Abstract
Introduction
Previous studies have shown that paroxetine, a selective serotonin reuptake inhibitor, affects brain motor pathway activity in healthy subjects using simple motor tasks. In this study, we explored the effects of paroxetine on the activity of cortical areas implicated in higher-order representations of goal-directed movements, i.e., action-related language processing.
Materials and methods
A double-blind, crossover, randomized paradigm was used to compare two 1-month treatment phases with either paroxetine (20 mg per day) or placebo. A functional magnetic resonance imaging experiment on 12 healthy subjects, conducted at the end of each treatment phase, comprised a single list of verbs and three tasks that consisted in repeating the verbs aloud, generating verbs depicting actions aloud, and mentally simulating the corresponding actions. The effects of the drug, i.e., paroxetine–placebo>0 (hyperactivation) and placebo–paroxetine >0 (hypoactivation) were assessed on the basis of the activation–rest contrast for each task.
Results and discussion
For both verb generation and mental simulation of action which both engaged higher-order representations of action, we observed hypoactivation in the left-sided prefrontal and right-sided medial premotor cortex. By contrast, we observed hyperactivation in the right-sided Brodmann’s area 6 for the less demanding verb repetition task.
Conclusion
Chronic treatment with paroxetine may modulate the cerebral activities elicited by action-related language tasks depending on the cognitive components involved in such tasks.
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References
Abdullaev Y, Kennedy BL, Tasman A (2002) Changes in neural circuitry of language before and after treatment of major depression. Hum Brain Mapp 17:156–167
Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38:1083–1052
Blacker D, Byrnes ML, Mastaglia FL, Thickbroom GW (2006) Differential activation of frontal lobe areas by lexical and semantic language tasks: a functional magnetic resonance imaging study. J Clin Neurosci 13:91–95
Boulenger V, Roy AC, Paulignan Y, Deprez V, Jeannerod M, Nazir TA (2006) Cross-talk between language processes and overt motor behavior in the first 200 msec of processing. J Cogn Neurosci 18:1607–1615
Cardebat D, Doyon B, Puel M, Goulet P, Joanette Y (1990) [Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level]. Acta Neurol Belg 90:207–217
Cardebat D, Candelon N, Kuznierek L, Viallard G, Demonet JF, Lambert J (2000) [Generation of isolated words in normal subjects]. Acta Neurol Belg 100:24–33
Dam M, Tonin P, De Boni A, Pizzolato G, Casson S, Ermani M, Freo U, Piron L, Battistin L (1996) Effects of fluoxetine and maprotiline on functional recovery in poststroke hemiplegic patients undergoing rehabilitation therapy. Stroke 27:1211–1214
de Boissezon X, Peran P, de Boysson C, Demonet JF (2006) Pharmacotherapy of aphasia: myth or reality? Brain Lang 102:114–125
Decety J, Perani D, Jeannerod M, Bettinardi V, Tadary B, Woods R, Mazziotta JC, Fazio F (1994) Mapping motor representations with positron emission tomography. Nature 371:600–602
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. Neuropsychopharmacology 30:1724–1734
Demonet JF, Thierry G, Cardebat D (2005) Renewal of the neurophysiology of language: functional neuroimaging. Physiol Rev 85:49–95
D'Esposito M, Detre JA, Alsop DC, Shin RK, Atlas S, Grossman M (1995) The neural basis of the central executive system of working memory. Nature 378:279–281
Dunner D, Kumar R (1998) Paroxetine: a review of clinical experience. Pharmacopsychiatry 31:89–101
Fiez JA (1997) Phonology, semantics, and the role of the left inferior prefrontal cortex. Hum Brain Mapp 5:79–83
Furey ML, Pietrini P, Haxby JV, Alexander GE, Lee HC, VanMeter J, Grady CL, Shetty U, Rapoport SI, Schapiro MB, Freo U (1997) Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory. Proc Natl Acad Sci U S A 94:6512–6516
Gadian DG, Connelly A, Jackson GD (1996) Functional magnetic resonance imaging and the supplementary sensorimotor area. Adv Neurol 70:161–165
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
Geyer MA (1996) Serotonergic functions in arousal and motor activity. Behav Brain Res 73:31–35
Grezes J, Decety J (2001) Functional anatomy of execution, mental simulation, observation, and verb generation of actions: a meta-analysis. Hum Brain Mapp 12:1–19
Grezes J, Fonlupt P, Bertenthal B, Delon-Martin C, Segebarth C, Decety J (2001) Does perception of biological motion rely on specific brain regions? Neuroimage 13:775–785
Grossman M, Koenig P, DeVita C, Glosser G, Alsop D, Detre J, Gee J (2002) Neural representation of verb meaning: an fMRI study. Hum Brain Mapp 15:124–134
Hall LM, Anderson GM, Cohen DJ (1995) Acute and chronic effects of fluoxetine and haloperidol on mouse brain serotonin and norepinephrine turnover. Life Sci 57:791–801
Hamon M, Bourgoin S (2006) Pharmacological profile of antidepressants: a likely basis for their efficacy and side effects? Eur Neuropsychopharmacol 16(Suppl 5):S625–S632
Hasbroucq T, Rihet P, Blin O, Possamai CA (1997) Serotonin and human information processing: fluvoxamine can improve reaction time performance. Neurosci Lett 229:204–208
Hillis AE, Work M, Barker PB, Jacobs MA, Breese EL, Maurer K (2004) Re-examining the brain regions crucial for orchestrating speech articulation. Brain 127:1479–1487
Jacobs BL, Fornal CA (1999) Activity of serotonergic neurons in behaving animals. Neuropsychopharmacology 21:9S–15S
Kennedy SH, Evans KR, Kruger S, Mayberg HS, Meyer JH, McCann S, Arifuzzman AI, Houle S, Vaccarino FJ (2001) Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry 158:899–905
Klein D, Watkins KE, Zatorre RJ, Milner B (2006) Word and nonword repetition in bilingual subjects: a PET study. Hum Brain Map 27:153–161
Loubinoux I, Carel C, Alary F, Boulanouar K, Viallard G, Manelfe C, Rascol O, Celsis P, Chollet F (2001) Within-session and between-session reproducibility of cerebral sensorimotor activation: a test–retest effect evidenced with functional magnetic resonance imaging. J Cereb Blood Flow Metab 21:592–607
Loubinoux I, Pariente J, Rascol O, Celsis P, Chollet F (2002) Selective serotonin reuptake inhibitor paroxetine modulates motor behavior through practice. A double-blind, placebo-controlled, multi-dose study in healthy subjects. Neuropsychologia 40:1815–1821
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
Martin A, Haxby JV, Lalonde FM, Wiggs CL, Ungerleider LG (1995) Discrete cortical regions associated with knowledge of color and knowledge of action. Science 270:102–105
Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113
Pariente J, Loubinoux I, Carel C, Albucher JF, Leger A, Manelfe C, Rascol O, Chollet F (2001) Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke. Ann Neurol 50:718–729
Perani D, Cappa SF, Schnur T, Tettamanti M, Collina S, Rosa MM, Fazio F (1999) The neural correlates of verb and noun processing. A PET study. Brain 122(Pt 12):2337–2344
Petersen SE, Fox PT, Posner MI, Mintun M, Raichle ME (1988) Positron emission tomographic studies of the cortical anatomy of single-word processing. Nature 331:585–589
Price GW, Roberts C, Watson J, Burton M, Mulholland K, Middlemiss DN, Jones BJ (1996) Species differences in 5-HT autoreceptors. Behav Brain Res 73:79–82
Pulvermuller F (2005) Brain mechanisms linking language and action. Nat Rev Neurosci 6:576–582
Raichle ME, Fiez JA, Videen TO, MacLeod AM, Pardo JV, Fox PT, Petersen SE (1994) Practice-related changes in human brain functional anatomy during nonmotor learning. Cereb Cortex 4:8–26
Tanaka Y, Albert ML (2004) Serotonergic therapy for fluent aphasia. 2004 AAN San Francisco meeting poster
Tatsumi IF, Fushimi T, Sadato N, Kawashima R, Yokoyama E, Kanno I, Senda M (1999) Verb generation in Japanese—a multicenter PET activation study. Neuroimage 9:154–164
Tyler LK, Bright P, Fletcher P, Stamatakis EA (2004) Neural processing of nouns and verbs: the role of inflectional morphology. Neuropsychologia 42:512–523
Vigneau M, Beaucousin V, Herve PY, Duffau H, Crivello F, Houde O, Mazoyer B, Tzourio-Mazoyer N (2006) Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence processing. Neuroimage 30:1414–1432
Vollm B, Richardson P, McKie S, Elliott R, Deakin JF, Anderson IM (2006) Serotonergic modulation of neuronal responses to behavioural inhibition and reinforcing stimuli: an fMRI study in healthy volunteers. Eur J Neurosci 23:552–560
Warburton E, Wise RJ, Price CJ, Weiller C, Hadar U, Ramsay S, Frackowiak RS (1996) Noun and verb retrieval by normal subjects. Studies with PET. Brain 119(Pt 1):159–179
Wilkinson D, Halligan P (2004) The relevance of behavioural measures for functional-imaging studies of cognition. Nat Rev Neurosci 5:67–73
Wise R, Hadar U, Howard D, Patterson K (1991) Language activation studies with positron emission tomography. Ciba Found Symp 163:218–228 (discussion 228–234)
Zatorre RJ, Meyer E, Gjedde A, Evans AC (1996) PET studies of phonetic processing of speech: review, replication, and reanalysis. Cereb Cortex 6:21–30
Zilles K, Palomero-Gallagher N, Schleicher A (2004) Transmitter receptors and functional anatomy of the cerebral cortex. J Anat 205:417–432
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In memory of Dominique Cardebat.
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Péran, P., Démonet, JF. & Cardebat, D. Paroxetine-induced modulation of cortical activity supporting language representations of action. Psychopharmacology 195, 487–496 (2008). https://doi.org/10.1007/s00213-007-0939-0
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DOI: https://doi.org/10.1007/s00213-007-0939-0