Eero Pekkonen

Processing of novel sounds and frequency changes in the human auditory cortex: Magnetoencephalographic recordings

Whole-head magnetoencephalographic (MEG) responses to repeating standard tones and to infrequent slightly higher deviant tones and complex novel sounds were recorded together with event-related brain potentials (ERPs). Deviant tones and novel sounds elicited the mismatch negativity (MMN) component of the ERP and its MEG counterpart (MMNm) both when the auditory stimuli were attended to and when they were ignored. MMNm generators were located bilateral to the superior planes of the temporal lobes where preattentive auditory discrimination appears to occur. A subsequent positive P3a component was elicited by deviant tones and with a larger amplitude by novel sounds even when the sounds were to be ignored. Source localization for the MEG counterpart of P3a (P3am) suggested that the auditory cortex in the superior temporal plane is involved in the neural network of involuntary attention switching to changes in the acoustic environment.

Combined mapping of human auditory EEG and MEG responses

Auditory electric and magnetic P50(m), N1(m) and MMN(m) responses to standard, deviant and novel sounds were studied by recording brain electrical activity with 25 EEG electrodes simultaneously with the corresponding magnetic signals measured with 122 MEG gradiometer coils. The sources of these responses were located on the basis of the MEG responses; all were found to be in the supratemporal plane. The goal of the present paper was to investigate to what degree the source locations and orientations determined from the magnetic data account for the measured EEG signals. It was found that the electric P50, N1 and MMN responses can to a considerable degree be explained by the sources of the corresponding magnetic responses. In addition, source-current components not detectable by MEG were shown to contribute to the measured EEG signals.

Auditory sensory memory impairment in Alzheimer's disease: an event-related potential study.

Auditory event-related potentials (ERP) were recorded from 10 healthy older subjects and 9 patients with Alzheimers disease (AD) to investigate whether auditory sensory memory is impaired in AD. Standard (85%) and deviant (15%) tones were presented in random order with interstimulus intervals (ISI) of 1 s or 3 s in separate blocks. Deviant tones elicited a specific ERP component called mismatch negativity (MMN) which reflects automatic stimulus change detection and thus presumably, the neural basis of sensory memory in audition. The MMN amplitude decreased as a function of the ISI more in the AD group than in the control group. This suggests that the memory trace decays faster in the AD patients than in age-matched healthy controls.

Variability and replicability of the mismatch negativity

The interindividual variation and test-retest stability of the mismatch negativity (MMN) and N1 components of the event-related potential (ERP) were investigated by presenting standard (85%) and deviant tones (15%) to 10 young subjects in 2 sessions separated by 1 month. Deviant tones in different blocks were either frequency or duration changes with interstimulus intervals (ISIs) of 0.5 and 1.5 sec. The results showed a fairly good test-retest stability of the MMN amplitude for both types of changes with each ISI at the group level. The amplitude of the duration MMN showed significant individual test-retest stability. The N1 amplitude showed high stability at both the group and individual levels. Both the MMN and N1 showed considerable interindividual variation. The results suggest that MMN and N1 can be used in follow-up studies not only at the group level but possibly at the individual level also.

Aging effects on auditory processing : An event-related potential study

Deviant tones randomly embedded in a sequence of standard tones elicit an event-related potential (ERP) called the mismatch negativity (MMN), which reflects automatic stimulus-change detection in the human auditory system. When the tones are attended, deviant tones elicit also an N2b component that partly overlaps the MMN. Sequences of standard and deviant (probability 0.15) tones were presented to 13 healthy younger and 13 older subjects. Deviant stimuli were, in separate blocks, either occasional shorter duration or higher frequency tones. The interstimulus interval (ISI) was, in separate blocks, either 0.5 s or 1.5 s, and in the frequency-change condition also 4.5 s. Aging affected neither frequency nor duration of MMN with the 0.5 s ISI. This finding indicates that automatic stimulus discrimination per se is not impaired with normal aging. However, with a 4.5-s ISI the MMN/N2b-complex attenuated significantly more in the older than younger subjects. This suggests that the stimulus trace decays faster or that involuntary attention switching is less sensitive with aging.

Mismatch negativity area and age-related auditory memory

The deviant tones embedded in a sequence of standard tones elicit an event-related potential (ERP) component called mismatch negativity (MMN). Because MMN is partly overlapped by other ERP components at 100-200 msec latency (N1 and P2) and its shape varies, MMN peak latency and amplitude may be ambiguous. We used the difference area between the deviant and standard ERP to evaluate the age and interstimulus interval (ISI) dependence of MMN. Sequences of standard (85%) and deviant (15%) tones were presented to 27 normal subjects (age 18-85 years) using 1 sec and 3 sec ISIs and to 6 young subjects using an additional ISI of 5 sec. With this method MMN was clearly seen in 26 out of 27 healthy subjects (96.3%). MMN area was quite stable regardless of age with 1 sec ISI. With 3 sec ISI MMN area was significantly smaller in the old than in the young subjects. This may reflect the shortening of the sensory auditory memory trace with increasing age.

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

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 right-handed 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, 1,100 Hz to the right ear) and deviant (770 and 1,210 Hz, respectively) tones. Subjects were instructed to count the tones presented to one ear; whereas, the tones presented to the other ear were to be ignored. Haloperidol significantly attenuated processing negativity (PN), an event-related potential (ERP) component elicited by selectively attended standard tones at 300–500 ms after stimulus presentation. These results, indicating impaired selective attention by a blockade of dopamine D2 receptors, were further accompanied with increased mismatch negativity (MMN), elicited by involuntary detection of task-irrelevant deviants. Taken together, haloperidol seemed to induce functional changes in neural networks accounting for both selective and involuntary attention, suggesting modulation of these functions by dopamine D2 receptors.

Altered generation of spontaneous oscillations in Alzheimer's disease.

Slowing of spontaneous alpha oscillations and an anterior shift of a source of alpha activity (8-13 Hz) have been consistently reported in the EEG studies of Alzheimers disease (AD). It is unknown whether these changes are associated with a gradual shift in location and frequency of existing sources or rather with the involvement of a new set of oscillators. We addressed this question by applying source modeling (minimum current estimates, MCE) to spontaneous alpha activity recorded with a 306-channel MEG system from eleven non-medicated AD patients with mild to moderate cognitive impairment and twelve age-matched controls during the eyes-closed session. AD patients had predominant lower alpha band sources in the temporal regions, whereas in the controls, robust alpha sources were found near the parieto-occipital sulcus. Activation within the parieto-occipital region was significantly weaker, and activation in the right temporal area was significantly enhanced in the AD patients. These results suggest an increased temporal-lobe contribution coinciding with parieto-occipital deficits. We propose that MCE, which provides simultaneous mapping of several oscillatory sources, might be useful for detecting neurophysiological abnormalities associated with AD in combination with other neuropsychological and neurological measures.

Dopamine modulates involuntary attention shifting and reorienting: an electromagnetic study

OBJECTIVE Dopaminergic function has been closely associated with attentional performance, but its precise role has remained elusive. METHODS Electrophysiological and behavioral methods were used to assess the effects of dopamine D2-receptor antagonist haloperidol on involuntary attention shifting using a randomized, double-blind, placebo-controlled cross-over design. Eleven subjects were instructed to discriminate equiprobable 200 and 400ms tones in a forced-choice reaction-time (RT) task during simultaneous measurement of whole-head magnetoencephalography and high-resolution electroencephalography. RESULTS Occasional changes in task-irrelevant tone frequency (10% increase or decrease) caused marked distraction on behavioral performance, as shown by significant RT increases to deviant stimuli and subsequent standard tones. Furthermore, while the standard tones elicited distinct P1-N1-P2-N2-P3 waveforms, deviant tones elicited additional mismatch negativity (MMN), P3a, and reorienting negativity (RON) responses, indexing brain events associated with involuntary attention shifting. While haloperidol did not affect the source loci of the responses of magnetic N1 and MMN, the amplitude of the electric P3a and that of RON were significantly reduced and the latency of magnetic RON were delayed following haloperidol administration. CONCLUSIONS The present results suggest that dopamine modulates involuntary attention shifting to task-irrelevant deviant events. It appears that dopamine may disrupt the subsequent re-orienting efforts to the relevant task after distraction.

Auditory sensory memory and the cholinergic system: implications for Alzheimer's disease.

Auditory sensory memory represents one of the simplest types of short-term memory that can be studied electrophysiologically with mismatch negativity (MMN); a specific auditory event-related potential indexing automatic comparison of incoming stimuli to an existing memory trace. Previous results suggest that auditory sensory memory deteriorates in aging and especially in Alzheimers disease (AD). It has remained unsettled, however, whether MMN is regulated by the cholinergic system, which is deteriorated in AD contributing to cognitive impairments. We recorded cortical auditory responses with a magnetometer from 13 healthy subjects after intravenous injection of scopolamine, centrally acting cholinergic antagonist, or glycopyrrolate, a drug with a peripheral anticholinergic properties without penetrating the blood-brain barrier, using a double-blind protocol. Scopolamine reduced MMNm amplitude in response to frequency, but not duration, change, increased P50m amplitude, and delayed N100m latency. These findings suggest that the cholinergic system regulates the frequency-specific comparison of incoming stimuli to existing memory trace and modulates the preattentive processing related to stimulus detection. Further, neural mechanisms responsible for cortical frequency- and duration-specific discrimination appear to have different sensitivities to cholinergic modulation. Auditory evoked potentials might be suitable to monitor cholinergic activity in AD.