Reduction In Theta Research Articles

Long-term effects of theta/beta neurofeedback on EEG power spectra in children with attention deficit hyperactivity disorder

ObjectiveNeurofeedback has been proposed as an effective alternative for pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD), with potentially long-term and delayed benefits. However, the specificity of such long-term behavioral improvements remains inconclusive and therefore additional research into the neurophysiological effects of neurofeedback is needed. We compared long-term effects of theta/beta neurofeedback (NFB) to methylphenidate (MPH) and physical activity (PA, semi-active control intervention) on electroencephalogram (EEG) power spectra. Based on the vigilance stabilization model, we hypothesized further reductions in theta and alpha power in the NFB compared to the control groups. MethodEEG power spectra (theta, alpha and beta) during resting and task conditions were recorded at pre-, post-intervention and 6-months follow-up in 67 children, aged 7–13 (NFB: n = 24, MPH: n = 23, or PA: n = 20). ResultsAnalyses revealed no power spectra differences at follow-up between MPH and NFB (range p = .165–.905) and PA and NFB (range p = .172–.822). ConclusionsNo evidence was found for the specificity of theta/beta NFB at follow-up. SignificanceThis was the first study into long-term neurophysiological effects of theta/beta NFB. Future studies are encouraged to explore both specific and non-specific mechanisms of NFB.Clinical trials registration: Train Your Brain? Exercise and neurofeedback intervention for ADHD, https://clinicaltrials.gov/show/NCT01363544, Ref. No. NCT01363544.

Suboptimal Engagement of High-Level Cortical Regions Predicts Random-Noise-Related Gains in Sustained Attention

Interindividual variability in outcomes across individuals poses great challenges for the application of noninvasive brain stimulation in psychological research. Here, we examined how the effects of high-frequency transcranial random-noise stimulation (tRNS) on sustained attention varied as a function of a well-studied electrocortical marker: spontaneous theta:beta ratio. Seventy-two participants received sham, 1-mA, and 2-mA tRNS in a double-blind, crossover manner while they performed a sustained-attention task. Receiving 1-mA tRNS was associated with improved sustained attention, whereas the effect of 2-mA tRNS was similar to the effect of sham tRNS. Furthermore, individuals’ baseline theta:beta ratio moderated the effects of 1-mA tRNS and provided explanatory power beyond baseline behavioral performance. The tRNS-related effects on sustained attention were also accompanied by reductions in theta:beta ratio. These findings impart novel insights into mechanisms underlying tRNS effects and emphasize how designing studies that link variability in cognitive outcomes to variability in neurophysiology can improve inferential power in neurocognitive research.

Electroencephalographic Correlates of Continuous Postural Tasks of Increasing Difficulty

Cortical involvement in postural control is well recognized, however the role of non-visual afferents remains unclear. Parietal cortical areas are strongly implicated in vestibulo-spatial functions, but topographical localization during balance tasks remains limited. Here, we use electroencephalography (EEG) during continuous balance tasks of increasing difficulty at single electrode positions. Twenty-four healthy, right-handed individuals performed four balance tasks of increasing difficulty (bipedal and unipedal) and a seated control condition with eyes closed. Subjective ratings of task difficulty were obtained. EEG was recorded from 32 electrodes; 5 overlying sensory and motor regions of interest (ROIs) were chosen for further investigation: C3, Cz, C4, P3, P4. Spectral power and coherence during balance tasks were analyzed in theta (4–8 Hz) and alpha (8–12 Hz) bands. Alpha power reduced as task difficulty increased and this reduction correlated with subjective difficulty ratings. Alpha coherence increased with task difficulty between C3–Cz–C4 electrode pairs. Differential changes in power were observed in Cz, suggestive of a distinct role at this electrode location, which captures lower limb cortical representation. Hemispheric asymmetry was observed, as reflected by greater reductions in theta and alpha power in right-sided areas. Our results demonstrate the functional importance of bilateral central and parietal cortices in continuous balance control. The hemispheric asymmetry observed implies that the non-dominant hemisphere is involved with online monitoring of postural control. Although the posterior parietal asymmetry found may relate to vestibular, somatosensory or multisensory feedback processing, we argue that the finding relates to active balance control rather than simple sensory-intake or reflex circuit activation.

Neuronal Oscillations Indicate Sleep-dependent Changes in the Cortical Memory Trace.

Sleep promotes the consolidation of newly acquired associative memories. Here we used neuronal oscillations in the human EEG to investigate sleep-dependent changes in the cortical memory trace. The retrieval activity for object-color associations was assessed immediately after encoding and after 3 hr of sleep or wakefulness. Sleep had beneficial effects on memory performance and led to reduced event-related theta and gamma power during the retrieval of associative memories. Furthermore, event-related alpha suppression was attenuated in the wake group for memorized and novel stimuli. There were no sleep-dependent changes in retrieval activity for missed items or items retrieved without color. Thus, the sleep-dependent reduction in theta and gamma oscillations was specific for the retrieval of associative memories. In line with theoretical accounts on sleep-dependent memory consolidation, decreased theta may indicate reduced mediotemporal activity because of a transfer of information into neocortical networks during sleep, whereas reduced parietal gamma may reflect effects of synaptic downscaling. Changes in alpha suppression in the wake group possibly index reduced attentional resources that may also contribute to a lower memory performance in this group. These findings indicate that the consolidation of associative memories during sleep is associated with profound changes in the cortical memory trace and relies on multiple neuronal processes working in concert.

Sleep alterations following exposure to stress predict fear-associated memory impairments in a rodent model of PTSD.

Sleep abnormalities, such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of posttraumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We havehypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stressor exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops. SPS resulted in acute increases in REM sleepand transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. Reductions in theta (4-10Hz) and sigma (10-15Hz) band power during transition to REM sleep also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure.

Age-related changes in slow wave activity rise time and NREM sleep EEG with and without zolpidem in healthy young and older adults

ObjectiveWhether there are age-related changes in slow wave activity (SWA) rise time, a marker of homeostatic sleep drive, is unknown. Additionally, although sleep medication use is highest among older adults, the quantitative electroencephalographic (EEG) profile of the most commonly prescribed sleep medication, zolpidem, in older adults is also unknown. We therefore quantified age-related and regional brain differences in sleep EEG with and without zolpidem. MethodsThirteen healthy young adults aged 21.9 ± 2.2 years and 12 healthy older adults aged 67.4 ± 4.2 years participated in a randomized, double-blind, within-subject study that compared placebo to 5 mg zolpidem. ResultsOlder adults showed a smaller rise in SWA and zolpidem increased age-related differences in SWA rise time such that age differences were observed earlier after latency to persistent sleep. Age-related differences in EEG power differed by brain region. Older, but not young, adults showed zolpidem-dependent reductions in theta and alpha frequencies. Zolpidem decreased stage 1 in older adults and did not alter other age-related sleep architecture parameters. ConclusionsSWA findings provide additional support for reduced homeostatic sleep drive or reduced ability to respond to sleep drive with age. Consequences of reduced power in theta and alpha frequencies in older adults remain to be elucidated.

CPP alters theta/gamma oscillations in rat hippocampus: simulation and experiment

Several different NMDA receptor (NMDAR) antagonists are used to produce pharmacological models for schizophrenia. These antagonists have different molecular mechanisms of action: non-competitive (e.g. ketamine, which binds at a site different from glutamate) and competitive (e.g. CPP, which displaces glutamate). Because competitive antagonism results in more glutamate availability, this may result in glutamate spill-over either onto other receptors of the same synapse or to neighboring synapses. In this study, we modeled the effects of competitive blockade by simultaneously blocking NMDAR and increasing activity of AMPAR (spillover). We looked at alterations of network oscillations and synchronization using our biophysical model of the CA1 region of hippocampus using the NEURON simulator. We then compared the results with data obtained from the CA1 region of hippocampus in rats injected with CPP. Our network consisted of 800 five-compartment pyramidal cells (PYR), 200 one-compartment basket cell interneurons (BAS), and 200 one-compartment oriens lacunosum-moleculare interneurons (OLM) [1]. All cells contained leak current, transient sodium current and delayed rectifier current. Additionally, pyramidal cells contained potassium type A current and pyramidal and OLM cells had Ih current. Cell classes were interconnected probabilistically with AMPA/NMDA synapses, and two classes of GABAa synapses. The OLM cells formed synapses on the distal dendrites of pyramidal cells, while the basket cells synapsed proximally on pyramidal and other basket cells. Pyramidal cells synapsed on both types of interneurons with AMPA/NMDA synapses. All synapses were bombarded with external Poisson inputs to generate network activity. Competitive inhibition was modeled by setting the conductance across NMDAR to zero, and increasing current conductance across AMPAR on the same set of synapses. We modeled this on synaptic sites on all cell populations. Also, given the possible variation of the affinity of competitive inhibitors to NMDAR on different cells, we studied this effect when it took place at the receptors of the 3 different cell populations separately. Experimental recordings were made from tetrode arrays implanted in the CA1 region of Long Evans rats chasing sugar pellets in a box. CPP at a dose of 5 mg/kg was injected intraperitoneally in the rats. Recordings were for 16 min sessions, separated by 30 min breaks during which the rats were returned to their cages. Recordings from CA1 of rat hippocampus under the effect of CPP, showed that there is a reduction in theta and an increase in gamma. Modeling competitive inhibition to glutamate at all synapse locations (on OLM, BAS, and PYR) resulted in a reduction in the theta power and an increase in gamma power, differing from the noncompetitive effect with ketamine, which reduced both theta and gamma when given across all synapses. However, this result was also seen when the effect of competitive inhibition was restricted to only OLM cell NMDARs. Therefore, our model demonstrates both of these interpretations of CPP action. We will examine further correlates between simulation and experiment to reduce this uncertainty.

Investigating the Neurophysiological Effects of Direct Current Stimulation (IN6-1.005)

Objective: To create a mouse model of direct current stimulation. Background Although transcranial direct current stimulation (tDCS) and deep brain stimulation(DBS) are currently being used as investigative tools in neuroscience and as potential therapies for a variety of neurological conditions, their neurophysiologic mechanisms remain poorly understood. Importantly, no animal studies to date have directly measured physiological changes associated with direct, low-current brain stimulation. Design/Methods: Twenty-four mice were assigned to anodal, cathodal, and sham groups and were implanted with electrodes in left auditory cortex. Mice underwent direct current stimulation for 20min at 20microAmps. Auditory evoked potentials were recorded pre-stimulation, 1hr, 1wk, and 2wk post-stimulation. EEG was analyzed for amplitude/latency of P1, N1, and P2 signals. We assessed EEG power and intertrial coherence using event-related spectral perturbations. Results: In the anodal condition there was significant reduction in delta, theta, and alpha power that persisted through the two-week timepoint. In the cathodal condition there was significant reduction in delta that persisted through the one-week timepoint and reduction in theta and alpha power observed only at the one-hour timepoint (all p values Conclusions: Observed reductions in low frequency power bands after direct current stimulation were consistent with recent clinical studies using tDCS and extracranial EEG recordings (Keeser et al., 2010). In humans, attenuation of low frequency power may be associated with improved cognitive function and increased BOLD signal changes (Hlinka et al., 2010). Our approach may thus provide a means examine the use of direct current stimulation relevant to tDCS and DBS to improve brain function in animal models. Supported by: Summer Research Scholarship, American Academy of Neurology, 2011 and T32 Brain Injury Training Grant, NINDS, 2011. Disclosure: Dr. Rojas has nothing to disclose. Dr. Hamilton has nothing to disclose. Dr. Luminais has nothing to disclose. Dr. Siegel has nothing to disclose.

Tinnitus: where is the source (Commentary on Vanneste et al.)

The paper by Vanneste et al. (2011) addresses the very intriguing issue of the brain source for tinnitus generation. For those of us who consider subjectivity to be the ultimate question of science (given that all of the rest of science is fully dependent on such brain activity), tinnitus is indeed of extraordinary significance. One does not wish such inner sound on anyone and, given its persistent nature, abhorring it should be the rule. However, for those wanting a glimpse into the physical nature of subjectivity, tinnitus is riveting. Tinnitus may be considered a member of a very significant brain activity class, along with deduction, inspiration, dreaming and brooding, in the sense that they are all intrinsically generated functional states, with clear subjective content, not requiring sustaining sensory input. As opposed to the other mentioned intrinsic subjective conditions, tinnitus is, however, omnipresent and thus an odious event. Its functional relatives, visual hallucinations in psychosis, central pain and a host of other neuropsychiatric ailments, do represent a class. We have addressed them as ‘thalamocortical dysrhythmias’ (TCDs) (Llinás et al., 1999). These events have the following in common: positive and negative sensory/motor components, a resilient nature, the fact that they disappear during sleep, and the fact that they present unambiguous markers by their electrical signature. Thus, in the case of tinnitus, persistent sound (positive symptom) that can be masked with other sound and the often-accompanying deafness (negative symptoms) represent well the functional phenotype. Beyond diagnostics and therapeutics, TCDs represent one of the truly remarkable neuroscience events that our brains can experience. They present us with petrified sensations and autonomous ever-present movements (e.g. tremor and rigidity) unreferenced to the external world. As such, they constitute a window into the otherwise transient and evanescent nature of brain activity. In the case of tinnitus subjectivity, it presents us with ever-lasting notes or hisses that can be analyzed, quantified and localized (Llinás et al., 2005). With these introductory remarks out of the way, let us consider the implications of the Vanneste et al. (2011) paper. Our colleagues have dug deep into the understanding of tinnitus. Whereas, to most neuroscientists, the subjective represents only neocortical activity, the present paper addresses other aspects that relate beyond the sensation itself, into the memory of its persistence and the affective resonance that it develops with time. Much of the suffering in tinnitus is related to the chronic, unforgiving nature of the ailment. The authors deal well with the possible correlates that support such chronicity, the ‘it will remain for the rest of your life’ aspect, ‘unless medical intervention can exert its therapeutic bliss’. The authors have published a well-designed, significant paper. Unilateral left-sided narrow-band tinnitus is an excellent patient choice, as is differentiating between acute and chronic ailments. The message is clear and very significant – long-term tinnitus is accompanied by an overall reduction in theta, alpha and gamma resonance. There is, however, a clear increase in the specific gamma component between parahippocampal cortex and auditory cortex, as well as between primary and secondary auditory cortex projecting to ipsilateral insula and the contralateral prefrontal cortex. Thus, the basic hypothesis presents long-term tinnitus as the remembered past. This is an interesting thought, although somewhat on the cortical chauvinistic side for a thalamocortical chauvinist such as myself. Clearly, however, this work is an unambiguous step in the correct direction, pointing the way towards more to come.

Electroencephalographic correlates of Chronic Fatigue Syndrome

BackgroundUnremitting fatigue and unrefreshing sleep, hallmark traits of Chronic Fatigue Syndrome (CFS), are also pathognomonic of sleep disorders. Yet, no reproducible perturbations of sleep architecture, multiple sleep latency times or Epworth Sleepiness Scores are found to be associated consistently with CFS. This led us to hypothesize that sleep homeostasis, rather than sleep architecture, may be perturbed in CFS. To probe this hypothesis, we measured and compared EEG frequencies associated with restorative sleep between persons with CFS and matched controls, both derived from a population-based sample.MethodsWe evaluated overnight polysomnography (PSG) in 35 CFS and 40 control subjects. PSG records were manually scored and epochs containing artifact removed. Fast Fourier Transformation was utilized to deconstruct individual EEG signals into primary frequency bands of alpha, delta, theta, sigma, and beta frequency domains. The spectral power of each frequency domain for each sleep state was compared between persons with CFS and matched controls.ResultsIn persons with CFS, delta power was diminished during slow wave sleep, but elevated during both stage 1 and REM. Alpha power was reduced during stage 2, slow wave, and REM sleep. Those with CFS also had significantly lower theta, sigma, and beta spectral power during stage 2, Slow Wave Sleep, and REM.DiscussionEmploying quantitative EEG analysis we demonstrate reduced spectral power of cortical delta activity during SWS. We also establish reduced spectral power of cortical alpha activity, with the greatest reduction occurring during REM sleep. Reductions in theta, beta, and sigma spectral power were also apparent.ConclusionUnremitting fatigue and unrefreshing sleep, the waking manifestations of CFS, may be the consequence of impaired sleep homeostasis rather than a primary sleep disorder.

Theta activity attenuation correlates with avoidance learning progress in gerbils

Changes of cortical activity were examined with electrocorticograms sampled from gerbils during learning. Animals were subjected to tone-conditioned avoidance training in a shuttle-box. Electrocorticograms were recorded from an electrode placed over medial prefrontal cortex. Temporal patterns of theta activity were analyzed across 180 successive trials. With the start of conditioning strong theta activity occurred in each trial in the phase immediately after hurdle crossing. With reliable occurrence of conditioned responses, that is at the stage of retrieval of the avoidance response, the theta activity became reduced. A negative correlation exists between the theta power and the development of learning progress. Theta reduction thus could reflect decreasing demands on information processing in the course of avoidance success monitoring across trials.

AN INTEGRATIVE APPROACH TO DETERMINE THE BEST BEHAVIORAL AND BIOLOGICAL MARKERS OF METHYLPHENIDATE

To distinguish the most sensitive markers of methylphenidate (MPH) effects on behavior and underlying biology using an integrated cognitive and brain function test battery. A randomized placebo-controlled trial with 32 healthy adult males. Subjects were tested on MPH doses across 18 sessions with subjective mood, objective behavioral and biological endpoints. From a computerized battery of tests, behavioral measures were cognitive performance scores, while biological measures of brain function included electroencephalographs (EEG) and event-related potentials (ERPs) with complementary measures of autonomic arousal. Using mixed modeling analyses; we determined which measures were most affected by MPH dose and correlation analyses determined the associations among them. MPH dose had the most pronounced effect on cognitive performance (sustained attention/vigilance), baseline autonomic arousal (heart rate, blood pressure) and baseline brain activity (EEG theta power). The faster reaction time, reduced errors, increased autonomic arousal and reductions in theta showed strong to moderate inter-correlations. MPH least affected subjective mood measures and early sensory ERP components. These findings suggest that MPH increases cortical and autonomic arousal, facilitating vigilance. The combination of behavioral and biological measures may provide an objective set of markers of MPH response. This approach has provided additional insight into the mechanism of the stimulant medication, MPH, which would not be achieved by using such measures in isolation.

Naltrexone alteration of the nicotine-induced EEG and mood activation response in tobacco-deprived cigarette smokers.

The neural mechanisms contributing to the arousal-eliciting actions of smoking and nicotine involve multiple neurotransmitter systems. The current study examined the role of opioid neurotransmission in modulating the neuroelectric- and mood-activating response to acute nicotine administration in overnight tobacco-deprived smokers. In a randomized, double-blind, placebo-controlled design involving 18 (10 male, 8 female) overnight tobacco-abstinent smokers, spectrally analyzed electroencephalographic (EEG) activity and subjective reports of mood, euphoria, and smoking withdrawal were assessed in response to nicotine gum (4 mg) after pretreatment with placebo or with 50 mg of the opioid antagonist naltrexone. In addition to reducing withdrawal symptoms and increasing euphoria ratings, as well as subjective alertness in male participants, nicotine induced an EEG arousal response consisting of diffuse slow wave (delta, theta) amplitude reductions, frontal fast alpha wave amplitude increments, and elevations in beta wave amplitude, which were greater in female than in male smokers. Naltrexone attenuated the alerting and euphoric actions of nicotine but did not affect nicotine's ameliorating effects on withdrawal symptoms. Nicotine-induced frontal reductions in delta and global reductions in theta were prevented by naltrexone pretreatment, as were increases in anterior recordings of relative fast alpha. These findings suggest that the opioid system is involved in nicotine-induced subjective and neuroelectric arousal and implicate opioid-cholinergic interactions in the elicitation of these arousal responses to nicotine.

Effects of glomerular filtration rate on Ficoll sieving coefficients (θ) in rats

The purpose of the present study was to assess the role of diffusion and convection during filtration of Ficoll across the glomerular filter by comparing glomerular sieving coefficients (theta) to neutral fluorescein isothiocyanate (FITC)-Ficoll 70/400 obtained at low (hydropenic) vs raised (normal) glomerular filtration rates (GFRs). The theta for FITC-Ficoll was determined in anesthetized Wistar rats (304 +/- 18 g) following laparotomy and cannulation of the ureters, used for urine sampling. After surgery, GFR was 1.2 +/- 0.16 ml/min (+/- s.e.), assessed using the plasma to urine clearance of FITC-inulin and (51)Cr-ethylenediaminetetraacetic acid. FITC-Ficoll 70/400 was infused intravenously (i.v.) following an initial bolus dose. To raise GFR, to an average of approximately 2 ml/min, 5 ml of serum together with glucagon (3 microg/min) was given i.v. FITC-inulin and FITC-Ficoll were determined in plasma and urine using size-exclusion high-performance liquid chromatography. The theta for Ficoll as a function of Stokes-Einstein radius was significantly reduced in the range of 13-43 A when GFR was raised. The maximal theta lowering effect, in relative terms, of raising GFR was obtained for a Ficoll a(e) of approximately 32 A. For Ficoll(36 A) (cf. albumin), theta was reduced from 0.111+/- 0.009 to 0.081+/- 0.012 (P < 0.05; n = 7) for the GFR increment imposed. The reduction in theta for Ficoll after raising GFR indicates the presence of a high diffusive component of glomerular Ficoll filtration in rats in vivo and contradicts the notion of a significant concentration polarization effect in the glomerular filter upon Ficoll molecules < 50 A in radius.

EEG deficits in chronic marijuana abusers during monitored abstinence: preliminary findings.

Cognitive, cerebrovascular, and psychiatric impairments have been documented with chronic marijuana users. To better understand the nature and duration of these neurocognitive changes in marijuana abusers, we recorded the resting EEG of 29 abstinent chronic marijuana abusers and 21 control subjects. The marijuana abusers were tested twice: the first evaluation occurred within 72 hours of admission to the inpatient research unit; the second evaluation occurred after 28 to 30 days of monitored abstinence. A three-minute period of EEG was recorded during resting eyes-closed conditions from eight electrodes (F(3), C(3), P(3), O(1), F(4), C(4), P(4), and O(2)). The artifacted EEG was converted to six frequency bands (delta, theta, alpha(1), alpha(2), beta(1), and beta(2)) using a fast Fourier transform. During early abstinence, absolute power was significantly lower (p < 0.05) for the marijuana abusers than for the control subjects for the theta and alpha(1) bands. These reductions in theta and alpha(1) power persisted for 28 days of monitored abstinence. These EEG changes, together with cerebral blood flow deficits, might underlie the cognitive alterations observed in marijuana abusers. Additional research is needed to determine how long these deficits persist during abstinence and if treatment with neuroprotective agents may reverse them.

Glomerular permselectivity in early stages of overt diabetic nephropathy

Impairment of glomerular size selectivity has been demonstrated by the dextran-sieving technique in nephropathic diabetics with heavy, but not mild proteinuria. The purpose of the present study was to determine whether such a barrier defect could be demonstrated with mild proteinuria by substituting Ficoll 70, a polysucrose, for dextran as a probe of the filtration barrier. Differential solute clearances were performed in 12 individuals with early diabetic nephropathy on two occasions: after 60 days of treatment with losartan 50 mg daily or a placebo. An uncharged preparation of nonreabsorbable Ficoll 70 was infused along with inulin. Fractional clearance (theta) of Ficoll of discrete size was determined after separating molecules in urine and plasma in narrow 2 A fractions over a 20 to 60 A radius interval by size exclusion high-performance liquid chromatography (HPLC). A hydrodynamic theory of hindered ficoll transport through water-filled pores was used to characterize the pore size distribution of the glomerular barrier. The theta for Ficoll molecules with radii> 50 A was selectively enhanced in placebo-treated diabetic nephropathy versus corresponding theta in healthy control subjects (N = 12). Computations revealed a lower distribution of glomerular pores that was unaltered in nephropathic diabetics. However, an upper distribution of large, shunt-like pores was more prominent, exceeding healthy controls by one order of magnitude in diabetic nephropathy (P = 0.01). A trend to lower theta for Ficoll in the 56 to 60 A radius range during losartan therapy is computed to have lowered the fraction of shunted filtrate by 26 to 44%, depending on whether glomerular pressure declined. The corresponding reduction in theta for endogenous albumin, IgG, and IgG4 was by 19 to 23% (P < 0.05). Our findings suggest that shunt-like defects, partially reversible by angiotensin II blockade, are present early in the course of diabetic nephropathy. We estimate that such defects can account for immunoglobulinuria in this disorder. Additional impairment of either charge- or shape-selectivity must be invoked to explain the observed level of albuminuria, however.

Human electroencephalographic (EEG) response to olfactory stimulation: Two experiments using the aroma of food

The present studies sought to examine the effect of olfactory stimulation on human Central Nervous System activity. In the first experiment ( n=21), EEG response to the `synthetic' odours of chocolate, spearmint, almond, strawberry, vegetable, garlic and onion, and cumin or no odour was recorded from 19 electrodes (F3, F4, F7, F8, Fz, T3, T4, T5, T6, P3, P4, Pz, O1, O2, C3, C4, Cz) in all EEG frequencies (delta, theta, alpha, beta1 and beta2). Exposure to the odour of chocolate was associated with significant reductions in theta activity when compared with the odours of almond and cumin, with a trend towards significance when compared with no-odour control. Exposure to the odour of spearmint was associated with a significant reduction in EEG theta when compared with the no-odour control. No significant effects were observed in other frequencies. In a second experiment ( n=15), EEG response to the odours of real foods (chocolate, baked beans, rotting pork) and two controls (no odour and hot water) was recorded as in Experiment 1. The odour of chocolate was associated with significantly less theta activity than was any other stimulus. It is hypothesised that the alterations in theta reflect shifts in attention or cognitive load during olfactory perception, with a reduction in theta indicating a reduced level of attention.

58 Frequency analysis of narrow band EEG during hypnosis

The present studies sought to examine the effect of olfactory stimulation on human Central Nervous System activity. In the first experiment (n=21), EEG response to the `synthetic' odours of chocolate, spearmint, almond, strawberry, vegetable, garlic and onion, and cumin or no odour was recorded from 19 electrodes (F3, F4, F7, F8, Fz, T3, T4, T5, T6, P3, P4, Pz, O1, O2, C3, C4, Cz) in all EEG frequencies (delta, theta, alpha, beta1 and beta2). Exposure to the odour of chocolate was associated with significant reductions in theta activity when compared with the odours of almond and cumin, with a trend towards significance when compared with no-odour control. Exposure to the odour of spearmint was associated with a significant reduction in EEG theta when compared with the no-odour control. No significant effects were observed in other frequencies. In a second experiment (n=15), EEG response to the odours of real foods (chocolate, baked beans, rotting pork) and two controls (no odour and hot water) was recorded as in Experiment 1. The odour of chocolate was associated with significantly less theta activity than was any other stimulus. It is hypothesised that the alterations in theta reflect shifts in attention or cognitive load during olfactory perception, with a reduction in theta indicating a reduced level of attention.

Anisotropic conduction characteristics in ischemia-reperfusion induced chronic myocardial infarction.

Anisotropic properties of cardiac tissue play an important role in initiation and perpetuation of ventricular tachycardia. However, anisotropic conduction properties in different morphologic types of chronic myocardial infarctions as well as frequency dependency still need to be elucidated. In the present study, the characteristics of anisotropic conduction were investigated in situ in the setting of ischemia-reperfusion induced chronic myocardial infarction. Myocardial infarction was induced in 12 dogs by a percutaneous transcatheter left anterior descending coronary artery occlusion-reperfusion technique. Four additional dogs served as normal controls. After 14 to 20 days, epicardial mapping was performed using simultaneous unipolar recordings from 240 electrodes of a plaque electrode array placed on the epicardial border zone overlying the infarctions. Constant rate pacing with five cycle lengths (CL) ranging from 500 to 200 ms as well as programmed electrical stimulation (PES) with four basic cycle lengths (BCL) ranging from 430 to 300 ms and single extrastimuli (S2) were performed. Two anatomically different patterns of epicardial surface morphology were analyzed, designated as type I and type II. In seven animals, there was a continuous thin layer of surviving epicardial muscle fibers overlying the infarction (type I). During pacing with CL of 500 vs 200 ms, conduction velocity longitudinal to fiber orientation (theta L) decreased significantly in the infarcted animals compared to control group (10.9% vs 5.2%, p < 0.05) whereas conduction velocity transverse to fiber axis (theta T) decreased to a similar degree in control and infarcted animals (6.9 vs 7.4%, n.s.). After premature stimulation, there was considerably greater reduction in theta L in infarcted animals than in controls (39.8% vs 31.5%, p < 0.05) whereas theta T decreased to a similar extend in infarcted and control animals (22.2% vs 21.4%, n.s.). During constant rate pacing and premature stimulation, no functional conduction block was induced in type I infarctions. In five animals, the transmural infarctions clearly extended to the epicardial surface, but continuous strands of surviving epicardial muscle fibers traversed the area of necrosis (type II). During PES with S2, functional conduction block and areas of very slow conduction were observed in each case. In ischemia-reperfusion induced chronic myocardial infarctions, different epicardial patterns of morphology were observed. Anisotropic conduction was frequency dependent in the longitudinal but not in the transverse direction. In type I infarctions, functional conduction block was not inducible during PES whereas in type II infarctions, prerequisites for reentrant arrhythmias like functional conduction block and very slow conduction were induced in each case by single extrastimuli.

Effects of acute ischemia on anisotropic conduction in canine ventricular muscle.

The effects of acute ischemia on conduction velocities in the longitudinal (theta L) and transverse (theta T) fiber axis were determined from epicardial activation patterns, recorded with 48 bipolar electrodes (plaque electrode, 25 x 35 mm) on the left anterior ventricular wall of eight dogs and the posterior wall of seven dogs. During left ventricular stimulation (cycle length = 300 msec) in the center of the plaque electrode, theta L, theta T, and the ratio of longitudinal to transverse conduction velocities (theta L/T) were measured before and 2 to 5 minutes after occlusion of the left anterior descending coronary artery or the left circumflex coronary artery. During the control state theta L was greater than theta T demonstrating anisotropic properties of cardiac muscle, not only in the anterior but also in the posterior wall. During acute ischemia theta L and theta T were decreased from the control value and theta T was decreased by a greater extent than theta L resulting in an increase in theta L/T from 1.83 +/- 0.31 (mean +/- SD) to 2.19 +/- 0.36 in the anterior wall and from 1.58 +/- 0.17 to 1.92 +/- 0.28 in the posterior wall. During ventricular fibrillation some lines of conduction block were parallel to the long axis of epicardial muscle fiber bundle and the others were perpendicular. In conclusion, acute ischemia increased anisotropic conduction (theta L/T) in the epicardial ventricular muscle mainly due to greater reduction in theta T, in the anterior and the posterior wall. This augmented anisotropic ventricular conduction may have some relation to the initiation of ventricular fibrillation during acute ischemia.