Cognitive- and movement-related potentials ... - Wiley Online Library

Movement Disorders Vol. 20, No. 5, 2005, pp. 562–568 © 2005 Movement Disorder Society

Cognitive- and Movement-Related Potentials Recorded in the Human Basal Ganglia Ivan Rektor, MD,* Martin Baresˇ, MD, Milan Bra´zdil, MD, Petr Kanˇovsky´, MD, Irena Rektorova´, MD, Daniela Sochuˇrkova´, MD, Dagmar Kubova´, MD, Robert Kuba, MD, and Pavel Daniel, Ing First Department of Neurology, Masaryk University, St. Anne’s Teaching Hospital, Brno, Czech Republic

Abstract: Sources of potentials evoked by cognitive processing of sensory and motor activities were studied in 9 epilepsy surgery candidates with electrodes implanted in the basal ganglia (BG), mostly in the putamen. Several contacts were also located in the pallidum and the caudate. The recorded potentials were related to a variety of cognitive and motor activities (attentional, decisional, time estimation, sensory processing, motor preparation, and so on). In five different tests, we recorded P3-like potentials evoked by auditory and visual stimuli and sustained potential shifts in the Bereitschaftspotential and Contingent Negative Variation protocols. All of the studied potentials were generated in the BG. They were recorded from

all over the putamen. Various potentials on the same lead or nearby contacts were recorded. A functional topography in the BG was not displayed. We presume that the cognitive processes we studied were produced in clusters of neurons that are organized in the basal ganglia differently than the known functional organization, e.g., of motor functions. The basal ganglia, specifically the striatum, may play an integrative role in cognitive information processing, in motor as well as in nonmotor tasks. This role seems to be nonspecific in terms of stimulus modality and in terms of the cognitive context of the task. © 2005 Movement Disorder Society Key words: basal ganglia; cognitive; motor; potentials; ERP

The basal ganglia (BG) participate in cognitive activities related (as well as unrelated) to motor functions1–3; however, the cognitive role of BG is not well understood. We had the opportunity to record electrical brain activity directly from the BG in nine epilepsy surgery candidates. We recorded from various parts of the putamen, and a few recordings from the caudate and the pallidum were also obtained. In previous studies, we reported the recordings of studied potentials in the cortex and in the BG.4 –11 This study comprises data obtained in a series of protocols that have been published elsewhere. The data are reviewed from another point of view. Various implications of the study, including the recordings of several types of event-related potentials in the basal ganglia and the impact of deep generators upon the scalp recorded

potentials, have already been published. The present study presents a review of the data from the point of view of the distribution of the potentials inside the basal ganglia. Our results indicated that the basal ganglia, specifically the putamen (from which we obtained the bulk of our recordings), and possibly also the pallidum and the caudate, not only receive external sensory information, but participate in the cognitive processing of such information. This processing occurs in the BG with, as well as without, a motor task. Similarly, the electrical activity, which is linked with several mostly cognitive processes that are related to the movement preparation, occurs in the basal ganglia. In this study, we located the potentials related to a variety of cognitive and motor activities (attentional, decisional, motor preparation, sensory processing, and so on) inside the BG, mostly in the putamen. In accordance with the known regional functional differentiation of the BG, we presumed that cognitive tasks are processed mostly in the “cognitive” parts of the BG, whereas motor tasks are processed mostly in the “motor” part. According to this presumption, the sources of cognitive- and

*Correspondence to: Dr. Ivan Rektor, First Department of Neurology, Masaryk University, St. Anne’s Hospital, Pekarska 53, 656 91 Brno, Czech Republic. E-mail: [email protected] Received 25 February 2004; Revised 29 July 2004; Accepted 15 August 2004 Published online 19 January 2005 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20368

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FIG. 1. A magnetic resonance imaging scan, inversion recovery sequence. Electrode inserted diagonally into the amygdalohippocampal complex through the putamen. The actual volume of the electrode corresponds to approximately 10% of the visible artefact.

movement-related potentials should have displayed some topographic organization, but this was not the case in our study. To our knowledge, this report is the first study mapping the potentials evoked by cognitive and motor activity in the human BG. SUBJECTS AND METHODS The study protocol was approved by the local ethics committee. Informed consent was obtained from each patient. Recordings were obtained from 9 epilepsy surgery candidates recommended by a special commission for stereotactic exploration. The patients (8 men, 1 woman; mean age 33 years) all suffered from pharmacoresistant mesiotemporal epilepsy. All the patients had normal motor performance, normal hearing, and normal or corrected-to-normal vision. The detailed characteristics of the patients have already been reported elsewhere4 –9; cases of serious cognitive disturbances were excluded. Depth electrodes were implanted to localize the seizure origin. Each patient was implanted with four to nine orthogonal electrodes using the methodology of Talairach and Bancaud12 and with one or two diagonal electrodes inserted by means of the frontal approach into the amygdalo– hippocampal complex, passing through the BG. Fifteen contact platinum semiflexible electrodes, each with a diameter of 0.8 mm, a contact length of 2 mm, and intercontact intervals of 1.5 mm, were used. The exact positions of the electrodes were verified using postplacement magnetic resonance imaging with electrodes in situ (Fig. 1). The mutual position of the electrode contacts and the brain structures could be seen on the magnetic resonance image and was further verified

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on the Talairach–Tournoux stereotactical atlas. In this study, the only patients that were involved were those in whom the exact location in the BG of individual contacts was possible to determine. Recordings from intracerebral electrode contacts were done in a referential montage (with the contact serving as the active pole, and connected earlobes used as the reference). The signal was filtered in the range between 0.1 Hz and 100 Hz, and the time base was 1,000 (auditory) or 2,000 (visual) msec for the oddball P3 recordings; for the contingent negative variation (CNV) and Bereitschaftspotential (BP) recordings, the signal was filtered in the range between 0.01 Hz and 100 Hz, and the time base was 5,000 msec. In the BP and CNV paradigm, 30 to 60 artefact-free trials were averaged; in the oddball paradigm for each type of stimulus, target and frequent, 40 sweeps were independently averaged. At least two recording sessions using each paradigm were made to ensure reproducibility. For the surface electromyography (EMG) recordings, the band pass filter was 200 Hz to 3 kHz. All recordings were done using either the 8-channel EP/EMG device (Kohden Neuropack 4200; Nihon Kohden Electronics, Osaka, Japan) or the 64-channel EEG system (Brain Quick; Micromed, Mestre, Italy) with ScopeWin (Jura´k Electronics, Brno, Czech Republic) tailored software. Subjects were seated comfortably in a semireclined chair in a moderately lighted room during the recordings. Eye movement artefacts were monitored using an electro-oculography channel placed at the outer canthus of the right eye. Any other outgoing artefacts (saturating DC shift of the trace, erratic movement of the patient, blinking, and so on) were rejected on-line when possible or during the off-line analysis. The details of protocol and recording parameters have been published elsewhere.4 –9 In this study, we present a brief overview of the tests performed. The following paradigms were tested. Auditory Oddball P3 Paradigms Standard Auditory Oddball Paradigm (aP3c). Tones were delivered through earphones at a 2 Hz frequency: frequent (”masking”) tones were delivered at 1,000 Hz and 70 dB, for a 0.1-second duration; rare (“target”) tones were delivered at 2,000 Hz and 70 dB, for a 0.1-second duration. The tones were randomly generated at a 5:1 ratio. Subjects were instructed to recognize the target tones and to silently count them and not to perform any motor activity during the test.

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Motor and Oddball Paradigm (aP3). All parameters, see above. Subjects were instructed to respond to the target stimulus by pressing a response switch in the dominant hand and to silently count the target. Visual P3 Paradigm (vP3) The standard visual oddball paradigm was performed with two types of emotionally neutral stimuli in random order: yellow uppercase Xs (target) and Os (frequent) on a white background, with a stimulus exposure duration of 200 msec. The ratio of target to frequent stimuli was 1:5. The stimuli were displayed on a black screen subtended at a visual angle of 3 degrees. The interstimulus interval varied between 2 and 5 seconds. Subjects were instructed to respond to the target stimulus by pressing a response switch button in the dominant hand and to silently count the target. Sustained Potential Shifts Bereitschaftspotential. Subjects were instructed to perform a brisk hand flexion, without any external stimulus (i.e., in the self-paced mode). Slow potentials appearing before a simple repetitive distal limb movement were recorded. In one series, a more complex movement (turning pages in a book) was used.4 Contingent Negative Variation. The recordings were performed in an audiovisual paradigm (S1-S2 task) with 3-second interstimulus interval. The imperative stimulus was followed by a brisk flexion of the hand. As a warning stimulus (S1), a single acoustic tone was randomly presented through headphones (80 dB intensity, 0.1 Hz stimulus rate, 0.1-msec duration). The imperative stimulus (S2) was a visual stimulus, a single 0.1 Hz flash delivered through goggles. The CNV (slow shift in the interstimulus interval) was analyzed, as well as the P3-like potentials that followed the auditory warning (aCNV) and the visual imperative (vCNV) stimuli. Analysis of Recorded Potentials All recordings were analyzed by two electrophysiologists experienced in the field. Furthermore, all data were displayed and debated in sessions comprising nearly all team members. Any dubious data were excluded. Only the potentials with phase reversal or steep voltage change across neighboring leads, indicating the proximity to the generating structure, were considered. A steep voltage change is widely accepted as a sign of proximity to


generating structures. An amplitude that is clearly larger in one structure than in neighboring structures suggests a local generation of potentials. To our knowledge, a consensual definition of how to measure exactly the difference of potentials has not been published. In our group, we have been considering an amplitude difference of at least 30% across a short distance of brain tissue as a steep current gradient. P3-like Potentials. We evaluated the first distinctive potential to occur in the 250- to 600-msec time window after the target stimuli in the oddball paradigm, or after the S1-S2 stimuli in the CNV paradigm. BP and CNV: sustained potential shifts compared to the baseline were considered.7 The baseline was defined as the electrical activity that occurred 3,000 to 3,500 msec before the movement in the BP protocol and 500 msec preceding the warning stimulus in the CNV protocol. The distance from the electrode to the generator heavily influences the amplitudes of intracerebrally recorded potentials; thus, the absolute amplitudes were not evaluated in this study. A clearly larger amplitude in one contact than in neighboring contacts (i.e., a steep voltage gradient) and a polarity inversion over a short distance suggested a local generator. The potentials that had amplitudes that remained unchanged over several consecutive contacts were considered as far-field potentials and were excluded from evaluation. RESULTS No pathological activity, i.e., no epileptiform activity, was recorded in the BG.13 This study was performed on patients with epilepsy; however, we believe that the underlying disease did not have any considerable influence on recorded results. There were no epileptiform discharges in the BG and no clinical signs of disturbance of the BG. The recordings were performed from the putamen in 7 patients on the right side and in 4 patients in the left side; from the pallidum in 2 patients; and from the caudate in 1 patient. There were 39 electrode contacts located in the putamen (right side 26, left side 13); 5 contacts in the internal pallidum (right, 2; left, 3); one left-sided contact in the external pallidum; and 3 contacts in the left caudate. A clear amplitude gradient or a phase reversal of the evoked potential components and of slow potential shifts was repeatedly found in the BG (Figs. 2 and 3). The potentials were distributed in all of the explored areas of the BG. No regional distribution of individual potentials or of groups of potentials was displayed.


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FIG. 2. The position of all electrode contacts in all patients in the left and right basal ganglia (BG). The distribution of the local field potentials of the P3-like potentials, the Bereitschaftspotentials (BP), and the contingent negative variation (CNV) in the BG. Based on the Talairach and Tournoux Atlas (1988). 1, vP3; 2, vCNV; 3, aCNV; 4, aP3; 5, aP3c; 6, BP; 7, CNV. Pu, putamen; GP, pallidum; NC, caudate.


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FIG. 3. Upper left: The position of the diagonal electrode in the right putamen and amygdala. Upper right: The coplanar stereotactic atlas reconstruction of the intracerebral electrode position (Talairach and Tournoux, 1988). Lower: Contingent negative variation (CNV) recording in the audiovisual paradigm. Electrode contracts: X5, the amygdala; X6, the border between the white matter and putamen; X7–X11, the putamen. as, auditory stimulus; VS, visual stimulus. Note the polarity inversion of the visual evoked potential component, the peak latency of 250 msec, the negative polarity on the electrode contact X7, the positive polarity on the electrode contacts X8 – X11. There is another polarity inversion of the visual evoked potential component, the peak latency of 405 msec (the positive polarity on X7 and negative polarity on X8 –X11). The peak latencies are indicated by black arrows. There is no apparent CNV on electrode contacts X5–X11.

The cortical recordings and their relationship to the potentials recorded in the BG are addressed in a separate study.11 In this study, we state only that the difference between the latencies of all potentials in the BG and in the cortex was insignificant. The basal ganglia activity was not driven from the cortex. DISCUSSION We studied the distribution of potentials evoked by several cognitive-related and motor-related activities in the BG, mostly in the putamen: (1) slow potential shifts expressing cognitive activities related to the self-initiated movement (BP) and to the externally cued movement (CNV)7,14,15 (CNV is also believed to include arousal, attention, expectation, and time estimation); and (2) cognitive processing of visual and acoustic signals in an oddball paradigm and in a more complex task in the CNV paradigm (P3-like potentials). In terms of the relation to the motor activity, we obtained three types of data: (1) Potentials related directly to the motor activity in terms of the timing, the


decision to perform the movement, planning, programming, preparing, initiating and executing a movement. The movement was self-initiated in the BP protocol and cued in the CNV protocol. BP are generated by processes specifically involved in the preparation for or intention to perform a movement. The processes associated with attention, cognition, and expectancy could not solely account for BP.4,7,14,16 The CNV reflects the will to elaborate the response, decisional performance, time estimation, and preparation of signaled movements.2,15,17–19 (2) The event-related potentials (ERPs) that were not related to the motor functions: In the auditory oddball protocol (aP3c), the auditory P3-like potential after a warning stimulus (aCNV) was not followed by any motor activity. There was no motor act, neither overt nor covert, in the aP3c oddball task. The behavioral meaning of the warning stimulus that elicited aCNV was that an imperative stimulus would follow in 3 seconds. (3) The ERPs not directly related to the movement, in which the paradigm included a motor task


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FIG. 4. P3-like potentials (aP3, vP3, vCNV) and slow potentials (contingent negative variation [CNV], Bereitschaftspotential [BP]) recorded from the contact X8 in the right-sided pallidum. Reproduced from I. Rektor et al.; Exp Brain Res 2004, Springer Verlag, with permission of the publisher.11

(vCNV, aP3, vP3): The ERPs covered identical cognitive activities (closure of sensory analysis; the update of working memory; the orientation, expectation, decisional processes; and so on) as those above when performed without an overt movement; however, in this case, the behavioral context was motor. Based on the known functional anatomy of the BG,20 –22 we predicted a different distribution of purely cognitive potentials and motor-related potentials. To our surprise, we were unable to reveal a focal concentration of any type of recorded potentials inside the BG. There is no clear functional topography of cognitive potentials inside the putamen; the various potential generators are mutually intermingled (Fig. 2). The cognitive- and motor-related potentials were generated all over the putamen. We found a similar situation in the pallidum and the caudate; however, we had only a limited number of contacts in these structures. A reasonable amount of data was acquired from the putamen. Subsequent discussion is valid, therefore, mainly for the putamen. A limitation of this study is that we were not able to systematically map the entire putamen. The restricted number of recording sites did not

enable us to uncover an internal organization of the studied phenomena in the BG. Nevertheless, we were able to record from various parts of the putamen characteristics of the electrodes that we used, e.g., up to seven consecutive contacts inside the BG, the small volume of the lead, and the short intercontact distance (1.5 mm) enabled the relatively precise localization of the signal source within the explored cerebral structure. The much less extensive data from the pallidum and from the caudate did not differ substantially from what we observed in the putamen. We recorded various potentials on the same lead or nearby contacts (Fig. 4). A depth electrode contact is submerged in the neuronal tissue and, thus, records from its immediate vicinity. This finding means that the neuronal pools generating various potentials are either very close to each other or even overlapping or that some neurons are active in several tasks. In multiunit recordings, Kropotov and colleagues16,17 similarly observed separate stimulus-related and response-related neuronal populations in an oddball paradigm. In the monkey putamen, cells producing activity after a visual trigger and


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cells responding to the auditory trigger of a movement could be recorded in the same location.18 The interpretation of our data is difficult. The potentials in the BG do not simply reflect the cortical distribution. In contrast to the distributed occurrence of the P3-like potentials in multiple cortical areas, the cortical distribution of the BP and CNV was much more restricted (for review, see Rektor7), although there is no difference in their occurrence in the BG. The cognitive activities in the BG were not driven from the cortex, as the difference of P3-like potential latencies between the BG and the cortex was nonsignificant.6 This finding indicates the parallel processing of information in the cortex and in the BG. One possible explanation of our findings is that the neuronal populations active in individual tasks overlap or are very close each to other, so that a contact is unable to distinguish between the activities of various active neuronal pools. These neuronal pools might form a network that could not be revealed by our electrodes due to their limited number. Nevertheless our data show that even such a hypothetical network would not be distributed according to known functional topography of the BG. The lack of regional distribution of various cognitive activities in the BG may also indicate that, from the point of view of the functioning of the BG, there is no substantial difference between the protocols used. The BG might play a nonspecific role in information processing and in some other cognitive activities. The central position of the striatum, which receives information from nearly all neocortical areas, leads us to the assumption that it may function as an information integrator. The multifunctional clusters of neuronal populations may form a substrate for an integrative function of the BG. This nonspecific integrative role may be the basis of the specific activities of the BG that were suggested, for example, the planning of movement, involvement in the attention process, a cognitive pattern generator, the program selection, or the selection of a particular movement associated with contextual sensory cues.2,16 –22 The BG is the site at which information from various functional systems (sensory, attentional, motor, memory) may be processed in a mutual context. This contextual modulation may be important for the functioning of the cortical areas that are the target of the cortico-basal ganglionicthalamocortical loop. Acknowledgment: This work is supported by research program MSˇ CˇR 0021622404.

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