Biomedical subjects

K Reinikainen

Publications and source records attributed to K Reinikainen.

At least 19 recordsLinked to original sources

PubMed2001

Selegiline treatment facilitates recovery after stroke.

OBJECTIVE: Selegiline (L-deprenyl) is a selective monoamine oxidase B (MAO-B) inhibitor used in the treatment of Parkinson's disease. In addition, it is thought to rescue neurons with a loss of target-derived trophic support. Several mechanisms have been proposed to explain these phenomena, such as the production of neurotrophic actions through astrocyte activation, reduction of free radical production, or the presence of antiapoptotic properties. The aim of this study was to investigate whether the systemic administration of selegiline facilitates recovery after a cerebral infarction in humans. METHODS: This phase II study was randomized, double-blind, and placebo controlled. Selegiline, 5 mg, or matched placebo was given twice a day for 3 months. The drug therapy was started within 48 h after a hemispheric infarction in the territory of middle cerebral artery. There were 24 patients recruited. Twenty patients were followed up to 3 months or until their death, and they represent the efficacy analysis group. The primary efficacy parameters were Scandinavian Stroke Scale (SSS), Barthel Index (BI), and Fugl-Meyer Scale (FMS). Secondary parameters were Zung Self-Rating Depression Scale (ZDS) and 15-Dimensional Measure of Health Related Quality of Life test (15-D). RESULTS: SSS improved statistically significantly from the baseline when compared with placebo (p = 0.019). The results were parallel among the other two primary efficacy variables (BI and FMS), showing a positive trend for selegiline, although they did not reach statistical significance. Similarly, in the analysis of the secondary efficacy variables, both the 15-D test and ZDS supported this positive trend in favor of selegiline, although no statistically significant differences between groups were found (p = 0.06 in 15-D test). CONCLUSIONS: Selegiline seems to be beneficial after a cerebral infarction. This benefit may be due to the enhancement of the recovery process.

Acute Disease↗

PubMed2000

Modulation of slow brain potentials by working memory load in spatial and nonspatial auditory tasks.

Slow event-related brain potentials were recorded from the human scalp during spatial and nonspatial auditory delayed matching-to-sample and n-back tasks to find out whether there are differences in the distribution of slow potentials during the retention of audiospatial and pitch information. The performance of both the location and pitch tasks produced slow potentials during the delay phase of the memory tasks. The delay-related slow potential was modulated by the amount of information to be processed during the tasks at the parietal-occipital sites. The distribution of mnemonic modulation was, however, not different between the tasks. The results suggest that there is integration of auditory information processing in the neuronal networks engaged in mnemonic processing of pitch and location.

Adolescent↗

PubMed1999

Pharmacokinetics of oral entacapone after frequent multiple dosing and effects on levodopa disposition.

OBJECTIVE: Entacapone is a peripherally acting catechol O-methyltransferase (COMT) inhibitor used as an adjunct to each daily levodopa/dopa decarboxylase (DDC) inhibitor dose in the treatment of Parkinson's disease. Parkinsonian patients with advanced disease and motor fluctuations take several doses of levodopa daily, due to the short action of levodopa in this patient population. The present study was conducted in order to evaluate the pharmacokinetics of entacapone after multiple dosing and the pattern of COMT inhibition in erythrocytes during the first day of dosing as well as during steady state. Furthermore, the disposition of plasma levodopa and carbidopa was studied after a single dose of levodopa/carbidopa during the same conditions. METHODS: Twelve healthy male volunteers received 200 mg entacapone eight times daily during study day 1 and day 6 at 2-h intervals from 0800 hours to 2200 hours. During days 3, 4 and 5, 200 mg of entacapone was taken ten times daily, from 0800 hours to 0200 hours on the following day. One levodopa/carbidopa tablet (100/25 mg) was taken on study day 1 and day 6 at 1000 hours. Plasma entacapone concentrations and erythrocyte COMT activities were measured frequently on study days 1-2 and 6-7, and twice daily on study days 3-5. Pharmacokinetic parameters calculated from plasma drug concentrations on days 1-2 and 6-7 were compared with each other. RESULTS: There were no differences in maximal plasma concentration (Cmax), time to maximal drug concentration in plasma (tmax), elimination half-life (t1/2) and area under the plasma concentration-time curve (AUC) of entacapone between day 1 and day 6. The mean t1/2 values of entacapone were 1.3 h and 1.8 h during the first and sixth days, respectively; the difference was not significant. No signs of accumulation of entacapone were noted after the first day. Entacapone reduced erythrocyte COMT activity after the first dose, and this effect was quite stable during frequent dosing. There were no indications of accumulation of COMT inhibition during frequent dosing of entacapone. There were no between-day differences in Cmax, t1/2 (2.4 h on days 1-2 and 2.3 h on days 6-7) or AUC of levodopa, whereas tmax occurred at 0.8 h on day 1 and at 1.2 h on day 6 (P = 0.03). There were no between-day differences in the pharmacokinetic parameters (Cmax, tmax and AUC) of carbidopa. CONCLUSION: Even when dosed frequently, there are neither indications of accumulation of entacapone nor of its COMT inhibiting activity.

Adult↗

PubMed1999

Selective tuning of the left and right auditory cortices during spatially directed attention.

Effects of spatially directed auditory attention on human brain activity, as indicated by changes in regional cerebral blood flow (rCBF), were measured with positron emission tomography (PET). Subjects attended to left-ear tones, right-ear tones, or foveal visual stimuli presented at rapid rates in three concurrent stimulus sequences. It was found that attending selectively to the right-ear input activated the auditory cortex predominantly in the left hemisphere and vice versa. This selective tuning of the left and right auditory cortices according to the direction of attention was presumably controlled by executive attention mechanisms of the frontal cortex, where enhanced activation during auditory attention was also observed.

Acoustic Stimulation↗

PubMed1998

Longitudinal study of cerebrospinal fluid amyloid proteins and apolipoprotein E in patients with probable Alzheimer's disease.

Levels of soluble amyloid beta protein (sAbeta), amyloid beta precursor protein (APP) and apolipoprotein E (apoE) were examined in cerebrospinal fluid (CSF) obtained twice, at baseline and after 3-year follow-up, from 25 patients with probable Alzheimer's disease (AD). Levels of sAbeta and apoE from patients with the apoE4 allele decreased with time, whereas the levels were similar in patients without apoE4 allele. Changes of sAbeta and apoE concentrations correlated significantly with those of mini-mental state examination (MMSE) scores. Levels of sAbeta did not change with time in patients with mild dementia, whereas they decreased significantly in patients with moderate dementia. ApoE concentrations decreased in both groups whereas APP levels were similar. We conclude that measurements of CSF sAbeta and apoE levels may be helpful in monitoring progression of the disease.

Aged↗

PubMed1998

Differential effects of alcohol on the cortical processing of foreign and native language.

The effect of alcohol (ethanol) on cortical processing of Finnish vs. English words in Finnish-speaking subjects was studied by recording auditory event-related potentials in 10 subjects who had started studying English at the age of 9-10 years. At the beginning of the block of 100 words, the subject heard an introductory sentence. Half of the words completed the sentence well and the other half did not. The subject pressed a reaction key immediately after hearing a proper word. After the control condition, the subject ingested alcohol (1 ml/kg). Alcohol attenuated the amplitude of N100 to both Finnish and English words, this attenuation being significantly stronger for English than for Finnish words. The early differential effect of alcohol suggests that language-specific information is extracted in the cortex already approximately 100 ms from the word onset. The results are in line with animal experiments demonstrating that alcohol selectively affects the activity of single units involved in newer forms of behavior.

Acoustic Stimulation↗

PubMed1998

Maturation of mismatch negativity in infants.

The mismatch negativity (MMN) is a pre-attentive change-specific component of the event-related brain potentials (ERPs). During the last decade this response has been intensively studied in adults, but investigations in children and especially in infants are still rare. Recent studies, however, have shown that MMN is also elicited in infants in response to changes in pure tones as well as in phonemes. The present study compared MMN in pre-term infants (conceptional age at the time of recording, 30-35 weeks), full-term newborns and full-term 3-month-old infants. Stimuli were Klatt-synthesized Finnish vowels /y/ and /i/. Previous studies have reported larger MMN amplitudes in school-age children compared with those obtained in adults. According to the results, however, the infant MMN amplitude seems to resemble that of adults. No significant differences in MMN amplitudes were found between the three age groups either. The mean MMN latency, however, decreased significantly with age, although in 3-month-old infants it was not much longer than in a previous study conducted in adults with the same stimuli.

Acoustic Stimulation↗

PubMed1997

Rate effect and mismatch responses in the somatosensory system: ERP-recordings in humans.

In the first experiment, somatosensory event-related potentials (SERPs) were recorded to tactile pulses and vibration bursts applied to the left middle finger in trains of 4-8 stimuli with 1 s intervals. In addition to the negative N140 deflection, also the positive P50, P100 and P300 waves attenuated in amplitude with stimulus repetition. These decreases were immediate, there being no marked further amplitude attenuation after the second stimulus. The locus of this rate effect appears not to be the primary SI or SII, but rather prefrontal cortices or some deeper structures. In the second experiment, vibratory stimuli of different frequencies or at different skin sites were presented using the oddball paradigm. When the deviant stimulus was a high-frequency vibration burst, it elicited a distinct N250 deflection, probably analogous to the auditory N2b. When the deviation was a change in the stimulation site, no N250 deflection but instead an extra negativity between 100-200 ms latency, probably analogous to the auditory mismatch negativity, was observed.

Adult↗

PubMed1997

Temporal window of integration revealed by MMN to sound omission.

The central auditory system for event perception involves the integrating mechanism of sequential information addressed by the present study. The mismatch negativity (MMN) component of the event-related potentials (ERP) reflects the automatic detection of sound change. ERPs to occasionally omitted stimuli were measured when sequences with constant stimulus onset asynchronies (SOAs) were presented. In separate blocks, the SOA was from 100 to 350 ms. A clear MMN was elicited by a stimulus omission in a sequence of regularly spaced tone pips only when the SOA was shorter than 150 ms, yielding an estimate for the duration of the temporal window of integration used the perceptual segregation of auditory events.

Acoustic Stimulation↗

PubMed1997

Visuospatial mnemonic load modulates event-related slow potentials.

Electroencephalographic slow wave potentials were recorded during the performance of visuospatial working memory tasks. The aim was to study the effects of varying mnemonic loads on slow potentials, and to dissociate the contribution of mnemonic and motor components. Subjects were tested with three spatial delayed matching-to-sample tasks in which the mnemonic load varied while the preparatory motor demands remained constant. The delay-related slow potential was more negative during the tasks in which the subjects had to memorize the locations of six or four stimuli than when only one location had to be memorized. Significant differences between the slow potentials in the tasks with different mnemonic loads were recorded at frontal and temporal recording sites. Since the preparatory motor requirements were similar in all tasks, the modulation of slow potentials reflects working memory processing rather than motor preparatory activity.

Adolescent↗

PubMed1997

Lack of adverse interactions between concomitantly administered selegiline and citalopram.

We have evaluated the risk for pharmacokinetic and/or pharmacodynamic interactions of concomitantly administered selegiline, a selective monoamine oxidase type B inhibitor, and citalopram, a widely used selective serotonin uptake inhibitor antidepressant. Two parallel groups of healthy volunteers received 20 mg of citalopram (n = 12) or placebo (n = 6) once daily for 10 days in a randomized, double-blind fashion, followed by concomitant selegiline 10 mg once daily for 4 days. The safety of this drug combination was assessed by measurements of blood pressure, heart rate, body temperature, and inquiries for adverse events. Blood samples were taken for the analysis of serum concentrations of both study drugs and their metabolites and plasma prolactin, adrenaline, noradrenaline, and 3,4-dihydroxyphenylglycol (DHPG); urinary excretion of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were assessed. After a 5-week washout, the 12 subjects who took citalopram in the first part of the study received 10 mg of selegiline once daily for 4 days to compare the pharmacokinetics of selegiline with and without concomitant citalopram. The safety analysis showed no significant differences in vital signs or the frequency of adverse events between the study groups. Plasma prolactin concentrations were increased by 40% after 10 days' treatment with citalopram (p = 0.03); this was not potentiated by concomitantly administered selegiline. The comparison of plasma concentrations of noradrenaline, adrenaline, and DHPG and the amount of serotonin and 5-HIAA excreted into urine between the study groups indicated no signs of subclinical pharmacodynamic interaction between selegiline and citalopram. The relative bioavailability of selegiline was slightly reduced (by 29%; p = 0.008) when citalopram was coadministered compared with selegiline alone. However, no indication of a pharmacokinetic interaction was found in the analysis of serum concentrations of the three main metabolites of selegiline. The pharmacokinetics of citalopram remained unaffected by concomitant selegiline. The present results indicate lack of clinically relevant pharmacodynamic or pharmacokinetic interactions between selegiline and citalopram.

Adult↗

PubMed1996

Is the somatosensory N250 related to deviance discrimination or conscious target detection?

Effects of attention to, and probability of sudden changes in, repetitive stimuli on somatosensory evoked potentials (SEP) were studied. Low - (30 Hz) and high-frequency (140 Hz) vibratory stimuli were delivered in random order to the middle finger of the left hand with different presentation probabilities in different blocks. Also ignore conditions were administered. In the ignore conditions, the probability had no effect on SEPs. However, when the standard stimuli were omitted, the "deviants" elicited small N140 and P300 deflections not observed in response to deviants when standards were also present. In the attention conditions, deviant stimuli (targets) elicited large N250 and P300 deflections which increased in amplitude with a decreased target probability. However, when subjects counted infrequently presented "deviants" alone (standards omitted) the enhanced N140 and the P300 with shortened latency were elicited, but no N250 wave could be found. At the ipsilateral side, a distinct N200 deflection was seen which could be the N250 with a shorter latency because of an easier task (detection instead of discrimination). The results might be interpreted as suggesting that the somatosensory N250 is related to conscious detection of target stimuli.

Adult↗

PubMed1996

The ontogenetically earliest discriminative response of the human brain.

Speech sounds elicited electric brain responses in healthy premature infants born 30-35 weeks after conception, demonstrating that the human brain is able to discriminate speech sounds even at this early age, well before term, and supporting previous results suggesting that the human fetus may learn to discriminate sounds while still in the womb. We presented preterm infants with stimulus sequences consisting of a repetitive vowel that was occasionally replaced by a different vowel. This infrequent vowel elicited a response resembling the adult mismatch negativity, which is known to reflect the brain's automatic detection of stimulus change. The present results constitute the ontogenetically earliest discriminative response of the human brain ever recorded.

Brain↗

PubMed1995

Auditory and somatosensory event-related brain potentials in early blind humans.

Previous event-related potential (ERP) studies have suggested a possible participation of the visual cortex of the blind in auditory processing. In the present study, somatosensory and auditory ERPs of blind and sighted subjects were recorded when subjects were instructed to attend to stimuli of one modality and to ignore those of the other. Both modalities were stimulated with frequent ("standard") and infrequent ("deviant") stimuli, which differed from one another in their spatial locus of origin. In the sighted, deviant stimuli of the attended modality elicited N2 type of deflections (auditory N2b and somatosensory N250) over the lateral scalp areas. In contrast, in the blind, these ERP components were centroposteriorly distributed, suggesting an involvement of posterior brain areas in auditory and somatosensory stimulus discrimination. In addition, the mismatch negativity, elicited by deviant auditory stimuli even when the somatosensory stimuli were attended, was larger in the blind than in the sighted. This appears to indicate enhanced automatic processing of auditory stimulus changes in the blind. Thus, the present data suggest several compensatory changes in both auditory and somatosensory modalities after the onset of early visual deprivation.

Adult↗

PubMed1995

Automatic auditory discrimination is impaired in Parkinson's disease.

Deviant tones embedded in a sequence of standard tones elicit an event-related potential (ERP) component called the mismatch negativity (MMN), which reflects automatic stimulus change detection in the human auditory system. To determine whether stimulus change detection is impaired in Parkinson's disease (PD), we recorded ERPs in 13 non-demented patients with PD and in 11 age-matched healthy control subjects both when tones were attended and when they were unattended. The difference area between deviant and standard ERPs was used to evaluate the MMN in the 'unattended' condition. The MMN was significantly smaller in patients with PD than in controls. In the attended condition, the amplitudes of both N1 and the N2 complex were smaller in the patient group than in controls. MMN attenuation suggests that PD patients have impaired automatic stimulus change detection compared with healthy controls. This might be caused by dopamine deficiency in PD.

Acoustic Stimulation↗

PubMed1995

Mismatch negativity indicates vowel discrimination in newborns.

The present study shows that an infrequent vowel ('deviant') presented among frequent vowels ('standard') elicits in sleeping human newborns a negativity in the auditory event-related potential (ERP) resembling the mismatch negativity (MMN) recorded in adults. Thus, the MMN appears to provide means to investigate brain mechanisms of vowel perception in infants.

Acoustic Stimulation↗

PubMed1995

Mismatch negativity to auditory stimulus change recorded directly from the human temporal cortex.

Mismatch negativity (MMN) is an event-related potential (ERP) component elicited by any discernible change in a repetitive sound even in the absence of attention. Previous studies have established that MMN is generated by change detection in a process comparing the deviant sensory input with the neural memory trace encoding the physical features of the repetitive sound. In the present study, we recorded MMNs to tonal frequency changes directly from the human temporal cortex of patients with electrodes implanted in the brain for diagnosis and therapy. The intracranially recorded MMN was found to be attention independent and modality specific. It was confined to a rather small area in temporal cortex, which was different from the structures where attention-dependent N2 and P3 responses to the frequency change could be recorded.

Acoustic Stimulation↗

PubMed1994

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 Alzheimer's 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.

Aged↗