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Experimental Brain Research

, Volume 234, Issue 12, pp 3483–3495 | Cite as

Prefrontal activity decline in women under a single dose of diazepam during rule-guided responses: an fMRI study

  • Z. Muñoz-Torres
  • J. L. Armony
  • D. Trejo-Martínez
  • R. Conde
  • M. Corsi-Cabrera
Research Article

Abstract

Daily life events confront us with new situations demanding responses to usual and unusual rules. Diazepam (DZ), a clinically important drug, facilitates the inhibitory activity of the GABAergic system. Prefrontal cortex, rich in DZ receptors, coordinates necessary resources to direct actions according to rules. The balance between excitatory and inhibitory activity is critical to achieve optimal function of brain systems leading to complex functions. Major sex differences in the physiological mechanisms of the GABAergic system have been reported. However, the differential influence of DZ on men and women in neural activity during behavior directed by frontal lobes remains unexplored. The ability of healthy volunteers to select responses following usual/congruent and novel/incongruent rules, and brain correlates were measured with fMRI under the administration of DZ and a placebo. 10 mg of DZ was enough to decrease the performance in a different manner between men and women. While reaction times increased in both men and women, women committed more errors selecting responses than men under DZ. Men demonstrated increased activity, while women demonstrated decreased activity in frontal regions involved in response selection of rules. These findings could have important consequences in understanding the differential influences of DZ between the sexes in complex daily life situations. More importantly, this study emphasizes the importance of understanding the differential effects on men and women of drugs widely employed by society, thereby achieves better therapeutic results and avoids side effects that the present study revealed to be different between sexes.

Keywords

Benzodiazepine Diazepam Sex differences fMRI Rule-guided behavior Frontal lobes 

Notes

Acknowledgments

We are very grateful to Madalyn Marabella for correcting the English version of the manuscript. This work was supported by CONACYT, Project: 50709. Z. Muñoz-Torres received a grant from CONACYT. This work constitutes part of an academic thesis of the Biomedical Science Ph.D. program at UNAM. We thank Dr. Julian A. Sanchez Cortazar of Aceleracion Nuclear y Resonancia Magnetica S.A. de C.V.; Dr. Bernardo Ronzon Fernandez, and QFB Alma Delia Guerrero Huesca at Laboratorio y Banco de Sangre for the facilities of fMRI and blood analyses at Hospital Angeles del Pedregal.

Supplementary material

221_2016_4746_MOESM1_ESM.docx (41 kb)
Supplementary material 1 (DOCX 40 kb)

References

  1. Allen JS, Damasio H, Grabowski TJ et al (2003) Sexual dimorphism and asymmetries in the gray-white composition of the human cerebrum. Neuroimage 18:880–894. doi: 10.1016/S1053-8119(03)00034-X CrossRefPubMedGoogle Scholar
  2. Altemus M, Sarvaiya N, Neill Epperson C (2014) Sex differences in anxiety and depression clinical perspectives. Front Neuroendocrinol 35:320–330. doi: 10.1016/j.yfrne.2014.05.004 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Annett M (1967) The binomial distribution of right, mixed and left handedness. Q J Exp Psychol 4:327–333CrossRefGoogle Scholar
  4. Azuar C, Reyes P, Slachevsky A et al (2014) Testing the model of caudo-rostral organization of cognitive control in the human with frontal lesions. Neuroimage 84:1053–1060. doi: 10.1016/j.neuroimage.2013.09.031 CrossRefPubMedGoogle Scholar
  5. Bednark JG, Campbell MEJ, Cunnington R (2015) Basal ganglia and cortical networks for sequential ordering and rhythm of complex movements. Front Hum Neurosci 9:1–13. doi: 10.3389/fnhum.2015.00421 CrossRefGoogle Scholar
  6. Bonzano L, Tacchino A, Roccatagliata L et al (2015) An engineered glove for investigating the neural correlates of finger movements using functional magnetic resonance imaging. Front Hum Neurosci 9:1–12. doi: 10.3389/fnhum.2015.00503 CrossRefGoogle Scholar
  7. Botvinick MM (2007) Conflict monitoring and decision making: reconciling two perspectives on anterior cingulate function. Cogn Affect Behav Neurosci 7:356–366CrossRefPubMedGoogle Scholar
  8. Buckley MJ, Mansouri FA, Hoda H et al (2009) Dissociable components of rule-guided behavior depend on distinct medial and prefrontal regions. Science 325:52–58. doi: 10.1126/science.1172377 CrossRefPubMedGoogle Scholar
  9. Bunge SA, Wallis JD, Parker A et al (2005) Neural circuitry underlying rule use in humans and nonhuman primates. J Neurosci 25:10347–10350. doi: 10.1523/JNEUROSCI.2937-05.2005 CrossRefPubMedGoogle Scholar
  10. Buzsáki G, Kaila K, Raichle M (2007) Inhibition and brain work. Neuron 56:771–783CrossRefPubMedPubMedCentralGoogle Scholar
  11. Christoff K, Keramatian K, Gordon A et al (2009) Prefrontal organization of cognitive control according to levels of abstraction. Brain Res 1286:94–105CrossRefPubMedGoogle Scholar
  12. Colzato L, Hertsig G, van der Wildenberg W, Hommel B (2010) Estrogen modulates inhibitory control in healthy human females: evidence from the stop-signal paradigm. Neuroscience 167:709–715CrossRefPubMedGoogle Scholar
  13. Compte A, Constantinidis C, Tegner J et al (2003) Temporally irregular mnemonic persistent activity in prefrontal neurons of monkeys during a delayed response task. J Neurophysiol 90:3441–3454. doi: 10.1152/jn.00949.2002 CrossRefPubMedGoogle Scholar
  14. Corsi-Cabrera M, Ugalde E, del Río-Portilla Y, Fernandez-Guasti A (2000) Organizational and activational effects of gonadal steroid hormones on the EEG of male and female rats. Dev Psychobiol 37:194–207CrossRefPubMedGoogle Scholar
  15. Corsi-Cabrera M, del Río-Portilla Y, Muñoz-Torres Z (2007) Sex-steroid dimorphic effects on functional brain organization: differences in cognition, emotion and anxiolysis. In: Czerbska M (ed) Psychoneuroendocrinology research trends. Nova Biomedical Books, New York, pp 7–72Google Scholar
  16. Cotto JH, Davis E, Dowling GJ et al (2010) Gender effects on drug use, abuse, and dependence: a special analysis of results from the National Survey on Drug Use and Health. Gend Med 7:402–413. doi: 10.1016/j.genm.2010.09.004 CrossRefPubMedGoogle Scholar
  17. Coull J, Sahakian B, Middleton H et al (1995) Differential effects of clonidine, haloperidol, diazepam and tryptophan depletion on focused attention and attentional search. Psychopharmacology 121:222–230CrossRefPubMedGoogle Scholar
  18. Coull J, Frith C, Dolan R (1999) Dissociating neuromodulatory effects of diazepam on episodic memory encoding and executive function. Psychopharmacol 145:213–222CrossRefGoogle Scholar
  19. Curtis CE, D’Esposito M (2003) Persistent activity in the prefrontal cortex during working memory. Trends Cogn Sci 7:415–423. doi: 10.1016/S1364-6613(03)00197-9 CrossRefPubMedGoogle Scholar
  20. Deakin J, Aitken M, Dowson J et al (2004) Diazepam produces disinhibitory cognitive effects in male volunteers. Psychopharmacology 173:88–97. doi: 10.1007/s00213-003-1695-4 CrossRefPubMedGoogle Scholar
  21. Epperson C, Haga K, Mason G (2002) Cortical {gamma}-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic. Arch Gen Psychiatry 59:851–858CrossRefPubMedGoogle Scholar
  22. Esterlis I, McKee SA, Kirk K et al (2013) Sex-specific differences in GABAA-benzodiazepine receptor availability: relationship with sensitivity to pain and tobacco smoking craving. Addict Biol 18:370–378. doi: 10.1111/j.1369-1600.2011.00403.x CrossRefPubMedGoogle Scholar
  23. Evans A, Kamber M, Collins D, Macdonald D (1994) An MRI-based probabilistic atlas of neuroanatomy. In: Shorvon S, Fish D, Andermann F et al (eds) Magnetic resonance scanning and epilepsy. Plenum, New York, pp 263–274CrossRefGoogle Scholar
  24. Fernandez-Guasti A, del Río-Portilla Y, Ugalde E, Corsi-Cabrera M (2003) Diazepam and progesterone produce sexually dimorphic actions on the rat EEG: role of the neonatal sexual differentiation process. Pshychoneuroendocrinology 28:85–100CrossRefGoogle Scholar
  25. Filipek P, Richelme C, Kennedy D, Caviness VJ (1994) The young adult human brain: an MRI-based morphometric analysis. Cereb Cortex 4:344–360CrossRefPubMedGoogle Scholar
  26. Fluck E, Fernandes C, File S (2001) Are lorazepam-induced deficits in attention similar to those resulting from aging? J Clin Psychopharmacol 21:126–130CrossRefPubMedGoogle Scholar
  27. Friedman H, Ochs H, Greenblatt D, Shader R (1985) Tissue distribution of diazepam and its metabolite desmethyldiazepam: a human autopsy study. J Clin Pharmacol 25:613–615CrossRefPubMedGoogle Scholar
  28. Friston K, Holmes A, Worsley K et al (1995) Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 2:189–210CrossRefGoogle Scholar
  29. Gluck J, Fitting S (2003) Spatial strategy selection: interesting incremental information. Int J Test 3:293–308CrossRefGoogle Scholar
  30. Hammerslag LR, Gulley JM (2016) Sex differences in behavior and neural development and their role in adolescent vulnerability to substance use. Behav Brain Res 298:15–26. doi: 10.1016/j.bbr.2015.04.008 CrossRefPubMedGoogle Scholar
  31. Hausmann M, Schoofs D, Rosenthal H, Jordan K (2009) Interactive effects of sex hormones and gender stereotypes on cognitive sex differences–a psychobiosocial approach. Psychoneuroendocrinology 34:389–401CrossRefPubMedGoogle Scholar
  32. Hoshi E (2008) Differential involvement of the prefrontal, premotor and primary motor cortices in rule-based motor behavior. In: Bunge SA, Wallis JD (eds) Neuroscience of rule behavior. Oxford University Press, New York, p 472Google Scholar
  33. Jackson A, Stephens D, Duka T (2005) Gender differences in response to lorazepam in a human drug discrimination study. J Psychopharmacol 19:614–619. doi: 10.1177/0269881105056659 CrossRefPubMedGoogle Scholar
  34. Larson M, South M, Clayson P (2011) Sex differences in error-related performance monitoring. NeuroReport 22:44–48CrossRefPubMedGoogle Scholar
  35. Li CR, Zhang S, Duann J-R et al (2009) Gender differences in cognitive control: an extended investigation of the stop signal task. Brain Imaging Behav 3:262–276. doi: 10.1007/s11682-009-9068-1 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Maguire J, Mody I (2009) Steroid hormone fluctuations and GABA A R plasticity. Psychoneuroendocrinology 34:1–12. doi: 10.1016/j.psyneuen.2009.06.019.Steroid CrossRefGoogle Scholar
  37. Mansouri FA, Fehring DJ, Gaillard A et al (2016) Sex dependency of inhibitory control functions. Biol Sex Differ 7:11. doi: 10.1186/s13293-016-0065-y CrossRefPubMedPubMedCentralGoogle Scholar
  38. Muñoz-Torres Z, Armony JL, Trejo-Martínez D et al (2011a) Behavioural and neural effects of diazepam on a rule-guided response selection task. Neurosci Res 70:260–268. doi: 10.1016/j.neures.2011.03.009 CrossRefPubMedGoogle Scholar
  39. Muñoz-Torres Z, del Río-Portilla Y, Corsi-Cabrera M (2011b) Diazepam-induced changes in EEG oscillations during performance of a sustained attention task. J Clin Neurophysiol 28:394–399PubMedGoogle Scholar
  40. Munro CA, Winicki JM, Schretlen DJ et al (2012) Sex differences in cognition in healthy elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 19:759–768. doi: 10.1080/13825585.2012.690366.Sex CrossRefPubMedPubMedCentralGoogle Scholar
  41. Passingham RE, Rowe J (2002) Dorsal prefrontal cortex: Maintenance in memory or attentional selection? In: Stuss DT, Knight RT (eds) Principles of frontal lobe function. Oxford University Press, Oxford, pp 221–232CrossRefGoogle Scholar
  42. Pletzer B (2014) Sex-specific strategy use and global-local processing: a perspective toward integrating sex differences in cognition. Front Neurosci 8:1–6. doi: 10.3389/fnins.2014.00425 Google Scholar
  43. Ridderinkhof K, Ullsperger M, Crone E, Nieuwenhuis S (2004) The role of the medial frontal cortex in cognitive control. Science 306(5695):443–447CrossRefPubMedGoogle Scholar
  44. Romano-Torres M, Borja-Lascurain E, Chao-Rebolledo C et al (2002) Effect of diazepam on EEG power and coherent activity: sex differences. Psychoneuroendocrinology 27:821–833. doi: 10.1016/S0306-4530(01)00082-8 CrossRefPubMedGoogle Scholar
  45. Rushworth MFS, Buckley MJ, Behrens TEJ et al (2007) Functional organization of the medial frontal cortex. Curr Opin Neurobiol 17:220–227. doi: 10.1016/j.conb.2007.03.001 CrossRefPubMedGoogle Scholar
  46. Sæther L, Van Belle W, Laeng B et al (2009) Anchoring gaze when categorizing faces’ sex: evidence from eye-tracking data. Vis Res 49:2870–2880. doi: 10.1016/j.visres.2009.09.001 CrossRefPubMedGoogle Scholar
  47. Sanacora G, Mason GF, Rothman DL et al (1999) Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry 56:1043–1047CrossRefPubMedGoogle Scholar
  48. Saucier D, Green S, Leason J et al (2002) Are sex differences in navigation caused by sexually dimorphic strategies or by differences in the ability to use the strategies? Behav Neurosci 116:403–410CrossRefPubMedGoogle Scholar
  49. Schlaepfer T, Harris G, Tien A et al (1995) Structural differences in the cerebral cortex of healthy female and male subjects: a magnetic resonance imaging study. Pshychiatry Res 61:129–135CrossRefGoogle Scholar
  50. Schöning S, Engelien A, Kugel H et al (2007) Functional anatomy of visuo-spatial working memory during mental rotation is influenced by sex, menstrual cycle, and sex steroid hormones. Neuropsychologia 45:3203–3214. doi: 10.1016/j.neuropsychologia.2007.06.011 CrossRefPubMedGoogle Scholar
  51. Solís-Ortiz S, Corsi-Cabrera M (2008) Sustained attention is favored by progesterone during early luteal phase and visuo-spatial memory by estrogens during ovulatory phase in young women. Psychoneuroendocrinology 33:989–998CrossRefPubMedGoogle Scholar
  52. Solís-Ortiz S, Ramos J, Arce C et al (1994) EEG oscillations during menstrual cycle. Int J Neurosci 76:279–292CrossRefPubMedGoogle Scholar
  53. Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system: an approach to cerebral imaging. Thieme, New YorkGoogle Scholar
  54. Thakkar KN, Congdon E, Poldrack RA et al (2014) Women are more sensitive than men to prior trial events on the stop signal task. Br J Psychol 105:254–272CrossRefPubMedGoogle Scholar
  55. Ugalde E, del Rı́o-Portilla I, Juarez J et al (1998) Effect of diazepam and sex hormones on EEG of gonadectomized male and female rats. Pshychoneuroendocrinology 23:701–712CrossRefGoogle Scholar
  56. Weis S, Hausmann M, Stoffers B, Sturm W (2011) Dynamic changes in functional cerebral connectivity of spatial cognition during the menstrual cycle. Hum Brain Mapp 32:1544–1556. doi: 10.1002/hbm.21126 CrossRefPubMedGoogle Scholar
  57. Weiss E, Siedentopf CM, Hofer A et al (2003) Sex differences in brain activation pattern during a visuospatial cognitive task: a functional magnetic resonance imaging study in healthy volunteers. Neurosci Lett 344:169–172CrossRefPubMedGoogle Scholar
  58. Wittchen HU, Jacobi F (2005) Size and burden of mental disorders in Europe—a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 15:357–376. doi: 10.1016/j.euroneuro.2005.04.012 CrossRefPubMedGoogle Scholar
  59. Wurster DC, Graf H, Ackermann H et al (2015) Neural correlates of rate-dependent finger-tapping in Parkinson’ s disease. Brain Struct Funct 220:1637–1648. doi: 10.1007/s00429-014-0749-1 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Z. Muñoz-Torres
    • 1
    • 2
  • J. L. Armony
    • 3
  • D. Trejo-Martínez
    • 4
  • R. Conde
    • 4
  • M. Corsi-Cabrera
    • 1
  1. 1.Laboratory of Sleep, Faculty of PsychologyUniversidad Nacional Autonoma de MexicoMexico CityMexico
  2. 2.Unidad de Trastornos del Movimiento y Sueño (TMS), Hospital General Ajusco MedioSecretaria de SaludMexico CityMexico
  3. 3.Department of Psychiatry and Douglas Mental Health University InstituteMcGill UniversityMontrealCanada
  4. 4.Department of Magnetic ResonanceHospital Angeles del PedregalMexico CityMexico

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