Background
Although the major principles of dopamine (DA) signaling have been well described
previously, its precise modulatory impact on the prefrontal cortex (PFC) in humans
is poorly understood. Two major neurophysiological models propose segregated functional
circuits on the systems level as well as D1 and D2 receptor-dependent processing states on the cellular level (two-state model).
Methods
We examined the predictive validity of these models in 10 healthy male volunteers
with a haloperidol challenge (HLP). Cortico-striatal-thalamo-cortical (CSTC) motor
loop functions were examined during functional magnetic resonance imaging (fMRI) with
a sequential finger opposition task. Neuropsychological implications of the two-state
model were evaluated with a test battery of D1- or D2-sensitive prefrontal measures.
Results
Analysis of fMRI data revealed a significant HLP-induced blood oxygen level dependent–signal
decrease in the sensorimotor striatum and a lateralized activation loss of ipsilateral
higher order motor cortices and contralateral cerebellum. Neuropsychological evaluation
demonstrated a preferential impairment of D2-sensitive functions, whereas D1 or non-dopaminergic domains were unaffected.
Conclusions
Our data support the hypothesis that mesocortical D1 and D2 receptors exert differential influences in the PFC for cognitive function, but the
nigrostriatal CSTC network model for the motor domain could not be confirmed.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Anatomical and physiological evidence for D1 and D2 dopamine receptor colocalization in neostriatal neurons.Nat Neurosci. 2000; 3: 226-230
- Basal ganglia-thalamocortical circuits: Parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions.Prog Brain Res. 1990; 85: 119-146
- Parallel organization of functionally segregated circuits linking basal ganglia and cortex.Annu Rev Neurosci. 1986; 9: 357-381
- Anterior cingulate and the monitoring of response conflict: Evidence from an fMRI study of overt verb generation.J Cogn Neurosci. 2000; 12: 298-309
- Effects of haloperidol challenge on regional cerebral glucose utilization in normal human subjects.Am J Psychiatry. 1994; 151: 681-686
- Functional lateralization of the sensorimotor cortex in patients with schizophrenia: Effects of treatment with olanzapine.Biol Psychiatry. 2004; 56: 190-197
- Functional imaging studies on dopamine and motor control.J Neural Transm. 2001; 108: 1283-1298
- Visualizing fronto-striatal circuitry and neuroleptic effects in schizophrenia.Acta Psychiatr Scand Suppl. 1999; 395: 129-137
- Striatal metabolic rate and clinical response to neuroleptics in schizophrenia.Arch Gen Psychiatry. 1992; 49: 966-974
- Pharmacologically modulated fMRI - cortical responsiveness to levodopa in drug-naive hemiparkinsonian patients.Brain. 2003; 126: 451-461
- Physiological characteristics of capacity constraints in working memory as revealed by functional MRI.Cereb Cortex. 1999; 9: 20-26
- The functional neuroanatomy of simple and complex sequential finger movements: A PET study.Brain. 1998; 121: 253-264
- Classification of drugs according to receptor binding profiles.Naunyn Schmiedebergs Arch Pharmacol. 1984; 327: 95-101
- Lobular patterns of cerebellar activation in verbal working-memory and finger-tapping tasks as revealed by functional MRI.J Neurosci. 1997; 17: 9675-9685
- Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex.J Neurophysiol. 2000; 83: 1733-1750
- Neurocomputational models of working memory.Nat Neurosci. 2000; 3: 1184-1191
- Effects of dopaminergic agonists and antagonists on isolated cerebral blood vessels.Acta Physiol Scand. 1978; 104: 349-359
- Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia.Proc Natl Acad Sci U S A. 2001; 98: 6917-6922
- Language mapping in less than 15 minutes: Real-time functional MRI during routine clinical investigation.Neuroimage. 2001; 14: 585-594
- Multiple dopamine receptor subtypes in the medial prefrontal cortex of the rat regulate set-shifting.Neuropsychopharmacology. 2006; 31: 297-309
- Delay-dependent modulation of memory retrieval by infusion of a dopamine D1 agonist into the rat medial prefrontal cortex.Behav Neurosci. 2001; 115: 934-939
- Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission.Nat Neurosci. 2003; 6: 968-973
- Prefrontal cortex and the bridging of temporal gaps in the perception-action cycle.Ann N Y Acad Sci. 1990; 608 (discussion 330–336): 318-329
- The neurobiology of dopamine signaling.Arch Neurol. 2004; 61: 641-644
- Dopamine release during sequential finger movements in health and Parkinson’s disease: A PET study.Brain. 2003; 126: 312-325
- Cellular basis of working memory.Neuron. 1995; 14: 477-485
- D1 receptors in prefrontal cells and circuits.Brain Res Brain Res Rev. 2000; 31: 295-301
- Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior.Nat Neurosci. 2005; 8: 805-812
- Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia.J Neural Transm Gen Sect. 1993; 91: 111-134
- Specialized neural systems underlying representations of sequential movements.J Cogn Neurosci. 2000; 12: 56-77
- Event-related functional magnetic resonance imaging in Parkinson’s disease before and after levodopa.Brain. 2001; 124: 558-570
- The role of lateral premotor-cerebellar-parietal circuits in motor sequence control: A parametric fMRI study.Brain Res Cogn Brain Res. 2002; 13: 159-168
- Wisconsin Card Sorting Test, computer version. Psychological Assessment Resources, Odessa, Florida1993
- Impaired activation of the supplementary motor area in Parkinson’s disease is reversed when akinesia is treated with apomorphine.Ann Neurol. 1992; 32: 749-757
- Regional cerebral blood flow changes of cortical motor areas and prefrontal areas in humans related to ipsilateral and contralateral hand movements.Brain Res. 1993; 623: 33-40
- Organization of the thalamo-cortical connexions to the frontal lobe in the rhesus monkey.Exp Brain Res. 1977; 29: 299-322
- The Comparative Anatomy and Histology of the Cerebellum: The Human Cerebellum, Cerebellar Connections, and Cerebellar Cortex. University of Minnesota Press, Minneapolis, Minnesota1972
- Elimination half-life and bioavailability of haloperidol in schizophrenic patients.J Clin Psychiatry. 1985; 46: 20-21
- An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets.Neuroimage. 2003; 19: 1233-1239
- Effects of dextroamphetamine on cognitive performance and cortical activation.Neuroimage. 2000; 12: 268-275
- Hemispheric control of motor function: A whole brain echo planar fMRI study.Psychiatry Res. 1998; 83: 7-22
- Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine.PNAS. 2003; 100: 6186-6191
- Impaired set-shifting and dissociable effects on tests of spatial working memory following the dopamine D2 receptor antagonist sulpiride in human volunteers.Psychopharmacology. 2004; 176: 331-342
- Systemic sulpiride modulates striatal blood flow: Relationships to spatial working memory and planning.Neuroimage. 2003; 20: 1982-1994
- Midbrain dopamine and prefrontal function in humans: Interaction and modulation by COMT genotype.Nat Neurosci. 2005; 8: 594-596
- Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia.Arch Gen Psychiatry. 2005; 62: 379-386
- Basal ganglia and cerebellar loops: Motor and cognitive circuits.Brain Res Brain Res Rev. 2000; 31: 236-250
- Effect of antipsychotics on regional cerebral blood flow measured with positron emission tomography.Neuropsychopharmacology. 1997; 17: 230-240
- Reciprocal dopamine-glutamate modulation of release in the basal ganglia.Neurochem Int. 1998; 33: 383-397
- fMRI evidence that the neural basis of response inhibition is task-dependent.Brain Res Cogn Brain Res. 2003; 17: 419-430
- Neuronal activity in the primate premotor, supplementary, and precentral motor cortex during visually guided and internally determined sequential movements.J Neurophysiol. 1991; 66: 705-718
- Neural circuits and topographic organization of the basal ganglia and related regions.Brain Dev. 2000; 22: S5-S16
- Neural circuits and functional organization of the striatum.J Neurol. 2000; 247: V1-V15
- Pathophysiologic basis of surgery for Parkinson’s disease.Neurology. 2000; 55: S7-S12
- The assessment and analysis of handedness: The Edinburgh inventory.Neuropsychologia. 1971; 9: 97-113
- Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex.J Cereb Blood Flow Metab. 1996; 16: 1250-1254
- Supplementary and primary sensory motor area activity in Parkinson’s disease.Arch Neurol. 1992; 49: 144-148
- Parametric analysis of rate-dependent hemodynamic response functions of cortical and subcortical brain structures during auditorily cued finger tapping: A fMRI study.Neuroimage. 2003; 18: 731-739
- Mapping motor inhibition: Conjunctive brain activations across different versions of go/no-go and stop tasks.Neuroimage. 2001; 13: 250-261
- Cortical motor reorganization in akinetic patients with Parkinson’s disease: A functional MRI study.Brain. 2000; 123: 394-403
- Evidence for lateral premotor and parietal overactivity in Parkinson’s disease during sequential and bimanual movements.Brain. 1997; 120: 963-976
- Motor imagery in normal subjects and Parkinson’s disease patients: An H215O PET study.Neuroreport. 2001; 12: 821-828
- The origin of thalamic inputs to the arcuate premotor and supplementary motor areas.J Neurosci. 1984; 4: 539-560
- Laterality, somatotopy and reproducibility of the basal ganglia and motor cortex during motor tasks.Brain Res. 2000; 879: 204-215
- Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons.J Neurosci. 2001; 21: 3628-3638
- The principal features and mechanisms of dopamine modulation in the prefrontal cortex.Prog Neurobiol. 2004; 74: 1-58
- The basal ganglia and inhibitory mechanisms in response selection: Evidence from subliminal priming of motor responses in Parkinson’s disease.Brain. 2004; 127: 330-339
- Microcircuitry of the direct and indirect pathways of the basal ganglia.Neuroscience. 1998; 86: 353-387
- Lateralization of motor circuits and handedness during finger movements.Eur J Neurol. 2001; 8: 425-434
- Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus.J Neurosci. 2001; 21: RC157
- Corticostriatal projections from the somatic motor areas of the frontal cortex in the macaque monkey: Segregation versus overlap of input zones from the primary motor cortex, the supplementary motor area, and the premotor cortex.Exp Brain Res. 1998; 120: 114-128
- Co-Planar Stereotactic Atlas of the Human Brain. Georg Thieme Verlag, Stuttgart, Germany1988
- Neural networks: Neural systems VI: Basal ganglia.Am J Psychiatry. 2001; 158: 185
- Sequential organization of multiple movements: Involvement of cortical motor areas.Annu Rev Neurosci. 2001; 24: 631-651
- Selective D2 receptor actions on the functional circuitry of working memory.Science. 2004; 303: 853-856
- Effects of individual and concurrent stimulation of striatal D1 and D2 dopamine receptors on electrophysiological and behavioral output from rat basal ganglia.J Pharmacol Exp Ther. 2002; 300: 850-861
- Modulation of memory fields by dopamine D1 receptors in prefrontal cortex.Nature. 1995; 376: 572-575
- Genes, dopamine and cortical signal-to-noise ratio in schizophrenia.Trends Neurosci. 2004; 27: 683-690
- Localization of the motor hand area to a knob on the precentral gyrus.Brain. 1997; 120: 141-157
- Testbatterie zur Aufmerksamkeitsprüfung (TAP). Psytest, Herzogenrath, Germany1994
Article info
Publication history
Published online: September 04, 2006
Accepted:
April 13,
2006
Received in revised form:
March 13,
2006
Received:
August 8,
2005
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
