Oili Salonen

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 ∼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.

Signal-space projections of MEG data characterize both distributed and well-localized neuronal sources

We describe the use of signal-space projection (SSP) for the detection and characterization of simultaneous and/or sequential activation of neuronal source distributions. In this analysis, a common signal space is used to represent both the signals measured by an array of detectors and the underlying brain sources. This presents distinct advantages for the analysis of EEG and MEG data. Both highly localized and distributed sources are characterized by the components of the field patterns which are measured by the detectors. As a result, a unified description of arbitrary source configurations is obtained which permits the consistent implementation of a variety of analysis techniques. The method is illustrated by the application of SSP to auditory, visual and somatosensory evoked-response MEG data. Single-trace evoked responses obtained by SSP of spontaneous activity demonstrate that a considerable discrimination against both system noise and uncorrelated brain activity may be achieved. Application of signal-space projections determined in the frequency domain to spontaneous activity illustrates the possibility of including temporal relationships into the analysis. Finally, we demonstrate that SSP is particularly useful for the description of multiple sources of distributed activity and for the comparison of the strengths of specific neuronal sources under a variety of different paradigms or subject conditions.

Viral encephalitis: a review of diagnostic methods and guidelines for management

Viral encephalitis is a medical emergency. The spectrum of brain involvement and the prognosis are dependent mainly on the specific pathogen and the immunological state of the host. Although specific therapy is limited to only several viral agents, correct immediate diagnosis and introduction of symptomatic and specific therapy has a dramatic influence upon survival and reduces the extent of permanent brain injury in survivors. We searched MEDLINE (National Library of Medicine) for relevant literature from 1966 to May 2004. Review articles and book chapters were also included. Recommendations are based on this literature based on our judgment of the relevance of the references to the subject. Recommendations were reached by consensus. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. Diagnosis should be based on medical history, examination followed by analysis of cerebrospinal fluid for protein and glucose contents, cellular analysis and identification of the pathogen by polymerase chain reaction (PCR) amplification (recommendation level A) and serology (recommendation level B). Neuroimaging, preferably by magnetic resonance imaging, is an essential aspect of evaluation (recommendation level B). Lumbar puncture can follow neuroimaging when immediately available, but if this cannot be obtained at the shortest span of time it should be delayed only in the presence of strict contraindications. Brain biopsy should be reserved only for unusual and diagnostically difficult cases. All encephalitis cases must be hospitalized with an access to intensive care units. Supportive therapy is an important basis of management. Specific, evidence‐based, anti‐viral therapy, acyclovir, is available for herpes encephalitis (recommendation level A). Acyclovir might also be effective for varicella‐zoster virus encephalitis, gancyclovir and foscarnet for cytomegalovirus encephalitis and pleconaril for enterovirus encephalitis (IV class of evidence). Corticosteroids as an adjunct treatment for acute viral encephalitis are not generally considered to be effective and their use is controversial. Surgical decompression is indicated for impending uncal herniation or increased intracranial pressure refractory to medical management.

Effects of interstimulus interval on somatosensory evoked magnetic fields (SEFs): a hypothesis concerning SEF generation at the primary sensorimotor cortex

Cerebral responses evoked by peripheral stimuli are known to depend critically on the interstimulus interval (ISI). Here we report on the effects of ISI on somatosensory evoked magnetic fields (SEFs) to right median nerve stimulation, obtained in 9 healthy adults with ISIs of 0.15 0.3, 1,3 and 5 s. At the contralateral (left) primary sensorimotor cortex (SMI), the first cortical response, N20m, was stable between the ISIs 0.3 and 5 s, but slightly attenuated at the shortest ISI of 0.15 s. In contrast, the P35m and P60m deflections were very sensitive to changes of the ISI, declining steadily with shortening of the ISI throughout the entire range. These deflections were frequently undetectable at the shortest ISI of 0.15 s. Concomitant with the reductions of P35m and P60m, an N45m deflection was enhanced toward the short ISIs. Responses from second somatosensory cortex (SII) and posterior parietal cortex (PPC) were seen only with ISIs of 1 s or greater, being strongest at the 5 s ISI. Based on known effects of the ISI on intracellular evoked potentials, we present the following tentative model for the generation mechanism of the SMI response: N20m represents early excitatory postsynaptic potentials (EPSPs), P35m early inhibitory postsynaptic potentials (IPSPs), N45m secondary EPSPs and P60m late IPSPs in pyramidal neurones of area 3b. For practical purposes, SEFs from SMI can be obtained with short ISIs, while responses from SII and PPC require an ISI of at least 1 s.

Variable Agreement Between Visual Rating Scales for White Matter Hyperintensities on MRI Comparison of 13 Rating Scales in a Poststroke Cohort

BACKGROUND AND PURPOSE Previous reports on the frequency, extent, and clinical correlates of white matter hyperintensities (WMHIs) have been contradictory. The purpose of this study was to test whether part of this variation could be explained by the different properties of the visual WMHI rating scales used. METHODS The periventricular (PVHIs) and deep white matter (DWMHIs) hyperintensities of 395 poststroke patients were systematically analyzed and transformed to correspond to 13 different rating scales. The scales were compared with the use of Goodman-Kruskal measures of association. The relative frequencies, means, and medians of PVHI and DWMHI grades as well as Spearman rank correlations between WMHI grade and hypertension were calculated. RESULTS At best more than 80% of the patients received an equivalent WMHI grade by different scales, but at worst the corresponding values were only 0.4% for PVHI and 18% for DWMHI. At best different scales categorized patients similarly in regard to WMHI grade, but at worst the corresponding values were 8% for PVHI and 57% for DWMHI ratings. The distribution of WMHI grades also varied, and when the effect of age on WMHI was assessed, some of the scales had a ceiling effect and some had a floor effect. Only 1 of the 7 PVHI, 5 of the 9 DWMHI, and 1 of the 3 combined rating scales showed a significant correlation with arterial hypertension, a putative risk factor for WMHIs. CONCLUSIONS Some of the inconsistencies in previous studies of WMHIs are due to differences in visual rating scales. Our findings may warrant international debate regarding harmonization of WMHI ratings.

Off-Label Thrombolysis Is Not Associated With Poor Outcome in Patients With Stroke

Background and Purpose— Numerous contraindications included in the license of alteplase, most of which are not based on scientific evidence, restrict the portion of patients with acute ischemic stroke eligible for treatment with alteplase. We studied whether off-label thrombolysis was associated with poorer outcome or increased rates of symptomatic intracerebral hemorrhage compared with on-label use. Methods— All consecutive patients with stroke treated with intravenous thrombolysis from 1995 to 2008 at the Helsinki University Central Hospital were registered (n=1104). After excluding basilar artery occlusions (n=119), the study population included 985 patients. Clinical outcome (modified Rankin Scale 0 to 2 versus 3 to 6) and symptomatic intracerebral hemorrhage according to 3 earlier published criteria were analyzed with a logistic regression model adjusting for 21 baseline variables. Results— One or more license contraindications to thrombolysis was present in 51% of our patients (n=499). The most common of these were age >80 years (n=159), mild stroke National Institutes of Health Stroke Scale score <5 (n=129), use of intravenous antihypertensives prior to treatment (n=112), symptom-to-needle time >3 hours (n=95), blood pressure >185/110 mm Hg (n=47), and oral anticoagulation (n=39). Age >80 years was the only contraindication independently associated with poor outcome (OR, 2.18; 95% CI, 1.27 to 3.73) in the multivariate model. None of the contraindications were associated with an increased risk of symptomatic intracerebral hemorrhage. Conclusions— Off-license thrombolysis was not associated with poorer clinical outcome, except for age >80 years, nor with increased rates of symptomatic intracerebral hemorrhage. The current extensive list of contraindications should be re-evaluated when data from ongoing randomized trials and observational studies become available.

Visual cortex activation in blind humans during sound discrimination

We used a whole-scalp magnetometer with 122 planar gradiometers to study the activity of the visual cortex of five blind humans deprived of visual input since early infancy. Magnetic responses were recorded to pitch changes in a sound sequence when the subjects were either counting these changes or ignoring the stimuli. In two of the blind subjects, magnetic resonance images were also obtained, showing normal visual cortex macroanatomy. In these subjects, the magnetic responses to counted pitch changes were located at visual and temporal cortices whereas ignored pitch changes activated the temporal cortices almost exclusively. Also in two of the other three blind, the visual-cortex activation was detectable in the auditory counting task. Our results suggest that the visual cortex of blind humans can participate in auditory discrimination.

Cognitive and motor loops of the human cerebro-cerebellar system

We applied fMRI and diffusion-weighted MRI to study the segregation of cognitive and motor functions in the human cerebro-cerebellar system. Our fMRI results show that a load increase in a nonverbal auditory working memory task is associated with enhanced brain activity in the parietal, dorsal premotor, and lateral prefrontal cortices and in lobules VII–VIII of the posterior cerebellum, whereas a sensory-motor control task activated the motor/somatosensory, medial prefrontal, and posterior cingulate cortices and lobules V/VI of the anterior cerebellum. The load-dependent activity in the crus I/II had a specific relationship with cognitive performance: This activity correlated negatively with load-dependent increase in RTs. This correlation between brain activity and RTs was not observed in the sensory-motor task in the activated cerebellar regions. Furthermore, probabilistic tractography analysis of the diffusion-weighted MRI data suggests that the tracts between the cerebral and the cerebellar areas exhibiting cognitive load-dependent and sensory-motor activity are mainly projected via separated pontine (feed-forward tracts) and thalamic (feedback tracts) nuclei. The tractography results also indicate that the crus I/II in the posterior cerebellum is linked with the lateral prefrontal areas activated by cognitive load increase, whereas the anterior cerebellar lobe is not. The current results support the view that cognitive and motor functions are segregated in the cerebellum. On the basis of these results and theories of the function of the cerebellum, we suggest that the posterior cerebellar activity during a demanding cognitive task is involved with optimization of the response speed.

Familial perisylvian polymicrogyria: a new familial syndrome of cortical maldevelopment

Two familial X‐linked dominant syndromes of cortical maldevelopment have recently been described: double cortex/lissencephaly syndrome and bilateral periventricular nodular heterotopia. We report on 12 kindreds with familial perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical presentation in these familial cases, and propose a possible mode of inheritance. The clinical and radiological pattern was variable among the 42 patients, with clinical differences among the families and even within members of the same family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies were not found in all patients. When present, they displayed a spectrum of severity. The only clear correlation in this study was between bilateral imaging findings and abnormal tongue movements and/or pronounced dysarthria. Most of the families provided evidence suggestive of, or compatible with, X‐linked transmission. On the other hand, the pedigrees of 2 families ruled out X‐linked inheritance. The most likely mode of inheritance for these 2 families was autosomal dominant with decreased penetrance; however, autosomal recessive inheritance with pseudodominance could not be ruled out in 1 family. We conclude that FPP appears to be genetically heterogeneous. However, most of the families probably represent a third previously undescribed X‐linked syndrome of cortical maldevelopment. Ann Neurol 2000;48:39–48

MRI findings in children with school problems who had been exposed prenatally to alcohol.

This study examined 17 children (nine males, eight females; mean age 13 years) with prenatal alcohol exposure of various durations. The aim of the study was to detect specific brain morphological alterations by means of MRI and to see if findings correlated with particular cognitive deficits. Of the 17 children, five had been exposed to heavy maternal consumption of alcohol (over 10 drinks/week) during the first trimester only; four had been exposed during the first and second trimester; and eight had been exposed throughout pregnancy. Five children had alcohol related neurobehavioural disorder, seven were diagnosed as having foetal alcohol effects and five were diagnosed as having foetal alcohol syndrome. Hypoplasia of the vermis was observed in 10 children and malformed posterior vermis in one additional child. Five children had hypoplastic cerebellar hemispheres. Hypoplasia of the corpus callosum was observed in two children. Small hippocampi were observed in three children and wide cortical sulci in six. No specific structural anomaly correlated with a particular neuropsychological deficit. In this study, deviations in the development of the vermis was the most sensitive morphological indicator of the effects of prenatal alcohol exposure. It was seen in every diagnostic group including children who had been exposed during only the first trimester of pregnancy.