104
Electroencephalography and Clinical Neurophysiology, 1978, 4 4 : 1 0 4 - - 1 0 7 © Elsevier/North-Holland Scientific Publishers, Ltd.
Laboratory note LIMBIC SPINDLES: GENUINE CEREBRAL ACTIVITY OR ARTIFACT? RUGGERO G. F A R I E L L O and SHEILAH FRANZOSO
EEG Laboratory, Department of Neurology, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin, 53 706 (U.S.A.) (Accepted for publication: June 3, 1977)
Depth electrode recordings in primates revealed the existence of a rhythmic spindling activity in various limbic structures (Domino and Ueki 1960). In animals with chronic recordings this activity was influenced by variations in state of alertness (Reite et al. 1967), by olfactory stimuli and by electrical stimulation of distant cerebral nuclei (Delgado et al. 1970). Essential prerequisite for the spindles appearance is an intact upper respiratory system: in fact, tracheostomy and anesthesia of the ansal mucosa abolish spindles (Delgado et al. 1970). Apparently, the same kind of activity can be recorded from electrodes implanted in the olfactory bulb and amygdala of human subjects (Hughes 1972). A recent report (Reite 1975) advanced the suggestion of the identity between limbic spindles and a peculiar spindling activity occasionally obselwed from nasopharyngeal (NP) leads in clinical EEG laboratories. In an attempt to correlate such EEG activity with physiological functions or pathological conditions we reviewed the NP recordings obtained from patients during a 3 year period in our laboratory, from 1974 to 1976.
Materials and methods NP recordings were obtained from 358 patients aged from 7 to 78 years. Scalp electrodes were placed according to the 10-20 international system, Recordings were done by means of 16 ehennel polygraph Grass models 78B or 6. Fifteen patients were monitored for respiration and ECG. Morphology, topographic and temporal distribution were used as guidelines in the recognition of 'limbic spindles', Thus, all EEG activity with fusiform shape, showing frequency between 8 and 60 c/see, occurring with a periodicity of 0.3--0.15 complexes/see and being exclusively or preferentially localized to NP lead(s) was considered as possible 'limbic spindles'. Amplitude was not a discriminative factor,
Results One hundred and eight records presented activity which met the above outlined criteria for selection of spindles. In most cases spindles appeared during sleep, especially stage I and II, although occasionally spindling was observed during awake periods in which case spindles assumed features reminiscent of muscle activity (Fig. 1A). Behavioral observation and/or concomitant respirogram showed that periodicity was strictly connected with the respiratory rhythm, the beginning of the spindle being coincident with the very end of inspiration or the onset of expiration (Fig. 2). In 58 records it was noted that spindling was associated with snoring. During occurrence of spindles in 18 patients various olfactory stimuli (orange, acetone and alcohol) were presented which did not modify spindles unless change in respiration rate and/or awakening were obtained. Eight patients with spindles had a second NP EEG (5 with Brevital actiration) and spindles were not reproducible. In approximately 2/3 of cases with spindles clear electrode artifacts were present sometime during the record. These were localized to or clearly predominant in the same leads where spindles occurred. Periodic spindles were never seen to diffuse to homologous scalp electrodes even when attaining very high voltage (up to 1 mV) in the NP leads (Figs. 1, 2). Fifty-five records showed mixed transitional patterns from clear artifacts to spindling activity and spindle feature were often changing during the same record (Fig. 1) Attempts to make significant statistical correlations as to age distribution, sex, normal or abnermal EEG and neurological diagnosis failed when compared to a representative sample of our laboratory population. In nine patients another type of spindling activity was observed. This, although at times pseudoperiodic, was never associated with respiratory rhythm. Further, it occurred during sleep and it was associated with similar events on the vertex.
A.
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............................................................
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........................
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Fig. 1. Samples taken from the same recording. In A, periodic muscle-like activity appeared during the awake stage. B and C show extreme variability of "spindles" going from a single spike-like element (arrow in C) to a typical "spindle" (third one in B) and eventually (D) a clear electrode artifact precedes each spindle.
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26B
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Fig. 2. S t r i c t c o r r e l a t i o n s o f " s p i n d l i n g " w i t h r e s p i r a t i o n . P a t i e n t is s n o r i n g . N o t e also m a x i m a l a m p l i t u d e a t t a i n e d b e t w e e n t h e t w o NP electrodes,
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LIMBIC SPINDLES IN HUMANS The utilization of the criteria which have been used to suggest the analogy between amygdaloid spindles in primates and in man (Reite, 1975) led us to the selection of a large variety of EEG activities many of which are certainly of artifactual origin. Thus these criteria are not sufficient nor accurate enough to identify a phenomenon of genuine cerebral origin. Further, important differences exist between the spindles in primates and man. In the chimpanzee, spindles diminished during sleep (Reite, 1967) whereas in man we observed them preferentially during sleep; in the monkey olfactory cues increased them (Delgado, 1971) and in man do not affect them. The identity of the two phenomena is, therefore, questionable. In consideration of: (1) lack of reproducibility of the phenomenon in the same patient, also upon administration of Brevital, a compound which favors spindle formation in the EEG; (2) absence of transmission of the spindles to other scalp electrodes; (3) frequent association of artifacts in the same leads where spindles occurred and (4) presence of transitional, mixed patterns from clear artifacts to possible spindles we suggest that at the present time it is unwise to consider as genuine cerebral activity an obscure phenomenon which is intimately connected with respiratory artifacts, We believe that the only genuine spindles are the non-periodic ones associated with vertex spindles and sharp waves. These are definitely different from the 'limbic spindles' in primates and probably represent sleep spindles which occasionally are preferentially projected to mesial limbic structures,
Summary A periodic spindling activity recorded in clinical EEG laboratories from nasopharyngeal (NP) leads has been interpreted as expression of genuine cerebral rhythms originating in the limbic system. Evidence is here presented to suggest that such activity is indeed an artifact. Genuine spindling occasionally occurs in NP leads but this is intimately related to sleep spindles occurring also in other surface electrodes.
107 R6sum6
Fuseaux limbiques: activite cdrdbrale veritable ou artefact? L'activit6 p6riodique de fuseaux, enregistr6e en 61ectroenc6phalographie clinique au moyen d'61ectrodes naso-pharyng6es a 6t6 interpr6t6e comme l'expression d'un rythme c6r6bral v6ritable prenant son origine dans le syst6me limbique. Les auteurs pr6sentent ici des arguments qui sugg6rent qu'une telle activit6 est en r6alit6 un art6fact. Une activit6 en fuseau authentique survient occasionnellement dans les 6lectrodes naso-pharyng6es, mais seulement en liaison avec les fuseaux de sommeil qui s'observent alors sur les autres 61ectrodes de surface.
References Delgado, J.M.R., Johnston, V.A., Wallace, J.D. and Bradley, R.G. Operant conditioning of amygdala spindling in the free chimpanzee. Brain Res., 1970, 22: 347--362. Domino, E.E. and Ueki, S. An analysis of the electrical burst phenomena in some rhinencephalic structures of the dog and monkey, Electroenceph. clin. Neurophysiol., 1960, 1: 653--648. Hughes, J.R., Hendrix, D.E., Andy, O.J., Wang, C., Peeler, D. and Wetzel, N. Correlations between electrophysiological and subjective responses to odorants as recorded from the olfactory bulb, tract and amygdala of waking man. In G.G. Somjen (Ed.), Neurophysiology Studied in Man, Excerpta Medica, Amsterdam, 1972 : 260--280. Reite, M., Stephens, L. and Pegram, G.V. Uncal spindling in the chimpanzee, Brain Res., 1967, 3: 392--395. Reite, M. Non-invasive recording of limbic spindles in man, Electroenceph. clin. Neurophysiol., 1975, 38: 539--541.
Electroencephalography and Clinical Neurophysiology, 1978, 4 4 : 1 0 4 - - 1 0 7 © Elsevier/North-Holland Scientific Publishers, Ltd.
Laboratory note LIMBIC SPINDLES: GENUINE CEREBRAL ACTIVITY OR ARTIFACT? RUGGERO G. F A R I E L L O and SHEILAH FRANZOSO
EEG Laboratory, Department of Neurology, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin, 53 706 (U.S.A.) (Accepted for publication: June 3, 1977)
Depth electrode recordings in primates revealed the existence of a rhythmic spindling activity in various limbic structures (Domino and Ueki 1960). In animals with chronic recordings this activity was influenced by variations in state of alertness (Reite et al. 1967), by olfactory stimuli and by electrical stimulation of distant cerebral nuclei (Delgado et al. 1970). Essential prerequisite for the spindles appearance is an intact upper respiratory system: in fact, tracheostomy and anesthesia of the ansal mucosa abolish spindles (Delgado et al. 1970). Apparently, the same kind of activity can be recorded from electrodes implanted in the olfactory bulb and amygdala of human subjects (Hughes 1972). A recent report (Reite 1975) advanced the suggestion of the identity between limbic spindles and a peculiar spindling activity occasionally obselwed from nasopharyngeal (NP) leads in clinical EEG laboratories. In an attempt to correlate such EEG activity with physiological functions or pathological conditions we reviewed the NP recordings obtained from patients during a 3 year period in our laboratory, from 1974 to 1976.
Materials and methods NP recordings were obtained from 358 patients aged from 7 to 78 years. Scalp electrodes were placed according to the 10-20 international system, Recordings were done by means of 16 ehennel polygraph Grass models 78B or 6. Fifteen patients were monitored for respiration and ECG. Morphology, topographic and temporal distribution were used as guidelines in the recognition of 'limbic spindles', Thus, all EEG activity with fusiform shape, showing frequency between 8 and 60 c/see, occurring with a periodicity of 0.3--0.15 complexes/see and being exclusively or preferentially localized to NP lead(s) was considered as possible 'limbic spindles'. Amplitude was not a discriminative factor,
Results One hundred and eight records presented activity which met the above outlined criteria for selection of spindles. In most cases spindles appeared during sleep, especially stage I and II, although occasionally spindling was observed during awake periods in which case spindles assumed features reminiscent of muscle activity (Fig. 1A). Behavioral observation and/or concomitant respirogram showed that periodicity was strictly connected with the respiratory rhythm, the beginning of the spindle being coincident with the very end of inspiration or the onset of expiration (Fig. 2). In 58 records it was noted that spindling was associated with snoring. During occurrence of spindles in 18 patients various olfactory stimuli (orange, acetone and alcohol) were presented which did not modify spindles unless change in respiration rate and/or awakening were obtained. Eight patients with spindles had a second NP EEG (5 with Brevital actiration) and spindles were not reproducible. In approximately 2/3 of cases with spindles clear electrode artifacts were present sometime during the record. These were localized to or clearly predominant in the same leads where spindles occurred. Periodic spindles were never seen to diffuse to homologous scalp electrodes even when attaining very high voltage (up to 1 mV) in the NP leads (Figs. 1, 2). Fifty-five records showed mixed transitional patterns from clear artifacts to spindling activity and spindle feature were often changing during the same record (Fig. 1) Attempts to make significant statistical correlations as to age distribution, sex, normal or abnermal EEG and neurological diagnosis failed when compared to a representative sample of our laboratory population. In nine patients another type of spindling activity was observed. This, although at times pseudoperiodic, was never associated with respiratory rhythm. Further, it occurred during sleep and it was associated with similar events on the vertex.
A.
T4-Cz
............................................................
-
........................
C z -]-3 .................................... " .............................................
50,uV'[
I SEC
I
D ~ . ~ . , ~ , . . ~ m' ~
~,.~..
Fig. 1. Samples taken from the same recording. In A, periodic muscle-like activity appeared during the awake stage. B and C show extreme variability of "spindles" going from a single spike-like element (arrow in C) to a typical "spindle" (third one in B) and eventually (D) a clear electrode artifact precedes each spindle.
I SEC
~,;lilJ/,, ,
26B
~@!l'l.,,,-.-.-~~,,'4~J':/,..,,~...-~.---~.-.~.-~,'""'
~67
"' : , ' - , ~ - ~
Fig. 2. S t r i c t c o r r e l a t i o n s o f " s p i n d l i n g " w i t h r e s p i r a t i o n . P a t i e n t is s n o r i n g . N o t e also m a x i m a l a m p l i t u d e a t t a i n e d b e t w e e n t h e t w o NP electrodes,
50,~VT
p,...-,- p~ -~..-~'~,~,~-.~.-~-.--.-.~-~.-~
~I
:Z N © ©
©
if) *q
LIMBIC SPINDLES IN HUMANS The utilization of the criteria which have been used to suggest the analogy between amygdaloid spindles in primates and in man (Reite, 1975) led us to the selection of a large variety of EEG activities many of which are certainly of artifactual origin. Thus these criteria are not sufficient nor accurate enough to identify a phenomenon of genuine cerebral origin. Further, important differences exist between the spindles in primates and man. In the chimpanzee, spindles diminished during sleep (Reite, 1967) whereas in man we observed them preferentially during sleep; in the monkey olfactory cues increased them (Delgado, 1971) and in man do not affect them. The identity of the two phenomena is, therefore, questionable. In consideration of: (1) lack of reproducibility of the phenomenon in the same patient, also upon administration of Brevital, a compound which favors spindle formation in the EEG; (2) absence of transmission of the spindles to other scalp electrodes; (3) frequent association of artifacts in the same leads where spindles occurred and (4) presence of transitional, mixed patterns from clear artifacts to possible spindles we suggest that at the present time it is unwise to consider as genuine cerebral activity an obscure phenomenon which is intimately connected with respiratory artifacts, We believe that the only genuine spindles are the non-periodic ones associated with vertex spindles and sharp waves. These are definitely different from the 'limbic spindles' in primates and probably represent sleep spindles which occasionally are preferentially projected to mesial limbic structures,
Summary A periodic spindling activity recorded in clinical EEG laboratories from nasopharyngeal (NP) leads has been interpreted as expression of genuine cerebral rhythms originating in the limbic system. Evidence is here presented to suggest that such activity is indeed an artifact. Genuine spindling occasionally occurs in NP leads but this is intimately related to sleep spindles occurring also in other surface electrodes.
107 R6sum6
Fuseaux limbiques: activite cdrdbrale veritable ou artefact? L'activit6 p6riodique de fuseaux, enregistr6e en 61ectroenc6phalographie clinique au moyen d'61ectrodes naso-pharyng6es a 6t6 interpr6t6e comme l'expression d'un rythme c6r6bral v6ritable prenant son origine dans le syst6me limbique. Les auteurs pr6sentent ici des arguments qui sugg6rent qu'une telle activit6 est en r6alit6 un art6fact. Une activit6 en fuseau authentique survient occasionnellement dans les 6lectrodes naso-pharyng6es, mais seulement en liaison avec les fuseaux de sommeil qui s'observent alors sur les autres 61ectrodes de surface.
References Delgado, J.M.R., Johnston, V.A., Wallace, J.D. and Bradley, R.G. Operant conditioning of amygdala spindling in the free chimpanzee. Brain Res., 1970, 22: 347--362. Domino, E.E. and Ueki, S. An analysis of the electrical burst phenomena in some rhinencephalic structures of the dog and monkey, Electroenceph. clin. Neurophysiol., 1960, 1: 653--648. Hughes, J.R., Hendrix, D.E., Andy, O.J., Wang, C., Peeler, D. and Wetzel, N. Correlations between electrophysiological and subjective responses to odorants as recorded from the olfactory bulb, tract and amygdala of waking man. In G.G. Somjen (Ed.), Neurophysiology Studied in Man, Excerpta Medica, Amsterdam, 1972 : 260--280. Reite, M., Stephens, L. and Pegram, G.V. Uncal spindling in the chimpanzee, Brain Res., 1967, 3: 392--395. Reite, M. Non-invasive recording of limbic spindles in man, Electroenceph. clin. Neurophysiol., 1975, 38: 539--541.
