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Biomedical subjects

R C Frysinger

Publications and source records attributed to R C Frysinger.

At least 19 recordsLinked to original sources

Functional magnetic resonance imaging responses to expiratory loading in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by diminished upper airway muscle phasic and tonic activation during sleep, but enhanced activity during waking. We evaluated neural mechanisms underlying these patterns with functional magnetic resonance imaging procedures during baseline and expiratory loading conditions in nine medication-free OSA and 16 control subjects. Both groups developed similar expiratory loading pressures, but appropriate autonomic responses did not emerge in OSA cases. Reduced neural signals emerged in OSA cases within the frontal cortex, anterior cingulate, cerebellar dentate nucleus, dorsal pons, anterior insula and lentiform nuclei. Signal increases in OSA over control subjects developed in the dorsal midbrain, hippocampus, quadrangular cerebellar lobule, ventral midbrain and ventral pons. Fastigial nuclei and the amygdala showed substantially increased variability in OSA subjects. No group differences were found in the thalamus. OSA patients show aberrant responses in multiple brain areas and inappropriate cardiovascular responses to expiratory loading, perhaps as a consequence of previously-demonstrated limbic, cerebellar and motor area gray matter loss.

Adult↗

A device for feline head positioning and stabilization during magnetic resonance imaging.

Minimization of head movement and reproduction of standard head positions are essential for reliable brain functional magnetic resonance imaging. Devices for stabilization and alignment of feline preparations are not available currently. We describe a system that involves minimal surgery, allows for both acute and chronic atraumatic positioning, and has the potential to be used for unanesthetized animals. The device uses non-metallic materials and stabilizes the head by means of an apparatus that fixes the head with nylon screws and dental cement in the frontal sinuses. Application of the head-stabilizing device decreases head movements by more than a factor of ten. Anatomical images show that this device provides 3 dimensional head placement at a precision comparable to that of a stereotactic frame, i.e. within 1 mm.

Animals↗

Interspike intervals during interictal periods in human temporal lobe epilepsy.

We recorded 259 single neurons from mesial temporal lobe structures of 21 patients with complex partial seizures. Interspike intervals within clusters of action potentials (clustered interspike intervals) recorded from cells in mesial temporal structures ipsilateral to seizure initiation were compared to clustered interspike intervals in the contralateral temporal lobe. 'Clusters' were defined as any group of three or more spikes separated by intervals of less than a defined maximum, or two spikes separated by less than half that maximum. The maximum interspike interval which defined a cluster was varied from 5 to 40 ms in 5-ms steps. Significantly smaller proportions of clustered spikes were discharged by neurons in the amygdala, hippocampus and entorhinal cortex from the temporal lobe commonly initiating seizures, compared to neurons in contralateral homotopic regions. When data from the same three structures were combined, significantly fewer cluster interspike intervals between 10 and 25 ms were recorded from cells on the side of seizure onset. Because clustered action potential discharge is a normal pattern of firing for cells that discharge endogenous bursts, the relative decrease in proportions of 10-25 ms clustered interspike intervals occurring in the temporal lobe initiating seizures might reflect a reduction in endogenous burst discharges from that side. Reduced endogenous bursting could be due to the loss of burst discharging neurons as a product of seizure-related excitotoxicity. The identification of decreased interictal single neuronal burst discharge in epileptogenic structures stresses the difference between the interictal and ictal states in patients with complex partial seizures, and the importance of the transition between those states.

Action Potentials↗

Decreased neuronal burst discharge near site of seizure onset in epileptic human temporal lobes.

We examined auto-correlation and interval distribution characteristics of neuronal discharge from patients with complex partial seizures. The objective was to compare the interictal firing patterns of neurons in mesial temporal structures ipsilateral to the site of seizure onset with firing patterns of neurons in homologous contralateral structures. Spontaneous interictal recordings of 258 single neurons were acquired from 23 patients. A "burst area" measure was derived from the neuronal auto-correlation to assess the likelihood of grouped action potential discharge (burst discharge). Large burst area measures indicate a tendency for single neuronal burst discharge, but do not disclose information about interspike intervals within bursts. Although several measures based on single neuronal interspike interval distributions showed no overall difference between hemispheres, burst area was significantly reduced in mesial temporal structures ipsilateral to the site of seizure onset. Possible mechanisms of decreased burst discharge in epileptogenic regions include selective loss of burst-discharging neurons and increased recurrent inhibition.

Action Potentials↗

Neuronal synchrony in relation to burst discharge in epileptic human temporal lobes.

1. Synchronous interactions between neurons in mesial temporal structures of patients with complex partial seizures were studied using cross-correlation analyses. We recorded spontaneous activity from 293 neurons in 24 patients during the interictal state. Patients had depth microelectrodes chronically implanted in amygdala, hippocampal formation, and parahippocampal gyrus to record epileptic activity. One hundred twenty-five cells were recorded from the temporal lobe commonly initiating seizures (ipsilateral temporal lobe), and 168 cells from the contralateral temporal lobe. Eight hundred forty-three cross-correlograms were constructed between all pairs of simultaneously recorded neurons. Cross-correlogram peaks or troughs that exceeded confidence limits within 200 ms of the origin were considered evidence of synchronous neuronal interaction. 2. Synchronous neuronal interactions were observed in 223 of 843 cross-correlograms. Eighty-six percent of these 223 cross-correlograms showed significant central peaks (peak interactions), suggesting excitatory interactions, whereas the remainder displayed significant central troughs (trough interactions), suggesting inhibitory interactions. 3. Cross-correlograms constructed using cells from the ipsilateral temporal lobe (ipsilateral cross-correlograms) were more likely to display significant central troughs (14/262) than cross-correlograms constructed using cells from the contralateral temporal lobe (6/376; contralateral cross-correlograms). Similarly, cross-correlograms constructed using one cell from each hemisphere (11/205; bilateral cross-correlograms) were also more likely to display significant central troughs (trough interactions) than contralateral cross-correlograms. Both ipsilateral (77/262) and contralateral cross-correlograms (102/376) were more likely to display significant central peaks (peak interactions) than bilateral cross-correlograms (13/205). 4. Cells from different structures in the ipsilateral temporal lobe were more likely to display significant trough interactions (10/ 114) than neurons in different contralateral structures. We also compared the proportion of significant peak interactions between cells within the ipsilateral and contralateral sides of each structure. Neurons in the contralateral entorhinal cortex were more likely to show peak interactions (21/55) than cells from the ipsilateral entorhinal cortex (3/31). Also, cells in the ipsilateral presubiculum showed a higher proportion of peak interactions (9/16) than their contralateral homologues (5/30). 5. Neuronal burst discharges were defined as three or more action potentials (or spikes) separated by interspike intervals of < or = 30 ms, or two spikes separated by an interval of < or = 15 ms. The contribution of burst discharge to synchronous peak interaction was compared between temporal lobes. Cells used to construct ipsilateral cross-correlograms displaying significant central peaks (n = 154) were found to have significantly reduced burst discharge contributions to the observed synchronous peaks in comparison with their contralateral homologues (n = 204). When cross-correlograms were separated by regions, burst discharge contributions to synchronous peak interactions between cells in the ipsilateral hippocampus (n = 72) were significantly smaller than the contributions from cells in the contralateral hippocampus (n = 44). 6. The results suggest that in the interictal state, synchronous neuronal burst discharge is not a distinguishing feature of epileptogenic regions of patients with complex partial seizures, but inhibitory neuronal interactions are increased in regions of seizure initiation. Increases in the strength and spread of local inhibition in seizure initiating regions in these patients may result in a greater proportion of inhibitory interactions and could also cause increased synchrony between isolated action potentials.(ABSTRACT TRUNCATED)

Action Potentials↗

Interictal heart rate patterns in partial seizure disorders.

Epileptogenic mesial temporal damage may alter interictal autonomic patterning. Analysis of heart rate variability in 19 patients with complex partial seizures revealed cases of persistent, high-amplitude, 4 to 9 per minute fluctuations in heart rate during alert waking. This pattern was most pronounced in poor candidates for anterior temporal lobe resection (2/19). The 4 to 9 per minute heart-rate variability pattern may emerge following diffuse, extratemporal, or bilateral mesial temporal damage, which interferes with descending forebrain influences on cardiovascular regulation.

Adolescent↗

Recurring discharge patterns in multiple spike trains. II. Application in forebrain areas related to cardiac and respiratory control during different sleep-waking states.

Simultaneously recorded spike trains were obtained using microwire bundles from unrestrained, drug-free cats during different sleep-waking states in forebrain areas associated with cardiac and respiratory activity. Cardiac and respiratory activity was simultaneously recorded with the spike trains. We applied the recurring discharge patterns detection procedure described in a companion paper (Frostig et al. 1990) to the spike and cardiorespiratory trains. The pattern detection procedure was applied to detect only precise (in time and structure) recurring patterns. Recurring discharge patterns were detected in all simultaneously recorded groups. Recurring discharge patterns were composed of up to ten spikes per pattern and involved up to four simultaneously recorded spike trains. Fourty-two percent of the recurring patterns contained cardiac and/or respiratory events in addition to neuronal spikes. When patterns were compared over different sleep-waking states it was found the the same units produced different patterns in different states, that patterns were significantly more compact in time during quiet sleep, and that changes in the discharge rates accompanying changes in sleep-waking states were not correlated with changes in pattern rate.

Action Potentials↗

Cardiac and respiratory correlations with unit discharge in human amygdala and hippocampus.

Animal studies have shown that epileptiform seizures can cause cardiac arrhythmias and death. The amygdala and hippocampus are implicated in epileptogenesis and autonomic and respiratory control. We examined cardiac and respiratory correlations with single cell discharge in hippocampus and amygdala of patients with epilepsy. We recorded respiration, ECG, and neuronal discharge of amygdala and hippocampus from patients undergoing chronic depth electrode monitoring. Cross-correlation histograms were used to test for neuronal discharge timing relationships with inspiration or the ECG. Inspiratory time, respiratory period and heart rate were calculated for each breath, and linear regression was used to test for correlations with tonic unit rate. Of 183 cells from 24 patients, 20% had cardiac timing relationships and 23% showed tonic correlations with changes in heart rate. Only 2% had timing relationships with the respiratory cycle, while 15% showed tonic rate relationships with respiratory period. Recording sites did not differ in mean discharge rate or proportion of cells showing these correlations. These results indicate that a significant number of human forebrain cells show discharge modulation by the cardiac cycle and discharge rate correlation with changes in respiration and heart rate. This is supportive of animal models designed to explore the role of mesial temporal lobe structures in regulation of cardiovascular and respiratory systems, although a lower proportion of cells in human temporal lobe showed timing relationships with respiration and there was no clear evidence of anatomic specificity between amygdala and hippocampus.

Amygdala↗

Cardiovascular and respiratory relationships with neuronal discharge in the central nucleus of the amygdala during sleep-waking states.

We examined state-related relationships of neuronal discharge in the central nucleus of the amygdala (ACE) with cardiac and respiratory patterning. ACE cell discharges correlated with cardiac and respiratory timing, arterial pressure, and several respiratory parameters in undrugged, freely moving cats during waking, quiet sleep, and rapid eye movement sleep. Phasic discharge with the cardiac or respiratory cycle was examined using cross-correlation histograms. Of 80 cells in 8 cats, 24% showed a timing relationship with the cardiac or respiratory cycle, i.e., a tendency to discharge with each cardiac R-wave or with each breath, 12% with the cardiac cycle, and 14% with the respiratory cycle (2 cells showed both). All timing relationships were state dependent, usually observed in only one sleep-waking state per cell. Over half the cells showed a significant Pearson's r rate correlation with respiratory period or arterial pressure. Two-thirds of the cells showing arterial pressure correlations also correlated with respiratory period. A substantial proportion of ACE cells thus shows a state-dependent modulation of discharge rate and pattern by cardiovascular and respiratory variables. Rate and timing relationships were mutually exclusive within states, suggesting a state-dependent functional differentiation within the ACE.

Amygdala↗

State-dependent respiratory depression elicited by stimulation of the orbital frontal cortex.

The effect of electrical stimulation of the orbital frontal cortex on respiration was studied in unanesthetized, freely moving cats across sleep-waking states. Single trains of forty 300-microA, 0.5-ms, constant-current pulses at 60 Hz were delivered to the orbital frontal cortex at four points in the respiratory cycle. Stimuli delivered during expiration produced an immediate switch to inspiration. Stimuli delivered during inspiration reduced inspiratory EMG slope and peak EMG amplitude, and prolonged inspiration. Stimuli delivered during early inspiration produced greater effects than stimuli delivered during late inspiration. Stimulation effects were elicited during quiet waking and quiet sleep but not during rapid-eye-movement sleep. These results suggest that the orbital frontal cortex may contribute to respiratory phase switching, and that its influence on brain stem structures is attenuated during rapid-eye-movement sleep.

Animals↗

Respiratory modulation of neuronal discharge in the central nucleus of the amygdala during sleep and waking states.

The relationship between neuronal discharge in the central nucleus of the amygdala (ACE) and timing of the respiratory cycle was assessed during quiet and active sleep and during the waking state. Of 169 neurons recorded from the ACE in intact, drug-free cats, 22% discharged phasically with the respiratory cycle during at least one sleep or waking state. The dependency between neuronal discharge and the respiratory cycle was typically strong in only one state. Forty-three percent of the respiratory-related neurons were most strongly correlated with the respiratory cycle during the waking state (AW). An additional 30% were most strongly related to the respiratory cycle during quiet sleep (QS), whereas only 11% showed the strongest dependency during rapid eye movement (REM) sleep. Half of the ACE neurons (49%) discharged at frequencies less than 10 spikes per second, and the most common trend in firing rate across states was one in which neurons fired more rapidly during AW and REM than during QS. No relationship between discharge rate of ACE neurons in the three states and propensity for phasic discharge with the respiratory cycle could be demonstrated.

Amygdala↗

Cardiac and respiratory relationships with neural discharge in the anterior cingulate cortex during sleep-walking states.

The discharge properties of single neurons in the anterior cingulate cortex were correlated with timing aspects of the respiratory and cardiac cycle and with arterial pressure in undrugged, freely moving cats during waking, quiet sleep, and rapid eye movement sleep (REM). Two types of analyses were carried out. Discharge timing relationships with the cardiac or respiratory cycle were examined using cross-correlation histograms. Tonic rate correlations were calculated as a linear regression between breath-by-breath mean discharge rate of the cell and breath-by-breath values of respiratory parameters or arterial pressure. Eight of fifty-five cells recorded showed a discharge timing relationship with either the cardiac or the respiratory cycle. Seven of these were state-dependent (six in waking, one in REM). Thirty cells showed a tonic rate correlation with the respiratory period, and 23 cells had tonic correlations with maximum arterial pressure. All tonic correlations for a given cell were state-dependent, but such correlations were observed in all states. Correlation coefficients, while statistically significant, were generally low, and r2 values rarely exceeded 0.2. The relative paucity of discharge timing relationships, the state dependency, and the low r values of the tonic rate correlations suggest that the anterior cingulate cortex has a complex and indirect relationship to central cardiovascular and respiratory control mechanisms.

Animals↗

State-dependent alteration of respiratory cycle timing by stimulation of the central nucleus of the amygdala.

The effect of electrical stimulation of the amygdaloid central nucleus (ACE) on respiration was studied in unanesthetized, unrestrained cats during sleep-waking states. Single 0.5-ms 500-microA constant-current pulses delivered to the ACE at various points on the respiratory cycle, produced a transient inspiratory effort which summated with ongoing inspiratory activity and reduced inspiratory time. Stimulus pulses delivered during the expiratory phase resulted in an earlier shift to inspiration. Repetitive single pulse stimuli delivered to the ACE at a rate slightly faster than the spontaneous respiratory cycle during the alert state, were capable of 'entraining' respiration at the stimulus frequency. This entrainment disappeared in quiet sleep. Atropine, however, which produced synchronous high voltage slow waves and 12-14-Hz EEG spindle activity in the alert cat, did not impair this entrainment. Short (300-500 ms) 100-Hz trains of 0.5-ms pulses to the ACE produced rapid onset, sustained inspiration and a rise in blood pressure in the alert animal. During quiet sleep the response was attenuated but qualitatively similar, and also aroused the animal. Single pulse stimuli, however, were not associated with cardiovascular changes or generalized arousal. These results suggest that the ACE contributes to excitation of the inspiratory cycle, possibly through the large projection of this nucleus to the parabrachial pons.

Amygdala↗

Sleep states attenuate the pressor response to central amygdala stimulation.

We examined the cardiovascular response to electrical stimulation of the region of the central nucleus of the amygdala during sleep and waking states in the intact cat. Stimulation for 0.5 s produced a profound pressor response in the awake animal. This response was attenuated by quiet sleep and greatly attenuated during REM sleep. The attenuation was present even when the animal aroused from the sleep state in which the stimulus was delivered. The degree of sinus arrhythmia during the bradycardia associated with the hypertensive phase was greater during waking than during quiet sleep. We speculate that REM sleep entails a "functional dissociation" between forebrain and brain stem systems involved in cardiovascular regulation.

Amygdala↗

Cerebellar cortical activity during antagonist cocontraction and reciprocal inhibition of forearm muscles.

Monkeys were trained to perform a maintained isometric grip of the thumb and forefinger that elicited a simultaneous cocontraction of the antagonist muscles of the forearm. The same monkeys were also trained to flex and extend the wrist against a stop with the fingers extended and to maintain an isometric wrist position for 1.0-1.5 s. During wrist movement, some of the synergist forearm muscles contracted during both flexion and extension. However, during the maintained isometric wrist position, the prime mover and synergist muscles were reciprocally active or silent. In the culmen-simplex region of the cerebellar cortex bordering on the primary fissure, 62% of the Purkinje cells that were identified by the climbing fiber discharge and that changed firing frequency decreased activity during maintained prehension. Almost all of these same Purkinje cells were reciprocally active during isometric wrist flexion and extension, although three neurons had similar discharge patterns during movements in both directions. In contrast, 79% of the unidentified neurons recorded from the same region of the cerebellar cortex increased discharge frequency during prehension. In general, most of these same neurons had reciprocal patterns of discharge during wrist movement even though a few cells were active during the dynamic phase in both directions. Together, the Purkinje cells and the unidentified neurons with bidirectional response patterns were thought to be related to muscles active during both flexion and extension wrist movements. No cells were found that increased discharge with the static isometric wrist torque exerted in both directions. The discharge frequency of some Purkinje and some unidentified neurons could be shown to be related to prehensile force as well as wrist movement velocity and isometric wrist torque. These data suggest that the discharge of about two-thirds of the Purkinje cells related to forearm muscles located along the borders of the primary fissure may depend on whether antagonist muscles are activated reciprocally or coactively. As a consequence, these cells may play a role in the selection or alternation between either of these two modes of muscular contraction. The increased discharge of the remaining one-third of the Purkinje cells excited during antagonist coactivation may provide inhibition of nuclear cells to stabilize the posture at joints other than the wrist and fingers or, alternatively, they may act to reduce nuclear cell discharge in proportion to the intensity of cutaneous stimulation.

Animals↗