Biomedical subjects

E Pekkonen

Publications and source records attributed to E Pekkonen.

At least 19 recordsLinked to original sources

PubMed2001

No evidence for dependence of early cortical auditory processing on dopamine D(2)-receptor modulation: a whole-head magnetoencephalographic study.

Magnetoencephalography (MEG) was used to determine the effect of neuroleptic challenge on brain responses in healthy subjects. In a double-blind, randomized, placebo-controlled, cross-over design study, the dopamine D(2) receptor antagonist haloperidol (2 mg) was given orally to 12 healthy volunteers. The middle-latency auditory evoked magnetic fields (MAEF) were recorded 3 h after administration of haloperidol or placebo with a whole-head 122-channel MEG. Haloperidol did not significantly affect MAEF responses. The dipole moments and source locations of the responses were not significantly influenced by haloperidol. These results suggest that dopamine D(2) receptors are not involved in the early phases of auditory cortical processing.

Adult↗

PubMed2001

Preserved stimulus deviance detection in Alzheimer's disease.

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.

Acoustic Stimulation↗

PubMed2001

Scopolamine reduces the P35m and P60m deflections of the human somatosensory evoked magnetic fields.

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.

Adult↗

PubMed2001

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 Alzheimer's 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.

Adult↗

PubMed2001

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.

Acoustic Stimulation↗

PubMed2001

The processing of sound duration after left hemisphere stroke: event-related potential and behavioral evidence.

The ability of left-hemisphere stroke patients (n = 8) and healthy control subjects (n = 8) to process sounds preattentively and attentively was studied by recording auditory event-related potentials (ERPs) and behavioral responses. For the right-ear stimulation, the mismatch negativity (MMN) was significantly smaller in the patients than control subjects over both hemispheres. For the left-ear stimuli, the MMN was significantly smaller in the patient group than in the control group over the left hemisphere, whereas no group differences were obtained over the right hemisphere. In addition, the N1 amplitude was reduced bilaterally for the right-ear stimulation (with the reduction being larger over the left hemisphere), whereas no significant effects on the N1 amplitude were found for the left-ear stimulation. Behaviorally, the patients detected significantly fewer deviant tones than did the control subjects irrespective of the stimulated ear. The present results thus suggest that the long-latency ERPs can be used to probe such auditory processing deficits that are difficult to define with behavioral measures. Especially by recording MMN to monaural stimuli, the discrimination accuracy can be separately determined for the left and right temporal lobes.

Acoustic Stimulation↗

PubMed2000

Suppression of transient 40-Hz auditory response by haloperidol suggests modulation of human selective attention by dopamine D2 receptors.

Cognitive processes including selective attention may depend on synchronous activity of neurons at the gamma-band (around 40Hz). To determine the effect of neuroleptic challenge on transient auditory evoked 40-Hz response, simultaneous measurement of 122-channel magnetoencephalogram (MEG) and 64-channel electroencephalogram (EEG) was used. Either 2mg of dopamine D(2)-receptor antagonist haloperidol or a placebo was administered orally to 11healthy subjects in a double-blind randomized crossover design in two separate sessions. The subjects attended to tones presented to one ear and ignored those presented to the other ear. Haloperidol significantly suppressed the transient 40-Hz electric response to the attended stimuli, while no significant effect was observed in the electric responses to the unattended tones or in the magnetic responses. The present result suggests that dopamine D(2) receptors modulate selective attention.

Acoustic Stimulation↗

PubMed2000

Global field power of auditory N1 correlates with impaired verbal-memory performance in human alcoholics.

First weeks after alcohol withdrawal, associated with profound changes in neural transmission, constitute the critical period for relapse prevention and pharmacological intervention in alcoholism. Here, 20 male alcoholics with 1-6 weeks of abstinence and 20 age-matched healthy controls were studied using auditory event-related potentials (ERP), measured with a 32-channel electroencephalogram, and neuropsychological tests of auditory-verbal memory. Global field power maximum of ERP during 80-150 ms period after presentation of unattended tones (binaural 700 Hz pure tones, inter-stimulus interval 2.5 s) was significantly (P<0.01) larger in the alcoholics than controls. This effect, reflecting augmented N1 generation, significantly correlated (r=0.5) with impaired memory performance in the alcoholics. The profound change in pre-attentive auditory processing, predicting impaired memory performance, might reflect impaired cerebral inhibitory transmission in alcoholics.

Adult↗

PubMed2000

Dose-dependent suppression by ethanol of transient auditory 40-Hz response.

RATIONALE: Acute alcohol (ethanol) challenge is known to induce various cognitive disturbances, yet the neural basis of the effect is poorly known. The auditory transient evoked gamma-band (40-Hz) oscillatory responses have been suggested to be associated with various perceptual and cognitive functions in humans; however, alcohol effects on auditory 40-Hz responses have not been investigated to date. OBJECTIVES: The objective of the study was to test the dose-related impact of alcohol on auditory transient evoked 40-Hz responses during a selective-attention task. METHODS: Ten healthy social drinkers ingested, in four separate sessions, 0.00, 0. 25, 0.50, or 0.75 g/kg of 10% (v/v) alcohol solution. The order of the sessions was randomized and a double-blind procedure was employed. During a selective attention task, 300-Hz standard and 330-Hz deviant tones were presented to the left ear, and 1000-Hz standards and 1100-Hz deviants to the right ear of the subjects (P=0. 425 for each standard, P=0.075 for each deviant). The subjects attended to a designated ear, and were to detect the deviants therein while ignoring tones to the other ear. RESULTS: The auditory transient evoked 40-Hz responses elicited by both the attended and unattended standard tones were significantly suppressed by the 0.50 and 0.75 g/kg alcohol doses. CONCLUSIONS: Alcohol suppresses auditory transient evoked 40-Hz oscillations already with moderate blood alcohol concentrations. Given the putative role of gamma-band oscillations in cognition, this finding could be associated with certain alcohol-induced cognitive deficits.

Acoustic Stimulation↗

PubMed2000

Increased distractibility by task-irrelevant sound changes in abstinent alcoholics.

BACKGROUND: Chronic alcoholism is accompanied by "frontal" neuropsychological deficits that include an inability to maintain focus of attention. This might be associated with pronounced involuntary attention shifting to task-irrelevant stimulus changes and, thereafter, an impaired reorienting to the relevant task. The neural abnormalities that underlie such deficits in alcoholics were explored with event-related potential (ERP) components that disclosed different phases of detection and orienting to stimulus changes. METHODS: Twenty consecutive abstinent male alcoholics (DSM-IV) and 20 age-matched male controls (healthy social drinkers) were instructed to discriminate equiprobable 100 and 200 msec tones in a reaction-time task (RT) and to ignore occasional, either slight (7%) or wide (70%), frequency changes (hypothesized to increase RT) during an ERP measurement. RESULTS: In the alcoholics, we found pronounced distractibility, evidenced by a RT lag (p < 0.01) caused by deviants, that correlated (Spearman p = 0.5) with a significantly enhanced (p < 0.01) amplitude of mismatch negativity (MMN) to deviants. Significantly increased RT lag for trials subsequent to deviants (slight p < 0.001, wide p < 0.05) in the alcoholics suggested impaired reorienting to the relevant task. The MMN enhancement also predicted poorer hit rates in the alcoholics (Spearman p = 0.6-0.7). Both the MMN enhancement and pronounced distractibility correlated (Spearman p = 0.4) with an early onset of alcoholism. CONCLUSIONS: Attentional deficits in the abstinent alcoholics were indicated by the increased distractibility by irrelevant sound changes. The MMN enhancement suggested that this reflects impaired neural inhibition of involuntary attention shifting, being most pronounced in early-onset alcoholics.

Adult↗

PubMed1999

Scopolamine augments transient auditory 40-hz magnetic response in humans.

The influence of neocortical muscarinic transmission on auditory-evoked 40-Hz magnetic response was studied in 13 healthy subjects in a double-blind randomized cross-over design. Either a centrally (scopolamine hydrobromide, 0.3 mg, i.v.) or a peripherally (glycopyrrolate, 0.2 mg, i.v.) acting antagonist of muscarinic transmission was administered during two sessions of magnetoencephalographic recording of 40-Hz response elicited by monaural tones. Scopolamine significantly (P < 0.01) augmented the 40-Hz magnetic response over the hemispheres ipsi- and contralateral to the ear stimulated. This finding suggests muscarinic modulation of the auditory evoked transient 40-Hz response.

Adult↗

PubMed1999

Post-withdrawal changes in middle-latency auditory evoked potentials in abstinent human alcoholics.

We investigated the effects of chronic alcoholism on middle-latency auditory evoked potentials (MAEP) in 14 male alcoholics with 1-6 weeks of abstinence (without other severe disorders) and 13 age-matched male social-drinker controls. The peak amplitude of a positive deflection (Pa) of the MAEP, peaking at about 30 ms post-stimulus, was significantly larger in the alcoholics than in the controls (P < 0.01), and notably, a significant negative correlation (r = -0.65) was observed between the Pa amplitude and duration of abstinence in the alcoholics. The present results suggest that the post-withdrawal brain hyperexcitability in the alcoholic brain, gradually recovering with abstinence, could be objectively and non-invasively studied with the MAEP.

Adult↗

PubMed1999

Benzodiazepine temazepam suppresses the transient auditory 40-Hz response amplitude in humans.

To discern the role of the GABA(A) receptors in the generation and attentive modulation of the transient auditory 40-Hz response, the effects of the benzodiazepine temazepam (10 mg) were studied in 10 healthy social drinkers, using a double-blind placebo-controlled design. Three hundred Hertz standard and 330 Hz rare deviant tones were presented to the left, and 1000 Hz standards and 1100 Hz deviants to the right ear of the subjects. Subjects attended to a designated ear and were to detect deviants therein while ignoring tones to the other. Temazepam significantly suppressed the amplitude of the 40-Hz response, the effect being equal for attended and non-attended tone responses. This suggests involvement of GABA(A) receptors in transient auditory 40-Hz response generation, however, not in the attentive modulation of the 40-Hz response.

Adult↗

PubMed1999

Decay of cortical pre-attentive sound discrimination in middle-age.

Ageing effects on pre-attentive cortical detection of sound change, as indexed by magnetic mismatch negativity (MMNm), were disclosed with whole-head magnetoencephalography (MEG). Seventy healthy subjects (aged 17-82 years) were presented with a sequence of homogeneous standard tones and occasional deviants of shorter duration. The MMNm elicited by the shorter tones was diminished in amplitude (r = -0.42, p < 0.001) and increased in latency in the hemisphere ipsilateral to the ear stimulated (r = 0.38, p < 0.01), these effects being significant even in middle-aged subjects. The results suggest that pre-attentive comparison of incoming stimuli to a short-lived sensory memory trace in the central auditory system is impaired, and delayed in the ipsilateral hemisphere, already by the middle-age.

Acoustic Stimulation↗

PubMed1999

Scopolamine enhances middle-latency auditory evoked magnetic fields.

To study the influence of central cholinergic muscarinic transmission on human cortical middle-latency auditory evoked magnetic fields (MAEF), centrally acting antagonist scopolamine hydrobromide (0.3 mg, i.v.), and peripheral muscarinic receptor antagonist glycopyrrolate (0.2 mg, i.v.), were administered to 13 healthy subjects in a double-blind randomized cross-over design. MAEF, measured with whole-head magnetoencephalography (MEG), were elicited with clicks applied at 10-Hz rate to the left ear. The amplitudes of N(b)m and P(a)m responses were augmented by scopolamine (P < 0.01 and P < 0.08). These effects were about equally strong for responses from ipsi- and contralateral auditory cortices. Thus, the present MEG findings revealed specific modulation of cortical generators of middle-latency auditory evoked responses by muscarinic transmission. These findings might be associated with auditory processing deficits observed in dementias with cholinergic disturbances.

Acetylcholine↗

PubMed1999

Impaired preconscious auditory processing and cognitive functions in Alzheimer's disease.

OBJECTIVE: To study whether preconscious auditory processing is deteriorated in patients with Alzheimer's disease (AD) having mild to moderate cognitive symptoms. To investigate whether auditory processing correlates with the impairment of the higher cortical functions. METHODS: P50m and N100m responses elicited by a sequence of repetitive tones were recorded with a whole-head magnetometer from 22 patients with probable AD and from 18 healthy age-matched controls. In addition, an extensive neuropsychological test battery assessing main cognitive domains was administered to all subjects. RESULTS: The patients with AD had significantly delayed N100m responses in the left hemisphere that correlated with the impairment of the language functions. CONCLUSIONS: N100m auditory responses measured with magnetoencephalography may be useful in evaluating the severity and progression of the cortical dysfunction in dementia.

Aged↗

PubMed1999

Altered parallel auditory processing in schizophrenia patients.

Patients with schizophrenia have impaired auditory processing that has been demonstrated by diminished P50 response to paired auditory stimuli in event-related potential (ERP) studies. Cerebral processing can also be studied with magnetoencephalography (MEG). With a whole-head MEG, which enables one to simultaneously measure brain activity in both hemispheres, we investigated whether early parallel auditory processing is impaired in schizophrenia. Sequences of tones were monaurally presented to schizophrenia patients and healthy controls in a passive condition, and the event-related magnetic fields were recorded simultaneously over both auditory cortices. The interhemispheric latency difference of the P50m, but not that of the N100m, was significantly shorter in the patient group in the right-ear but not in the left-ear stimulus condition. Further, the ipsilateral P50m was significantly earlier in schizophrenia patients in the right-ear condition. This result suggests that schizophrenia affects the consecutive preconscious auditory processing in a different manner.

Adult↗

PubMed1999

Suppression of mismatch negativity by backward masking predicts impaired working-memory performance in alcoholics.

BACKGROUND: Pronounced disruption of memory traces by subsequent distractors may result in impaired behavioral memory performance in alcoholics. METHODS: This hypothesis was investigated with an electrophysiological index of auditory sensory-memory traces, mismatch negativity, a preattentive event-related potential component elicited by a "deviant" tone within a train of "standard" tones. RESULTS: Inserting a masking stimulus after these tones abolished mismatch negativity in alcoholics (DSM-IV) but not in social-drinker controls. This effect predicted working-memory impairment in alcoholics, and correlated significantly with self-reported alcohol consumption of the subjects. Furthermore, the backward-masking mismatch negativity paradigm detected sensory-memory impairment in 9 of 20 alcoholics (sensitivity 45%), whereas all 20 social drinkers were unimpaired (specificity 100%). CONCLUSIONS: Vulnerability to memory trace disruption by shortly following sounds may be one of the factors contributing to behavioral memory dysfunction in alcoholics. The present result may provide an objective neurophysiological tool for investigation of alcohol-induced and other degenerative brain disorders.

Adult↗