mechanisms may underlie ders. Boston: Butterworth Scientific, 1982:41-58. 18. Stern Y, Mayeux R, Cote L. Reaction time and vigilance in Parchoice RT performance. They demonstrated that cogkinson’s disease. Arch Neurol1984;41:1086-1089. nitive motor functioning in Parkinson’s disease corre19. Mason ST, Fibiger HC. Noradrenaline and selective attention. lated with rCBF in the DLPC. In addition, L-dopa Life Sci 1979;25:1949-1956. treatment resulted in an increase in rCBF over DLPC 20. Steriade M, Glenn LL. Neocortical and caudate projections of intralaminar thalamic neurons and their synaptic excitation from during functional testing of this cortical region, a result midbrain reticular core. J Neurophysiol 1982;48:352-371. that parallels our finding that choice RT performance 21. Brooks VB.The neural basis of motor control. New York: Oxford improved with L-dopa treatment. University Press, 1986:290-315. We have shown that simple and choice RTs are both 22. Taylor AE, Saint-Cyr JA, Lang AE. Frontal lobe dysfunction in abnormal in Parkinson’s disease, but differentially afParkinson’s disease. Brain 1986;109:845-883. 23. Thierry AM, Tassin JP, Blanc G, Glowinski J. Studies on mesofected by dopamine replacement.Examination of the neucortical dopamine systems. Adv Biochem Psychopharmacol ral mechanisms involved suggests that simple and choice 1978;19205-216. RT processes may reside separately within the basal gan24. Weinberger DR, Berman KF, Chase TN. Prefrontal cortex physiglia-thalamo-corticalparallel circuits designed to control ological activation: effect of L-dopa in Parkinson’s disease. Abstract. Neurology 1986;36(suppl 1):170. motor and cognitive functions independently. 254 NEUROLOGY 38 February 1988