Intrinsic connections between thalamic sub-regions and the lateral prefrontal cortex are differentially impacted by acute methylphenidate.
Adult
Dopamine Uptake Inhibitors
/ administration & dosage
Double-Blind Method
Female
Healthy Volunteers
Humans
Magnetic Resonance Imaging
/ methods
Male
Memory, Short-Term
/ drug effects
Methylphenidate
/ administration & dosage
Nerve Net
/ diagnostic imaging
Prefrontal Cortex
/ diagnostic imaging
Thalamus
/ diagnostic imaging
Young Adult
Acute methylphenidate
Dopamine
Intrinsic functional connectivity
Prefrontal cortex
Resting state fMRI
Thalamus
Journal
Psychopharmacology
ISSN: 1432-2072
Titre abrégé: Psychopharmacology (Berl)
Pays: Germany
ID NLM: 7608025
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
19
07
2019
accepted:
10
03
2020
pubmed:
21
4
2020
medline:
30
9
2020
entrez:
21
4
2020
Statut:
ppublish
Résumé
The thalamus is a major target of dopaminergic projections and is densely connected with the prefrontal cortex. A better understanding of how dopamine changes thalamo-cortical communication may shed light on how dopamine supports cognitive function. Methylphenidate has been shown to facilitate cognitive processing and reduce connectivity between the thalamus and lateral prefrontal cortex. The thalamus is a heterogeneous structure, and the present study sought to clarify how the intrinsic connections of thalamic sub-regions are differentially impacted by acute dopamine transporter blockade. Sixty healthy volunteers were orally administered either 20 mg of methylphenidate (N = 29) or placebo (N = 31) in a double-blind, randomized, between-subject design. Multi-echo fMRI was used to assess intrinsic functional connectivity of sub-regions of the thalamus during a resting state scan. An N-back working-memory paradigm provided a measure of cognitive performance. Acute methylphenidate significantly reduced connectivity of the lateral prefrontal cortex with the motor and somatosensory sub-regions of the thalamus and reduced connectivity with the parietal and visual sub-regions at a trend level. Connectivity with the premotor, prefrontal, and temporal sub-regions was not impacted. The intrinsic connectivity between the thalamus and the lateral prefrontal cortex was not associated with working-memory performance. Methylphenidate decreases functional connections between the lateral prefrontal cortex and thalamus broadly, while sparing intrinsic connectivity with thalamic sub-regions involved with working-memory and language related processes. Collectively, our results suggest that the dopamine transporter regulates functional connections between the prefrontal cortex and non-cognitive areas of the thalamus.
Sections du résumé
BACKGROUND
BACKGROUND
The thalamus is a major target of dopaminergic projections and is densely connected with the prefrontal cortex. A better understanding of how dopamine changes thalamo-cortical communication may shed light on how dopamine supports cognitive function. Methylphenidate has been shown to facilitate cognitive processing and reduce connectivity between the thalamus and lateral prefrontal cortex.
AIMS
OBJECTIVE
The thalamus is a heterogeneous structure, and the present study sought to clarify how the intrinsic connections of thalamic sub-regions are differentially impacted by acute dopamine transporter blockade.
METHODS
METHODS
Sixty healthy volunteers were orally administered either 20 mg of methylphenidate (N = 29) or placebo (N = 31) in a double-blind, randomized, between-subject design. Multi-echo fMRI was used to assess intrinsic functional connectivity of sub-regions of the thalamus during a resting state scan. An N-back working-memory paradigm provided a measure of cognitive performance.
RESULTS
RESULTS
Acute methylphenidate significantly reduced connectivity of the lateral prefrontal cortex with the motor and somatosensory sub-regions of the thalamus and reduced connectivity with the parietal and visual sub-regions at a trend level. Connectivity with the premotor, prefrontal, and temporal sub-regions was not impacted. The intrinsic connectivity between the thalamus and the lateral prefrontal cortex was not associated with working-memory performance.
CONCLUSIONS
CONCLUSIONS
Methylphenidate decreases functional connections between the lateral prefrontal cortex and thalamus broadly, while sparing intrinsic connectivity with thalamic sub-regions involved with working-memory and language related processes. Collectively, our results suggest that the dopamine transporter regulates functional connections between the prefrontal cortex and non-cognitive areas of the thalamus.
Identifiants
pubmed: 32307560
doi: 10.1007/s00213-020-05505-z
pii: 10.1007/s00213-020-05505-z
pmc: PMC7437544
mid: NIHMS1617803
doi:
Substances chimiques
Dopamine Uptake Inhibitors
0
Methylphenidate
207ZZ9QZ49
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1873-1883Subventions
Organisme : Intramural NIH HHS
ID : ZIA MH002798
Pays : United States
Organisme : NIMH NIH HHS
ID : ZIAMH002798
Pays : United States
Références
Arnsten AF, Scahill L, Findling RL (2007) Alpha-2 adrenergic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: emerging concepts from new data. J Child Adolesc Psychopharmacol 17(4):393–406
pubmed: 17822336
doi: 10.1089/cap.2006.0098
Baddeley A (1992) Working memory. Science 255(5044):556–559. https://doi.org/10.1126/science.1736359
pubmed: 1736359
doi: 10.1126/science.1736359
Barbas H, García-Cabezas MÁ, Zikopoulos B (2013) Frontal-thalamic circuits associated with language. Brain Lang 126(1):49–61
pubmed: 23211411
doi: 10.1016/j.bandl.2012.10.001
Behrens TE, Johansen-Berg H, Woolrich MW, Smith SM, Wheeler-Kingshott CAM, Boulby PA, Barker GJ, Sillery EL, Sheehan K, Ciccarelli O (2003) Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nat Neurosci 6(7):750–757
pubmed: 12808459
doi: 10.1038/nn1075
Chen G, Adleman NE, Saad ZS, Leibenluft E, Cox RW (2014) Applications of multivariate modeling to neuroimaging group analysis: a comprehensive alternative to univariate general linear model. Neuroimage 99:571–588
pubmed: 24954281
doi: 10.1016/j.neuroimage.2014.06.027
Collins DP, Anastasiades PG, Marlin JJ, Carter AG (2018) Reciprocal circuits linking the prefrontal cortex with dorsal and ventral thalamic nuclei. Neuron 98(2):366–379
pubmed: 29628187
pmcid: 6422177
doi: 10.1016/j.neuron.2018.03.024
Cox RW (1996) AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 29(3):162–173
pubmed: 8812068
doi: 10.1006/cbmr.1996.0014
Cox RW, Reynolds RC, Taylor PA (2016) AFNI and clustering: false positive rates redux. BioRxiv 065862
de Bourbon-Teles J, Bentley P, Koshino S, Shah K, Dutta A, Malhotra P, Egner T, Husain M, Soto D (2014) Thalamic control of human attention driven by memory and learning. Curr Biol 24(9):993–999
pubmed: 24746799
pmcid: 4012133
doi: 10.1016/j.cub.2014.03.024
Demiral ŞB, Tomasi D, Wiers CE, Manza P, Shokri-Kojori E, Studentsova Y, Wang G-J, Volkow ND (2018) Methylphenidate’s effects on thalamic metabolism and functional connectivity in cannabis abusers and healthy controls. Neuropsychopharmacology 1
Ding Y-S, Fowler JS, Volkow ND, Dewey SL, Wang G-J, Logan J, Gatley SJ, Pappas N (1997) Chiral drugs: comparison of the pharmacokinetics of [11C] d-threo and L-threo-methylphenidate in the human and baboon brain. Psychopharmacology 131(1):71–78
pubmed: 9181638
doi: 10.1007/s002130050267
Eklund A, Nichols TE, Knutsson H (2016) Cluster failure: why fMRI inferences for spatial extent have inflated false-positive rates. Proc Natl Acad Sci 113(28):7900–7905
pubmed: 27357684
doi: 10.1073/pnas.1602413113
pmcid: 4948312
Ernst M, Lago T, Davis A, Grillon C (2016) The effects of methylphenidate and propranolol on the interplay between induced-anxiety and working memory. Psychopharmacology 233(19):3565–3574. https://doi.org/10.1007/s00213-016-4390-y
pubmed: 27492789
pmcid: 5131568
doi: 10.1007/s00213-016-4390-y
Farr OM, Zhang S, Hu S, Matuskey D, Abdelghany O, Malison RT, Li CR (2014) The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults. Int J Neuropsychopharmacol 17(8):1177–1191
pubmed: 24825078
doi: 10.1017/S1461145714000674
First MB, Spitzer RL, Gibbon M, Williams JB (2002) Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edn. SCID-I/P, New York
Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, Van Der Kouwe A, Killiany R, Kennedy D, Klaveness S (2002) Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33(3):341–355
pubmed: 11832223
doi: 10.1016/S0896-6273(02)00569-X
García-Cabezas MÁ, Rico B, Sánchez-González MÁ, Cavada C (2007) Distribution of the dopamine innervation in the macaque and human thalamus. Neuroimage 34(3):965–984
pubmed: 17140815
doi: 10.1016/j.neuroimage.2006.07.032
Hagoort P (2014) Nodes and networks in the neural architecture for language: Broca’s region and beyond. Curr Opin Neurobiol 28:136–141
pubmed: 25062474
doi: 10.1016/j.conb.2014.07.013
Hannestad J, Gallezot J-D, Planeta-Wilson B, Lin S-F, Williams WA, van Dyck CH, Malison RT, Carson RE, Ding Y-S (2010) Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo. Biol Psychiatry 68(9):854–860
pubmed: 20691429
pmcid: 3742016
doi: 10.1016/j.biopsych.2010.06.017
Hauser TU, Fiore VG, Moutoussis M, Dolan RJ (2016) Computational psychiatry of ADHD: neural gain impairments across Marrian levels of analysis. Trends Neurosci 39(2):63–73
pubmed: 26787097
pmcid: 4746317
doi: 10.1016/j.tins.2015.12.009
Huang Q, Zhou D, Chase K, Gusella JF, Aronin N, DiFiglia M (1992) Immunohistochemical localization of the D1 dopamine receptor in rat brain reveals its axonal transport, pre- and postsynaptic localization, and prevalence in the basal ganglia, limbic system, and thalamic reticular nucleus. Proc Natl Acad Sci 89(24):11988–11992
pubmed: 1281547
doi: 10.1073/pnas.89.24.11988
pmcid: 50683
Iglesias JE, Insausti R, Lerma-Usabiaga G, Bocchetta M, Van Leemput K, Greve DN, van der Kouwe A, Fischl B, Caballero-Gaudes C, Paz-Alonso PM (2018) A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology. NeuroImage 183:314–326. https://doi.org/10.1016/j.neuroimage.2018.08.012
pubmed: 30121337
doi: 10.1016/j.neuroimage.2018.08.012
Jacob SN, Nieder A (2014) Complementary roles for primate frontal and parietal cortex in guarding working memory from distractor stimuli. Neuron 83(1):226–237. https://doi.org/10.1016/j.neuron.2014.05.009
pubmed: 24991963
doi: 10.1016/j.neuron.2014.05.009
Koelsch S, Schulze K, Sammler D, Fritz T, Müller K, Gruber O (2009) Functional architecture of verbal and tonal working memory: an FMRI study. Hum Brain Mapp 30(3):859–873
pubmed: 18330870
doi: 10.1002/hbm.20550
Konova AB, Moeller SJ, Tomasi D, Volkow ND, Goldstein RZ (2013) Effects of methylphenidate on resting-state functional connectivity of the mesocorticolimbic dopamine pathways in cocaine addiction. JAMA Psychiatry 70(8):857–868
pubmed: 23803700
pmcid: 4358734
doi: 10.1001/jamapsychiatry.2013.1129
Konova AB, Moeller SJ, Tomasi D, Goldstein RZ (2015) Effects of chronic and acute stimulants on brain functional connectivity hubs. Brain Res 1628:147–156
pubmed: 25721787
pmcid: 4547912
doi: 10.1016/j.brainres.2015.02.002
Kundu P, Voon V, Balchandani P, Lombardo MV, Poser BA, Bandettini PA (2017) Multi-echo fMRI: a review of applications in fMRI denoising and analysis of BOLD signals. Neuroimage 154:59–80
pubmed: 28363836
doi: 10.1016/j.neuroimage.2017.03.033
Kupferschmidt DA, Gordon JA (2018) The dynamics of disordered dialogue: prefrontal, hippocampal and thalamic miscommunication underlying working memory deficits in schizophrenia. Brain Neurosci Adv 2:2398212818771821
pmcid: 6497416
doi: 10.1177/2398212818771821
Linssen AMW, Vuurman E, Sambeth A, Riedel WJ (2012) Methylphenidate produces selective enhancement of declarative memory consolidation in healthy volunteers. Psychopharmacology 221(4):611–619
pubmed: 22169884
doi: 10.1007/s00213-011-2605-9
Mitchell AS (2015) The mediodorsal thalamus as a higher order thalamic relay nucleus important for learning and decision-making. Neurosci Biobehav Rev 54:76–88. https://doi.org/10.1016/j.neubiorev.2015.03.001
pubmed: 25757689
doi: 10.1016/j.neubiorev.2015.03.001
Mueller S, Costa A, Keeser D, Pogarell O, Berman A, Coates U, Reiser MF, Riedel M, Möller H-J, Ettinger U (2014) The effects of methylphenidate on whole brain intrinsic functional connectivity. Hum Brain Mapp 35(11):5379–5388
pubmed: 24862742
doi: 10.1002/hbm.22557
pmcid: 6869774
Owen AM, Stern CE, Look RB, Tracey I, Rosen BR, Petrides M (1998) Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex. Proc Natl Acad Sci 95(13):7721–7726. https://doi.org/10.1073/pnas.95.13.7721
pubmed: 9636217
doi: 10.1073/pnas.95.13.7721
pmcid: 22736
Parnaudeau S, O’Neill P-K, Bolkan SS, Ward RD, Abbas AI, Roth BL, Balsam PD, Gordon JA, Kellendonk C (2013) Inhibition of mediodorsal thalamus disrupts thalamofrontal connectivity and cognition. Neuron 77(6):1151–1162. https://doi.org/10.1016/j.neuron.2013.01.038
pubmed: 23522049
pmcid: 3629822
doi: 10.1016/j.neuron.2013.01.038
Pergola G, Danet L, Pitel A-L, Carlesimo GA, Segobin S, Pariente J, Suchan B, Mitchell AS, Barbeau EJ (2018) The regulatory role of the human mediodorsal thalamus. Trends Cogn Sci
Power JD, Mitra A, Laumann TO, Snyder AZ, Schlaggar BL, Petersen SE (2014) Methods to detect, characterize, and remove motion artifact in resting state fMRI. Neuroimage 84:320–341
pubmed: 23994314
doi: 10.1016/j.neuroimage.2013.08.048
Ramaekers JG, Evers EA, Theunissen EL, Kuypers KPC, Goulas A, Stiers P (2013) Methylphenidate reduces functional connectivity of nucleus accumbens in brain reward circuit. Psychopharmacology 229(2):219–226
pubmed: 23604336
doi: 10.1007/s00213-013-3105-x
Ranganath A, Jacob SN (2016) Doping the mind: dopaminergic modulation of prefrontal cortical cognition. Neuroscientist 22(6):593–603. https://doi.org/10.1177/1073858415602850
pubmed: 26338491
doi: 10.1177/1073858415602850
Sakai K, Rowe JB, Passingham RE (2002) Active maintenance in prefrontal area 46 creates distractor-resistant memory. Nat Neurosci 5(5):479–484
pubmed: 11953754
doi: 10.1038/nn846
Sánchez-González MÁ, García-Cabezas MÁ, Rico B, Cavada C (2005) The primate thalamus is a key target for brain dopamine. J Neurosci 25(26):6076–6083
pubmed: 15987937
pmcid: 6725054
doi: 10.1523/JNEUROSCI.0968-05.2005
Schmitt LI, Wimmer RD, Nakajima M, Happ M, Mofakham S, Halassa MM (2017) Thalamic amplification of cortical connectivity sustains attentional control. Nature 545(7653):219–223
pubmed: 28467827
pmcid: 5570520
doi: 10.1038/nature22073
Sherman SM (2011) Functioning of circuits connecting thalamus and cortex. Compr Physiol 7(2):713–739
Spencer RC, Devilbiss DM, Berridge CW (2015) The cognition-enhancing effects of psychostimulants involve direct action in the prefrontal cortex. Biol Psychiatry 77(11):940–950
pubmed: 25499957
doi: 10.1016/j.biopsych.2014.09.013
Swanson JM, Volkow ND (2003) Serum and brain concentrations of methylphenidate: implications for use and abuse. Neurosci Biobehav Rev 27(7):615–621
pubmed: 14624806
doi: 10.1016/j.neubiorev.2003.08.013
Tanaka M (2007) Cognitive signals in the primate motor thalamus predict saccade timing. J Neurosci 27(44):12109–12118. https://doi.org/10.1523/JNEUROSCI.1873-07.2007
pubmed: 17978052
pmcid: 6673367
doi: 10.1523/JNEUROSCI.1873-07.2007
Taylor PA, Saad ZS (2013) FATCAT: (an efficient) functional and tractographic connectivity analysis toolbox. Brain Connect 3(5):523–535
pubmed: 23980912
pmcid: 3796333
doi: 10.1089/brain.2013.0154
Tomasi D, Volkow ND (2012) Abnormal functional connectivity in children with attention-deficit/hyperactivity disorder. Biol Psychiatry 71(5):443–450
pubmed: 22153589
doi: 10.1016/j.biopsych.2011.11.003
Volkow ND, Wang G-J, Fowler JS, Gatley SJ, Logan J, Ding Y-S, Hitzemann R, Pappas N (1998) Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatr 155(10):1325–1331
pubmed: 9766762
doi: 10.1176/ajp.155.10.1325
Wimmer RD, Schmitt LI, Davidson TJ, Nakajima M, Deisseroth K, Halassa MM (2015) Thalamic control of sensory selection in divided attention. Nature 526(7575):705–709
pubmed: 26503050
pmcid: 4626291
doi: 10.1038/nature15398
Xiaob D, Barbas H (2004) Circuits through prefrontal cortex, basal ganglia, and ventral anterior nucleus map pathways beyond motor control. Thalamus Relat Syst 2(4):325–343
doi: 10.1017/S1472928804030018
Zikopoulos B, Barbas H (2006) Prefrontal projections to the thalamic reticular nucleus form a unique circuit for attentional mechanisms. J Neurosci 26(28):7348–7361
pubmed: 16837581
pmcid: 6674204
doi: 10.1523/JNEUROSCI.5511-05.2006