Tom Brismar

Publications of Tom Brismar

• Attenuation of long-range temporal correlations in the amplitude dynamics of alpha and beta neuronal oscillations in patients with schizophrenia.

  Authors: Vadim V Nikulin, Erik G Jönsson, Tom Brismar

  NeuroImage. 03/2012; 61(1):162-169.

  Although schizophrenia was previously associated with affected spatial neuronal synchronization, surprisingly little is known about the temporal dynamics of neuronal oscillations in this disease.Although schizophrenia was previously associated with affected spatial neuronal synchronization, surprisingly little is known about the temporal dynamics of neuronal oscillations in this disease. However, given that the coordination of neuronal processes in time represents an essential aspect of practically all cognitive operations, it might be strongly affected in patients with schizophrenia. In the present study we aimed at quantifying long-range temporal correlations (LRTC) in patients (18 with schizophrenia; 3 with schizoaffective disorder) and 28 healthy control subjects matched for age and gender. Ongoing neuronal oscillations were recorded with multi-channel EEG at rest condition. LRTC in the range 5-50s were analyzed with Detrended Fluctuation Analysis. The amplitude of neuronal oscillations in alpha and beta frequency ranges did not differ between patients and control subjects. However, LRTC were strongly attenuated in patients with schizophrenia in both alpha and beta frequency ranges. Moreover, the cross-frequency correlation between LRTC belonging to alpha and beta oscillations was stronger for patients than healthy controls, indicating that similar neurophysiological processes affect neuronal dynamics in both frequency ranges. We believe that the attenuation of LRTC is most likely due to the increased variability in neuronal activity, which was previously hypothesized to underlie an excessive switching between the neuronal states in patients with schizophrenia. Attenuated LRTC might allow for more random associations between neuronal activations, which in turn might relate to the occurrence of thought disorders in schizophrenia.

• Decreased cortical connectivity and information flow in type 1 diabetes.

  Authors: Gerald K Cooray, Lars Hyllienmark, Tom Brismar

  Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 04/2011; 122(10):1943-50.

  To investigate the effect of type 1 diabetes on EEG connectivity and information flow and study the relationship between these parameters and electrophysiological, neuropsychological and clinicalTo investigate the effect of type 1 diabetes on EEG connectivity and information flow and study the relationship between these parameters and electrophysiological, neuropsychological and clinical variables. Connectivity was assessed using several measures (phase coherence, phase lag index, synchronization likelihood and phase slope index) on 119 patients and 61 healthy controls over several frequency bands (between 0.5 and 45 Hz). Data was further correlated to EEG power, event related potentials, neuropsychological function and demographic variables. Multivariate test on the connectivity data showed a difference between patients and controls both with mastoid reference (p<0.01) and current source density estimates (p<0.04). Connectivity and information flow correlated with EEG power but not with event related potentials or neuropsychological function. Connectivity and information flow are decreased in diabetes. These variables assess other functions of the brain than captured by the present cognitive tests. Several tests need to be performed in order to monitor the effect of diabetes on brain function. The decrease in connectivity and cortical information flow are EEG abnormalities that add to the previously described EEG and ERP abnormalities described for type 1 diabetes.

• Effect of valproate, lamotrigine and levetiracetam on excitability and firing properties of CA1 neurons in rat brain slices.

  Authors: Marita Englund, Lars Hyllienmark, Tom Brismar

  Cellular and molecular neurobiology. 02/2011; 31(4):645-52.

  The purpose of this study was to analyze the rapid effects of the antiepileptic drugs valproate, lamotrigine, and levetiracetam on excitability and firing properties of hippocampal neurons. The drugThe purpose of this study was to analyze the rapid effects of the antiepileptic drugs valproate, lamotrigine, and levetiracetam on excitability and firing properties of hippocampal neurons. The drug effects on resting potential, action potential, and repetitive firing properties were studied in whole-cell current-clamp recordings of CA1 neurons in rat brain slices. Lamotrigine changed action potential rising slope by -24 ± 38 V/s (mean ± SD), peak amplitude by -6.8 ± 5.0 mV, and maximum firing frequency by -60 ± 13%. Lamotrigine thereto increased the voltage threshold by 4.3 ± 4.2 mV and augmented the action potential attenuation during repetitive firing. All effects were significant (P < 0.01 to P < 0.0002) compared to control cells. Valproate and levetiracetam showed no significant effects on these parameters. None of the tested drugs had a significant effect on the resting potential. The lamotrigine effects are consistent with sodium channel blocking which may explain or contribute to the antiepileptic mode of action. Valproate and levetiracetam did not show these effects and the mechanism of their antiepileptic action need to be different. These findings (valproate) differ in some respects from findings reported in cultured or dissociated neurons. In a slice where the neurons have largely preserved connections, drug effects are likely to be more similar to the therapeutic action in the brain.

• Effects of intensified metabolic control on CNS function in type 2 diabetes.

  Authors: Gerald Cooray, Erik Nilsson, Ake Wahlin, Erika J Laukka, Kerstin Brismar, Tom Brismar

  Psychoneuroendocrinology. 01/2011; 36(1):77-86.

  The mild cognitive decline associated with type 2 diabetes (T2DM) has been suggested to be reversible with improved glycemic control. In order to characterise this cognitive decline and study theThe mild cognitive decline associated with type 2 diabetes (T2DM) has been suggested to be reversible with improved glycemic control. In order to characterise this cognitive decline and study the effects of improved glycemic control we have studied patients with T2DM (N=28) and healthy control subjects (N=21). One group of patients with diabetes (N=15) were given a 2-month treatment of intensified glycemic control, whereas the other group (N=13) maintained their regular treatment. Cognitive function in four different domains, auditory event-related potentials (ERPs) and resting EEG power spectrum were studied in the two groups of patients and in healthy control subjects before and after the 2-month trial period. There were significant differences at baseline (p<0.02) between patients with T2DM and controls. Patients had lower scores in two cognitive domains: verbal fluency (p<0.01) and visuospatial ability (p<0.03). T2DM also affected ERP with a decrease in N100 amplitude (p<0.04) and an increase in P300 latency (p<0.03). Furthermore, resting EEG activity in the beta band (13-30Hz) was reduced (p<0.04). The change between 1st and 2nd investigation was significantly different in the three groups of patients/subjects (p<0.03). Patients receiving intensified treatment for glycemic control had an improvement of cognitive ability in visuospatial ability (p<0.02) and semantic memory performance (p<0.04) together with increased resting EEG activity in the alpha band (8-13Hz, p<0.02) and connectivity in the theta (4-8Hz, p<0.03) and alpha bands (p<0.03) over central and lateral regions. Furthermore, there was an increase in the connectivity in the beta band (p<0.04) over the central regions of the scalp. In conclusion, subjects with T2DM had a similar type of cognitive function impairment and EEG/ERP abnormality as previously demonstrated for subjects with type 1 diabetes (T1DM). Intensified therapy showed cognitive improvement not shown for regular treatment, suggesting that the negative effect of T2DM on cognition is reversible by means of improved glycemic control. Furthermore, there was an improvement in electro-physiological measures, suggesting increased availability of compensatory mechanisms in subjects with intensified treatment.

• Age- and time-dependent effects on functional outcome and cortical activation pattern in patients with median nerve injury: a functional magnetic resonance imaging study.

  Authors: Lotta Fornander, Torbjörn Nyman, Thomas Hansson, Mattias Ragnehed, Tom Brismar

  Journal of neurosurgery. 11/2009;

  Object The authors conducted a study to determine age- and time-dependent effects on the functional outcome after median nerve injury and repair and how such effects are related to changes in theObject The authors conducted a study to determine age- and time-dependent effects on the functional outcome after median nerve injury and repair and how such effects are related to changes in the pattern of cortical activation in response to tactile stimulation of the injured hand. Methods The authors studied 11 patients with complete unilateral median nerve injury at the wrist repaired with epineural suture. In addition, 8 patients who were reported on in a previous study were included in the statistical analysis. In the entire study cohort, the mean age at injury was 23.3 +/- 13.4 years (range 7-57 years) and the time after injury ranged from 1 to 11 years. Sensory perception was measured with the static 2-point discrimination test and monofilaments. Functional MR imaging was conducted during tactile stimulation (brush strokes) of Digits II-III and IV-V of both hands, respectively. Results Tactile sensation was diminished in the median territory in all patients. The strongest predictor of 2-point discrimination was age at injury (p < 0.0048), and when this was accounted for in the regression analysis, the other age- and time-dependent predictors had no effect. The activation ratios (injured/healthy hand) for Digit II-III and Digit IV-V stimulation were positively correlated (rho 0.59, p < 0.011). The activation ratio for Digit II-III stimulation correlated weakly with time after injury (p < 0.041). The activation ratio of Digits IV-V correlated weakly with both age at injury (p < 0.048) and time after injury (p < 0.033), but no predictor reached significance in the regression model. The mean ratio of ipsi- and contralateral hemisphere activation after stimulation of the injured hand was 0.55, which was not significantly different from the corresponding ratio of the healthy hand (0.66). Conclusions Following a median nerve injury (1-11 years after injury) there may be an initial increase in the volume of the cortical representation, which subsequently declines during the restoration phase. These dynamic changes may involve both median and ulnar nerve cortical representation, because both showed negative correlation with time after injury. These findings are in agreement with animal studies showing that cortical plasticity is an important mechanism for functional recovery after peripheral nerve injury and repair.

• Cognitive impairment correlates to low auditory event-related potential amplitudes in type 1 diabetes.

  Authors: Gerald K Cooray, Liselotte Maurex, Tom Brismar

  Psychoneuroendocrinology. 08/2008; 33(7):942-50.

  Type 1 diabetes may be associated with a mild decline in cognitive function and mostly in mental speed. In order to study the pathophysiology of this, we have investigated auditory event-relatedType 1 diabetes may be associated with a mild decline in cognitive function and mostly in mental speed. In order to study the pathophysiology of this, we have investigated auditory event-related potentials (AERP) and their relation to cognitive function in diabetes patients. AERP was recorded in patients with type 1 diabetes (n=119) and in a healthy control group (n=61). AERP was obtained with an odd-ball and a two-stimulus paradigm. Cognitive function was evaluated in 10 domains in the patients. Patients had normal N100 latency, but a highly significant decrease in auditory N100 amplitude (p<10(-6)), which correlated with a decrease in psychomotor speed but not with function in other domains. Psychomotor speed also correlated with P300 amplitude, although P300 amplitude was only slightly decreased in the patients. Even stronger correlations were found with the parietal N100-P300 peak-to-peak amplitude, which correlated both to psychomotor speed (rho=0.61, p<10(-7)) and processing speed (p<0.005). P300 latency was increased in patients, and this correlated to low global cognitive score and older age. We conclude that the decline in psychomotor speed in type 1 diabetes is associated with a highly significant decrease in the auditory N100 peak amplitude. This association and the relatively small abnormality in P300 latency is quite different from those generally found in dementia, and suggest that the underlying defect is located in the brain stem or the white matter. Presumably small conduction defects in ascending fibers can distort the firing synchrony necessary for signal generation in the cortex.

• Robustly estimating the flow direction of information in complex physical systems.

  Authors: Guido Nolte, Andreas Ziehe, Vadim V Nikulin, Alois Schlögl, Nicole Krämer, Tom Brismar, Klaus-Robert Müller

  Physical review letters. 06/2008; 100(23):234101.

  We propose a new measure (phase-slope index) to estimate the direction of information flux in multivariate time series. This measure (a) is insensitive to mixtures of independent sources, (b) givesWe propose a new measure (phase-slope index) to estimate the direction of information flux in multivariate time series. This measure (a) is insensitive to mixtures of independent sources, (b) gives meaningful results even if the phase spectrum is not linear, and (c) properly weights contributions from different frequencies. These properties are shown in extended simulations and contrasted to Granger causality which yields highly significant false detections for mixtures of independent sources. An application to electroencephalography data (eyes-closed condition) reveals a clear front-to-back information flow.

• Robustly estimating the flow direction of information in complex physical systems

  Authors: Guido Nolte, Andreas Ziehe, Vadim V Nikulin, Alois Schlögl, Nicole Krämer, Tom Brismar, Klaus-Robert Müller

  12/2007;

  We propose a new measure to estimate the direction of information flux in multivariate time series from complex systems. This measure, based on the slope of the phase spectrum (Phase Slope Index) hasWe propose a new measure to estimate the direction of information flux in multivariate time series from complex systems. This measure, based on the slope of the phase spectrum (Phase Slope Index) has invariance properties that are important for applications in real physical or biological systems: (a) it is strictly insensitive to mixtures of arbitrary independent sources, (b) it gives meaningful results even if the phase spectrum is not linear, and (c) it properly weights contributions from different frequencies. Simulations of a class of coupled multivariate random data show that for truly unidirectional information flow without additional noise contamination our measure detects the correct direction as good as the standard Granger causality. For random mixtures of independent sources Granger Causality erroneously yields highly significant results whereas our measure correctly becomes non-significant. An application of our novel method to EEG data (88 subjects in eyes-closed condition) reveals a strikingly clear front-to-back information flow in the vast majority of subjects and thus contributes to a better understanding of information processing in the brain. Comment: 5 pages, 4 figures

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• The human EEG--physiological and clinical studies.

  Authors: Tom Brismar

  Physiology & behavior. 10/2007; 92(1-2):141-7.

  The present review summarizes the research in EEG performed by our group during the last 5 years. Our studies have been focussed on two areas: studies of variability and correlations in theThe present review summarizes the research in EEG performed by our group during the last 5 years. Our studies have been focussed on two areas: studies of variability and correlations in the oscillations during resting conditions of normal subjects, and the abnormalities related to type 1 diabetes. Recordings in normal subjects showed that also under standardized conditions with regular cycles of closed and open eyes, there is a temporal variability of the spectral components in EEG that necessitates samples>124 s in order to achieve estimates of alpha power with a coefficient of variation<0.1 in all recording channels (brain regions). The temporal variability in alpha and beta power demonstrates long-range temporal correlations, i.e., periods of large power (alpha or beta) are more likely to be followed by large power, and vice versa. The long-range temporal correlations were reproducible, especially during the closed-eyes condition, stronger in males than females, and not age dependent. In patients with type 1 diabetes, the alpha and beta power components were both decreased with similar nadirs in the posterior temporal regions, and the slow spectral components were increased in the frontal regions. The cognitive function was presently not studied but in a group of adolescents with diabetes we found a correlation between the presence of slow activity and the number of hypoglycaemic episodes. The loss of alpha and beta power was highly correlated which initiated a study of the normal alpha-beta correlation. A significant 1:2 phase synchronization was present between alpha and beta oscillations with a phase lag of about pi/2 in all electrode derivations. The strong frequency relationship between the resting beta and alpha oscillations suggested that they are generated by a common mechanism.

• C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy.

  Authors: Karin Ekberg, Tom Brismar, Bo-Lennart Johansson, Per Lindström, Lisa Juntti-Berggren, Anders Norrby, Christian Berne, Hans J Arnqvist, Jan Bolinder, John Wahren

  Diabetes care. 01/2007; 30(1):71-6.

  OBJECTIVE: C-peptide replacement in animals results in amelioration of diabetes-induced functional and structural abnormalities in peripheral nerves. The present study was undertaken to examineOBJECTIVE: C-peptide replacement in animals results in amelioration of diabetes-induced functional and structural abnormalities in peripheral nerves. The present study was undertaken to examine whether C-peptide administration to patients with type 1 diabetes and peripheral neuropathy improves sensory nerve function. RESEARCH DESIGN AND METHODS: This was an exploratory, double-blinded, randomized, and placebo-controlled study with three study groups that was carried out at five centers in Sweden. C-peptide was given as a replacement dose (1.5 mg/day, divided into four subcutaneous doses) or a dose three times higher (4.5 mg/day) during 6 months. Neurological examination and neurophysiological measurements were performed before and after 6 months of treatment with C-peptide or placebo. RESULTS: The age of the 139 patients who completed the protocol was 44.2 +/- 0.6 (mean +/- SE) years and their duration of diabetes was 30.6 +/- 0.8 years. Clinical neurological impairment (NIA) (score >7 points) of the lower extremities was present in 86% of the patients at baseline. Sensory nerve conduction velocity (SCV) was 2.6 +/- 0.08 SD below body height-corrected normal values at baseline and improved similarly within the two C-peptide groups (P < 0.007). The number of patients responding with a SCV peak potential improvement >1.0 m/s was greater in C-peptide-treated patients than in those receiving placebo (P < 0.03). In the least severely affected patients (SCV < 2.5 SD below normal at baseline, n = 70) SCV improved by 1.0 m/s (P < 0.014 vs. placebo). NIA score and vibration perception both improved within the C-peptide-treated groups (P < 0.011 and P < 0.002). A1C levels (7.6 +/- 0.1% at baseline) decreased slightly but similarly in C-peptide-and placebo-treated patients during the study. CONCLUSIONS: C-peptide treatment for 6 months improves sensory nerve function in early-stage type 1 diabetic neuropathy.

• Time course and variability of power in different frequency bands of EEG during resting conditions.

  Authors: José Maltez, Lars Hyllienmark, Vadim V Nikulin, Tom Brismar

  Neurophysiologie clinique = Clinical neurophysiology. 01/2005; 34(5):195-202.

  The aim of the present study was to evaluate the variability of EEG power spectrum data, considering the time course of the EEG spectrum in resting conditions, and the relationship between theThe aim of the present study was to evaluate the variability of EEG power spectrum data, considering the time course of the EEG spectrum in resting conditions, and the relationship between the spectral parameters and the length of the analyzed segments. Recordings were performed in 57 normal subjects, with a protocol consisting of regular cycles with open eyes (5 s) followed by closed eyes (55 s) repeated during 10 min. Towards the end of the recording there was a decrease in the alpha and beta power and an increase in the delta and theta power. The coefficient of variation (CV) for the power of 4 s epochs was in the range 0.49-0.67 (delta), 0.53-0.58 (theta), 0.58-0.76 (alpha), 0.37-0.49 (beta) and 0.09-0.12 for the alpha peak frequency. CV decreased with the increase of the sample size, being inversely proportional to the square root of the sample size. Increasing the recording length from 40 to 400 s increased CV by 36% (alpha), 41% (beta), 29% (delta) and 35% (theta), while the standard error of the mean decreased by 55-60%. It is concluded that the power estimates of the EEG activity are heavily dependent on the length of the analyzed segments, and the way they are selected. This observation is particularly relevant for clinical and drug studies where short recordings are often used, thus significantly biasing the estimation of the EEG parameters. The present data provide an estimate on the minimal length of EEG required for a given level of variability.

• Long-range temporal correlations in alpha and beta oscillations: effect of arousal level and test-retest reliability.

  Authors: Vadim V Nikulin, Tom Brismar

  Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 09/2004; 115(8):1896-908.

  OBJECTIVE: The aim of the present study was to evaluate test-retest reliability and condition sensitivity of long-range temporal correlations in the amplitude dynamics of electroencephalographicOBJECTIVE: The aim of the present study was to evaluate test-retest reliability and condition sensitivity of long-range temporal correlations in the amplitude dynamics of electroencephalographic alpha and beta oscillations. METHODS: Twelve normal subjects were measured two times with a test-retest interval of several days. Open- and closed-eyes conditions were used, representing different levels of arousal. The amplitude of the alpha and beta oscillations was extracted with bandpass filtering and the Hilbert transform. The long-range temporal correlations were quantified with detrended fluctuation analysis. RESULTS: The amplitude dynamics of the alpha and beta oscillations demonstrated power-law long-range temporal correlations lasting for tens of seconds. These correlations were degraded in the open- compared to the closed-eyes condition. Test-retest statistics demonstrated that the long-range temporal correlations had significant reliability, which was greatest in the closed-eyes condition. CONCLUSIONS: The presence of long-range temporal correlations indicates that the amplitude of neuronal oscillations at a given time is dependent on the amplitude at times as remote in the past as tens of seconds. The reliability of long-range temporal correlations suggests that the mechanisms generating the amplitude fluctuations are not perturbed over several days. The systematic changes in the scaling exponents at different levels of arousal indicate that these changes occur on many time scales (5-80 s) as a result of modifications in the intrinsic dynamics of the neuronal oscillations. SIGNIFICANCE: This study demonstrates that the dynamics of spontaneous neuronal oscillations possess long-range temporal correlations with properties suitable for functional and clinical studies.

• Comment on "Multiscale entropy analysis of complex physiologic time series".

  Authors: Vadim V Nikulin, Tom Brismar

  Physical review letters. 03/2004; 92(8):089803; author reply 089804.

• Loss of sensory discrimination after median nerve injury and activation in the primary somatosensory cortex on functional magnetic resonance imaging.

  Authors: Thomas Hansson, Tom Brismar

  Journal of neurosurgery. 08/2003; 99(1):100-5.

  OBJECT: The aim of this study was to assess the effects of median nerve injury and regeneration on neuronal activation in the somatosensory cortex by means of functional magnetic resonance (fMR)OBJECT: The aim of this study was to assess the effects of median nerve injury and regeneration on neuronal activation in the somatosensory cortex by means of functional magnetic resonance (fMR) imaging and somatosensory evoked potentials (SSEPs). METHODS: Ten injured male patients (mean age 26 years) were examined 15 to 58 months after a total transection of the median nerve at the wrist that was repaired with epineural sutures. Two-point discrimination was lost in Digit II-III and sensory nerve conduction displayed decreased velocity (-29%) and amplitude (-84%) in the median nerve at the wrist. The fMR images were obtained during tactile stimulation (gentle strokes) performed separately on the volar surface of either Digit II-III or Digit IV-V (eight patients: two were excluded because of movement artifacts). The SSEPs were obtained using electrical stimulation proximal to the median nerve lesion. CONCLUSIONS: Patients with loss of sensory discrimination after median nerve damage and regeneration had larger areas of activation in fMR imaging near the contralateral central sulcus during tactile stimulation of the injured compared with the noninjured hand. The increase relative to the unaffected hand was 43% (p < 0.02) for Digit II-III stimulation and 46% (p < 0.02) for Digit IV-V stimulation. The SSEP data showed normal latency and amplitude. The enlarged area of cortical activation may be the result of reorganization, and it may indicate that larger cortical areas are involved in the discriminatory task after a derangement of the peripheral input.

• Amelioration of sensory nerve dysfunction by C-Peptide in patients with type 1 diabetes.

  Authors: Karin Ekberg, Tom Brismar, Bo-Lennart Johansson, Björn Jonsson, Per Lindström, John Wahren

  Diabetes. 02/2003; 52(2):536-41.

  Studies have demonstrated that proinsulin C-peptide stimulates the activities of Na(+),K(+)-ATPase and endothelial nitric oxide synthase, both of which are enzyme systems of importance for nerveStudies have demonstrated that proinsulin C-peptide stimulates the activities of Na(+),K(+)-ATPase and endothelial nitric oxide synthase, both of which are enzyme systems of importance for nerve function and known to be deficient in type 1 diabetes. The aim of this randomized double-blind placebo-controlled study was to investigate whether C-peptide replacement improves nerve function in patients with type 1 diabetes. Forty-nine patients without symptoms of peripheral neuropathy were randomized to either 3 months of treatment with C-peptide (600 nmol/24 h, four doses s.c.) or placebo. Forty-six patients (15 women and 31 men, aged 29 years, diabetes duration 10 years, and HbA(1c) 7.0%) completed the study. Neurological and neurophysiological measurements were performed before and after 6 and 12 weeks of treatment. At baseline the patients showed reduced nerve conduction velocities in the sural nerve (sensory nerve conduction velocity [SCV]: 50.9 +/- 0.70 vs. 54.2 +/- 1.2 m/s, P < 0.05) and peroneal nerve (motor nerve conduction velocity: 45.7 +/- 0.55 vs. 53.5 +/- 1.1 m/s, P < 0.001) compared with age-, height-, and sex-matched control subjects. In the C-peptide treated group there was a significant improvement in SCV amounting to 2.7 +/- 0.85 m/s (P < 0.05 compared with placebo) after 3 months of treatment, representing 80% correction of the initial reduction in SCV. The change in SCV was accompanied by an improvement in vibration perception in the patients receiving C-peptide (P < 0.05 compared with placebo), whereas no significant change was detectable in cold or heat perception. In conclusion, C-peptide administered for 3 months as replacement therapy to patients with early signs of diabetic neuropathy ameliorates nerve dysfunction.

• Loss of temporal lobe beta power in young adults with type 1 diabetes mellitus.

  Authors: Tom Brismar, Lars Hyllienmark, Karin Ekberg, Bo-Lennart Johansson

  Neuroreport. 12/2002; 13(18):2469-73.

  Cognitive defects have been reported in type 1 diabetes mellitus with possible correlation to recurrent episodes of hypoglycemia. The purpose of the present study was to identify signs of brainCognitive defects have been reported in type 1 diabetes mellitus with possible correlation to recurrent episodes of hypoglycemia. The purpose of the present study was to identify signs of brain dysfunction with quantitative EEG in adults with insulin-dependent (type 1) diabetes. Patients (n = 49) with type 1 diabetes and controls (n = 51) were recruited. All patients had good glycemic control, no diabetic polyneuropathy and a minor history of severe hypoglycaemia. EEG was recorded for 15 min following a standardized protocol, power spectra were obtained from 236-584 s of artefact-free EEG from each subject and EEG was repeated in diabetic patients after 3 and 9 months. The most pronounced finding was a loss of fast oscillations (alpha, beta and gamma activity) in both posterior temporal regions, with p< 0.001 for beta and p< 0.05 or 0.01 for alpha and gamma activity in the diabetes patients. A decrease in beta activity was also present bilaterally in the anterior temporal and occipital regions (p< 0.05 or 0.01). The alpha peak frequency was lower in patients than in controls, with reductions bilaterally in the temporo-central regions (p< 0.01). These changes were not found to correlate to a previous history of hypoglycaemia. The alpha and beta power showed a high test-retest reliability at both 3 and 9 months (0.88-0.92). The focal decrease in temporal lobe fast activity suggests that these brain regions are preferentially affected by type 1 diabetes. This abnormality may be related to the mechanism underlying the cognitive dysfunction described in diabetes.

• Normal values of nerve conduction in children and adolescents

  Authors: Lars Hyllienmark, Johnny Ludvigsson, Tom Brismar

  Electroencephalography and Clinical Neurophysiology/Electromyography and Motor Control.

  Healthy children and adolescents (n = 128) ranging in age from 6 to 20 years and in height from 114 to 193 cm underwent studies of median, peroneal and sural nerves bilaterally, including nerveHealthy children and adolescents (n = 128) ranging in age from 6 to 20 years and in height from 114 to 193 cm underwent studies of median, peroneal and sural nerves bilaterally, including nerve conduction velocity, amplitude and motor distal latencies. Arms and legs were heated in all subjects to obtain skin temperatures around 34°C. Both motor and sensory nerve conduction velocities were found to correlate more with height than with age. There was a strong negative correlation between height and peroneal conduction velocity (r = −0.40, P < 0.0001). On the contrary, a positive correlation was found between height and both median sensory (r = 0.30, P < 0.0001) and motor (r = 0.22, P < 0.001) conduction velocities. Skin temperature, even near 34°C, had a strong effect on conduction velocity and motor distal latencies. It is concluded that consideration of height and temperature will improve the diagnostic safety of nerve conduction measurements in children and young adults.

• Tactile stimulation of the hand causes bilateral cortical activation: a functional magnetic resonance study in humans

  Authors: Thomas Hansson, Tom Brismar

  Neuroscience Letters.

  The purpose of the present study was to assess the somatotopy of the cortical sensory representation of the fingers using a natural tactile stimulation of the glabrous skin. Multislice echoplanarThe purpose of the present study was to assess the somatotopy of the cortical sensory representation of the fingers using a natural tactile stimulation of the glabrous skin. Multislice echoplanar imaging techniques were utilized to investigate blood oxygen level dependent (BOLD) signal changes as a measure of cortical activation. Repetitive sensory stimulation of the glabrous skin of digit II–III and digit IV–V resulted in a multifocal signal increase in a restricted area near the central sulcus in the contralateral hemisphere with a considerable overlap between the activated areas of digit II–III and digit IV–V. In addition, in all subjects tactile stimulation resulted in ipsilateral signal increase near the central sulcus, which was 15–22% of the contralateral effect. Stimulation of digit II–III caused significantly (P<0.05) more activated voxels than digit IV–V in the contralateral hemisphere for both hands and for the left hand in the ipsilateral hemisphere. These findings suggest an ipsilateral activation of the primary somatosensory cortex during a natural tactile stimulation of the digits in humans.

• Predictors of cognitive impairment in type 1 diabetes.

  Authors: Tom Brismar, Liselotte Maurex, Gerald Cooray, Lisa Juntti-Berggren, Per Lindström, Karin Ekberg, Nils Adner, Sten Andersson

  Psychoneuroendocrinology. 32(8-10):1041-51.

  A decline in cognitive function has been reported in type 1 diabetes, but its relation to different disease factors such as hypoglycemic events and peripheral neuropathy is controversial. TheA decline in cognitive function has been reported in type 1 diabetes, but its relation to different disease factors such as hypoglycemic events and peripheral neuropathy is controversial. The objective of the present study was to identify factors that are important for cognitive impairment in type 1 diabetes. A cross-sectional study was performed in adult patients (N=150) with type 1 diabetes (duration 26.6+/-11.4 years). Function in different cognitive domains was evaluated by the same trained examiner, in order to eliminate inter-rater variability. Peripheral nerve function was tested quantitatively. Predictors of cognitive impairment were identified using multiple regression analysis. The major finding was that long diabetes duration and young age of diabetes onset were the strongest predictors of low scores in psychomotor speed, memory, processing speed, attention, working memory, verbal ability, general intelligence, executive functions and a low global score. The number of previous hypoglycemic events had no defined effect upon cognitive functioning. Other significant predictors were low compound muscle action potential (CMAP) (for visual perception-organization), old age (for visual-spatial ability), short stature, high BMI and hypertension. Presence of retinopathy and long-term metabolic control correlated with nerve conduction defects, but not with cognitive impairment. Although a history of hypoglycemic events was not a predictor of cognitive impairment, we cannot exclude the possibility that the influence of young age of diabetes onset depends on the effect of hypoglycemic events early in life. The clinical relationships of cognitive impairment differ from those of peripheral neuropathy, indicating a different pathogenesis. The influence of diabetes duration, BMI, height, age and CMAP may suggest that loss of the neuroprotective effects of insulin or insulin-like growth factors plays a role.

• Predictors of cognitive impairment in type 1 diabetes

  Authors: Tom Brismar, Liselotte Maurex, Gerald Cooray, Lisa Juntti-Berggren, Per Lindström, Karin Ekberg, Nils Adner, Sten Andersson

  Psychoneuroendocrinology.

  A decline in cognitive function has been reported in type 1 diabetes, but its relation to different disease factors such as hypoglycemic events and peripheral neuropathy is controversial. TheA decline in cognitive function has been reported in type 1 diabetes, but its relation to different disease factors such as hypoglycemic events and peripheral neuropathy is controversial. The objective of the present study was to identify factors that are important for cognitive impairment in type 1 diabetes. A cross-sectional study was performed in adult patients (N=150) with type 1 diabetes (duration 26.6±11.4 years). Function in different cognitive domains was evaluated by the same trained examiner, in order to eliminate inter-rater variability. Peripheral nerve function was tested quantitatively. Predictors of cognitive impairment were identified using multiple regression analysis. The major finding was that long diabetes duration and young age of diabetes onset were the strongest predictors of low scores in psychomotor speed, memory, processing speed, attention, working memory, verbal ability, general intelligence, executive functions and a low global score. The number of previous hypoglycemic events had no defined effect upon cognitive functioning. Other significant predictors were low compound muscle action potential (CMAP) (for visual perception–organization), old age (for visual–spatial ability), short stature, high BMI and hypertension. Presence of retinopathy and long-term metabolic control correlated with nerve conduction defects, but not with cognitive impairment. Although a history of hypoglycemic events was not a predictor of cognitive impairment, we cannot exclude the possibility that the influence of young age of diabetes onset depends on the effect of hypoglycemic events early in life. The clinical relationships of cognitive impairment differ from those of peripheral neuropathy, indicating a different pathogenesis. The influence of diabetes duration, BMI, height, age and CMAP may suggest that loss of the neuroprotective effects of insulin or insulin-like growth factors plays a role.