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Biomedical subjects

J Karhu

Publications and source records attributed to J Karhu.

At least 55 records · Page 3Linked to original sources

THA disrupts mismatch negativity in Alzheimer disease.

The present study investigates the effects of 25 or 50 mg tetrahydroaminoacridine (THA), a cholinesterase inhibitor, on auditory mismatch negativity (MMN) event-related response in 19 patients with Alzheimer disease (AD). MMN is produced by the deviant tones representing passive attention and automatic detection of stimulus change. In an inattentive task condition, standard (85%) and deviant (15%) tones were represented in a random order with interstimulus interval of 1 s in separate blocks. THA 25 mg had no effect on MMN in AD patients. In contrast, THA 50 mg diminished MMN in AD subjects. The results suggests that acute treatment of AD subjects with a cholinesterase inhibitor disrupts the passive detection of change in an auditory input.

Aged↗

Single-photon emission tomography imaging of monoamine transporters in impulsive violent behaviour.

Several studies have shown that impulsive violent and suicidal behaviour is associated with a central serotonin deficit, but until now it has not been possible to use laboratory tests with high sensitivity and specificity to study this kind of deficit or to localize the sites of serotonergic abnormalities in the living human brain. The aim of this study was to test the hypothesis that monoamine transporter density in brain is decreased in subjects with impulsive violent behaviour. We studied serotonin (5-HT) and dopamine (DA) transporter specific binding in 52 subjects (21 impulsive violent offenders, 21 age- and sex-matched healthy controls, and ten non-violent alcoholic controls) with single-photon emission tomography (SPET) using iodine-123-labelled 2beta-carbomethoxy-3beta(4-iodophenyl)tropane ([123I]beta-CIT) as the tracer. The blind quantitative analysis revealed that the 5-HT specific binding of [123I]beta-CIT in the midbrain of violent offenders was lower than that in the healthy control subjects (P<0. 005; t test) or the non-violent alcoholics (P<0.05). The results imply that habitual impulsive aggressive behaviour in man is associated with a decrease in the 5-HT transporter density.

Adult↗

Environmental specimen banking of nationwide biomonitoring samples in Finland.

An environmental specimen bank was built in 1994 by the Finnish Forest Research Institute. The main material stored is moss samples collected from the permanent nationwide sampling network every five years since 1985 for both national and international heavy metal surveys. Correspondingly there are nationwide biomonitoring samples of epiphytic lichen, pine bark and humus for surveying atmospheric heavy metal deposition. The bank is also storage of forest litter collected from 1960's onwards. This large material, tens of thousands of sorted samples, is valuable for indicating environmental changes of the forest ecosystem.

Academies and Institutes↗

ERPs reveal deficits in automatic cerebral stimulus processing in patients with NIDDM.

We compared auditory event-related potentials (ERPs) and neuropsychological test scores in nine patients with non-insulin-dependent diabetes mellitus (NIDDM) and in nine control subjects. The measures of automatic stimulus processing, habituation of auditory N100 and mismatch negativity (MMN) were impaired in patients. No differences were observed in the N2b and P3 components, which presumably reflect conscious cognitive analysis of the stimuli. A trend towards impaired performance in the Digit Span backward was found in diabetic subjects, but in the tests of secondary or long-term memory the groups were comparable. Patients with NIDDM may have defects in arousal and in the automatic ability to redirect attention, which can affect their cognitive performance.

Acoustic Stimulation↗

Non-invasive detection of neuronal population activity in human hippocampus.

Medial temporal brain structures and hippocampus are associated with memory encoding and activate during registration and transfer of information within cortico-hippocampal circuits. Hippocampal dysfunction may cause learning and memory deficits as well as epileptogenesis. We monitored neuronal population activity of the human hippocampal formation with a whole-head magnetoencephalographic array. Attention-dependent hippocampal responses were elicited by auditory oddball stimuli. The most prominent responses emerged 200-500 ms after attended oddballs in good agreement with earlier intracranial recordings. Some activation of hippocampal source areas was seen at 60-100 ms. This completely non-invasive method permits access to cortico-hippocampal neural networks on the millisecond time scale during normal and abnormal brain activation and thus provides a new tool for evaluation of cognitive processes and pathological conditions involving hippocampal formation.

Acoustic Stimulation↗

Imaging of serotonin and dopamine transporters in the living human brain.

Alterations in brain serotonin (5-HT) and dopamine (DA) activity are associated with several neuropsychiatric disorders, but until now it has not been possible to simultaneously visualize or quantify the 5-HT and the DA transporter density in the living human brain. In this paper we report on the imaging of 5-HT and DA transporters in 28 healthy controls with single-photon emission tomography using iodine-123 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I] beta-CIT) as the tracer. The [123I] beta-CIT distribution showed the most prominent 5-HT activity in the medial frontal cortex, hypothalamus, midbrain and occipital cortex and the greatest DA activity in the basal ganglia. The specific binding of the 5-HT transporters in the medial frontal cortex was 0.377 +/- 0.031 and that of the DA transporters in the basal ganglia, 0.916 +/- 0.007. Gjedde-Patlak plots indicated two separate components: the first was assumed to represent 5-HT transporters with a slope of 1.29 +/- 0.27 h-1 and the second, DA transporters with a slope of 0.30 +/- 0.04 h-1. This distinct kinetic pattern and the fact that 5-HT and DA transporters are situated in different parts of the brain provides an opportunity to study in vivo patients suffering from various neuropsychiatric disorders.

Adult↗

Iodine-123 labelled N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane for dopamine transporter imaging in the living human brain.

There are several cocaine analogs which have potential for imaging the dopamine transporters (DAT). Earlier studies have shown that iodine-123 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I]beta-CIT) and N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane ([123I]beta-CIT-FP) are promising DAT imaging agents in the living human brain with single-photon emission tomography (SPET). Here we report a pilot comparison of [123I]beta-CIT and [123I]beta-CIT-FP with a new tropane derivative, [123I]N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane ([123I]beta-CIT-FE), using SPET imaging in four healthy male subjects. Peak uptake of [123I]beta-CIT-FE into the basal ganglia occurred very rapidly (0.5 h after injection of tracer), after which the striatal washout obeyed a bi-exponential form. The specific DAT binding of [123I]beta-CIT-FE into the basal ganglia was somewhat less (0.785 +/- 0.117) than that of [123I]beta-CIT (0.922 +/- 0.004) or [123I]beta-CIT-FP (0.813 +/- 0.047). All these tracers have excellent imaging quality in healthy control subjects. However, the relatively fast washout of [123I]beta-CIT-FE and low temporal resolution of older SPET cameras may limit the use of this tracer to the measurement of the DAT density.

Adult↗

Habituation of auditory N100 correlates with amygdaloid volumes and frontal functions in age-associated memory impairment.

We studied the habituation of auditory N100 responses in subjects with age-associated memory impairment (AAMI) and in healthy age-matched volunteers. The findings were correlated with volumes of the amygdala, hippocampus, and frontal lobe measured by magnetic resonance imaging (MRI), as well as with subjects' performance on tests assessing frontal lobe functions and memory. Habituation of N100 did not differ across AAMI subjects and controls. However, in AAMI subjects there was a significant correlation between habituation of N100 and volumes of the amygdala; the more reduced habituation, the smaller volume. In addition, decline in habituation of N100 correlated with impaired performance on a visual memory test (Heaton Visual memory test (Heaton Visual Retention Test; r = 0.77; p < 0.001) and impairment on tests assessing frontal functions (Verbal Fluency, Trail Making Test, and Stroop). Habituation of N100 was not related to age or sex. To our knowledge this is the first study to demonstrate a relationship between habituation of evoked responses, MRI volumetric measures, and performance on psychometric tests. The results suggest that impaired memory and frontal lobe functions in AAMI subjects may be associated with poor habituation of N100. Since habituation reflects focusing of attention to relevant features of stimuli, impairment of this mechanism and subsequent defective memory trace formation may contribute to the observed deficits on memory tests.

Aged↗

Altered striatal dopamine re-uptake site densities in habitually violent and non-violent alcoholics.

Animal studies suggest that development of substance dependence is associated with dopaminergic activity in striatum and the limbic system. Several genetic studies indicate that allele A1 is associated with both D2 receptor density and alcoholism, although these findings have remained controversial. We studied striatal dopamine (DA) re-uptake site densities in 48 subjects (19 healthy controls, 19 habitually impulsive violent alcoholics, and 10 non-violent alcoholics) with single photon emission computed tomography (SPECT) using iodine-123-labelled 2 beta-carbomethoxy-3 beta(4-iodophenyl)tropane, (beta-CIT) as a tracer. Blind quantitative analysis revealed that the striatal DA transporter density was markedly lower in non-violent alcoholics than in healthy controls (P < 0.001), while violent alcoholics had slightly higher DA transporter densities than controls (P < 0.10). The results indicate that both types of alcoholics have alterations in striatal dopaminergic system, though these occur in opposite directions.

Adult↗

Cortical reactivity in progressive myoclonus epilepsy.

We studied 4 patients with progressive myoclonus epilepsy (Unverricht-Lundborg disease; ULD). Somatosensory evoked fields (SEFs), auditory evoked fields (AEFs), and spontaneous activity over the somatomotor cortex were recorded with a 24-channel SQUID gradiometer. All patients had "giant" 20-45 msec median nerve SEFs at the first somatomotor cortex, with 2-6 times larger amplitudes than the healthy control subjects. Later deflections were not similarly enhanced. The dependence of SEF amplitudes on interstimulus interval (0.2-4 sec) and on successive ulnar-median nerve stimulation (stimulus interval 40 msec) was comparable to that in controls. Cortical AEFs were attenuated and delayed. In 3 patients, the spontaneous activity consisted of 6-8 Hz mu rhythm, which originated within 2 cm from the sources of SEFs and was abolished by clenching of the contralateral fist. Control subjects had major spectral peaks around 10 and 20 Hz. The SEF amplitudes and the strength of the 6-10 Hz mu correlated strongly, suggesting that some components of evoked and spontaneous activity obtain contributions from overlapping neuronal populations. The results imply that ULD is associated with thalamo-cortical hyperreactivity in the sensorimotor but not in the auditory system.

Acoustic Stimulation↗

Suppression of magnetic mu rhythm during parkinsonian tremor.

We recorded spontaneous magnetoencephalographic (MEG) activity and somatosensory-evoked fields (SEFs) with a 24-channel planar SQUIDgradiometer in five patients with hemiparkinsonism. The SEFs of the patients were within normal limits. During tremorless periods, the spontaneous activity over the somatomotor cortex had a frequency peak at approximately 10 Hz in all five patients and another at approximately 20 Hz in three. Tremor dampened the 10-Hz activity in all patients; in three the effect was bilateral. Tremor did not increase MEG activity at the tremor frequency. The suppression of the mu rhythm by the parkinsonian tremor resembled that occurring during voluntary movements in healthy subjects.

Adult↗

Functional organization of the human first and second somatosensory cortices: a neuromagnetic study.

Multichannel neuromagnetic recordings were used to differentiate signals from the human first (SI) and second (SII) somatosensory cortices and to define representations of body surface in them. The responses from contralateral SI, peaking at 20-40 ms, arose mainly from area 3b, where representations of the leg, hand, fingers, lips and tongue agreed with earlier animal studies and with neurosurgical stimulations and recordings on convexial cortex in man. Representations of the five fingers were limited to a cortical strip of approximately 2 cm in length. Responses from SII peaked 100-140 ms after contra- and ipsilateral stimuli and varied considerably from one subject to another. Signs of somatotopical organization were seen also in SII. Responses of SII were not fully recovered at interstimulus intervals of 8 s.

Acoustic Stimulation↗

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.

Acoustic Stimulation↗

Magnetoencephalographic localization of epileptic cortex--impact on surgical treatment.

A 24-channel, planar, superconducting quantum interference device gradiometer, sampling a fourth of the head surface over brain tissue, was used to determine the site of an epileptic focus in a 36-year-old woman with intractable complex partial epilepsy. The other presurgical findings appeared divergent: a large arachnoid cyst over the right parietal convexity, dissimilar interictal electroencephalographic patterns, and several neuropsychological dysfunctions. The equivalent current sources of magnetoencephalographic spikes were in the right posterior temporal region of the cortex, 4 cm apart from the cyst. Surgical exploration of the area pinpointed by magnetoencephalography revealed a pachygyric patch of cortex displaying focal discharges on the electrocorticogram. After resection, a dramatic reduction of seizures occurred. The good agreement between electrocorticography and magnetoencephalography warrants future investigation of multichannel magnetoencephalography as a potential alternative to invasive presurgical recordings.

Adult↗

Cortical somatosensory magnetic responses in multiple sclerosis.

Somatosensory evoked magnetic fields (SEFs) to contralateral median and ulnar nerve stimulation were analyzed in 10 patients with multiple sclerosis and in 8 healthy controls. SEFs were recorded with a 24-channel SQUID gradiometer over both hemispheres. Seven patients showed abnormally large-amplitude SEF deflections at 60-80 msec; 5 of them had multiple lesions around lateral ventricles in magnetic resonance imaging. In 2 patients with plaques at the level of 3rd and 4th ventricles and medulla, the 30 msec responses were enlarged. The equivalent sources of 20 msec and 30-80 msec responses were in the primary hand sensorimotor cortex both in patients and in control subjects. The results suggest that early and middle-latency SEFs reflect parallel processing of somatosensory input. Recording of middle-latency evoked responses, electric or magnetic, may give additional information about the somatosensory function in multiple sclerosis.

Adult↗

Magnetoencephalographic 10-Hz rhythm from the human auditory cortex.

Spontaneous magnetoencephalographic activity was recorded with a 24-SQUID gradiometer over the lateral aspects of the head in 3 healthy adults. All subjects displayed 8-10 Hz rhythmic activity which was not affected by opening of the eyes but was occasionally dampened by auditory stimuli. The equivalent sources of the rhythm were in the supratemporal auditory cortex, and the activity may therefore represent 'idling' of the auditory cortex. Obviously each sensory projection cortex has its own local spontaneous rhythm.

Acoustic Stimulation↗

Bilateral electrical stimulation of a congenitally-deaf ear and of an acquired-deaf ear.

Two identical multichannel intracochlear prostheses were implanted in the same patient. The first prosthesis, implanted in the congenitally-deaf right ear, elicited clear sound perception but no speech recognition. After 2 years, a second prosthesis, implanted in the acquired-deaf left ear, enabled the patient to understand speech without lip-reading. Brainstem and middle-latency evoked potentials were similar with electrical stimulation of both ears and resembled those evoked by acoustic stimuli in subjects with normal hearing. Cortical electric and magnetic responses differed for right- and left-sided electrical stimulation suggesting that stimulation of the congenitally-deaf ear elicited an abnormal activation of the auditory cortex. These results suggest that only cortical responses were affected by the different histories of deafness of the ears.

Cochlear Implants↗

Cerebral magnetic fields to lingual stimulation.

We recorded cerebral magnetic fields to electric stimulation of the tongue in 7 healthy adults. The two main deflections of the response peaked around 55 msec (P55m) and 140 msec (N140m). During both of them the magnetic field pattern, determined with a 7- or 24-channel SQUID magnetometer, suggested a dipolar current source. The topography of P55m can be explained by a tangential dipole at the first somatosensory cortex (SI) in the posterior wall of the central sulcus. The equivalent source of N140m is, on average, about 1 cm lateral to the source of P55m. The reported method allows non-invasive determination of the cortical tongue representation area.

Adult↗