Activity of neurones in the inferotemporal cortex of the alert monkey.

The activity of neurones in the inferotemporal cortex of the alert rhesus monkey was recorded while the monkey was shown visual stimuli, which included both food and non-food objects for comparison with the activity of neurones in the lateral hypothalamus and substantia innominata. In the anteroventral part of the inferotemporal cortex, neurones were found with visual responses which were sustained while the animal looked at the appropriate visual stimuli. The latency of the responses was 100 msec or more. The majority (96/142 or 68%) of these neurones responded more strongly to some stimuli than to others. These units usually had different responses when objects were shown from different views, and physical factors such as shape, size, orientation, colour and texture appeared to account for the responses of some of these units. Association of visual stimuli with a food reward (glucose solution) or an aversive taste (5% saline solution) did not affect the magnitude of the responses of the neurones to the stimuli either during the learning or after the period of learning. Nor did feeding the monkey to satiety affect the responses of the neurones to their effective stimuli.     

Visual responses related to food discrimination in monkey lateral hypothalamus during operant feeding behavior

Single neuron activity was recorded from monkey lateral hypothalamic area (LHA) to relate neuronal events to food discrimination and initiation of procurement movement in operant bar press feeding behavior. Of 429 neurons tested, 68 (16%) responded during visual phase. Of these, 30 (7%) responded selectively to the sight of food or non-food associated with a juice reward, but not to the sight of meaningless non-food or food associated with aversive saline. Neuronal activity related to discrimination was readily influenced by extinction, reversal or satiation. The strength of visual responses was correlated with latency of bar press initiation and speed of bar pressing, but was not related directly to bar press movement. These suggest that the LHA is deeply involved in discrimination of reinforcement or non-reinforcement, and might be associated with higher functions to regulate internal states such as physiological need to get food during operant feeding behavior.     

Amygdaloid neuronal responses to complex visual stimuli in an operant feeding situation in the monkey

In chronically prepared monkeys, 337 neurons were recorded from the anterolateral amygdala during an operant task that required visual discrimination. Twelve percent (39/337) of the neurons responded to one or more of food or non-food visual stimuli. A subset of these responsive neurons was selectively sensitive to the sight of non-food objects with aversive associations. Simultaneous presentation of a food stimulus with the aversive object inhibited the response of these neurons. These response characteristics could not be explained by simple sensory processing of the visual stimuli. It is suggested that the amygdala plays an important role in the elaboration of motivational behavior by using the complex or associative properties of visual stimuli.     

The activity of neurones in the lateral hypothalamus and zona incerta of the sheep responding to the sight or approach of food is modified by learning and satiety and reflects food preference

Single unit recordings were made from neurones in the lateral hypothalamus and zona incerta of conscious sheep during the static visual presentation of food or visible approach of food towards the animal's mouth. The ability of this population of neurones to modulate their activity as a result of learning and satiety was investigated together with the extent to which their responsiveness reflected individual food preference. These neurones did not respond to either the sight or visible approach of a nonsense object or a food which they would not eat. Further, when the sight or approach of food which the animal desired to eat was not paired with ingestion the neurones rapidly extinguished their response. The magnitude of the neuronal response and the number of trials to extinction was dependent upon the animal's preference for a particular food: the most preferred food evoking the greatest response and being the most resistant to extinction. Following extinction the neuronal response to the sight or approach of food could be re-established after one or two trials with food reinforcement. If the sheep was repeatedly given the same food to eat the magnitude of the neuronal response and the number of trials to extinction gradually declined until no response occured when the animal refused to eat. These cells could also be induced to respond differentially to the approach of non-food objects dependent upon whether they were associated with a food reward or not. Thus a response could be evoked to the sight or approach of a black bottle if it was associated with a food reward but not to a yellow bottle unassociated with feeding. Acquired neuronal responses to novel foods could also be demonstrated.     

Limbic projections to the ventromedial hypothalamus of the opossum

Limbic projection systems which influence neuronal activity of the ventromedial nucleus of the hypothalamus of the opossum were studied by an evoked potential method. Bipolar concentric recording electrodes were placed in the ventromedial nucleus to monitor activity while exploring the forebrain with a stimulating electrode delivering single rectangular pulses (0.5 msec, 0.4 ma, 0.5–1/sec). Responses in the ventromedial nucleus were consistently evoked by stimulating three forebrain systems. From the dorsal septum, responses with one monophasic component were evoked (latency 3–9 msec). Stimulation more ventrally in the septum evoked, in addition, a second slower component. Stimulation of the corticomedial amygdala produced biphasic responses in the ventromedial nucleus at latencies of 4–9 msec; stimulation of the stria terminalis, the efferent pathway from this division of the amygdaloid complex, yielded almost identical responses at 4- to 6-msec latencies. Responses in the ventromedial nucleus were also recorded to stimulation of the dorsal hippocampus and adjacent fimbria (latencies, 3–7 msec). These responses demonstrate three possibly direct limbic influences on the ventromedial nucleus of a metatherian mammal, and provide new data on the anatomic relationships of this behaviorally significant hypothalamic area.     

Tuberoinfundibular neurons in the basomedial hypothalamus of the rat: electrophysiological evidence for axon collaterals to hypothalamic and extrahypothalamic areas.

In pentobarbital or urethane anesthetized rats, the activity of 889 mediobasal hypothalamic neurons was studied for evidence of a response to median eminence stimulation. Evidence of antidromic invasion, which indicated a projection to the median eminence, identified 134 cells (15%) as 'tuberoinfundibular' neurons. Antidromic spike latencies ranged from 0.5 to 14.0 msec (4.3 +/- 2.9 S.D.); conduction velocities were under 1.0 m/sec and were generally slower for tuberoinfundibular neurons located closest to the ventral surface of the hypothalamus. Certain tuberoinfundibular neurons followed paired median eminence shocks at frequencies up to 500 Hz; an increase in both the threshold and the latency for the second antidromic spike was observed with interstimulus intervals under 4 msec. Only 38% of tuberoinfundibular neurons were spontaneously active; 24 of 29 spontaneously active neurons displayed evidence of recurrent inhibition with durations up to 150 msec and at latencies which approximated that of the antidromic spike but which did not depend upon antidromic invasion. Similar responses were observed from 33 spontaneously active non-tuberoinfundibular neurons. Evidence of orthodromic excitation in response to median eminence shocks was observed from 22 other medial hypothalamic neurons. Latencies for excitation ranged from 1.5 to 9.0 msec (mean 4.5 +/- 2.1 S.D.). Simultaneous antidromic invasion from other hypothalamic and extrahypothalamic sites was observed from 8 tuberoinfundibular neurons. These sites included the anterior hypothalamic area (2 cells), the preoptic area (3 cells) and the thalamic nucleus medialis dorsalis (3 cells). These results indicate the presence of axon collaterals within the tuberoinfundibular system; some appear to terminate locally within the hypothalamus, while others extend rostrally and dorsally into extrahypothalamic areas. These connections may provide pathways for extrahypothalamic distribution of peptides which regulate adenohypophyseal secretion, and suggest that these peptides may subserve alternate regulatory roles within the central nervous system.     

Effects of microiontophoretically applied chemicals on hypothalamic neural activity

The effects of lateral hypothalamic (LH) stimulation on ipsilateral lateral preoptic area (LPA) neuronal activity were determined in anesthetized rats. The effects of LPA stimulation on LH neuronal activity were also determined. Recordings from 99 hypothalamic neurons indicate that reciprocal inhibitory relations exists between the LPA and LH. Following single rectangular pulse, 0.5 msec, 0–500 μA, stimulation short latency decreases in activity occurred. Longer latency increases in activity were also observed. Dose response relations were established for 90% of the LPA neurons following LH stimulation and for 80% of the LH neurons following LPA stimulation. Decreases and in a few cases increases in activity seemed to involve only one or two synapses. Antidromic responses revealed relatively slow conduction velocities of 0.4–0.9 m/sec. Results demonstrate a considerable degree of interconnectivity between the LPA and LH along the extent of the medial forebrain bundle. In addition to establishing the nature of these interconnections, the cross validation between the horseradish peroxidase neuroanatomical technique and electrophysiological methods was discussed as a means of determining hypothalamic organization and function.     

Response of rat superior salivatory units to chorda tympani stimulation

Unit responses to chorda tympani stimulation in urethane anesthetized rats were characterized by response latency and frequency following ability. One hundred and fifty one units responded with constant latencies, mean: 16.9 msec, S.D.: 7.8 msec. Responses recorded from within the superior salivatory nucleus (SSN) had significantly longer latencies (18.8 ± 6.8, n = 94) than those from surrounding areas (13.5 ± 8.3, n = 50) (p < 0.001). This difference was due to the higher incidence of responses with latencies between 2.7 and 10 msec outside of the SSN (44%) compared to SSN responses (8%). Ability to follow high frequency stimulation ranged from 2–550 Hz, and was the same for SSN neurons and those outside the nucleus. The population of responses localized to the SSN, with latencies greater than 10 msec and with high (> 100 Hz) frequency following, had a mean latency of 20.5 msec. The estimated conduction velocity for these presumed preganglionic, parasympathetic neurons is 0.85 M/sec ± 0.25, significantly slower than that reported for similar responses in cats. The antidromic nature of these responses requires confirmation.     

Pathways between the nucleus tractus solitarius and neurosecretory neurons of the supraoptic nucleus: Electrophysiological studies

In anesthetized cats recordings were made from hypothalamo-neurohypophysial neurons in a supraoptic nucleus (SON) of the hypothalamus. The region of the nucleus tractus solitarius in the medulla, identified electrophysiologically as the site of termination of the first relay neurons of the sinus and aortic nerves, was stimulated with single or short trains of pulses (2–3 at 200 Hz). Out of 133 SON neurons 67 were affected by such stimuli. In 14 cells (21% of ‘responsive’ neurons) the stimulus produced profound inhibition of SON neuron activity after a latency of 10–30 msec. In another 8 neurons (12%) the inhibitory effect was observed after a longer latency of over 100 msec. An increase in intensity of stimulus merely prolonged or increased the inhibitory effect without changing the response qualitatively. The other 45 (67%) SON neurons were excited by stimulation of the nucleus tractus solitarius. In a small proportion of these neurons (5 cells, 7%) the stimulus evoked discharges, even in spontaneously silent neurosecretory cells, after a latency of 10–20 msec with little fluctuation. In the remaining 40 neurons, i.e. 60% of the ‘responsive’ neurons, the excitatory effect was observed after a latency of 40–120 msec. Again, changes in intensity of stimulation did not alter the nature of this response. The results indicate that both ‘fast’ as well as ‘slow’ pathways between the nucleus tractus solitarius and SON neurons exist and impulses travelling through the latter pathway from the carotid sinus or aortic nerve affect the larger proportion of SON neurons.     

Auditory and visual event-related perturbations in the 40 Hz auditory steady-state response.

The effects of salient auditory and visual 'foreground' stimuli on responses to 'background' probe stimuli were investigated. The foreground stimuli were given at long and aperiodic intervals and required a discriminative judgment. Simultaneously, evoked potentials were obtained in response to background probe auditory stimuli presented in a continuous train at about 40/sec. The 40 Hz steady-state rhythm (SSR) evoked under such conditions was extracted using digital averaging and filtering techniques and examined continuously for evidence of change in latency or amplitude during the period surrounding the foreground stimulus. Within the first 200-300 msec after the onset of an acoustic foreground stimulus the latencies of individual peaks in the rhythm were momentarily reduced by a mean of 5.5 msec. A shift in the 40 Hz rhythm was also seen following visual foreground stimuli, although the shift was about one-third that following acoustic stimuli. A latency shift of comparable magnitude was not produced by deliberate manipulation of intensity or signal-to-noise ratio of the stimuli used to evoke the rhythm. The latency shift response is discussed in terms of a transient period of sensory facilitation during orienting or alerting associated with the foreground stimuli.     

Inhibition of spinal nociceptive responses after intramuscular injection of capsaicin involves activation of noradrenergic and opioid systems

Extracellular recordings of wide dynamic range neurones in the dorsal horn driven by electrical stimulation of the sciatic nerve were performed in intact urethane-anaesthetized Sprague–Dawley rats. The electrically evoked neuronal responses were defined as A- and C-fibres responses according to latencies, and the effect of a deep nociceptive conditioning stimulus induced by 200 μg capsaicin (8-methyl-N-vanillyl-6-noneamide) injected into the contralateral gastrocnemius–soleus muscle was studied for at least 30 min. Independent of the size and location of the receptive field of the neurone under study, a clear inhibition of the neuronal responses was observed. The electrically evoked C-fibre responses were inhibited to 53% of baseline 15–30 min after injection of capsaicin. This inhibition was only slightly attenuated by 125 nmol of the α-adrenoceptor antagonist phentolamine or 250 nmol of the opioid receptor antagonist naloxone applied directly onto the spinal cord when the two compounds were administered separately 5 min before capsaicin. In contrast, when a mixture of the two compounds was given 5 min before capsaicin, the effect of capsaicin was completely abolished. These results indicate that activation of the capsaicin-sensitive afferents in the gastrocnemius–soleus muscle inhibits the electrically evoked C-fibre responses in the dorsal horn by activating noradrenergic and opioidergic inhibitory systems. Moreover, our data indicate that the activation of these two systems following injection of capsaicin has a sub-additive inhibitory effect on the wide dynamic range neurones in the spinal cord. We conclude that only one of these systems is sufficient for the inhibition to occur.     

Subfornical organ-supraoptic nucleus connections: An electrophysiologic study in the rat

Extracellular recordings from antidromically-identified neurosecretory cells in the rat supraoptic nucleus (SON) indicate that electrical stimulation (1 Hz, 50 μs, 200 μA) in thesubfornical organ (SFO) alters the excitability of 89% (n= 31) of phasically-active (putative vasopressin-secreting) and 94% (n= 16) of continuously-active (putative oxytocin-secreting) neurons; 45% of cells display a long latency (mean 80.2 ± 20.5 ms, S.D.) prolonged (150–350 ms) increase in excitability; 26% of cells demonstrate a similar excitation, preceded by a brief decrease in firing at a latency of 30.5 ± 13.1 ms; 15% of cells display only a depression in their activity, lasting up to 150 ms. Ninety percent of non-neurosecretory (i.e. non-antidromic) neurons (n= 19) within or above the SON also display orthodromic excitatory or inhibitory responses to SFO stimulation; however, these cells usually respond with shorter latencies, and none demonstrate the prolonged excitation seen among neurosecretory cells. WithSON stimulation, antidromic activation observed from 6 of 18 SFO neurons (latency range of 12–27 ms) confirms a projection from SFO to the SON area. These data suggest a predominantly facilitatory influence of SFO neurons on the excitability of both vasopressinergicand oxytocinergic neurosecretory cells in the rat, thereby supporting a role for the SFO in body water balance.     

Responses evoked by stimulation of points in the diencephalon of unrestrained rabbits

Behavioural responses were obtained from unanaesthetized rabbits by stimulating the diencephalon through implanted electrodes (10–250 μA, 1 msec, 60 Hz). Mild arousal and related effects were evoked from widespread sites between stereotaxic planes P 1.5–P 4.5 and 0.1–3.5 mm from the midline. Stimulation readily evoked vigorous running responses, together with other responses suggestive of agitation with escape and concealment behaviour, at sites in the hypothalamus within 2 mm of the midline near or just caudal to the mammillothalamic tract. Signs of rage or aggression were infrequently seen. When the centre of this hypothalamic zone was stimulated after re-anaesthetizing the animals, bradycardia was obtained. The results are interpreted as suggesting that stimulation in this area, which is known to evoke cardiovascular responses different from the carnivore, also evokes a modified form of “Defence Reaction” appropriate to a species that is preyed upon.     

The effects of donepezil on the P300 auditory and visual cognitive evoked potentials of patients with Alzheimer's disease.

Donepezil is a cholinesterase inhibitor used for the treatment of patients with mild to moderately severe Alzheimer's disease (AD). The purpose of this study was to determine the effect of treatment with donepezil 5 mg qd on cognitive evoked potentials (EPs) of patients with AD. Although treatment with donepezil did not normalize EP latencies, treatment was associated with a significant decrease in the auditory P300 latency (mean latency pretreatment=401. 5 msec; posttreatment=392.7 msec.; P=0.04), and the visual P300 latency (mean latency pretreatment=605.7 msec; posttreatment=580.3 msec; P=0.04). Treatment with donepezil had no discernible effect on auditory or visual P300 EP amplitudes.     

Spinal cord conduction pathway for cerebellar evoked potentials from C-fibers

Evoked responses from saphenous nerve C fiber stimulation were identified on the ipsilateral intermediate cerebellar cortex. This late potential has a latency between 180 and 250 msec, duration 50–70 msec, and an amplitude 10–20 μV. The potential is conducted in the ipsilateral dorsal quadrant as determined by differential section of the spinal cord. The probable pathway is assigned to the dorsal spinocerebellar tract.     

An operant assay of thermal pain in conscious, unrestrained rats

Methods are described which provide quantification of learned operant and innate reflex responses to a thermal stimulus (heat or cold) and provide matched motor controls. The apparati and procedures consist of (1) an 'Escapetest' which measures latencies and durations of escape from a compartment where the floor is heated or cooled to a platform at neutral temperature in an adjacent compartment; (2) a motor and motivational control for the Escapetest, the 'Darkboxtest', which measures escape latency from bright light in a shuttle box; and (3) assessment of latencies and durations of licking or guarding responses to thermal stimulation in the absence of the escape option. Avoidance responses in the Escapetest (retreating to the escape platform in the absence of an experience of pain) are discouraged by bright illumination of the compartment containing the escape platform (brightly lit areas are aversive to rodents). Stimulus-response functions for escape from heat and cold are compared to stimulus response functions for innate lick/guard responses to the same temperatures. Substantial differences in the relationships between learned or innate responses and temperature attest to a need for methods which evaluate operant responses to nociceptive stimulation.     

Deprivation of pattern vision studied by visual evoked potentials in the rat cortex

In the present experiments we studied whether visual pattern deprivation affects the visual evoked potential (VEP) as has been assumed from modification of neuronal structures found in the rat cortex under this condition. The VEP of normal and of monocularly deprived rats is similar in waveform and composed of a small negative component at 40 msec, a large and fast positive wave (270 μV) with a latency of 67 msec and a negative afterpotential of 150 msec latency. The low ratio obtained in normal rats between the amplitudes of contralateral and ipsilateral VEPs (2.7:1) in comparison to the ratio of crossed and uncrossed fibers (15:1) indicates volume conduction interference with neural conduction. Mapping of the visual projection to the contralateral hemisphere in normal rats showed that area 17 was the visually most active region. Visual areas 18 and 18a were only secondary in their respnosiveness. Area 7, althought not considered to be a visual area, exhibited fair responses. The cortical region projected by the ipsilateral input overlapped the contralateral region. The mapping procedure was used to describe the responsiveness of monocularly deprived animals. Considering contralateral responses, area 17 of the normal hemisphere showed higher activity by 27% in comparison with the deprived hemisphere. Ipsilateral responses were similar in both cortices. The contralateral potentials recorded in control animals are higher in amplitude by 41% and their latencies are shorter than those recorded in the deprived animals contralaterally to the nondeprived eye. This may point to suppression of binocular interaction as a result of unilateral visual deprivation. It was concluded from the results in which animals were examined after deprivation of 70–170 days that specific neuronal changes occur due to visual deprivation and correlated with the suppression of the visual evoked potential. These changes differ from the gross processes characterized by neural degeneration since the visual system is still responsive.     

Neuronal responses related to reinforcement in the primate basal forebrain

In the present study neurones recorded in the substantia innominata, the diagonal band of Broca and a periventricular region of the basal forebrain responded differentially to stimuli signalling the availability of fruit juice or saline obtained by making lick responses in two different visual discrimination tasks. The activity of certain neurones reflected the rewarding nature of stimuli used to signal the availability of juice in the tasks, responding to the sight and delivery of both foods and syringes used to deliver juice in tests in which behavioural responses were irrelevant. The activity of other neurones reflected aversion, responding to task stimuli signalling availability of saline and to syringes used to deliver saline to the mouth. In another task an auditory cue that signalled the availability of juice elicited neuronal responses. These neurones also responded to a tone cue used to signal the onset of the trial, and during certain mouth and arm movements which the monkey used to obtain reinforcement. The responses of these differential neurones were similar in most respects in all 3 regions of the basal forebrain. Thus these neurones respond to a range of visual and auditory stimuli that monkeys have learned can be used to obtain reinforcement, but not on the basis of sensory properties such as shape or colour of the stimuli. We conclude that the reinforcement-related nature of the neuronal signal from the basal forebrain could be used to facilitate processing in cortical regions, optimising the functioning of sensory, motor and association cortices, thus increasing the probability of responding appropriately to learned environmental contingencies. We suggest that the properties of these neurones are due to afferent inputs from ventromedial regions of the prefrontal and temporal cortices and amygdala.     

Recording compound action potentials from the optic nerve in man and monkeys

Compound action potentials were recorded from the optic nerve in patients undergoing neurosurgical operations and in rhesus monkeys. The stimuli were short light flashes delivered by light-emitting diodes that were bonded to plastic contact lenses positioned on one or both eyes, and potentials were recorded simultaneously from electrodes placed on the scalp. Potentials recorded from the optic nerve in man have an initial small positive deflection, with a latency of about 45 msec, followed by a negativity with a latency of 60-70 msec. The wave form depends on the recording site on the optic nerve and, occasionally, oscillations with a frequency around 100 Hz were seen in the responses from the optic nerve. There was considerable individual variation in the shape and size of the recorded potentials, but most potentials recorded simultaneously from an electrode placed on Oz with a reference electrode on the forehead appeared as positive deflections with latencies of about 80 msec and, occasionally, with a small positivity with a latency of about 45 msec. Compound action potentials recorded from the optic nerve near the ocular globe in the rhesus monkey in response to similar light flashes appeared as negative deflections with latencies of about 17 msec. The potentials recorded at the chiasm appeared as initial positive deflections, with the latency of the earliest peak being about 35 msec, on which oscillations with frequencies of about 100-150 Hz occasionally could be seen. The recordings from electrodes placed on the scalp (Cz-Oz and Cz-shoulder) in the monkey showed a positive peak with a latency of about 65 msec.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early and late lower limb motor evoked potentials elicited by transcranial magnetic motor cortex stimulation.

Transcranial magnetic motor cortex stimulation can elicit a series of responses recorded with different latencies from relaxed muscles of the lower limbs. In 7 healthy subjects, ranging in age from 16 to 62 years, stimulation was delivered by a 9 cm coil centered over Cz with the subject in the supine position. Surface polyelectromyography was used to record motor evoked potentials (MEPs) from the quadriceps (QD), hamstrings (HS), tibialis anterior (TA) and triceps surae (TS) muscles bilaterally. Three characteristic responses were identified in each muscle group on the basis of amplitude and latency criteria, identified by latencies: the direct oligosynaptic response MEP30 appeared with a latency of 24.3 msec in the QD, 26.3 msec in the HS, 30.5 msec in the TA and 31.3 msec in the TS; MEP70 with latencies of 64 msec in the QD, 59 msec in the HS, 79 msec in the TA and 72 msec in the TS; MEP120 with latencies of 115 msec in the QD, 126 msec in the HS, 117 msec in the TA and 124 msec in the TS. These 3 responses have distinct latencies, amplitudes and durations. MEP70 appears to be the result of activation of long descending tracts which end on spinal interneuronal circuits. As MEP120 has different features, it may have a different mechanism.