Effects of Haloperidol on Selective Attention A Combined Whole-Head MEG and High-Resolution EEG Study

Abstract

We used 122-channel magnetoencephalography (MEG) and 64-channel electroencephalogrphy (EEG) simultaneously to study the effects of dopaminergic transmission on human selective attention in a randomized, double-blind placebo-controlled cross-over design. A single dose of dopamine D2 receptor antagonist haloperidol (2 mg) or placebo was given orally to 12 righthanded healthy volunteers 3 hours before measurement. In a dichotic selective attention task, subjects were presented with two trains of standard (700 Hz to the left ear, 1,100Hz to the right ear) and deviant (770 and 1,210 Hz, respectively) Selective attention refers to the ability to attend to relevant information simultaneously ignoring irrelevant information (Posner and Boies 1971). The neural basis of selective attention can be noninvasively studied with high temporal resolution using event-related potentials (ERP) and magnetic fields (ERF), which are electroencephalogram (EEG) or magnetoencephalogram (MEG) changes time-locked to the presentation of external stimuli (Hari and Lounasmaa 1989;Näätänen et al. 1992 (Näätänen 1992). MEG studies of selective attention have, in turn, indicated that the amplitude of the N1m, elicited at about 100 ms poststimulus, is increased by selective attention, but the PN seems to be less visible for the MEG than EEG (Fujiwara et al. 1998). The mismatch negativity (MMN), or magnetic counterpart MMNm, is a pre-attentive ERP/ERF component elicited by any change in a sequence of frequent standard tones reflecting automatic detection and orientation to sudden environmental changes (Alho 1995;Näätänen 1992;Näätänen et al. 1978;Tiitinen et al. 1994).Only a few studies have been devoted to drug effects on selective attention indexing by the PN. The NMDA receptor antagonist ketamine, alcohol, and adrenocorticotropic hormone (ACTH) have been shown to reduce PN (Smolnik et al. 1999;Hirvonen et al. 2000;Oranje et al. 2000). Opposite effects were observed after the administration of the antagonist of GABA receptors flumatzenil and cholecystokinin analog ceruletide (Schreiber et al. 1995;Smolnik et al. 1998). Anesthetic gas nitrous oxide (N 2 O) and adrenergic alpha 2-antagonist atipamezole had no effects on the PN (Mervaala et al. 1993;Pang and Fowler 1999). Shelley et al. (1997) studied effects of another adrenergic alpha 2-receptor agonist clonidine and dopamine D2 receptor antagonist droperidol on ERP indices of selective attention. They found that clonidine increased and droperidol decreased the PN.Haloperidol is a potent, partially selective dopamine D 2 receptor antagonist, which is widely used to treat psychotic disorders in clinical practice. Haloperidol affects spontaneous EEG activity, increasing slow waves and decreasing alpha and beta activity in healthy humans (McClelland et al. 1990). There is also evidence that haloperdiol decreases the transient 40 Hz response elicited by selectively attended tones (Ahveninen et al. 2000).Our study was designed to investigate with simultaneous MEG and EEG recordings whether haloperi...

Dopamine modulates attentional control of auditory perception: DARPP-32 (PPP1R1B) genotype effects on behavior and cortical evoked potentials

“…The present findings complement the results of other studies indicating that variations in dopamine functioning influence working memory (e.g., Cools et al, 2004;Frank et al, 2001;Landau et al, 2005;Lewis et al, 2003;McNab & Klingberg, 2008), executive control (e.g., Hesse et al, 2009;Siessmeier et al, 2006;Vernaleken et al, 2007;Volkow et al, 2007), and selective attention (e.g., Gorgoraptis et al, 2012;Kähkönen et al, 2001;Shelley et al, 1997). Human studies of striatal dopaminergic modulation of attention primarily investigated attentional control in the context of complex visual perception, such as video games (Koepp et al, 1998) and affective scenes (Siessmeier et al, 2006), or in the context of other cognitive processes such as Stroop interference (Vernaleken et al, 2007), visual attention as assessed by the Trail-Making test (Meyer-Lindenberg et al, 2007) and the attentional blink effect (Colzato et al, 2011).…”

“…Our findings of DARPP32 genotype effects on the behavioral performance and cortical evoked potentials that reflect attentional control of auditory perception when processing competing sensory information extend these previous findings. Specifically, our finding of A homozygotes performed better and showed a larger amplitude of the late N450 component in conditions that demanded more selective attention lend further support to earlier results showing pharmacological effects of dopamine antagonist (Kähkönen et al, 2001;Shelley et al, 1997) and agonist (Gorgoraptis et al, 2012) in modulating selective auditory and visual attention. The late N450 amplitude modulation effect found in the current study parallels effects of dopamine antagonists on later processing negativity (i.e., at least 200 ms after stimulus onset) that was associated with more complex attentional deployment (Kähkönen et al, 2001;Shelley et al, 1997).…”

“…Also of relevance to the current study, earlier pharmacological studies that used target detection dichotic listening paradigms found that catecholamine antagonists (e.g., haloperidol or droperidol) attenuated the processing negativity, which reflected selective attention, only in later time windows, i.e. at least 200 ms after stimulus onset (Kähkönen et al, 2001;Shelley et al, 1997). On the other side of the coin, a recent study showed that dopamine agonist (rotigotine) improved hemispatial neglect of patients' performance in visual search tasks that required selective attention (Gorgoraptis et al, 2012).…”

Auditory selective attention modulated by tryptophan depletion in humans

“…The later aspects of PN, in turn, were not affected by ATD. This contrasts effects of the dopamine D 2 -receptor antagonists droperidol and haloperidol, which have been shown to affect more profoundly the later than early PN [8,13]. Interestingly, immunohistochemical evidence indicates that the density of 5-HT innervation is clearly higher, as compared with that of dopamine, in the primate auditory cortex [2].…”

“…The later aspects of PN have might in turn depend on prefrontal brain activation [10]. Previous studies suggest that dopamine D 2 -receptor antagonists, such as haloperidol [8] and droperidol [13], reduce PN amplitude. However, few ERP/MEG results on 5-HT modulation of selective attention exist.…”