Gerald Cooray

Predictors of cognitive impairment in type 1 diabetes

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. 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.

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

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 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.

The Electromagnetic Fields of an Accelerating Charge: Applications in Lightning Return-Stroke Models

In the literature, three procedures have been used to calculate the electromagnetic fields from return strokes. In the first technique, the source is described only in terms of current density and the fields are expressed entirely in terms of the return-stroke current. In the second technique, the source is expressed in terms of the current and the charge densities and the fields are given in terms of both the current and the charge density. In the third technique, the fields are expressed in terms of the apparent charge density. The fields are connected to the source terms through the vector and scalar potentials. In this paper, the standard equations for the electromagnetic fields generated by an accelerating charge are utilized to evaluate the electromagnetic fields from lightning return strokes. It is shown that the total fields evaluated at any distance using these expressions are identical to those obtained using other techniques. However, the composition of the terms that vary as 1/R, 1/R2, and 1/R3 of the total electric field is different from those of other formulations. In the case of the transmission-line model, where the return stroke is described as a current pulse propagating with uniform velocity, radiation emanates only from the bottom of the channel where current is generated. When the speed of propagation is equal to the speed of light, the total field throughout the entire space becomes radiation. The procedure is also applied here to obtain the electric fields of the traveling-current-source model. The electric fields obtained for this case, too, agree with the previous study. It is also shown how the equations can be applied rather conveniently to evaluate: 1) the electromagnetic fields generated by current pulses propagating along overhead power lines; and 2) the electromagnetic fields generated by vertical conductors and towers during lightning strikes.

Decreased cortical connectivity and information flow in type 1 diabetes

OBJECTIVE 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 clinical variables. METHODS 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. RESULTS 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. CONCLUSIONS 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. SIGNIFICANCE 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.

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

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-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.

A mechanistic model of mismatch negativity in the ageing brain.

OBJECTIVE We investigated the neurophysiological mechanisms underpinning the generation of the mismatch negativity (MMN) in the ageing brain. METHODS We used dynamic causal modelling (DCM) to study connectivity models for healthy young and old subjects. MMN was elicited with an auditory odd-ball paradigm in two groups of healthy subjects with mean age 74 (n=30) and 26 (n=26). DCM was implemented using up to five cortical nodes. We tested models with different hierarchical complexities. RESULTS We showed that the network generating MMN consisted of 5 nodes that could modulate all intra- and inter-nodal connections. The inversion of this model showed that old subjects had increased input from rSTG to the rIFG (p<0.01) together with increased inhibition of pyramidal cells (p<0.05). Furthermore, there was reduced modulation of activity within rIFG (p<0.02) on stimulus change. CONCLUSION The age related change in MMN is due to a decline in frontal-based control mechanisms, with alterations in connectivity between temporal and frontal regions together with a dysregulation of the excitatory-inhibitory balance in the rIFG. SIGNIFICANCE This study provides for the first time a neurobiological explanation for the age related changes of the MMN in the ageing brain.

Could Some Ball Lightning Observations be Optical Hallucinations Caused by Epileptic Seizures

The great difficulty of encompassing all observed features of ball lightning into a single theory makes it highly probable that many observations and experiences which have no connection to ball lightning are also categorized as ball lightning experiences. In this note we compare the eyewitness reports of ball lightning and the symptoms of epileptic seizures of the occipital lobe as described in the medical literature and show that a person experiencing such a seizure for the first time may believe that he has witnessed a ball lightning event. Since many of the ball lightning reports are associated with nearby lightning strikes, the possibility that the rapidly changing magnetic field of a close lightning strike could trigger an epileptic seizure is analyzed. The results show that the time derivative of the magnetic field in the vicinity of an intense lightning flash is strong enough to stimulate neurons in the brain. This strengthens the possibility of inducing seizures in the occipital lobe of a person located in the vicinity of lightning strikes.

ELECTRIC AND MAGNETIC FIELDS PRODUCED BY A CURRENT FLOWING ALONG A HORIZONTAL CON- DUCTOR LOCATED OVER A PERFECTLY CONDUCT- ING GROUND PLANE | REVISITED

Electromagnetic flelds associated with the electric current ∞owing along a horizontal conductor located over perfectly conducting ground are estimated using electromagnetic flelds pertinent to acceleration of electric charges. It is shown that the electric and magnetic flelds that exist below a long overhead horizontal conductor are nothing but the radiation flelds generated by the acceleration of charge at the point of injection of current into the horizontal conductor.

Corona currents generated from a person's head in the vicinity of lightning strikes — Stimulation of phosphenes

Phosphene is a sensory experience which occurs due to the interaction of electric currents generated by an external agent with the visual cortex or retina. Occurrence of phosphenes has been documented in clinical Transcranial Magnetic Stimulation (TMS) studies where electric fields are induced in the brain by the application of time varying magnetic fields. In this paper the possibility of creating phosphenes by the corona currents developing from the head of a person located close to a lightning strike is investigated. The results show that the magnitude of the electric fields induced in the brain by corona currents are comparable to those generated by TMS. This in turn shows that the corona currents generated by long duration lightning flashes could excite phosphenes through their interaction with the visual cortex or retina in a human located in the vicinity of the lightning channel. It is suggested that some of the ball lightning observations reported in the literature could be luminous perceptions caused by the interaction of the corona currents with the visual cortex or retina of a person located in the vicinity of a lightning strike.

Stereotactic Brain Biopsy in Eloquent Areas Assisted by Navigated Transcranial Magnetic Stimulation: a Technical Case Report

BACKGROUND AND IMPORTANCE Stereotactic brain biopsy (SB) is an important part of the neurosurgical armamentarium, with the possibility of achieving histopathological diagnosis in otherwise inaccessible lesions of the brain. Nevertheless, the procedure is not without the risk of morbidity, which is especially true for lesions in eloquent parts of the brain, where even a minor adverse event can result in significant deficits. Navigated transcranial magnetic stimulation (nTMS) is widely used to chart lesions in eloquent areas, successfully guiding maximal safe resection, while its potential role in aiding with the planning of a stereotactic biopsy is so far unexplored. CLINICAL PRESENTATION Magnetic resonance imaging of a 67-yr-old woman presenting with dysphasia revealed a noncontrast enhancing left-sided lesion in the frontal and parietal pars opercularis. Due to the location of the lesion, nTMS was used to chart both primary motor and language cortex, utilizing this information to plan a safe SB trajectory and sampling area according to the initial work-up recommendations from the multidisciplinary neuro-oncology board. The SB was uneventful, with histology revealing a ganglioglioma, WHO I. The patient was discharged the following day, having declined to proceed with tumor resection (awake surgery) due to the non-negligible risk of morbidity. Upon 1- and 3-mo follow-up, she showed no signs of any procedure-related deficits. CONCLUSION nTMS can be implemented to aid with the planning of a stereotactic biopsy procedure in eloquent areas of the brain, and should be considered part of the neurosurgical armamentarium.