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Auditory P50 and N100 responses reflect preattentive processing, whereas subsequent mismatch negativity (MMN) response indexes memory-based comparison process. Divergent ERP responses have been found in schizophrenia and in Parkinson's disease (PD), which have abnormalities in cerebral dopamine activity. We used simultaneously magnetoencephalography and electroencephalography to investigate, whether a single dose of haloperidol, a dopamine D2-receptor antagonist, modulates preattentive auditory processing using a randomized, double-blind, placebo-controlled crossover design. Our results showed that haloperidol did not alter MMN to frequency and duration changes, whereas the magnetic MMN to frequency change was significantly accelerated. The amplitude and latency changes of the electric and magnetic P50 and N100 were insignificant. Our results indicate that memory-based sound comparison and preceding cortical processing underlying stimulus detection are not attenuated by haloperidol, whereas haloperidol appears to accelerate preattentive sound comparison.

Aging attenuates automatic auditory discrimination to duration change, whereas frequency change detection is relatively unimpaired in aging and in Alzheimer's disease (AD). Here we studied with a whole-head magnetometer whether cortical auditory discrimination to duration change as shown by magnetic mismatch negativity (MMNm) response is impaired in AD. Twenty AD patients with mild to moderate cognitive impairment and 18 age-matched healthy subjects were monaurally presented a sequence of frequent standard tones embedded with occasional deviants with shorter duration. MMNm was significantly delayed in the left hemisphere ipsilaterally to the ear stimulated in the patient group, whereas the MMNm amplitudes over both hemispheres were quite similar in both groups. This suggests that although MMNm is delayed in the left hemisphere, the automatic discrimination to duration change in the auditory cortex is not attenuated in the early stages of AD.

Acetylcholine (ACh) is a potent neuromodulator in the brain with multiple, complex effects on neuronal function, most of which are mediated by muscarinic receptors. Generally, the most significant effect is excitation of pyramidal neurones and facilitation of responses to afferent stimulation. Much of the information on the ACh effects comes from studies utilizing in vitro or anesthetized in vivo preparations, while fewer data are available from awake animals or humans. We studied human somatosensory evoked magnetic fields (SEFs), which reflect summated postsynaptic currents in pyramidal neurones in area 3b, and in the opercular somatosensory cortex, when cholinergic transmission was modulated either by a central (scopolamine, 0.3 mg, i.v.) or peripheral (glycopyrrolate, 0.2 mg, i.v.) muscarinic antagonist. A randomized, double-blind, cross-over design was employed. SEFs were elicited by right median nerve stimulation at the wrist with constant-current pulses above motor threshold. The first excitatory cortical response from area 3b (N20m) was not affected by the central muscarinic blockade, while later P35m and P60m deflections were significantly reduced. The responses from the opercular somatosensory cortex showed some tendency toward reduction, but no significant alterations. The results show that somatosensory cortical processing can be modulated by muscarinic transmission at a relatively early stage. Relative membrane hyperpolarization of pyramidal neurons due to scopolamine (caused by blocking an ACh-induced tonic depolarization) is discussed as a possible mechanism underlying the observed effects.

We tested the possible role of dopaminergic activity in the processing of somatosensory afferent information in healthy humans. Somatosensory evoked magnetic fields (SEFs) were recorded in seven subjects in response to left median nerve stimulation. SEFs were obtained in all subjects after oral administration of 2 mg haloperidol, an antagonist to dopaminergic D 2 receptors, and placebo, which were given in a randomized, double-blind cross-over design. SEFs were analyzed using a multiple equivalent current dipole (ECD) model, with one dipole at the right primary somatosensory cortex (SI) and at both left and right secondary somatosensory cortices (SII). The earliest responses from SI, peaking at about 20 ms (N20m) and 35 ms (P35m), were not affected by haloperidol. A later deflection peaking at about 75 ms (P60m), however, was slightly reduced (p < 0.05). Responses arising from SII were not significantly changed. The results suggest that dopaminergic activity may be involved in modulating somatosensory processing after the initial stages of cortical activation.

Auditory stimuli elicit auditory evoked magnetic fields (AEFs) called P50m and N100m, which index preconscious auditory processing in human. We investigated with a whole-head magnetometer whether Parkinson's disease (PD) impairs parallel preattentive auditory processing between the hemispheres. Stimulus blocks consisting of standard (80%) and deviant (20%) tones were monaurally presented in a passive condition to 11 PD patients with unilateral motor symptoms and to 11 age-matched healthy controls. The constant interstimulus intervals (ISIs) were 0.5 s and 2.5 s in separate blocks. The interhemispheric latency differences of the P50m and N100m were significantly lengthened in PD patients in the left-ear condition. This might be caused by the basal ganglia dysfunction in PD together with the simultaneous age-related neural degeneration predominant in the left auditory cortex.

Auditory evoked magnetic fields (AEFs) were recorded from 10 healthy younger and 10 older subjects using a whole-head magnetometer. Two blocks of tone pips were presented to the left ear with constant inter-stimulus intervals (ISIs) of 0.5 and 2.5 s. The amplitude of P50m, unlike that of N100m, was larger in the older subjects. In both groups, the peak latencies of P50m and N100m responses were significantly shorter over the contralateral than ipsilateral cortex. The interhemispheric latency difference of N100m was significantly increased with age. These findings suggest that ageing delays signal processing in the ipsilateral auditory cortex and that ageing affects consecutive AEFs in a different manner.