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Transient arrest of psychogenic tremor induced by contralateral ballistic movements
Neuroscience Letters 370 (2004) 135–139
Transient arrest of psychogenic tremor induced by contralateral ballistic movements Hatice Kumru, Josep Valls-Sol´e∗ , Francesc Valldeoriola, Maria Jos´e Marti, Maria Teresa Sanegre, Eduardo Tolosa Unitat d’EMG, Servei de Neurologia, Hospital Cl´ınic, Facultad de Medicina, Institut d’Investigacions Biom`ediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Villarroel, 170, Barcelona 08036, Spain Received 28 May 2004; received in revised form 20 July 2004; accepted 6 August 2004
Abstract One of the clinical characteristics of psychogenic tremors (PT) is the disruption or transient cessation of tremor with distractive manoeuvres, including those involving the performance of voluntary movements with the contralateral hand. Seven patients with PT, 11 patients with Parkinson’s disease (PD), 10 patients with essential tremor (ET) and 10 normal volunteers mimicking tremor (NV) were requested to perform a fast unilateral wrist movement to close a switch, at the perception of a visual cue, either at rest or during maintenance of a posture. We measured the time-locked changes in frequency and amplitude occurring in tremor oscillations of the contralateral hand. The reaction time task induced a significant reduction in amplitude or cessation of contralateral tremor oscillations in PT and NV, but not in PD and ET. The effect occurred with a delay with respect to the onset of the contralateral movement without significant differences in PT versus NV (p > 0.05). The physiological mechanisms accounting for the effect seen on tremor of NV and PT may involve the interhemispheric inhibition that accompanies the execution of a unilateral motor task. Tremor circuits in patients with PD and ET may be impervious to these inhibitory commands. The documentation and quantitation of the effects of a ballistic movement on contralateral rhythmic activity are of clinical relevance for the identification of patients with PT. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Psychogenic tremor; Reaction time; Movement; Parkinson’s disease; Essential tremor
Tremor is an involuntary mechanical oscillation of at least one functional body region, produced by either alternating or synchronous contractions of antagonistic muscles [6,12]. Mechanical oscillation is an intrinsic property of the motor system that is easily integrated in voluntary actions for the performance of repetitive movements in our daily activity. Tremor is, indeed, an easy to mimic motor behavior. Psychogenic tremor (PT) is considered to occur in as much as 3 to 10% of cases presenting with tremor [11,14]. Generally, PT begins or disappears suddenly, may be present in both resting and postural conditions, and changes its frequency with distractive manoeuvres or during voluntary movements of the contralateral hand [6,11,14]. The physiology of this ∗
Corresponding author. Tel.: +34 93 2275413; fax: +34 93 2275783. E-mail address: [email protected] (J. Valls-Sol´e).
0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.08.009
latter effect is poorly understood. It relates to the fact that non-trained subjects have difficulties in performing separate rhythmical movements of different frequencies with each hand [21]. The effect of distractive manoeuvres on tremor could be of clinical utility for the identification of PT patients [22]. Therefore, we investigated the effects of the execution of a unilateral ballistic wrist movement on tremor of the contralateral hand in patients with tremor recruited among those attending the Movement Disorders clinic of our Institution. The study protocol was approved by the Ethical Committee of our Institution. The patients finally selected were 11 patients with idiopathic Parkinson’s disease (PD), 10 patients with essential tremor (ET) and 7 patients with psychogenic tremor (PT). All patients, whose clinical characteristics are listed in Table 1, fulfilled the current diagnostic criteria for their respective disorder [1,9,11,16], and gave their informed
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Table 1 Demographic data for the normal volunteers and patients involved in the study, and predominant type of tremor in patients
Number of patients Gender (male/female) Age Disease duration Hoehn–Yahr stage Number of patients with rest tremor Number of patients with postural tremor Mean tremor score at rest Mean tremor score with posture holding
PD
ET
PT
11 7/4 67.6 ± 11.0 8.0 ± 5.1 2.0 ± 0.6 11 10 2.5 ± 0.8 2.1 ± 1.1
10 5/5 62.0 ± 9.2 14.8 ± 12.4 – 1 10 0.1 ± 0.3 2.2 ± 0.4
7 0/7 62.4 ± 17.5 4.4 ± 2.6 – 7 7 1.9 ± 0.4 2.3 ± 0.5
PD: patients with Parkinson’s disease; ET: patients with essential tremor; PT: patients with psychogenic tremor.
consent for the study. In PT patients, we ruled out possible causes of symptomatic tremor by clinical and laboratory assessment. ET and PD were excluded on the bases of clinical criteria and, in two PT patients, PD was ruled out on the bases of a normal (123 I)-FP-CIT SPECT (DatSCAN). All patients were off medication for at least 12 h before the study. For comparison, we also studied 10 normal volunteers (NV), 5 men and 5 women, with a mean age of 62.0 ± 9.2 years, who were requested to mimic hand tremor at rest and with posture holding. Commercially available movement transducers (model 348720; Bionic Ib´erica S.A., Barcelona, Spain) were attached to the dorsum of the hand, in both sides. Signals were recorded with a conventional electromyograph (MYSTRO5Plus; Oxford Medical Instruments, Surrey, UK). Subjects were sitting on a chair with the arms relaxed over armrests (condition rest) or, in a second run of the experiment, with the arms outstretched (condition posture). In both conditions subjects were asked to pay attention to the screen of a computer and be ready to make a ballistic movement with one hand (10 times with the right hand and 10 times with the left hand) at the perception of a visual cue (imperative signal (IS)). The IS, which consisted of a white 5 cm square on a black background was also used to externally trigger the oscilloscope sweep of the electromyograph with a delay of 1 s, allowing for recording pre- and post-IS events. The task assigned to the subjects was to hit a switch located on top of a table at a distance of about 30 cm from their hands. We measured the baseline hand oscillation mean period, as the mean time in ms elapsed between two consecutive turns, and mean amplitude of turns, in degrees, during the 1 s immediately preceding the IS (baseline). Tremor frequency, expressed in turns per second, was assessed by dividing 1000 by the mean oscillation period in ms. Reaction time was measured as the latency in ms between the IS and the onset of movement of the reacting hand. For assessment of the effects at individual level, we considered a change in period when the time interval between two consecutive turns dropped or rised beyond 50% of the mean calculated in the pre-IS segment, and a change in amplitude when the amplitude of two or more oscillations dropped or rised beyond 50% of the mean amplitude calculated in the pre-IS segment.
Whenever a change in period or amplitude was detected, we measured its latency difference with respect to the contralateral ballistic movement, and its duration from onset until the time in which the values matched again those of the pre-IS segment. We then determined the number of trials per subject in which we detected significant changes in period or amplitude of tremor oscillation, and considered that tremor was sensitive to the execution of a contralateral ballistic movement in subjects in whom significant changes were identified in 7 or more out of the 10 trials performed in each condition. Statistical analyses (ANOVA) were performed to know whether there were differences among groups of subjects regarding tremor frequency and amplitude in the pre-IS segment, latency of the significant effect of the ballistic movement on tremor-related oscillations, and duration of the effect. Post hoc comparisons were made using Bonferroni’s test. Table 2 summarizes the results obtained in all groups of patients in the pre-IS segment, in conditions rest and posture. In the condition rest, the groups compared were NV, PT and PD. In the condition posture, comparison was made between all four groups. Regarding tremor frequency there were statistically significant differences between groups in the condition rest (F2,25 = 19.4; p < 0.001), but not regarding tremor frequency in the condition posture (F3,34 = 1.1; p = 0.3) or tremor amplitude in either condition (F2,25 = 1.5; p = 0.2 in the rest condition; F3,34 = 2.8; p = 0.06 in the condition posture). Post hoc analysis showed that tremor frequency at rest was significantly higher in PT with respect to PD (p = 0.007) or NV (p < 0.001), and in PD versus NV (p = 0.009). Tremor diminished transiently for a few seconds when PD patients were requested to acquire the position of arms stretched. In all patients with ET, tremor oscillations were not apparent at rest except for a single patient with very mild rest tremor. In these patients, tremor became apparent as soon as they acquired the position of arms stretched. Tremor frequency in NV and PD was significantly higher in the condition posture with respect to rest (t test; p = 0.007 for PD patients, and p = 0.001 for NV) while this was not the case in patients with PT, who had similar mean tremor frequency in both conditions (t test; p = 0.9). Tremor-related oscillations were sensitive to performance of contralateral ballistic movements in all NV and PT patients, but not in PD or in ET patients. The tremor-related
H. Kumru et al. / Neuroscience Letters 370 (2004) 135–139
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Table 2 Tremor oscillation period (ms) and amplitude (◦ ) in the pre-IS segment Measurements (ms)∗
NV
PD
Rest
Period Frequency (Hz)∗ Amplitude (◦ )
237.6 ± 24.9 4.2 ± 2.0 17.8 ± 2.1
208.5 ± 14.1 4.8 ± 1.0 13.7 ± 8.7
Posture
Period (ms) Frequency (Hz) Amplitude (◦ )
189.4 ± 17.6 5.3 ± 1.1 16.2 ± 2.2
172.1 ± 25.0 5.8 ± 1.4 16.5 ± 5.6
ET
PT – – –
174.1 ± 27.9 5.7 ± 1.7 10.8 ± 6.9
175.6 ± 20.6 5.7 ± 1.2 13.3 ± 5.9 176.5 ± 19.7 5.6 ± 1.2 12.5 ± 7.3
NV: normal volunteers; PD: patients with Parkinson’s disease; ET: patients with essential tremor; PT: patients with psychogenic tremor. ∗ Statistically significant differences between PT vs. NV and PT vs. PD (p < 0.01).
oscillations showed a significant amplitude decrement or a complete stop in all NV and PT patients (Fig. 1A and B). The mean number of trials per subject showing significant changes was 8.9 ± 0.99 for NV and 8.7 ± 0.95 for PT, in the condition rest, and 8.7 ± 0.9 for NV and 8.8 ± 1.0 for PT, in the condition posture. In contrast, there was no significant effect in any of the patients with PD (Fig. 1C), either at rest (1.6 ± 1.7) or in posture (0.8 ± 0.6), nor in any of the patients with ET (Fig. 1D) in the condition posture (0.5 ± 0.7). Latency difference between onset of the significant change of tremor-related oscillations and reaction time of the con-
Fig. 1. Representative examples of the effects of a ballistic movement (upper traces of each pair) on contralateral tremor (lower traces of each pair) in normal volunteers (A), patients with psychogenic tremor (B), and patients with Parkinson’s disease (C) in the condition rest, and in patients with essential tremor (D) in the condition posture. Note the interruption of tremor at a certain delay from onset of the ballistic movement in NV and PT, and the absence of such effect in patients with PD and ET.
tralateral hand was not statistically significantly different in NV and PT in the condition rest (190.3 ± 22.6 ms for NV and 191.5 ± 84.4 ms for PT; ANOVA F1,15 = 0.012; p = 0.9), nor in the condition posture (169.4 ± 40.8 ms for NV and 226.8 ± 89.1 ms for PT; ANOVA F1,15 = 3.2; p = 0.09). However, duration of the effect was statistically significantly longer in PT than in NV in the condition rest (419.1 ± 152.6 ms for NV and 1037.6 ± 327.4 ms for PT; ANOVA F1,15 = 27.7; p < 0.001), and in the condition posture (551.8 ± 141.8 ms for NV and 936.8 ± 178.2 ms for PT; ANOVA F1,15 = 23.7; p < 0.001). These results indicate that the execution of a voluntary ballistic movement with one hand causes a transient interference with the performance of oscillatory movements with the contralateral hand in NV who imitate hand tremor, as well as in patients with PT. In contrast, these effects are not observed in patients with PD or ET. These observations lead to two different topics for discussion: (1) The physiological mechanisms accounting for the influence of unilateral ballistic movements on contralateral rhythmic movements and (2) The utility of the test described here for the documentation of voluntary-driven tremor-like movements, and its applicability to the diagnosis of patients with PT. Retrieval of appropriate motor programs from the central nervous system requires the inhibition of other programs in order to limit the movement to the desired extent [5,17]. In the case of strictly unilateral movements, inhibitory actions should be directed to the contralateral motor tract. The inhibitory influence of one motor cortex on the contralateral motor tract is probably exerted at multiple levels, involving most likely subcortical motor structures [13]. Selection in motor preparation could imply blocking of irrelevant motor behavior in order to ameliorate the signal-to-noise ratio in motor activity, which is aimed at the activation of just the required action, and not the other ones [3]. According to these observations, it is not unexpected that untrained healthy subjects performing a unilateral ballistic movement would transiently inhibit the tremor-like oscillatory activity of the contralateral arm, as it was the case in our study for NV and, also, for patients with PT, who are supposed to have intact neural circuits [22]. Inhibition of a rhythmic activity can also be explained by the requirement that the subject’s attention is directed to the performance of the ballistic movement. The fact that the sig-
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nificant change in tremor oscillations occurred a few ms after onset of the contralateral movement may be an argument favoring the role of diverted attention. The delay can be related to the fact that oscillatory movements are, actually, rhythmic, simple, sequential motor acts. With continuous repetition of the movement, the oscillatory muscle activity required to maintain voluntarily the tremor-like oscillations may become part of a reflex automatic behavior that could continue for a short time, driven by subcortical pathways, even if inhibitory motor commands have already issued from more rostral structures. Eventually, tremor oscillations cannot be maintained any longer because of the suppression by multilevel inhibitory inputs. Tremor at rest is often suggesting Parkinson’s disease [16,23], while postural tremor is most commonly a sign of essential tremor [1,7]. However, PT may be present in both resting and postural conditions alike [6,11,14,20]. Even though several clinical and electrophysiological tricks and methods can be used to recognize psychogenic disorders [10,15], the tests for positive diagnosis are lacking. Using the method described in this manuscript, we were able to demonstrate that clinically diagnosed PT patients had similar behavior as NV imitating tremor. The longer duration of the inhibitory effect in PT in comparison to NV can be explained by the fact that NV were warned to continue to imitate tremor after the ballistic movement whereas we did not do this type of warning in patients with PT. The inhibitory effects of a ballistic movement on contralateral tremor were not present in patients with PD and ET. The circuits responsible for tremor in these patients are only partially identified [7,8,19,24]. Actions that involve cortical activity, such as mental tasks or attention drawing motor tasks, may cause enhancement rather than decrease of tremor oscillations in PD and ET patients [4,9]. The mechanisms involved in such an effect are presently unknown, although they may be related to disinhibition of the subcortical circuits mediating tremor. The fact that the oscillations in the EMG activity underlying tremor are not coupled between arms in PD patients with bilateral tremor [18] may be a significant cue for the lack of effect of unilateral ballistic movements on contralateral tremor. Some authors [2,18] consider that tremor in PD results from the activity of independent circuits of oscillatory neural activity. It may be that these circuits are impervious to the contralateral action. At the present state of our knowledge on tremor mechanisms, it is probably safe to declare that, in PD and ET patients, the inhibitory commands originating in the execution of a unilateral ballistic movement are too weak to overcome the relatively more powerful oscillatory circuit responsible for tremor. In conclusion, tremor-like oscillations of NV and PT patients become dysregulated or completely abolished after onset of a contralateral ballistic movement. This effect does not occur in patients with PD or ET, whose tremor continues without significant changes during the contralateral movement. The test has shown consistent results in all patients. Although our sample of PT patients is rather small, we be-
lieve that the test used in our study might have a relevant role in the identification of PT, and may be of help in the differential diagnosis between PT and PD or ET.
Acknowledgement This work has been funded in part by grants V-2003 REDC06H-0 and Red CIEN IDIBAPS RTIC C03/06 from the Instituto de Salud Carlos III. Eduardo Tolosa was supported by grant 2001SGR00387, and “Distinci´o per a la Promoci´o de Recerca Universit`aria”, from the Generalitat de Catalunya.
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Transient arrest of psychogenic tremor induced by contralateral ballistic movements Hatice Kumru, Josep Valls-Sol´e∗ , Francesc Valldeoriola, Maria Jos´e Marti, Maria Teresa Sanegre, Eduardo Tolosa Unitat d’EMG, Servei de Neurologia, Hospital Cl´ınic, Facultad de Medicina, Institut d’Investigacions Biom`ediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Villarroel, 170, Barcelona 08036, Spain Received 28 May 2004; received in revised form 20 July 2004; accepted 6 August 2004
Abstract One of the clinical characteristics of psychogenic tremors (PT) is the disruption or transient cessation of tremor with distractive manoeuvres, including those involving the performance of voluntary movements with the contralateral hand. Seven patients with PT, 11 patients with Parkinson’s disease (PD), 10 patients with essential tremor (ET) and 10 normal volunteers mimicking tremor (NV) were requested to perform a fast unilateral wrist movement to close a switch, at the perception of a visual cue, either at rest or during maintenance of a posture. We measured the time-locked changes in frequency and amplitude occurring in tremor oscillations of the contralateral hand. The reaction time task induced a significant reduction in amplitude or cessation of contralateral tremor oscillations in PT and NV, but not in PD and ET. The effect occurred with a delay with respect to the onset of the contralateral movement without significant differences in PT versus NV (p > 0.05). The physiological mechanisms accounting for the effect seen on tremor of NV and PT may involve the interhemispheric inhibition that accompanies the execution of a unilateral motor task. Tremor circuits in patients with PD and ET may be impervious to these inhibitory commands. The documentation and quantitation of the effects of a ballistic movement on contralateral rhythmic activity are of clinical relevance for the identification of patients with PT. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Psychogenic tremor; Reaction time; Movement; Parkinson’s disease; Essential tremor
Tremor is an involuntary mechanical oscillation of at least one functional body region, produced by either alternating or synchronous contractions of antagonistic muscles [6,12]. Mechanical oscillation is an intrinsic property of the motor system that is easily integrated in voluntary actions for the performance of repetitive movements in our daily activity. Tremor is, indeed, an easy to mimic motor behavior. Psychogenic tremor (PT) is considered to occur in as much as 3 to 10% of cases presenting with tremor [11,14]. Generally, PT begins or disappears suddenly, may be present in both resting and postural conditions, and changes its frequency with distractive manoeuvres or during voluntary movements of the contralateral hand [6,11,14]. The physiology of this ∗
Corresponding author. Tel.: +34 93 2275413; fax: +34 93 2275783. E-mail address: [email protected] (J. Valls-Sol´e).
0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.08.009
latter effect is poorly understood. It relates to the fact that non-trained subjects have difficulties in performing separate rhythmical movements of different frequencies with each hand [21]. The effect of distractive manoeuvres on tremor could be of clinical utility for the identification of PT patients [22]. Therefore, we investigated the effects of the execution of a unilateral ballistic wrist movement on tremor of the contralateral hand in patients with tremor recruited among those attending the Movement Disorders clinic of our Institution. The study protocol was approved by the Ethical Committee of our Institution. The patients finally selected were 11 patients with idiopathic Parkinson’s disease (PD), 10 patients with essential tremor (ET) and 7 patients with psychogenic tremor (PT). All patients, whose clinical characteristics are listed in Table 1, fulfilled the current diagnostic criteria for their respective disorder [1,9,11,16], and gave their informed
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H. Kumru et al. / Neuroscience Letters 370 (2004) 135–139
Table 1 Demographic data for the normal volunteers and patients involved in the study, and predominant type of tremor in patients
Number of patients Gender (male/female) Age Disease duration Hoehn–Yahr stage Number of patients with rest tremor Number of patients with postural tremor Mean tremor score at rest Mean tremor score with posture holding
PD
ET
PT
11 7/4 67.6 ± 11.0 8.0 ± 5.1 2.0 ± 0.6 11 10 2.5 ± 0.8 2.1 ± 1.1
10 5/5 62.0 ± 9.2 14.8 ± 12.4 – 1 10 0.1 ± 0.3 2.2 ± 0.4
7 0/7 62.4 ± 17.5 4.4 ± 2.6 – 7 7 1.9 ± 0.4 2.3 ± 0.5
PD: patients with Parkinson’s disease; ET: patients with essential tremor; PT: patients with psychogenic tremor.
consent for the study. In PT patients, we ruled out possible causes of symptomatic tremor by clinical and laboratory assessment. ET and PD were excluded on the bases of clinical criteria and, in two PT patients, PD was ruled out on the bases of a normal (123 I)-FP-CIT SPECT (DatSCAN). All patients were off medication for at least 12 h before the study. For comparison, we also studied 10 normal volunteers (NV), 5 men and 5 women, with a mean age of 62.0 ± 9.2 years, who were requested to mimic hand tremor at rest and with posture holding. Commercially available movement transducers (model 348720; Bionic Ib´erica S.A., Barcelona, Spain) were attached to the dorsum of the hand, in both sides. Signals were recorded with a conventional electromyograph (MYSTRO5Plus; Oxford Medical Instruments, Surrey, UK). Subjects were sitting on a chair with the arms relaxed over armrests (condition rest) or, in a second run of the experiment, with the arms outstretched (condition posture). In both conditions subjects were asked to pay attention to the screen of a computer and be ready to make a ballistic movement with one hand (10 times with the right hand and 10 times with the left hand) at the perception of a visual cue (imperative signal (IS)). The IS, which consisted of a white 5 cm square on a black background was also used to externally trigger the oscilloscope sweep of the electromyograph with a delay of 1 s, allowing for recording pre- and post-IS events. The task assigned to the subjects was to hit a switch located on top of a table at a distance of about 30 cm from their hands. We measured the baseline hand oscillation mean period, as the mean time in ms elapsed between two consecutive turns, and mean amplitude of turns, in degrees, during the 1 s immediately preceding the IS (baseline). Tremor frequency, expressed in turns per second, was assessed by dividing 1000 by the mean oscillation period in ms. Reaction time was measured as the latency in ms between the IS and the onset of movement of the reacting hand. For assessment of the effects at individual level, we considered a change in period when the time interval between two consecutive turns dropped or rised beyond 50% of the mean calculated in the pre-IS segment, and a change in amplitude when the amplitude of two or more oscillations dropped or rised beyond 50% of the mean amplitude calculated in the pre-IS segment.
Whenever a change in period or amplitude was detected, we measured its latency difference with respect to the contralateral ballistic movement, and its duration from onset until the time in which the values matched again those of the pre-IS segment. We then determined the number of trials per subject in which we detected significant changes in period or amplitude of tremor oscillation, and considered that tremor was sensitive to the execution of a contralateral ballistic movement in subjects in whom significant changes were identified in 7 or more out of the 10 trials performed in each condition. Statistical analyses (ANOVA) were performed to know whether there were differences among groups of subjects regarding tremor frequency and amplitude in the pre-IS segment, latency of the significant effect of the ballistic movement on tremor-related oscillations, and duration of the effect. Post hoc comparisons were made using Bonferroni’s test. Table 2 summarizes the results obtained in all groups of patients in the pre-IS segment, in conditions rest and posture. In the condition rest, the groups compared were NV, PT and PD. In the condition posture, comparison was made between all four groups. Regarding tremor frequency there were statistically significant differences between groups in the condition rest (F2,25 = 19.4; p < 0.001), but not regarding tremor frequency in the condition posture (F3,34 = 1.1; p = 0.3) or tremor amplitude in either condition (F2,25 = 1.5; p = 0.2 in the rest condition; F3,34 = 2.8; p = 0.06 in the condition posture). Post hoc analysis showed that tremor frequency at rest was significantly higher in PT with respect to PD (p = 0.007) or NV (p < 0.001), and in PD versus NV (p = 0.009). Tremor diminished transiently for a few seconds when PD patients were requested to acquire the position of arms stretched. In all patients with ET, tremor oscillations were not apparent at rest except for a single patient with very mild rest tremor. In these patients, tremor became apparent as soon as they acquired the position of arms stretched. Tremor frequency in NV and PD was significantly higher in the condition posture with respect to rest (t test; p = 0.007 for PD patients, and p = 0.001 for NV) while this was not the case in patients with PT, who had similar mean tremor frequency in both conditions (t test; p = 0.9). Tremor-related oscillations were sensitive to performance of contralateral ballistic movements in all NV and PT patients, but not in PD or in ET patients. The tremor-related
H. Kumru et al. / Neuroscience Letters 370 (2004) 135–139
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Table 2 Tremor oscillation period (ms) and amplitude (◦ ) in the pre-IS segment Measurements (ms)∗
NV
PD
Rest
Period Frequency (Hz)∗ Amplitude (◦ )
237.6 ± 24.9 4.2 ± 2.0 17.8 ± 2.1
208.5 ± 14.1 4.8 ± 1.0 13.7 ± 8.7
Posture
Period (ms) Frequency (Hz) Amplitude (◦ )
189.4 ± 17.6 5.3 ± 1.1 16.2 ± 2.2
172.1 ± 25.0 5.8 ± 1.4 16.5 ± 5.6
ET
PT – – –
174.1 ± 27.9 5.7 ± 1.7 10.8 ± 6.9
175.6 ± 20.6 5.7 ± 1.2 13.3 ± 5.9 176.5 ± 19.7 5.6 ± 1.2 12.5 ± 7.3
NV: normal volunteers; PD: patients with Parkinson’s disease; ET: patients with essential tremor; PT: patients with psychogenic tremor. ∗ Statistically significant differences between PT vs. NV and PT vs. PD (p < 0.01).
oscillations showed a significant amplitude decrement or a complete stop in all NV and PT patients (Fig. 1A and B). The mean number of trials per subject showing significant changes was 8.9 ± 0.99 for NV and 8.7 ± 0.95 for PT, in the condition rest, and 8.7 ± 0.9 for NV and 8.8 ± 1.0 for PT, in the condition posture. In contrast, there was no significant effect in any of the patients with PD (Fig. 1C), either at rest (1.6 ± 1.7) or in posture (0.8 ± 0.6), nor in any of the patients with ET (Fig. 1D) in the condition posture (0.5 ± 0.7). Latency difference between onset of the significant change of tremor-related oscillations and reaction time of the con-
Fig. 1. Representative examples of the effects of a ballistic movement (upper traces of each pair) on contralateral tremor (lower traces of each pair) in normal volunteers (A), patients with psychogenic tremor (B), and patients with Parkinson’s disease (C) in the condition rest, and in patients with essential tremor (D) in the condition posture. Note the interruption of tremor at a certain delay from onset of the ballistic movement in NV and PT, and the absence of such effect in patients with PD and ET.
tralateral hand was not statistically significantly different in NV and PT in the condition rest (190.3 ± 22.6 ms for NV and 191.5 ± 84.4 ms for PT; ANOVA F1,15 = 0.012; p = 0.9), nor in the condition posture (169.4 ± 40.8 ms for NV and 226.8 ± 89.1 ms for PT; ANOVA F1,15 = 3.2; p = 0.09). However, duration of the effect was statistically significantly longer in PT than in NV in the condition rest (419.1 ± 152.6 ms for NV and 1037.6 ± 327.4 ms for PT; ANOVA F1,15 = 27.7; p < 0.001), and in the condition posture (551.8 ± 141.8 ms for NV and 936.8 ± 178.2 ms for PT; ANOVA F1,15 = 23.7; p < 0.001). These results indicate that the execution of a voluntary ballistic movement with one hand causes a transient interference with the performance of oscillatory movements with the contralateral hand in NV who imitate hand tremor, as well as in patients with PT. In contrast, these effects are not observed in patients with PD or ET. These observations lead to two different topics for discussion: (1) The physiological mechanisms accounting for the influence of unilateral ballistic movements on contralateral rhythmic movements and (2) The utility of the test described here for the documentation of voluntary-driven tremor-like movements, and its applicability to the diagnosis of patients with PT. Retrieval of appropriate motor programs from the central nervous system requires the inhibition of other programs in order to limit the movement to the desired extent [5,17]. In the case of strictly unilateral movements, inhibitory actions should be directed to the contralateral motor tract. The inhibitory influence of one motor cortex on the contralateral motor tract is probably exerted at multiple levels, involving most likely subcortical motor structures [13]. Selection in motor preparation could imply blocking of irrelevant motor behavior in order to ameliorate the signal-to-noise ratio in motor activity, which is aimed at the activation of just the required action, and not the other ones [3]. According to these observations, it is not unexpected that untrained healthy subjects performing a unilateral ballistic movement would transiently inhibit the tremor-like oscillatory activity of the contralateral arm, as it was the case in our study for NV and, also, for patients with PT, who are supposed to have intact neural circuits [22]. Inhibition of a rhythmic activity can also be explained by the requirement that the subject’s attention is directed to the performance of the ballistic movement. The fact that the sig-
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nificant change in tremor oscillations occurred a few ms after onset of the contralateral movement may be an argument favoring the role of diverted attention. The delay can be related to the fact that oscillatory movements are, actually, rhythmic, simple, sequential motor acts. With continuous repetition of the movement, the oscillatory muscle activity required to maintain voluntarily the tremor-like oscillations may become part of a reflex automatic behavior that could continue for a short time, driven by subcortical pathways, even if inhibitory motor commands have already issued from more rostral structures. Eventually, tremor oscillations cannot be maintained any longer because of the suppression by multilevel inhibitory inputs. Tremor at rest is often suggesting Parkinson’s disease [16,23], while postural tremor is most commonly a sign of essential tremor [1,7]. However, PT may be present in both resting and postural conditions alike [6,11,14,20]. Even though several clinical and electrophysiological tricks and methods can be used to recognize psychogenic disorders [10,15], the tests for positive diagnosis are lacking. Using the method described in this manuscript, we were able to demonstrate that clinically diagnosed PT patients had similar behavior as NV imitating tremor. The longer duration of the inhibitory effect in PT in comparison to NV can be explained by the fact that NV were warned to continue to imitate tremor after the ballistic movement whereas we did not do this type of warning in patients with PT. The inhibitory effects of a ballistic movement on contralateral tremor were not present in patients with PD and ET. The circuits responsible for tremor in these patients are only partially identified [7,8,19,24]. Actions that involve cortical activity, such as mental tasks or attention drawing motor tasks, may cause enhancement rather than decrease of tremor oscillations in PD and ET patients [4,9]. The mechanisms involved in such an effect are presently unknown, although they may be related to disinhibition of the subcortical circuits mediating tremor. The fact that the oscillations in the EMG activity underlying tremor are not coupled between arms in PD patients with bilateral tremor [18] may be a significant cue for the lack of effect of unilateral ballistic movements on contralateral tremor. Some authors [2,18] consider that tremor in PD results from the activity of independent circuits of oscillatory neural activity. It may be that these circuits are impervious to the contralateral action. At the present state of our knowledge on tremor mechanisms, it is probably safe to declare that, in PD and ET patients, the inhibitory commands originating in the execution of a unilateral ballistic movement are too weak to overcome the relatively more powerful oscillatory circuit responsible for tremor. In conclusion, tremor-like oscillations of NV and PT patients become dysregulated or completely abolished after onset of a contralateral ballistic movement. This effect does not occur in patients with PD or ET, whose tremor continues without significant changes during the contralateral movement. The test has shown consistent results in all patients. Although our sample of PT patients is rather small, we be-
lieve that the test used in our study might have a relevant role in the identification of PT, and may be of help in the differential diagnosis between PT and PD or ET.
Acknowledgement This work has been funded in part by grants V-2003 REDC06H-0 and Red CIEN IDIBAPS RTIC C03/06 from the Instituto de Salud Carlos III. Eduardo Tolosa was supported by grant 2001SGR00387, and “Distinci´o per a la Promoci´o de Recerca Universit`aria”, from the Generalitat de Catalunya.
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