Skip to main content
SpringerLink
Log in

The modulation of venlafaxine on cortical activation of language area in healthy subjects with fMRI study

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Previous studies have shown that selective serotonin reuptake inhibitors, activators of the cortex, apparently improved language functional recovery after brain damage rather than simply affective disorders.

Objective

Our aim was to determine whether venlafaxine (an agonist of both norepinephrine and 5-hydroxytryptamine) could modulate language cortex function.

Methods

A double-blind, crossover, randomized design was used to compare two 7-day treatment sessions with either venlafaxine (75 mg per day) or placebo. A functional magnetic resonance imaging experiment and two language function tests were performed on eight healthy males (mean age, 28.25 ± 3.15 years) at the end of each session, i.e., study entry, after venlafaxine, and after placebo (days 0, 7, and 18). Hyperactivation (venlafaxine minus placebo >0) or hypoactivation (placebo minus venlafaxine >0) by venlaxafine was assessed on the basis of the activation–baseline contrast.

Results

The naming score (P < .001) and spontaneous language fluency (P < .001) were significantly higher after venlafaxine than after placebo. Functional magnetic resonance imaging (fMRI) showed that (1) picture naming activated the left posterior gyrus frontalis medius and the bilateral fusiform gyrus and the bilateral outer occipital lobes, (2) hyperactivation was observed in the adjoining area of posterior upper Broca area and premotor area in the dominant hemisphere in venlafaxine session (after venlafaxine), (3) the hyperactivation of the left gyrus frontalis medius on fMRI and the increase in naming test score were positively correlated, and (4) by contrast, we observed hypoactivation in the temporo–parieto–occipital region in venlafaxine session (after venlafaxine). This improvement may be related to increased phonics-related output in the frontal language cortex of the dominant hemisphere.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Berends HI, Nijlant JM, Moviq KL, Van Putten MJ, Jannink MJ, Ijzerman MJ (2009) The clinical use of drugs influencing neurotransmitters in the brain to promote motor recovery after stroke; a Cochrane systematic review. Eur J Phys Rehabil Med 45:621–630

    PubMed  CAS  Google Scholar 

  • Bütefisch CM, Davis BC, Sawaki L, Waldvogel D, Classen J, Kopylev L, Cohen LG (2002) Modulation of use-dependent plasticity by d-amphetamine. Ann Neurol 51:59–68

    Article  PubMed  Google Scholar 

  • Cabeza R, Nyberg L (2000) Imaging cognition II: an empirical review of 275 PET and fMRI studies. J Cogn Neurosci 12:1–47

    Article  PubMed  CAS  Google Scholar 

  • Cao Y, Vikingstad EM, George KP, Johnson AF, Welch KM (1999) Cortical language activation in stroke patients recovering from aphasia with functional MRI. Stroke 30:2331–2340

    Article  PubMed  CAS  Google Scholar 

  • De Boissezon X, Peran P, de Boysson C, Démonet JF (2007) Pharmacotherapy of aphasia: myth or reality? J Brain Lang 102:114

    Article  Google Scholar 

  • Del-Ben CM, Deakin JF, McKie S, Delvai NA, Williams SR, Elliott R, Dolan M, Anderson IM (2005) The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: an FMRI study. Neuropsychopharmarmacology 30:1724–1734

    Article  CAS  Google Scholar 

  • Deleon J, Gottesman RF, Kleinman JT, Newhart M, Davis C, Heidler-Gary J, Lee A, Hillis AE (2007) Neural regions essential for distinct cognitive processes underlying picture naming. Brain 130:1408–1422

    Article  PubMed  Google Scholar 

  • Duman RS, Nakagawa S, Malberg J (2001) Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmarmacology 25:836–844

    Article  CAS  Google Scholar 

  • Feeney DM, Sutton RL (1987) Pharmacotherapy for recovery of function after brain injury. Crit Rev Neurobiol 3:135–137

    PubMed  CAS  Google Scholar 

  • Fernandez B, Cardebat D, Demonet JF, Joseph PA, Mazaux JM, Barat M, Allard M (2004) Functional MRI follow-up study of language processes in healthy subjects and during recovery in a case of aphasia. Stroke 35:2171–2176

    Article  PubMed  Google Scholar 

  • Gaspar P, Cases O, Maroteaux L (2003) The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 4:1002–1012

    Article  PubMed  CAS  Google Scholar 

  • Gerdelat-Mas A, Loubinoux I, Tombari D, Rascol O, Chollet F, Simonetta-Moreau M (2005) Chronic administration of selective serotonin reuptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects. NeuroImage 27:314–322

    Article  PubMed  CAS  Google Scholar 

  • Gernsbacher MA, Kaschak MP (2003) Neuroimaging studies of language production and comprehension. Annu Rev Psychol 54:91–114

    Article  PubMed  Google Scholar 

  • Grabowski TJ, Damasio H, Damasio AR (1998) Premotor and prefrontal correlates of category-related lexical retrieval. NeuroImage 7:232–243

    Article  PubMed  CAS  Google Scholar 

  • Horsfield SA, Rosse RB, Tomasino V, Schwartz BL, Mastropaolo J, Deutsch SI (2002) Fluoxetine's effects on cognitive performance in patients with traumatic brain injury. Int J Psychiatry Med 32:337–244

    Article  PubMed  Google Scholar 

  • Kan IP, Thompson-Schill SL (2004) Effect of name agreement on prefrontal activity during overt and covert picture naming. Cogn Affect Behav Neurosci 4:43–57

    Article  PubMed  Google Scholar 

  • Kohn SE, Goodglass H (1985) Picture-naming in aphasia. Brain Lang 24:266–283

    Google Scholar 

  • Levitt P, Harvey JA, Friedman E, Simansky K, Murphy EH (1997) New evidence for neurotransmitter influences on brain development. Trends Neurosci 20:269–274

    Article  PubMed  CAS  Google Scholar 

  • Lipton SA, Kater SB (1989) Neurotransmitter regulation of neuronal outgrowth, plasticity and survival. Trends Neurosci 12:265–270

    Article  PubMed  CAS  Google Scholar 

  • Loubinoux I, Tombari D, Pariente J, Gerdelat-Mas A, Franceries X, Cassol E, Rascol O, Pastor J, Chollet F (2005) Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer. NeuroImage 27:299–313

    Article  PubMed  Google Scholar 

  • Martin RC (2003) Language processing: functional organization and neuroanatomical basis. Annu Rev Psychol 54:85–89

    Article  Google Scholar 

  • Mattson MP, Maudsley S, Martin B (2004) BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends in Neurosicence 27:589–594

    Article  CAS  Google Scholar 

  • Mechelli A, Sartori G, Orlandi P, Price CJ (2006) Semantic relevance explains category effects in medial fusiform gyri. NeuroImage 30:992–1002

    Article  PubMed  Google Scholar 

  • Murtha S, Chertkow H, Beauregard M, Evans A (1999) The neural substrate of picture naming. Cogn Neurosci 11:399–423

    Article  CAS  Google Scholar 

  • Noppeney U (2008) The neural systems of tool and action semantics: a perspective from functional imaging. J Physiol Paris 102:40–49

    Article  PubMed  Google Scholar 

  • Péran P, Démonet JF, Cardebat D (2008) Paroxetine-induced modulation of cortical activity supporting language representations of action. Psychopharmacol 195:487–496

    Google Scholar 

  • Price CJ, Devlin JT (2003) The myth of the visual word form area. NeuroImage 19:473–481

    Article  PubMed  Google Scholar 

  • Raboyeau G, Marcotte K, Adrover-Roig D, Ansaldo AI (2010) Brain activation and lexical learning: the impact of learning phase and word type. NeuroImage 49:2850–2861

    Article  PubMed  CAS  Google Scholar 

  • Sarkisyan G, Hedlund PB (2009) The 5-HT7 receptor is involved in allocentric spatial memory information processing. Behav Brain Res 202:26–31

    Article  PubMed  CAS  Google Scholar 

  • Schweizer E, Theielen RJ, Frazer A (1997) Venlafaxine: a novel antidepressant compound. Exp Opin Invest Drugs 6:65–78

    Article  CAS  Google Scholar 

  • Struder HK, Weicker H (2001) Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Int J Sports Med 22:467–481

    Article  PubMed  CAS  Google Scholar 

  • Tanaka Y (2007) Pharmacotherapy for aphasia. Rinsho Shinkeigaku 47:859–861

    Google Scholar 

  • Vigneau M, Beaucousin V, Hervé PY, Duffau H, Crivello F, Houdé O, Mazoyer B, Tzourio-Mazoyer N (2006) Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence processing. NeuroImage 30:1414–1432

    Article  PubMed  CAS  Google Scholar 

  • Vitalis T, Parnavelas J (2003) The role of serotonin in early cortical development. Exp Neurol 25:245–256

    CAS  Google Scholar 

  • Völlm B, Richardson P, McKie S, Elliott R, Deakin JF, Anderson IM (2006) Serotonergic modulation of neuronal responses to behavioral inhibition and reinforcing stimuli: an fMRI study in healthy volunteers. Eur J Neurosci 23:552–560

    Article  PubMed  Google Scholar 

  • Walker-Batson D, Curtis S, Natarajan R (2001) A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia. Stroke 32:2093–2098

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Our experiments comply with the current laws of China. We would like to acknowledge Dr. Li-min Wang (Department of Neurosurgery, General Hospital of Guangzhou Military Command of PLA) for participating in the design of fMRI paradigm in this study. The study was also supported by Guangzhou Science and Technology Key Project (No. 122732961131543).

Author information

Authors and Affiliations

  1. Neurology Department and Rehabilitation Medicine Department, General Hospital of Guangzhou Military Command of PLA, Guangzhou, China

    Qi Xie

  2. Neurology Department, General Hospital of Guangzhou Military Command of PLA, No. 111 Liuhua Road, Guangzhou 510010, Guangzhou, People’s Republic of China

    Yan Liu, Chun-Yong Li & Xue-Zhu Song

  3. MRI Department, General Hospital of Guangzhou Military Command of PLA, Guangzhou, China

    Jun Wang & Li-Xin Han

  4. Neurosurgery Department, General Hospital of Guangzhou Military Command of PLA, Guangzhou, China

    Hong-Min Bai

Authors
  1. Qi Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chun-Yong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xue-Zhu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Li-Xin Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hong-Min Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yan Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xie, Q., Liu, Y., Li, CY. et al. The modulation of venlafaxine on cortical activation of language area in healthy subjects with fMRI study. Psychopharmacology 223, 417–425 (2012). https://doi.org/10.1007/s00213-012-2730-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-012-2730-0

Keywords

Search

Navigation