Changes In Background Activity Research Articles

Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

Short-Term Synaptic Plasticity Makes Neurons Sensitive to the Distribution of Presynaptic Population Firing Rates.

The ability to discriminate spikes that encode a particular stimulus from spikes produced by background activity is essential for reliable information processing in the brain. We describe how synaptic short-term plasticity (STP) modulates the output of presynaptic populations as a function of the distribution of the spiking activity and find a strong relationship between STP features and sparseness of the population code, which could solve this problem. Furthermore, we show that feedforward excitation followed by inhibition (FF-EI), combined with target-dependent STP, promote substantial increase in the signal gain even for considerable deviations from the optimal conditions, granting robustness to this mechanism. A simulated neuron driven by a spiking FF-EI network is reliably modulated as predicted by a rate analysis and inherits the ability to differentiate sparse signals from dense background activity changes of the same magnitude, even at very low signal-to-noise conditions. We propose that the STP-based distribution discrimination is likely a latent function in several regions such as the cerebellum and the hippocampus.

Decrease of global current source density predicts successful treatment in absence and juvenile myoclonic epilepsies

ObjectiveTo investigate relationship between treatment efficiency and EEG background activity changes in absence epilepsy (AE) and juvenile myoclonic epilepsy (JME) patients. Patients and methodsEEGs of 31 patients were analysed before treatment and after six months of treatment. Three minutes of artifact-free waking EEG background activity (without epileptiform potentials) were analysed for each patient in both conditions. All the EEG samples were processed to LORETA (Low Resolution Electromagnetic Tomography). Average of all the voxel-wise current source density (CSD) values within the 0.5–8.0Hz frequency range was computed for each EEG. Fischer's exact test was used to investigate association between the global CSD changes and the therapeutic outcome. ResultsTight connection was demonstrated between seizure freedom and decreased CSD, and between persisting seizures and increased CSD (p<0.001). SignificanceAn EEG-based biomarker that predicts successful drug treatment was described.

Mechanisms of Pain Caused by Surgical Incision Investigated in a Rat Model.

Mechanisms of Pain Caused by Surgical Incision Investigated in a Rat Model. Vandermeulen et al.(page 1294)Sensitization of the dorsal horn of the spinal cord via surgery (termed central sensitization) is not well-defined. Hypothesizing that a surgical incision would produce activation and enhanced responsiveness of single dorsal horn neurons, Vandermeulen et al. used a previously developed rat incisional pain model to study spontaneous and evoked activity from individual dorsal horn neurons in the lumbar spinal cord directly. After performing laminectomy in halothane-anesthetized rats, dorsal horn neurons from the lumbar enlargement were identified antidromically and characterized as low threshold, wide dynamic range, or high threshold based on their responses to brush and pinch of the animals’ paws. The receptive field for each neuron also was mapped. Then, an incision was made within the receptive field. Changes in background activity, punctate mechanical thresholds, receptive field size, and stimulus–response functions were recorded for up to 1 h after incision.In all cells, incisions produced a strong response and an increase in background activity, which remained increased in 3 of 9 high-threshold neurons and 16 of 28 wide-dynamic-range neurons 1 h later. The mechanical responsiveness was enhanced in 10 of 27 wide-dynamic-range neurons and in 2 of 8 high-threshold cells after incision. Wide-dynamic-range neurons may be the most important for pain signaling, and the increased background activity in these dorsal horn neurons may signal pain at rest after surgery. The receptive field size also expanded beyond the initial area around the incision, indicating a mechanism for amplification of dorsal horn response via surgery.

Alterations in ascending dorsal horn neurons by a surgical incision in the rat foot.

Little is known about the mechanisms of pain caused by a surgical incision. The authors have developed a rat model of postoperative pain characterized by decreased withdrawal thresholds to punctate mechanical stimuli after plantar incision. The present studies examined the response characteristics of dorsal horn neurons receiving input from the plantar aspect of the foot before and after a plantar incision placed adjacent to the low threshold area of the receptive field (RF). Individual dorsal horn neurons from the lumbar enlargement were antidromically identified and characterized as low threshold, wide dynamic range (WDR), and high threshold (HT) based on their responses to brush and pinch. Thresholds (in millinewtons), the pinch RF, and stimulus-response functions (SRFs) to von Frey filaments characterized the neurons. SRFs were analyzed using area under the curve. Changes in background activity, punctate mechanical thresholds, SRFs, and RF were recorded after an incision was made adjacent to the most sensitive area of the RF. In all cells, an incision increased background activity; this remained elevated in 3 of 9 HT and 16 of 28 WDR neurons 1 h later. The SRFs were enhanced in 10 of 27 WDR neurons and in 2 of 8 HT cells after incision. Only the WDR neurons were responsive to filaments that produced withdrawal responses after incision in behavioral experiments. Increases in the RFs outside of the injured area occurred after incision in 15 of 29 WDR and 2 of 9 HT cells. A plantar incision caused dorsal horn cell activation and central sensitization. Because the threshold of HT neurons did not decrease to the range of the withdrawal responses in behavioral experiments, particular WDR dorsal horn neurons likely contribute to the reduced withdrawal threshold observed in behavioral experiments. Both WDR and HT neurons are capable of transmitting enhanced responses to strong punctate mechanical stimuli after incision.

Incision-induced Changes in Receptive Field Properties of Rat Dorsal Horn Neurons

To learn more about pain mechanisms produced by surgery, responses of wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons were studied before and after an incision. For this study, an incision was made in a mechanically insensitive area of the receptive field (RF) of the dorsal horn neuron in the plantar aspect of the foot and changes in mechanical response properties were studied. Action potentials from single dorsal horn neurons were recorded in halothane anesthetized rats and these neurons were characterized as WDR or HT. Changes in background activity and responses to a variety of mechanical stimuli adjacent to the incision, distant to the injury, and in areas throughout the hindquarters were recorded. Fifty neurons were recorded (29 WDR, 21 HT cells); only nine of these had a sustained increase in background activity after incision. Marked decreases in threshold to von Frey filaments applied adjacent to the wound occurred in 9 of 28 WDR neurons but in none of 21 HT cells. Von Frey filament thresholds distant to the incision were largely not changed. A blunt mechanical stimulus activated 18 of 22 WDR neurons when applied directly on the incision. HT cells were largely not excited by this mechanical stimulus after incision. The RF to pinch was enlarged in 31 neurons to include areas outside the injury. Pinch RFs of both WDR and HT cells expanded. These results suggest that incisions in mechanically insensitive areas of the RF of dorsal horn neurons produced little change in background activity; expansion of pinch RFs outside the injury was common. Changing a mechanically insensitive area of the RF of WDR neurons to a mechanically sensitive area by an incision could contribute to pain behaviors that indicate primary mechanical hyperalgesia in behavioral studies.

Evidence for homeostatic adjustments of rat somatosensory cortical neurons to changes in extracellular acetylcholine concentrations produced by iontophoretic administration of acetylcholine and by systemic diisopropylfluorophosphate treatment

We describe the responses of single units in the awake (24 cells) or urethane-anesthetized (37 cells) rat somatosensory cortex during repeated iontophoretic pulses (1.0 s, 85 nA) of acetylcholine, both before and after systemic treatment with the irreversible acetylcholinesterase inhibitor diisopropylfluorophosphate (i.p., 0.3–0.5 ld 50). The time-course of the response to acetylcholine pulses differed among cortical neurons but was characteristic for a given cell. Different time-courses included monophasic excitatory or inhibitory responses, biphasic (excitatory–inhibitory, inhibitory–excitatory, excitatory–excitatory, and inhibitory–inhibitory), and triphasic (excitatory–excitatory–inhibitory, inhibitory–inhibitory–excitatory, and inhibitory–excitatory–inhibitory) responses. Although the sign and time-course of the individual responses remained consistent, their magnitude fluctuated across time; most cells exhibited either an initial increase or decrease in response magnitude followed by oscillations in magnitude that diminished with time, gradually approaching the original size. The time-course of the characteristic response to an acetylcholine pulse appeared to determine direction and rate of change in response magnitude with successive pulses of acetylcholine. Diisopropylfluorophosphate treatment, given 1 h after beginning repeated acetylcholine pulses, often resulted in a gradual increase in spontaneous activity to a slightly higher but stable level. Superimposed on this change in background activity, the oscillations in the response amplitude reappeared and then subsided in a pattern similar to the decay seen prior to diisopropylfluorophosphate treatment. Our results suggest that dynamic, homeostatic mechanisms control neuronal excitability by adjusting the balance between excitatory and inhibitory influences within the cortical circuitry and that these mechanisms are engaged by prolonged increases in extracellular acetylcholine levels caused by repeated pulses of acetylcholine and by acetylcholinesterase inhibition. However, this ability of neurons in the cortical neuronal network to rapidly adjust to changes in extracellular levels of acetylcholine questions the potential efficacy of therapeutic treatments designed to increase ambient levels of acetylcholine as a treatment for Alzheimer's disease or to enhance mechanisms of learning and memory.

Experiments on the nature of the signal that induces spinal neuroplastic changes following a peripheral lesion

This study aimed at identifying the signal(s) that elicit myositis-induced neuroplastic changes in background activity and responsiveness of spinal neurones. It is based on previous data suggesting that in dorsal horn neurones, responsiveness to peripheral input on one hand and background activity on the other are probably controlled by different mechanisms. In anaesthetized rats, myositis was induced in the gastrocnemius-soleus muscle and the activity of single dorsal horn neurones was recorded in segment L3. Impulse traffic and axoplasmatic transport in dorsal roots L4 and L5 were selectively blocked by lignocaine or vinblastine for various time periods relative to the induction of the myositis. The results show that the main triggering signal for the myositis-induced changes in both responsiveness and background activity is the altered impulse activity in primary afferent fibres. In contrast, 'no axonally transported chemical signal controlling the discharge behaviour of dorsal horn neurones was found. However, the time course of the electrical signals that cause the myositis-induced changes in background activity and responsiveness is different. For changes in responsiveness, a rather narrow time window of 2 h directly after induction of the myositis existed, during which the impulses from the inflamed muscle must reach the spinal cord. Accordingly, to prevent the increase in responsiveness, the electrical input had to be blocked during the first 2 h; a block of the same duration at another time had no effect. The change in background activity seems to be due to a continuous input from the inflamed muscle which adds up over the hours. Therefore, with regard to background activity, blocking the electrical signals is effective at any time, but only a block of long duration has a significant effect.

Attenuation of preparatory activity for reaching movements by a D1-dopamine antagonist in the monkey premotor cortex.

To examine the role of dopamine receptors in the function of the premotor cortex (PM) for preparing for reaching movements, dopamine antagonists (SCH23390 for D1 receptors and sulpiride for D2 receptors) were applied iontophoretically to neurons of the PM of monkeys that performed a delayed-reaching (DR) task with their arms. In the DR task, the monkey made a reaching movement to one of three target levers (left, upper, and right), which had been cued by a visuospatial stimulus before a delay period of 4 s. We focused on neurons (n = 56) that showed a sustained increase in activity during the delay period (delay-period activity; i.e., "set-related" activity), because such activity is considered to play a central role in preparing for forelimb movements. Iontophoretic application of SCH23390 (usually with a current of 50 nA) significantly decreased the activity of most of these neurons (n = 44/56, 79%), and delay-period activity was attenuated during its application. In contrast, application of sulpiride or SCH23388 (an inactive analogue of SCH23390), using the same current intensity, had no effect on most of the neurons tested with these drugs (n = 31/33 and n = 21/23, respectively), despite the fact that their activity was decreased by SCH23390. Furthermore, for neurons that were affected by SCH23390, the percent decrease in delay-period activity was significantly greater than the percent change in background activity. In more than one-half of the neurons (n = 26/44, 59%), background activity was either increased (n = 10) or not affected (n = 16) by SCH23390, even though it significantly attenuated delay-period activity. These findings suggest that the activation of D1-dopamine receptors plays a modulatory role in PM function in preparing for reaching movements.

Warm-sensitive afferent splanchnic C-fiber units in vitro.

Receptive fields of 41 slowly conducting sensory fibers were located using a thermal (warm) search stimulus in an in vitro splanchnic nerve-mesentery preparation. Warm-sensitive receptive fields were punctate and were densest in the region surrounding the prevertebral ganglia, an area with prominent deposits of brown adipose tissue, where the abdominal aorta branches into the major trunks supplying the abdominal viscera. Impulse activity was recorded while applying a warm stimulus to identified receptive fields (RFs). The warm stimulus consisted of a warming ramp (10-15 degrees C in 1-2 s to a 42-49 degrees C peak temperature) followed by a 10- to 30-s period during which the RF was maintained at this peak temperature (plateau phase). Eighty percent (33/41) of warm-sensitive units responded to warming with discharge comprising both a phasic and a tonic component (slowly adapting warm-sensitive, or SA-W, units). The remainder (8/41) responded with only phasic discharge (rapidly adapting warm-sensitive, or RA-W, units). Units' adaptation characteristics were consistent from trial to trial and when applying stimuli from different positions. Fifty percent of SA-W units (8/16) and 17% of RA-W units (1/6) were activated by transient exposure to 9-90 nM bradykinin (BK). Twenty-seven percent (9/33) of SA-W units and 12% (1/8) of RA-W units were activated by probing their RF with von Frey hairs with bending forces < 10 mN (approximately 1 g equivalent mass). An additional five SA-W units tested were activated by strong mechanical stimuli (compression with a metal probe or firm stretching). No BK-responsive warm-sensitive units were activated by von Frey probing < 10 mN, but two (both SA-W) responded to strong mechanical stimuli. In six SA-W units and one RA-W unit, the number of impulses evoked by warming approximately 5 min after exposure to BK was > 2 SD greater than the mean pre-BK response, indicating sensitization. This sensitization was transient, the response to warming returning to within one standard deviation of the pretrial mean or less over the course of the next 5-10 min. Changes in background activity, mechanical sensitivity, BK sensitivity, and BK-induced sensitization were noted in various splanchnic units over the course of prolonged observations, suggesting that these indices may not reliably distinguish unit type, but instead may indicate the functional state of the sense organ. Splanchnic neurons responsive to the intense warming used in the present in vitro experiments may participate in the cardiovascular responses observed in vivo in heat-stressed rats. The dense distribution of warm-receptive fields in the vicinity of the celiac-superior mesenteric ganglionic complex is consistent with the localization of splanchnic thermosensitive units previously noted in vivo in the rabbit.

Spinal dorsal horn neurons responding to noxious distension of the ureter in anesthetized rats.

1. Stimulation of the ureter in humans evokes only painful sensations. A large proportion of ureteric afferents show high activation thresholds to ureter pressure increases and encode stimuli within the noxious range. However, little is known about how these properties are reflected in the central processing of ureteric information. In this study, dorsal horn neurons recorded in the left side of the T12-L1 spinal cord of anesthetized rats have been tested for responses to innocuous and noxious pressure stimuli applied to the ipsilateral ureter. 2. Single-unit recordings were made from 76 neurons with somatic receptive fields on the left flank, of which 57 were fully characterized and tested by raising the ureter pressure to 80 mmHg for 30 s. Of these 57 neurons, 24 (42%) were influenced by the ureter stimulus, as follows: 18 were excited, 2 were inhibited, and 4 showed changes in background activity and/or in somatic receptive field area, without a time-locked change in firing rate. The remaining 33 cells (58%) showed no changes in firing rate, background activity, somatic receptive field area, or input properties as a result of ureter stimulation. 3. Neurons responding to the 80-mmHg stimulus were further tested with a range of ureter pressures (5-100 mmHg). No responses were evoked by stimuli of < 20 mmHg, and responses observed were proportional to stimulus intensity. Excitatory responses showed a long onset latency (median = 23 s) and long afterdischarges (median = 145 s). 4. All neurons with ureter input had nociceptive somatic inputs. When compared with neurons without ureter input, cells with ureter input were more likely to show background activity (80 vs. 27%) and more likely to have bilateral somatic receptive fields (30 vs. 6%). Neurons with ureter input had higher rates of background activity and larger somatic receptive fields. Ureter stimulation also produced changes in the somatic receptive field area of neurons excited or inhibited by the stimulus, indicating a high degree of plasticity in the ureteric nociceptive pathway. 5. We conclude that the characteristics of the responses of dorsal horn neurons with ureter input to noxious and innocuous ureter stimulation indicate that they receive ureteric input mainly from high-threshold afferents, and that their response properties correlate well with ureteric pain sensation in humans.

Withdrawal of antiepileptic drug treatment in childhood epilepsy: factors related to age.

The clinical and electroencephalographic changes with age were evaluated in 304 patients with childhood epilepsies, whose antiepileptic treatment had been discontinued after a seizure free period of more than three years. The withdrawal rate differed significantly between epileptic syndromes, being higher in idiopathic epilepsy and lower in symptomatic epilepsy. The age at withdrawal was characteristic for each epileptic syndrome, and generally showed two peaks: at preadolescence and early school age. Forty one (13.5%) of the 304 patients experienced relapses. The relapse rate differed between epileptic syndromes. Relapses occurred at a unique age in each epileptic syndrome, and were frequent in preadolescence and early adulthood. Electroencephalography that still showed paroxysmal discharges at withdrawal did not necessarily predict the occurrence of a relapse, but the changes in background activity with age, which may indicate maturation of the CNS, were significantly different between the patients with and those without relapses. The results suggest that age related to each epileptic syndrome should be considered when deciding on withdrawal of antiepileptic drugs.

Pathogenesis and Significance of Abnorma Nonepileptiform Rhythms in the EEG

In this article the present state of knowledge of physiological mechanisms underlying nonepileptiform EEG abnormalities is reviewed. Focal and widespread slow waves, background activity abnormalities, and bursts of rhythmic slow activity are discussed. Clinical and experimental data accumulated over the past four decades suggest that polymorphic slow activity is generated in cerebral cortex by layers of pyramidal cells and is probably due to partial deafferentation from subcortical areas. Unilateral background activity changes are probably due to thalamic dysfunction, and bilateral paroxysmal slow activity is due to abnormal thalamocortical circuits combined with cortical pathology. The fact that pathologic slow-wave phenomena are longer in duration than the average postsynaptic potential is also discussed.

The effects of electrical stimulation of A and C visceral afferent fibres on the excitability of viscerosomatic neurones in the thoracic spinal cord of the cat

Single unit electrical activity has been recorded from viscerosomatic neurones in the lower thoracic spinal cord of decerebrate spinalized cats. The responses of the cells to electrical stimulation of afferent fibres in the splanchnic (SPLN) nerve and the effects of repetitive stimulation of somatic and visceral afferent C-fibres have been studied. Four groups of viscerosomatic neurones could be distinguished according to the type of visceral afferent input of the cells: (1) A-only cells (32.9%), driven only by stimulation of Aδ afferent fibres in the SPLN nerve; (2) C-only cells (3%), driven only by stimulation of C afferent fibres in the SPLN nerve; (3) A+C cells (45.7%), driven by both Aδ and C afferent fibres in the SPLN nerve; and (4) A+C? cells (18.6%), driven by Aδ visceral afferents and showing signs of responsiveness to C-fibres though lacking a distinct response volley to visceral C-fibre activation. Two cells of the A+C group and located in lamina I of the dorsal horn responded to SPLN nerve stimulation in a manner consistent with the afferent fibre composition of the nerve, that is, showed evidence of strong monosynaptic links with SPLN afferent C-fibres and weaker responses to SPLN Aδ afferents. Excitability changes of viscerosomatic neurones (‘wind up’, ‘wind down’ and changes in background activity) were also observed in the majority of neurones following electrical stimulation of somatic and of visceral afferent C-fibres. It is concluded that the functional relay of visceral afferent fibres in the spinal cord does not merely follow a representation of the afferent fibre composition of visceral nerves. Evidence from this study suggests a strong and highly divergent action of visceral Aδ afferents in the spinal cord and a more diffuse effect of visceral C-fibres.

Interictal spiking increases after seizures but does not after decrease in medication

In patients with focal epilepsy, EEG spike rate fluctuates considerably over time. We had previously shown that seizure occurrence played an important role in these fluctuations. We undertook this study to confirm this finding with better control of critical variables such as state of alertness and spike quantification, and to assess the spatial extent of the changes. Background activity changes and antiepileptic drug levels were also examined in relation to spiking. Spike discharge rate increased in the hours and days following seizures in widespread brain regions including, but not restricted to, the seizure focus. Spike rate did not change systematically before seizures. Postictal changes in background activity did not parallel spike fluctuations. Decreased antiepileptic drug levels did not cause increased spike rate. These results indicate that, following seizures, there is activation of interictal spiking which is not paralleled by changes in background activity. It is most often widespread and not necessarily most prominent at the site of seizure onset.

Background does not Significantly Affect Power-Exponential Fitting of Gastric Emptying Curves

Using a procedure enabling the assessment of background radiation research was done to elucidate the course of changes in background activity during gastric emptying measurement. Attention was focused on the changes in the shape of power-exponential fitted gastric emptying curves after correction for background was performed. The observed pattern of background counts allowed to explain the shifts of the parameters characterizing power-exponential curves connected with background correction. It was concluded that background had a negligible effect on the power-exponential fitting of gastric emptying curves.

Physiological plasticity of single neurons in auditory cortex of the cat during acquisition of the pupillary conditioned response: I. Primary field (AI).

The effects of conditioning on the discharges of single neurons in primary auditory cortex (AI) were determined during acquisition of the pupillary conditioned response in chronically prepared cats. Acoustic stimuli (1-s white noise or tone) were presented with electrodermal stimulation unpaired during a sensitization control phase followed by pairing during a subsequent conditioning phase. Stimulus constancy at the periphery was ensured by the use of neuromuscular blockade. Discharge plasticity developed rapidly for both evoked and background activity, the former attaining criterion faster than the latter. The pupillary dilation conditioned response was acquired at the same rate as were changes in evoked activity (i.e., 10-15 trials) and faster than background activity (i.e., 20-25 trials). Increases in background activity were correlated with increasing level of tonic arousal, as indexed by pretrial size of the pupil.

Physiological plasticity of single neurons in auditory cortex of the cat during acquisition of the pupillary conditioned response: II. Secondary field (AII).

The discharges of 22 single neurons were recorded in the secondary auditory cortical field (AII) during acquisition of the pupillary dilation conditioned defensive response in chronically prepared cats. All 22 neurons developed discharge plasticity in background activity, and 21/22 cells developed plasticity in their responses to the acoustic conditioned stimulus (CS). Nonassociative factors were ruled out by the use of a sensitization phase (CS and US [unconditioned stimulus] unpaired) preceding the conditioning phase and by ensuring stimulus constancy at the periphery by neuromuscular paralysis. Changes in background neuronal activity were related to measures of behavioral learning or to changes in the level of arousal. Specifically, decreases in background activity (17/22 cells) developed at the time that subjects began to display conditioned responses. Increases in background activity (5/22) developed in animals that became more tonically aroused during conditioning. However, both increases (11/22) and decreases (10/22) in evoked activity developed independently of the rate of pupillary learning, tonic arousal level, or changes in background activity. These findings indicate that changes in background activity are closely related to behavioral processes of learning and arousal whereas stimulus-evoked discharge plasticity develops solely as a consequence of stimulus pairing. A comparative analysis of the effects of conditioning on secondary and primary (AI) auditory cortex indicates that both regions develop neuronal discharge plasticity early in the conditioning phase and that increases in background activity in primary auditory cortex are also associated with elevated levels of tonic arousal. In addition, the overall incidence of single neurons developing learning-related discharge plasticity is significantly greater in AII than in AI. The relevance of these findings is discussed in terms of parallel processing in sensory systems and multiple sensory cortical fields.

Jakob-Creutzfeldt Disease: Analysis of EEG and Evoked Potentials under Basal Conditions and Neuroactive Drugs

EEG and evoked potential (EP) recordings of a female (aged 70) affected with Jakob-Creutzfeldt disease (JCD) are reported. A comparison of neurophysiological tests under basal conditions and pharmacological stimulation with methylphenidate, diazepam and piracetam was performed. Diazepam and methylphenidate produced a flattening of triphasic complexes and changes in background activity; piracetam did not seem to influence the abnormal brain bioelectrical environment. The authors conclude that EEG and EP abnormalities in JCD can be ascribed to two separate and interacting sources: (1) exaggerated massive excitatory input coming from a deep thalamic pace-maker throughout the diffuse projecting system, and (2) lack of inhibitory intracortical mechanisms.

Behavioural and electrographic effects of L-5-hydroxytryptophan and D,L-parachlorophenyl-alanine on epileptic senegalese baboon ( Papio papio)

In the Senegalese baboon, Papio papio, the behavioural and electrographic effects of the serotonin precursor, L-5-hydroxytryptophan (5-HTP) and a serotonin depletor, D,L-para-chlorophenylalanine (pCPA) were examined with special attention to the pre-existing photosensitivity and epileptiform electrographic activity. 1. 1. L-5-HTP (10–35 mg/kg) depressed motor and EEG responses to photic stimulation for 1–4 h after injection. 2. 2. 48 h after D,L-pCPA (200–300 mg/kg), myoclonic responses to photic stimulation were enhanced. Consistent reduction of photosensitivity was observed 4–7 days after pCPA. 3. 3. Both drugs activated spontaneous epileptiform electrographic abnormalities. These changes in background activity were often chronologically independent of the changes in photically induced responses. 4. 4. It is suggested that serotonergic systems can play a role in the photomyoclonic syndrome in Papio papio.