Neurol Sci DOI 10.1007/s10072-015-2210-5

ORIGINAL ARTICLE

Somatosensory evoked potentials and blood lactate levels Valentina Perciavalle1 • Giovanna Alagona2 • Giulia De Maria2 • Giuseppe Rapisarda2 Erminio Costanzo2 • Vincenzo Perciavalle3 • Marinella Coco3



Received: 28 January 2015 / Accepted: 7 April 2015 Ó Springer-Verlag Italia 2015

Abstract We compared, in 20 subjects, the effects of high blood lactate levels on amplitude and latency of P1, N1, P2 and N2 components of lower limb somatosensory evoked potential (SEP), an useful, noninvasive tool for assessing the transmission of the afferent volley from periphery up to the cortex. SEPs were recorded from CPz located over the somatosensory vertex and referenced to FPz with a clavicle ground. Measurements were carried out before, at the end as well as 10 and 20 min after the conclusion of a maximal exercise carried out on a mechanically braked cycloergometer. After the exercise, P2– N2 amplitudes as well as latency of P1 and N1 components showed small but significant reductions. On the contrary, latency of N2 component exhibited a significant increase after the exercise’s conclusion. These results suggest that blood lactate appears to have a protective effect against fatigue, at least at level of primary somatosensory cortex, although at the expense of efficiency of adjacent areas. Keywords Maximal exercise  Blood lactate  Somatosensory evoked potentials  Man

& Vincenzo Perciavalle [email protected] 1

Department of Sciences of Formation, University of Catania, Catania, Italy

2

Neurological Operative Unit, Cannizzaro Hospital, Catania, Italy

3

Sezione di Fisiologia, Dipartimento di Scienze Biomediche e Biotecnologiche, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy

Introduction An exhaustive exercise induces a transient muscle’s inability to maintain an optimal performance, called fatigue, dependent on to the occurrence of several factors, having both peripheral and central origins [1]. In fact, there is a reduction in muscle phosphocreatine and ATP, as well as an increase of pyruvate and lactate [2], with the latter released into the blood [3]. Since it has been observed that oxygen, glucose and lactate extractions by the CNS increases during maximal exercise, it was hypothesized that brain activation is enhanced during an intense exercise [4, 5]. It has been suggested that in the brain, in particular in conditions of altered energy production, such as anoxia or hypoglycemia, lactate is the energetic metabolite used for sustaining glutamatergic synaptic activity [6]. However, it has been observed that an increase of blood lactate, induced by an exhaustive exercise or an intravenous infusion, is associated with a worsening of attentional processes [7], an improvement of excitability of primary motor cortex [8], without significant modifications of excitability of spinal [9] and brainstem structures [10], and different effects on neurons and astrocytes [11]. Furthermore, it has been recently observed in normal subject that an increase of blood lactate appears to influence visual evoked potentials, by inducing an improvement in the conduction time between eye and striate cortex and a worsening of intracortical communication between striate and extrastriate areas [12]. Somatosensory evoked potentials (SEPs) have been used clinically to diagnose central somatosensory pathway function and as a tool for studying the cortical mechanisms of somatoperceptual processing. A normal recording of SEPs reflects the functional integrity of connections from the stimulated body segment to the primary somatosensory

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cortex (S1). The SEPs recorded after stimulation of tibial nerve at the medial malleolus are characterized by several components: two early components, a positive wave (P1) followed by a negative wave (N1), that appear within 40 ms after stimulation and a second positive wave (P2) followed by a second negative wave (N2) that occur with latencies greater than 40 ms. The neural generators of these different components have been much debated. While there is widespread agreement (based on studies in both animals and humans) that short-latency components (\40 ms) originate from S1 [13–15], the generator for long-latency components of SEP has not yet been clarified. In intracranial recordings [16, 17] and magnetoencephalography studies [18, 19], it has been shown that the secondary somatosensory cortex (SII) responded to the somatosensory stimulation in a latency range [40 ms. The aim of the present study was to examine the possible correlations of high blood lactate levels, induced with a maximal exercise, on early and later components of SEP waveform.

Materials and methods Participants The subjects who volunteered for this study were 20 healthy adults, 10 women and 10 men, aging between 21 and 36 years (mean age 27.6 ± 4.36 SD), with a mean height of 170.5 cm (±5.96 SD) and a mean weight of 63.6 kg (±6.94 SD). The volunteers were all students at the University of Catania. All the subjects signed informed consent documentation in accordance with the Ethical Committee of our University prior to their participation in the study. Exercise The participants performed a maximal multistage discontinuous incremental cycling test on a mechanically braked cycloergometer (Monark, Sweden), at a pedaling rate of 60 rpm, while an electrocardiogram was monitored. Each subject started with unloaded cycling duration of 3 min, and the load was increased by 30 Watt (W) every 3 min until volitional exhaustion or the required pedaling frequency of 60 rpm could not be maintained [20]. Measures SEP waveforms as well as venous blood lactate and glucose levels were measured before, at the end as well as 10 and 20 min after the conclusion of the exercise.

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Blood lactate level was measured by using a ‘‘Lactate Pro’’ portable lactate analyzer (FaCT Canada Consulting Ltd). In fact, it has been shown [21] that this automated lactate analyzer has a good reliability. Blood glucose was measured with an ‘‘Ascensia Elite’’ portable blood glucose monitoring system (Bayer AG, Germany), that assures an acceptable consistency [22]. SEPs were recorded according to the protocol established by DeLisa et al. [23]. The tibial nerve was stimulated (square wave pulse, 0.5 ms duration, 0.5 Hz) at the medial malleolus (Grass SD 9, Grass Technologies, West Warwick, USA) with the cathode of the stimulating electrode placed approximately 2 cm proximal to the anode. SEPs were recorded from CPz located over the somatosensory vertex and referenced to FPz with a clavicle ground [24]. EEG recordings were amplified 10,0009 and filtered from 2 to 500 Hz (Intronix 2024F Isolated Preamplifier, Intronix Technologies Corporation, Bolton, Canada). Electrode impedances were maintained at \5 kX throughout the experiment (UFI Checktrode, Model 1089 Mk III, UFI, Morro Bay, California, USA). SEPs were collected in epochs of 150 ms including a 30-ms pre-stimulus period. SEPs were averaged from 120 nerve stimuli delivered every 2 s. Peak-to-peak SEP amplitudes were measured for the P1–N1 and P2–N2 tibial nerve cortical potentials by averaging 120 epochs during each time block. Statistical analysis Data were collected and averaged, and then compared with the paired t test (two-tailed) or one-way repeated measures analysis of variance (ANOVA; Friedman test), followed by Dunn’s multiple comparison test. The relationship between variables was analyzed with linear regression. Significance was set at P \ 0.05 and all data are reported as mean ± standard deviation (SD). All analyses were performed by means of using GraphPad Prism version 6.03 for Windows (GraphPad Software, San Diego, CA, USA).

Results As can be seen in Fig. 1, after an exhaustive exercise, blood lactate levels increased from 1.31 mmol/l (±0.30 SD) before the exercise, to 12.9 mmol/l (±2.54 SD) at its end, reduced to 4.59 mmol/l (±0.49 SD) after 10 min and returned to pre-exercise values after 20 min (2.3 mmol/ l ± 0.53 SD). On the contrary, blood glucose levels did non exhibit any significant change. In the upper part of Fig. 2, SEPs from the same subject before (pre) and at the end (post) of an exhaustive exercise are shown. It can be seen that latency of P1 wave decreases

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Fig. 1 Blood lactate values and blood glucose levels of the 20 subjects performing an exhaustive exercise. In both cases, data were measured before the exercise (pre), at its conclusion (end), as well as 10 and 20 min after its end. Symbols from ANOVA with Dunn’s multiple comparison test: ***P \ 0.001

from 29.2 to 27.3 ms (-6.5 %) and latency of N1 wave falls from 39.5 to 36.2 ms (-8.4 %). In the lower part of the same figure, it can be seen that only the earliest components of SEP (P1 and N1) showed a significant positive correlation with the height of the subjects. Table 1 shows mean values (±SD) of latency (ms) of N1, P2, N2 and P2 components of SEP, as well as amplitude (lV) of P1–N1 and P2–N2 waves, before the maximal exercise (pre) and at its end (post). As can be seen, at the end of the exercise, P2–N2 amplitudes as well as latency of P1 and N1 components of SEP showed small but significant reductions. On the contrary, latency of N2 component exhibited a significant increase after the exercise’s conclusion. P1–N1 amplitude and P2 latency did not exhibit any significant change (Table 1).

Discussion In the present study we compared, in 20 subjects, the effects of high blood lactate levels on amplitude and latency of P1, N1, P2 and N2 components of lower limb SEP, an useful, noninvasive tool for assessing the transmission of

Fig. 2 In the upper part SEPs from the same subject before (pre) and at the end (post) of an exhaustive exercise are shown. It can be seen that latency of P1 wave decreases from 29.2 to 27.3 ms (-6.5 %) and latency of N1 wave falls from 39.5 to 36.2 ms (-8.4 %). The lower part shows the relations between the four components of SEP with the height of the subjects. It can be seen that only the earliest components of SEP (P1 and N1) showed a significant positive correlation with the height of the subjects

the afferent volley from periphery up to the cortex. The SEP is characterized by several positive and negative components appearing at different latencies. In general, early cortical components of SEP (P1 and N1) are considered to be generated in the contralateral S1 and related to the processing of the physical stimulus attributes. Later components (P2 and N2) are supposed to be dependent on activation of additional cortical regions, such as the secondary somatosensory cortex (S2), and the posterior parietal and frontal cortices (e.g., [25]). We observed that, after an acute exhaustive exercise, a strong increase of blood lactate is associated with

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Neurol Sci Table 1 Mean values (± standard deviation, SD) of latency of P1, N1, P2 and N2 components, as well as P1–N1 and P2–N2 amplitude, of SEP waveforms recorded in all participants (N=20) before the

exhaustive exercise (pre) and at its conclusion (post). Results of paired t-test (two-tailed) are also shown

Pre

Post

Paired t test

P1 latency (ms)

30.06 ( ±1.14 SD)

28.20 (±1.22 SD)

P \ 0.0001****

N1 latency (ms)

40.02 ( ±1.13 SD)

38.84 (±1.72 SD)

P \ 0.0001****

P2 latency (ms)

47.79 ( ±1.40 SD)

47.13 (±1.55 SD)

P = 0.1757

N2 latency (ms) P1-N1 amplitude (lV)

70.06 ( ±4.13 SD) 5.00 ( ±0.83 SD)

75.66 (±2.64 SD) 5.37 (±0.85 SD)

P \ 0.0001**** P = 0.1143

P2-N2 amplitude (lV)

8.37 ( ±1.14 SD)

7.36 (±1.60 SD)

P = 0.0164*

* P\0.05; **** P\0.0001

significant changes of short-latency (\40 ms) components of SEP, i.e., P1 and N1 waves. In particular P1 and N1 show a significant (P \ 0.0001) decrease of latency at the end of exercise (from 30.06 ± 1.14 to 28.20 ± 1.22 and from 40.02 ± 1.13 to 38.84 ± 1.72 ms, respectively), whereas long-latency components N2 displays a significant increase (P \ 0.0001) of latency at the end of the effort rising from 70.06 ± 4.13 to 75.66 ± 2.64 ms. The latency shortening of early cortical components of SEP (P1 and N1) induced by lactate could result from changes in the magnitude and kinetics of the active sodium current [26] in corticipetal neurons. It appears more difficult to understand the effect of lactate on latency of N2 component, which probably reflects the activation of cortical areas located outside of the area S1 from which they likely receive the information evoked by the peripheral stimulation via cortico-cortical neurons on which evidently lactate exerts a negative effect. No significant change was detected with regard to the latency of P2 component of SEP waveform. Moreover, whereas the amplitude of P1–N1 component of SEP did not show any significant change, the amplitude of P2–N2 component exhibited a small but significant reduction (from 8.37 ± 1.14 to 7.36± 1.60 lV). The differential effect on P1N1 and P2N2 could be dependent on a reduced neuronal population activated outside S1. Also in this case the reduced excited population could be a consequence of a lower excitability due to changes in the magnitude and kinetics of the active sodium current [26] induced by lactate. These results suggest that the improvement in the conduction time between the lower limb and S1 and the worsening of intracortical communication between S1 and additional cortical regions (such as S2 and the posterior parietal and frontal cortices), observed after an exhaustive exercise, could be dependent on a strong increase of blood lactate levels. In this way, blood lactate appears to have a protective effect against fatigue, at least at level of primary cortical areas (as S1, striate cortex or primary motor cortex), although at the expense of efficiency of adjacent areas.

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This marked selectivity in the effects induced by lactate seems to imply the intervention of different receptors capable of inducing opposite effects at neuronal level, such as subtypes of lactate receptor GPR81 [27]. Conflict of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

References 1. Meeusen R, Watson P, Hasegawa H, Roelands B, Piacentini MF (2007) Brain neurotransmitters in fatigue and overtraining. Appl Physiol Nutr Metab 32:857–864 2. Bangsbo J (1998) Quantification of anaerobic energy production during intense exercise. Med Sci Sports Exerc 130:47–52 3. Medbø JI, Tabata I (1993) Anaerobic energy release in working muscle during 30 s to 3 min of exhausting bicycling. J Appl Physiol 74:1654–1660 4. Dalsgaard MK, Ide K, Cai Y, Quistorff B, Secher NH (2002) The intent to exercise influences the cerebral O2/carbohydrate uptake ratio in humans. J Physiol 540:681–689 5. Dalsgaard MK, Quistorff B, Danielsen ER, Selmer C, Vogelsang T, Secher NH (2004) A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain. J Physiol 554:571–578 6. Rouach N, Koulakoff A, Abudara V, Willecke K, Giaume C (2008) Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322:1551–1555 7. Coco M, Di Corrado D, Calogero RA, Va Perciavalle, Maci T, Perciavalle V (2009) Attentional processes and blood lactate levels. Brain Res 1302:205–211 8. Coco M, Alagona G, Rapisarda G, Costanzo E, Calogero RA, Va Perciavalle, Perciavalle V (2010) Elevated blood lactate is associated with increased motor cortex excitability. Somatosens Mot Res. doi:10.3109/08990220903471765 9. Coco M, Alagona G, Va Perciavalle, Cicirata V, Perciavalle V (2011) Spinal cord excitability is not influenced by elevated blood lactate levels. Somatosens Mot Res 28:19–24 10. Coco M, Alagona G, Perciavalle Va, Rapisarda G, Costanzo E, Perciavalle V (2013) Brainstem excitability is not influenced by blood lactate levels. Somatosens Mot Res 30:90–95 11. Coco M, Caggia S, Musumeci G, Perciavalle V, Graziano AC, Pannuzzo G, Cardile V (2013) Sodium L-lactate differently affects brain-derived neurotrophic factor, inducible nitric oxide synthase, and heat shock protein 70 kDa production in human

Neurol Sci

12.

13.

14.

15.

16.

17.

18.

19.

astrocytes and SH-SY5Y cultures. J Neurosci Res 91:313–320. doi:10.1002/jnr.23154 Coco M, Alagona G, De Maria G, Rapisarda G, Costanzo E, Perciavalle V, Va Perciavalle (2014) Relationship of high blood lactate levels with latency of visual-evoked potentials. Neurol Sci. doi:10.1007/s10072-014-2015-y Allison T, McCarthy G, Jones SJ, Jones SJ (1991) Potentials evoked in human and monkey cerebral cortex by stimulation of the median nerve. A review of scalp and intracranial recordings. Brain 114:2465–2503 Kakigi R, Jones SJ (1986) Influence of concurrent tactile stimulation on somatosensory evoked potentials following posterior tibial nerve stimulation in man. Electroencephalogr Clin Neurophysiol 65:118–129 Kakigi R, Koyama S, Hoshiyama M, Shimojo M, Kitamura Y, Watanabe S (1995) Topography of somatosensory evoked magnetic fields following posterior tibial nerve stimulation. Electroencephalogr Clin Neurophysiol 95:127–134 Frot M, Mauguie`re F (1999) Timing and spatial distribution of somatosensory responses recorded in the upper bank of the sylvian fissure (SII area) in humans. Cereb Cortex 9:854–863 Frot M, Garcı`a-Larrea L, Marc G, Mauguie`re F (2001) Responses of the suprasylvian (SII) cortex in humans to painful and innocuous stimuli. A study using intra-cerebral recordings. Pain 94:65–73 Hari R, Forss N (1999) Magnetoencephalography in the study of human somatosensory cortical processing. Phil Trans R Soc Lond B 354:1145–1154 Kakigi R, Hoshiyama M, Shimojo M, Naka D, Yamasaki H, Watanabe S, Xiang J, Maeda K, Lam K, Itomi K, Nakamura A (2000) The somatosensory evoked magnetic fields. Prog Neurobiol 61:495–523

20. Green JM, McLester JR, Crews TR, Wickwire PJ, Pritchett RC, Redden A (2005) RPE-lactate dissociation during extended cycling. Eur J Appl Physiol 94:145–150 21. Mc Naughton LR, Thompson D, Philips G, Backx K, Crickmore L (2002) A comparison of the lactate Pro, Accusport, Analox GM7 and Kodak Ektachem lactate analysers in normal, hot and humid conditions. Int J Sports Med 23:130–135 22. Kristensen GB, Christensen NG, Thue G, Sandberg S (2005) Between-lot variation in external quality assessment of glucose: clinical importance and effect on participant performance evaluation. Clin Chem 51:1632–1636 23. DeLisa JA, Lee HJ, Lai KS, Spielhocz N, MacKenzie K (1994) Manual of nerve conduction velocity and and clinical neurophysiology, 3rd edn. Raven Press, New York, p 494 24. Seyal M, Emerson RG, Pedley TA (1983) Spinal and early scalprecorded components of the somatosensory evoked potential following stimulation of the posterior tibial nerve. Electroencephalogr Clin Neurophysiol 55:320–330 25. Nuwer M (1998) Fundamentals of evoked potentials and common clinical applications today. Electroencephalogr Clin Neurophysiol 106:142–148 26. Barrett EF, Barrett JN (1982) Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing afterpotential. J Physiol 323:117–144 27. Lauritzen KH, Morland C, Puchades M, Holm-Hansen S, Hagelin EM, Lauritzen F, Attramadal H, Storm-Mathisen J, Gjedde A, Bergersen LH (2014) Lactate receptor sites link neurotransmission, neurovascular coupling, and brain energy metabolism. Cereb Cortex 24(10):2784–2795. doi:10.1093/cercor/bht136

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Somatosensory evoked potentials and blood lactate levels.

We compared, in 20 subjects, the effects of high blood lactate levels on amplitude and latency of P1, N1, P2 and N2 components of lower limb somatosen...
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