P300 is unaffected by glucose increase

BIOLOGICAL PSYCHOLOGY ELSEVIER

Biological Psychology 37 (1994) 235-245

P300 is unaffected by glucose increase Mark W. Geisler Department of Psychology, State Unicersity of New York, Stony Brook, Stony Brook, W,

John Polich Department of ~~e~op~urmacolo~

USA

*

TPC-IO, The Scripps Research Irzstitufe, f&566 IV Torrey Pines Road, La Jolla, CA 92037, USA

Abstract

The effects of glucose ingestion on the P3(00) event-related brain potential (ERP) were investigated by using a visual stimulus oddball paradigm in which subjects discriminated between checkerboard (target) and horizontal line (standard) stimuli. Subjects were assessed for six consecutive trial blocks that were spaced 20 min apart on two different occasions. For the glucose condition, an initial baseline trial block was recorded followed by ingestion of 100 mg of glucose and the remaining five trial blocks recorded. For the water condition, the same procedure was employed with water ingested instead of glucose. Blood glucose levels, heart rate, and body temperature measures also were obtained before each trial block. P3 amplitude and latency did not change across trial blocks for the glucose/water conditions. No glucose/water effects were observed for the Nl, P2, or N2 components as well. Blood glucose levels and heart rate increased for the glucose but not the water condition; body temperature decreased with the ingestion of both glucose and water and then returned to baseline levels. These findings suggest that ERPs are not influenced by increases of blood glucose level and are discussed in the context of previous ERP studies employing glucose manipulations. Key words: P3(00); Event-related

potential (ERP); Glucose; Cognition.

1. Introduction

Several recent reports have demonstrated that the P3(00) event-related potential (ERP) is sensitive to metabolic state. When glucose level is reduced to

* Corresponding author. Tel.: + 1 619 554 8176. Fax: + 1 619 5.54 6393. E-mail: polich~scripps,~du. 0301-0511/94/$07.00 0 1994 Elsevier Science B.V. AI1 rights reserved SSDI 0301-0511(93)00930-I

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hypoglycemic values by means of insulin infusion in normal subjects, increases in P3 latency have been observed (Blackman, Towle, Lewis, Spire & Polonsky, 1990; De Feo et al., 1988; Gallai, Mazzotta, Firenze & Del Gatto, 1988; Jones et al., 19901, with delayed latencies also obtained for diabetic patients (Pozzessere et al., 1991), and at least one study reporting decreases in N2-P3 peak-to-peak amplitude (Gallai et al., 1988). In addition, there is some indication that auditory brain stem and the Nl, P2, and N2 long-latency auditor components are affected by large glucose changes (Gallai et al., 1988; Jones et al., 1990), although no metabolic effects have been observed for sensory visual-evoked responses with hypoglycemic manipulations (Blackman et al., 1990; Gallai et al., 1988). Thus, the effects of metabolic processes appear to contribute to ERP production, at least when gIycemic levels are decreased markedly. Changes for P3 measures in normal subjects when hunger is varied have also been found. In an initial report, Geisler and Polich (1990) observed that P3 amplitude was smaller and peak latency somewhat slower for subjects who had not eaten within 6 h of testing compared with subjects who had eaten within 3 h of testing. A subsequent study manipulated the time of food consumption directly and obtained increased P3 amplitude after food ingestion (Geisler & Polich, 1992a). When subjects who varied with respect to their time-of-day activity preference (morning vs. evening) were compared under hungry vs. recently fed conditions, P3 amplitude was larger for the fed than for the hungry subjects, especially if they were assessed at their non-preferred time of day (Geisler & Polich, 1992b). The latter finding is supported by studies in which increases in P3 amplitude have been related to increases in metabolic activity stemming from exercise (Dustman et al., 1990; Geisler & Squires, 1992). In addition, P3 amplitude reflected hunger states when food-related words were used to elicit the ERPs (Baldeweg, Ullsperger, Pietrowsky, Fehm & Born, 1993). Taken together, all of these results strongly suggest that the P3 is affected by metabolic processes, although the precise nature of these effects is not well understood. The theoretical import of these results comes from the link between the P3 and attentional/ memory processes (Donchin & Coles, 1988; Donchin, Karis, Bashore, Coles & Gratton, 1986). Variation in P3 amplitude (Fabiani, Karis & Donchin, 1990; Noldy, Stelmack & Campbell, 1990; Smith & Halgren, 1989) and latency in normals (Emmerson, Dustman, Shearer & Turner, 1990; O’Donnell et al., 1990; Polich, Ladish & Burns, 1990), as well as in various clinical populations (Goodin, Aminoff & Chequer, 1992; Homberg, Hefter, Granseyer, Strauss, Lange & Hennerici, 1986; O’Donnell, Squires, Martz, Chen & Phay, 1987; Polich, Ehlers, Otis, Mandell & Bloom, 1986; Polich, Ladish & Bloom, 19901, suggests that P3 measures reflect individual differences in cognitive ability. Several different reports have found that glucose levels are related directly to performance on various neuropsychological tests involving attention and memory (Benton, 1989, 1990; Benton, Brett & Brain, 1987; Deijen, Heemstra & Orlebeke, 1989; Gonder-Frederick, Hall, Vogt, Cox, Green & Gold, 1987; Haier et al., 1988; Hall, Gonder-Frederick, Chewning, Silveira & Gold, 1989; Manning, Hall & Gold, 1990). Therefore, understanding how metabolic factors-typically glucose intake-contribute to P3 changes may

shed light on the theoretical underpinnings of the P3 ERP. Indeed, changes in P3 values with hypoglycemia and food ingestion also have been found ta correlate with changes in cognitive task performance (Blackman et al., 1990; Geisler & Polich, 199%). Thus, variation in metabolic state affects the P3 component directly and appears to influence neuropsychologica~ performance in a concomitant fashion. Despite this apparent connection between metabolic variation and the P3 ERP, however, the exact relationship between the effects of glucose intake per se on ERP measures is not clear, since most studies have employed ~~~o~~~~e~~~ manipulations to study metabolic influences on ERPs. Moreover, the one report in which food intake caused glucose increase did not find a direct association between blood glucose levels on P3 amplitude or latency (Geisler 8r Polich, 1992a). The present study was conducted to assess the effects of glucose uptake on ERPs directly. In the glucose condition, ERPs were obtained before and after ingestion of h~~~rg~~~~~~ amounts of glucose; in the water control condition, ERPs were obtained before and after ingestion of water. A visuaf oddbalf paradigm was emptoyed to elicit the ERPs so that habituation of P3 amplitude that occurs with repeated testing using auditory but apparently not with visual stimuli could be avoided (Lew & Polich, 1993; Polich, 1989; Pritchard, Brandt, Shappell, O’Dell & Barrett, 1986). If glucose intake does affect ERPs, then P3 amplitude should increase and P3 latency should decrease as a function of increases in the influence of the glucose on metabolic activity,

2. Method

Twenty-four undergraduate subjects, Cl2 male, 12 female; mean age = 22.5, SD = 3.4) were employed. All subjects were instructed to consume no food or beverages other than water after 8:00 p.m. the previous evening and were tested beginning at 11:OOa.m. the next day. The subjects reported normal health and no history of diabetes, psychiatric, or neurologic disorders. Subjects received course credit and/or pecuniary compensation for their participation. 2.2. Stimuli and procedure Checkerboard (target) and horizontal line (standard) patterns were used as stimuli and presented visuaIIy in a random series once every 2 s, with a duration of 100 ms and a target stimulus probability of .20. The lines were 2.5 cm wide, and the checks were 5.0 cm square and were presented on a CRT that was viewed from a distance of 1.5 m, Subjects were instructed to respond to the target stimuli by moving the index finger of their right hand whenever a checkerboard pattern was detected; 20 artifact-free target trials were obtained for each trial block. Six ERP trial blocks were collected for the glucose and water ingestion condi-

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J. Polich /Biological Psychology 37 (I 994) 235-245

tions on separate days. For the first trial block in each ~ndition, baseline ERPs, blood glucose level, heart rate, and oral body temperature were assessed. Before the second trial block, a chilled 10 oz cola drink containing 100 mg of glucose (Tru Glu-Cola: dextrose-based glucose, no caffeine) or 10 oz of chilled bottled water was ingested orally by the subject, with 5 min allowed to imbibe the entire amount. Water was employed to ensure that no hitherto unknown influences on ERPs would be ingested that might compromise the control drink. Subjects did not know which beverage they would be consuming on the first experimental day. For the second trial block, about 20 min after the baseline data were collected, ERPs and all physiological measures were obtained after the liquid had been consumed. The third through sixth trial blocks were then recorded every 20 min afterwards for a total of six trial blocks obtained over an 80 min period for each testing day. The order of the glucose/water conditions was counterbalanced across subjects within sex. Blood glucose levels were measured with a portable blood glucose monitoring system (Exactec). Heart rate was obtained by palpation of the radial pulse at the wrist. Body temperature was recorded orally with an electronic thermometer (Ivac model 821) immediately before each ERP task presentation.

Electroencephalographic (EEG) activity was recorded at the Fz, Cz, and Pz electrode sites of the lo-20 system, using gold-plated electrodes, affixed with electrode paste and tape, referred to linked earlobes with a forehead ground. Additional electrodes were placed at the outer canthus and supraorbitally to the left eye, with a bipolar recording made of electro-ocular activity. The impedance for all electrode sites was 10 kfi or less. The filter bandpass was 0.016-30 Hz (3 dB down, 12 dB octave/slope). The EEG was digitized at 3 ms per point for 768 ms with a 75 ms prestimulus baseline. Waveforms were averaged on-line by a commercial apparatus, which aIso controlled the stimuIus presentation and artifact rejection. Trials on which the EEG or EOG exceeded 290 FV were rejected automatically.

3. Results All analyses of variance employed Geisser-Greenhouse adjustments to the degrees of freedom to correct for violations of sphericity, with only the probability values (and epsilon) from the corrected df reported here. The overall error rate for the visual task was .OOl% missed target stimuli. This low error rate indicates that all subjects were able to perform the visual task quite well across all conditions. 3.1. P3

c5~~onen~

The grand averages for all target stimulus trials, from the glucose and water conditions, across all subjects, and each electrode site are presented in Fig. 1. The

M. W. Geisler, J. Polich /Biological Psychology 37 (1994) 235-245

Baseline

0 Minutes

20 Minutes

40 Minutes

60 Minutes

239

80 Minutes

~~~~~~~~

CzA,n,AdA,2n

Fig. 1. Grand averaged ERPs for the water and glucose conditions for each trial block and electrode site (N = 24).

P3 component from both the target and the standard stimuli was defined as maximum positive peak occurring after the Nl-P2-N2 components within latency window 300-500 ms, and its amplitude was measured relative to prestimulus baseline. The Nl, P2, and N2 components were assessed within latency windows of 80-160, 150-220, and 200-300 ms for both the target and standard stimuli. The mean P3 amplitude and latency values for each condition a function of trial block from the Pz electrode site are presented in Fig. 2.

the the the the the as

3.1.1. P3 amplitude A three-factor (glucose/glucose condition x trial block X electrode site) analysis of variance was performed on the P3 amplitude data from the target and standard stimuli for each subject. P3 amplitude from the &zarge#srimuli did not differ overall between the glucose and water conditions, F(1, 23) < 1, p > SO. P3 amplitude increased from the frontal to parietal electrode sites, F(2, 30.6) = 24.6, p < .OOl (epsilon = .664). P3 amplitude from the standard stimuli produced no difference between the glucose and water conditions, F(1, 23) < 1, p > .70, with amplitude found to increase from the frontal to parietal electrode sites, F(2, 43.5) = 36.4, p < 1 (epsilon = .945). P3 amplitude from the standard stimuli decreased as a function of trial block, F(5, 94.8) = 7.4, p < .OOl (epsilon = .824). A marginally significant tria1 block x electrode interaction was obtained; decreases in amplitude across trial blocks were greater for the central and parietal electrode sites than for the frontal recording site, F(10, 97.9) = 2.2, p < .lO (epsilon = .425).

240

M. W Geisler, J. Polich /Biological Psychology 37 (1994) 235-245

U ---a---

WATER GLUCOSE

TIME

Fig. 2. Mean P3 amplitudes and latencies from the target and glucose conditions as a function of trial block.

(min)

stimuli at the Pz electrode

site for the water

3.1.2. P3 latency The same three-factor analysis of variance was applied to the P3 latency from the target and standard data. For the target stimuli, no overall significant difference between the glucose and water conditions was obtained, F(1, 23) = 2.5, p > .lO. P3 latency from the targets increased from the frontal to parietal electrode sites, yielding a significant main effect for electrode site, F(2, 31.8) = 4.4, p < .03 (epsilon = .690X P3 latency increased across trial blocks, F(5, 92.5) = 4.8, p < .OOl (epsilon = .804X For the standard stimuli no overall difference between the glucose/water conditions was obtained, F(1, 23) < 1, p > .50. P3 latency decreased from the frontal to the parietal electrodes yielding a significant main effect for electrode site, F(2, 29.4) = 46.5, p < .OOl (epsilon = .690), and increased across the trials from baseline to trial number six, F(5, 76.1) = 3.0, p < .03 (epsilon = .661). 3.3. Nl -P2-N2

effects

The mean Nl-P2-N2 trials for each condition

amplitude and latency values for the standard stimulus as a function of trial block from just the Cz electrode site

M. W Geisler, J. Polich /Biological Psychology 37 (1994) 235-245

241

GLUCOSE

WATER

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4

Nl

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d

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Fig. 3. Mean Nl, P2, and N2 amplitudes and latencies from the standard stimuli at the Cz electrode site for the water and glucose conditions as a function of trial block.

are presented in Fig. 3. Only the results from the standard stimuli are presented, since no reliable effects were obtained for the Nl, P2, and N2 potentials from either the target or the standard stimuli. A three-factor (glucose/ water condition x trial block x electrode) analysis of variance was applied to the Nl-P2-N2 amplitude and latency data from each subject for the target and standard data. For both target and standard stimuli, no main effects or interaction with the glucose/ water conditions were obtained for the Nl, P2, or N2 component data. The only consistent effects for these components were those typically observed for the electrode factor. In addition, the Nl amplitude for the standard data yielded an apparently spurious electrode by block interaction (p < .05), and the N2 latency from the targets yielded a main effect for trial block (p < .Ol). 3.4. Physiological variables The mean values obtained for glucose, heart rate, and body temperature are presented in Fig. 4. A two-factor (glucose/water condition X trial block) analysis of variance was applied to the values of the physiological variables. Blood glucose levels increased for the glucose condition compared with water condition across

242

M. W Geisler, J. Polich /Biological Psychology 37 (1994) 235-245

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TIME Fig. 4. Mean blood glucose levels, heart conditions as a function of trial block.

rate,

and

Imin) body

temperature

for the water

and

glucose

measurement times, F(2, 23) = 182.1, p < ,001. This difference produced a significant main effect for trial block, N5, 74.5) = 28.2, p < .OOl. (epsilon = .766) and a highly significant interaction between the glucose/water and trial block factors, F(5, 66.0) = 29.5, p < .OOl (epsilon = .574).

M. W Ceder,

J. Polich /Biological

Psychology 37 (I 994) 235-245

243

Heart rate demonstrated similar effects, with a significant increase in heart rate for the glucose compared with the water condition obtained across trial blocks, F(2, 23) = 19.7, p < .OOl. The main effect for trial block, F(5, 74.0) = 3.7, p < .Ol (epsilon = .643), and the interaction between the glucose/water and trial block variables were significant, F(5, 88.4) = 11.57, p < .OOl (epsilon = .769). Temperature did not yield a main effect for the glucose/water manipulation (p > .30), although an effect for trial block was observed as is illustrated in the lower portion of Fig. 4, P(5, 38.2) = 6.0, p < .OOl (epsilon = ,332). The interaction between the glucose/water and trial block factors also was significant such that oral temperature was somewhat lower after the water was consumed compared to when the glucose was consumed, F(5, 69.1) = 6.0, p < .OOl (epsilon = .600).

4. Discussion Increases in blood glucose level did not affect either P3 amplitude, P3 latency, or the Nl, P2, and N2 components from the visual stimulus oddball paradigm. Although strong effects on blood glucose levels and heart rate were obtained with the glucose ingestion relative to the control water ingestion condition, these effects were not associated with any changes in ERPs. The present findings are consonant with a previous report in which auditory stimuli were used to elicit ERPs and blood glucose levels were assessed before and after food ingestion, with P3 changes found to be unrelated to glucose changes from the food (Geisler & Polich, 1992a). However, the present data stand in contrast to other studies in which hypoglycemic manipulations produced increases in P3 latency but no effects on P3 amplitude (Blackman et al., 1990; De Feo et al., 1988; Gallai et al., 1988; Jones et al., 1990). Thus, only when blood glucose levels are reduced can effects on ERP components be observed; when blood glucose levels are increased no effects on ERP components are obtained. The lack of variation for P3 amplitude and latency with increased blood glucose levels implies that the changes in cognitive performance observed with glucose manipulations are not mediated by processes related to the generation of ERPs (cf. Benton, 1989, 1990; Benton et al., 1987; Deijen et al., 1989; Gonder-Frederick et al., 1987; Haier, et al., 1988; Hall et al., 1989; Manning et al., 1990)-a conclusion supported by a previous ERP study in which glucose level and cognitive performance were assessed simultaneously (Geisler & Polich, 1992a). Despite these findings, it is important to note that the present study employed a relatively easy visual stimulus discrimination paradigm. A more cognitively challenging task situation that strongly engaged attentional processes may have demonstrated ERP effects for hyperglucose ingestion. However, given that all other previous ERP/ glucose studies also employed similar oddball tasks, it is not unreasonable to conclude that for simple stimulus discrimination tasks the effects of food on the P3 ERP originate from metabolic processes unrelated to changes in glucose levels (cf. Geisler & Polich, 1990, 1992ab; Pozzessere et al., 1991). Moreover, additional studies suggest that these effects may stem from the more general effects of food

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on arousal levels (cf. Dustman et al., 1990; Geisler & Squires, 1992). Although the mechanism underlying the influence of food on the P3 ERP is not clear, the present findings indicate that it is unrelated to increased blood glucose levels.

Acknowledgements This work was supported by NIA grant ROl-A610604-02. This paper is 7836NP from The Scripps Research Institute. We thank Jane Springer, R.N., and George Dailey, M.D., for their helpful suggestions and support throughout the course of this study.

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