Paroxetine-induced modulation of cortical activity supporting language representations of action

IntroductionPrevious 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 methodsA 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 discussionFor 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.ConclusionChronic treatment with paroxetine may modulate the cerebral activities elicited by action-related language tasks depending on the cognitive components involved in such tasks.

[1]  J. Démonet,et al.  Pharmacotherapy of aphasia: Myth or reality? , 2007, Brain and Language.

[2]  D. Dunner,et al.  Paroxetine: a review of clinical experience. , 1998, Pharmacopsychiatry.

[3]  A. Tasman,et al.  Changes in neural circuitry of language before and after treatment of major depression , 2002, Human brain mapping.

[4]  P. T. Fox,et al.  Positron emission tomographic studies of the cortical anatomy of single-word processing , 1988, Nature.

[5]  Trevor Sharp,et al.  A review of central 5-HT receptors and their function , 1999, Neuropharmacology.

[6]  J. Fiez Phonology, Semantics, and the Role of the Left Inferior Prefrontal Cortex , 2022 .

[7]  P. Halligan,et al.  The relevance of behavioural measures for functional-imaging studies of cognition , 2004, Nature Reviews Neuroscience.

[8]  Gary W. Thickbroom,et al.  Differential activation of frontal lobe areas by lexical and semantic language tasks: A functional magnetic resonance imaging study , 2006, Journal of Clinical Neuroscience.

[9]  F. Chollet,et al.  Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke , 2001, Annals of neurology.

[10]  O. Blin,et al.  Serotonin and human information processing: fluvoxamine can improve reaction time performance , 1997, Neuroscience Letters.

[11]  J. Gee,et al.  Neural representation of verb meaning: An fMRI study , 2002, Human brain mapping.

[12]  Friedemann Pulvermüller,et al.  Brain mechanisms linking language and action , 2005, Nature Reviews Neuroscience.

[13]  Rebecca Elliott,et al.  The Effect of Citalopram Pretreatment on Neuronal Responses to Neuropsychological Tasks in Normal Volunteers: An fMRI Study , 2005, Neuropsychopharmacology.

[14]  I. F. Tatsumi,et al.  Verb Generation in Japanese—A Multicenter PET Activation Study , 1999, NeuroImage.

[15]  J. Decety,et al.  Functional anatomy of execution, mental simulation, observation, and verb generation of actions: A meta‐analysis , 2001, Human brain mapping.

[16]  F. Chollet,et al.  Within-Session and Between-Session Reproducibility of Cerebral Sensorimotor Activation: A Test–Retest Effect Evidenced with Functional Magnetic Resonance Imaging , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  D. Cohen,et al.  Acute and chronic effects of fluoxetine and haloperidol on mouse brain serotonin and norepinephrine turnover. , 1995, Life sciences.

[18]  R. Elliott,et al.  Serotonergic modulation of neuronal responses to behavioural inhibition and reinforcing stimuli: an fMRI study in healthy volunteers , 2006, The European journal of neuroscience.

[19]  François Chollet,et al.  Selective serotonin reuptake inhibitor paroxetine modulates motor behavior through practice. A double-blind, placebo-controlled, multi-dose study in healthy subjects , 2002, Neuropsychologia.

[20]  M. D’Esposito,et al.  The neural basis of the central executive system of working memory , 1995, Nature.

[21]  P. Fletcher,et al.  Neural processing of nouns and verbs: the role of inflectional morphology , 2004, Neuropsychologia.

[22]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[23]  Richard S. J. Frackowiak,et al.  Noun and verb retrieval by normal subjects. Studies with PET. , 1996, Brain : a journal of neurology.

[24]  L. Piron,et al.  The effects of fluoxetine and maprotiline on functional recovery in post-stroke hemiplegic patients undergoing rehabilitation therapy. Stroke, 27, 1221-1214 (1996) , 1996 .

[25]  François Chollet,et al.  Chronic administration of selective serotonin reuptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects , 2005, NeuroImage.

[26]  S. Petersen,et al.  Practice-related changes in human brain functional anatomy during nonmotor learning. , 1994, Cerebral cortex.

[27]  M. Geyer Serotonergic functions in arousal and motor activity , 1995, Behavioural Brain Research.

[28]  B. Bertenthal,et al.  Does Perception of Biological Motion Rely on Specific Brain Regions? , 2001, NeuroImage.

[29]  Marc Jeannerod,et al.  Cross-talk between Language Processes and Overt Motor Behavior in the First 200 msec of Processing , 2006, Journal of Cognitive Neuroscience.

[30]  K Patterson,et al.  Language activation studies with positron emission tomography. , 1991, Ciba Foundation symposium.

[31]  A. Schleicher,et al.  Transmitter receptors and functional anatomy of the cerebral cortex , 2004, Journal of anatomy.

[32]  S. Houle,et al.  Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. , 2001, The American journal of psychiatry.

[33]  François Chollet,et al.  Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer , 2005, NeuroImage.

[34]  D. Middlemiss,et al.  Species differences in 5-HT autoreceptors , 1995, Behavioural Brain Research.

[35]  Y. Joanette,et al.  [Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level]. , 1990, Acta neurologica Belgica.

[36]  J. Mazziotta,et al.  Mapping motor representations with positron emission tomography , 1994, Nature.

[37]  G. Thierry,et al.  Renewal of the neurophysiology of language: functional neuroimaging. , 2005, Physiological reviews.

[38]  D. Perani,et al.  The neural correlates of verb and noun processing. A PET study. , 1999, Brain : a journal of neurology.

[39]  B. Jacobs,et al.  Activity of Serotonergic Neurons in Behaving Animals , 1999, Neuropsychopharmacology.

[40]  M. Hamon,et al.  Pharmacological profile of antidepressants: a likely basis for their efficacy and side effects? , 2006, European Neuropsychopharmacology.

[41]  Bernard Mazoyer,et al.  Meta-analyzing left hemisphere language areas: Phonology, semantics, and sentence processing , 2006, NeuroImage.

[42]  T. J. Grabowski Re-examining the Brain Regions Crucial for Orchestrating Speech Articulation , 2006 .

[43]  J. Haxby,et al.  Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Robert J Zatorre,et al.  Word and nonword repetition in bilingual subjects: A PET study , 2006, Human brain mapping.

[45]  Alan C. Evans,et al.  PET studies of phonetic processing of speech: review, replication, and reanalysis. , 1996, Cerebral cortex.

[46]  Leslie G. Ungerleider,et al.  Discrete Cortical Regions Associated with Knowledge of Color and Knowledge of Action , 1995, Science.