O. D. Creutzfeldt

Thalamocortical transformation of responses to complex auditory stimuli

SummaryIn unanesthetized guinea pigs, thalamic (CGM), and cortical (auditory I) neurons were recorded simultaneously. Nine of 69 neuron pairs showed a positive cross-correlation of their spontaneous activities, with increased discharge probability of the cortical neuron beginning 2–5 ms after the discharge of the CGM-neuron. The individual neurons of such pairs had an identical CF and the same spectral responsiveness.The responses of cortical neurons to pure tones were much more phasic than those of the corresponding CGM-neurons. Thalamic neurons could be driven up to much higher AM- and FM-modulation frequencies (100 Hz) than cortical neurons, which usually ceased to follow AM-frequencies above 20 Hz. Stronger or weaker suppression of tonic response components in cortical and thalamic neurons and the lower AM-range of cortical neurons is related to stronger or weaker intracortical and intrathalamic inhibition respectively. Response characteristics to FM-stimuli are similar to those of AM-stimuli.All CGM and cortical neurons responded to a variety of natural calls of the same or of other species. Responses of CGM-cells represented more components of a call than cortical cells even if the two cells were synaptically connected. In cortical cells, repetitive elements of a call were not represented if the repetition rate was too high. High modulation frequencies within a call, such as those of the fundamental frequency, could still be separated in the response of some CGM-neurons, but never in those of cortical neurons. Both CGM and cortical cells responded essentially to transients (amplitude or frequency modulations) within a call, if spectral components of such elements were within the spectral sensitivity of the cell. Spectral components outside the spectral sensitivity range could result in suppression of spontaneous discharge rate. Responses of cortical and CGM-cells, and thus the representation of call elements by neuronal responses, varied with the intensity of a call. It is suggested that, at higher levels of the auditory system, essential information about the temporal features of complex sounds may be represented by neural responses to transients in various spectral regions.

Relations between EEG phenomena and potentials of single cortical cells. I. Evoked responses after thalamic and epicortical stimulation

1. 1. The evoked EEG responses from the motor cortex of cats under Nembutal after electrical stimulation of nucleus VPL or VL of the thalamus, of midthalamic nuclei and of the cortex itself are compared with the cellular responses from the same area. The cellular responses were almost identical in different cells of a given experiment so that records from one cell can be taken as representative for the whole population of pyramidal cells from which the records were taken. The following correlations were found: 2. 2. VL stimulation: The primary surface positivity is accompanied at its peak by the primary EPSP which may lead to a discharge. If a secondary EPSP is recognizable, this is simultaneous with the surface negativity. The IPSP (present only during single stimuli or at medium frequencies at strong suprathreshold stimulation) begins during the surface positivity, and reaches its peak during the late surface positivity following the primary surface negativity. This positivity may continue as long as the IPSP lasts but is frequently surmounted by a late negativity (peak latency 30–50 msec). This corresponds to a third EPSP in the cellular record. The third as well as the secondary EPSP is frequently masked by the IPSP, especially during strong single stimuli. At medium stimulus frequencies both the late EPSPs as well as the surface negative responses are increased, whereas the IPSP and the secondary surface positivity decrease. At 15–20/sec stimulation the surface negativity becomes broader and the IPSP disappears. 3. 3. CM stimulation: The surface negative recruiting wave is accompanied by a summated cellular EPSP of the same time course. Waxing and waning is equally present in both records. Occasionally a positive notch on top of the recruiting wave is found which is accompanied by cellular discharges. The frequently observed slight surface positivity preceding the recruiting wave falls together with the first EPSPs; EEG arousal at high frequency stimulation is accompanied by corresponding cellular changes. 4. 4. Epicortical stimulation: The primary surface negativity (“superficial response”) is associated with a cellular excitation (direct excitation with spike discharge or EPSP) whereas the following surface positivity (deep response) comes together with the IPSP. This is especially clear in chronically isolated cortical slabs. IPSP and surface positivity have similar time courses. 5. 5. The cortical after-discharge after afferent or epicortical stimulation shows close relations between surface negative waves and cellular excitation. Some waves recorded with the surface electrode are not clearly related to cellular activity, which suggests that they are picked up from adjacent parts of the cortex. Further evidence is presented that the cortical after-discharge is due to thalamo-cortical activity. 6. 6. In the Discussion it is suggested that cortical evoked potentials are composed of different intracortical excitatory patterns: quick transients near the soma (with initial phase reversal in the surface record), superficially located, mostly slow dendritic potentials (without phase reversal), and synchronized afferent and efferent fiber activity.

Neuronal activity in the human lateral temporal lobe. I. Responses to speech.

SummarySingle and multiple unit neuronal activity was recorded from the cortex of the lateral temporal lobe in conscious humans during open brain surgery for the treatment of epilepsy. Recordings were obtained from the right and left superior, middle and inferior temporal gyrus of 34 patients (41 recording sites). Recordings were restricted to regions to be resected during subsequent surgery. This excluded recordings from language areas proper. Neuronal responses to words and sentences presented over a loudspeaker and during free conversation were recorded. No significant differences between the right and left hemisphere were obvious. All neurons in the superior temporal gyrus responded to various aspects of spoken language with temporally well defined activation/inhibition patterns, but not or only little to non-linguistic noises or tones. Excitatory responses were typically short or prolonged (up to several hundred ms) bursts of discharges at rates above 20/sec, reaching peak rates of 50–100/s. Such responses could be specifically related to certain combinations of consonants suggesting a function in categorization, they could depend on word length, could differentiate between polysyllabic and compound words of the same length or could be unspecifically related to language as such. No formant specific responses were found, but the prolonged excitations across syllables suggest that consonant/vowel combinations may play a role for some activation patterns. Responses of some neurons (or neuronal populations) depended on the attention paid to the words and sentences, or the task connected with them (repeat words, speech addressed to the patient demanding something). Neurons in the middle and inferior temporal gyrus were only little affected by listening to single words or sentences, but some were unspecifically activated by words or while listening to sentences. Excitatory responses varied within a limited range of discharge rates usually below 5–10/s. Phonetic distortion of spoken language could reduce responses in superior temporal gyrus neurons, but also the slight changes in discharge rate of middle temporal neurons could be absent during distorted and uncomprehensible speech sounds. We conclude that superior temporal gyrus neuron responses reflect some general phonetic but not semantic aspects of spoken language. Middle and inferior temporal gyrus neurons do not signal phonetic aspects of language, but may be involved in understanding language under certain conditions.

Modification of orientation sensitivity of cat visual cortex neurons by removal of GABA-mediated inhibition.

SummaryThe effects of an inhibitor of GABA synthesis, 3-mercaptopropionic acid (MP), and of the GABA antagonist bicuculline (BIC), on the direction and orientation sensitivity of visual cortical neurons were investigated using a computer-controlled stimulus presentation system. Intravenous administration of MP, which was usually more effective than if administered microelectrophoretically, induced a slight, but significant reduction in these properties of about half of the neurons tested. The effect of electrophoretic BIC was in the same direction but clearer than that of MP. In 71% of the simple cells, direction sensitivity was virtually lost during administration of BIC while orientation sensitivity was never completely eliminated in any neuron tested. Simultaneous administration of both drugs (MP systemically, BIC electrophoretically) caused more complete modification of the sensitivities than single administration of each. In four out of thirteen neurons tested, orientation sensitivity was completely abolished. The excitatory receptive fields slightly increased in size and became virtually round. The response magnitude to the optimal stimulus was increased by each drug alone and by both. The present results further support the hypothesis that intracortical inhibition plays a major if not an exclusive role for the orientation and direction sensitivity of cortical cells.

Relations between EEG phenomena and potentials of single cortical cells. II. Spontaneous and convulsoid activity.

Abstract 1. 1. The relations between spontaneous EEG waves, convulsoid potentials (induced by i.v. Metrazol injection or epicortical stimulation) and intracellularly recorded activity were analyzed in the motor cortex of cats under Nembutal. 2. 2. During regular surface negative spindle waves a close positive correlation exists between cellular depolarization and surface negativity. The cellular depolarizations are composed of several EPSPs which can be easily distinguished in some cells. Sometimes they begin to summate during a slight surface positivity preceding the negative wave. The summated post-synaptic depolarization is preceded by a period of synaptic silence, indicating an extracellular, probably extracortical, trigger mechanism. IPSPs are seen only if much spike activity is present. 3. 3. Another type of spindle wave (sometimes seen in isolation) is characterized by a relatively short and weak surface negative wave followed by a longer positive potential. The cellular activity shows more or less pronounced depolarization and spike activity during or just preceding the negative wavelet and an IPSP during the surface positive potential. The IPSP may begin during the peak or falling phase of the surface negative potential. The presence of active inhibition in these cases has been proved by intracellular stimulation. 4. 4. If biphasic positive-negative spindle waves are present their relation to the cellular activity depends upon the potential gradient of the wave. If the positive-negative gradient is steep, cellular activity with a relatively high discharge rate is located on the positive phase; if the gradient is relatively small the slow summation of EPSPs reaches its peak during the negative wave (see Fig. 9). 5. 5. At the beginning of Metrazol-induced seizures slow surface negative waves occur simultaneously with cellular depolarization. During the peak of the seizure, when mainly large biphasic positive-negative potentials are seen in the EEG, massive cellular depolarization, leading quickly to high frequency grouped spike discharges, occurs with the first surface positive phase. Cellular repolarization coincides with the positive-negative transition of the surface potential. The biphasic EEG potential is frequently followed by a longer positive potential which corresponds to a cellular IPSP. At the end of the seizure isolated IPSPs are frequently seen. 6. 6. Strong high frequency epicortical stimulation leads to a long lasting depolarization of cortical cells (down to 20–30 mV) with inactivation of the spike generator. After the end of the stimulation the membrane potential shows regular oscillations, the spike generator recovers and the cell polarizes slowly. Finally, oscillating depolarizations are interrupted by long polarizations. Some cells do not show a long lasting depolarization after the stimulus but are subsequently synaptically depolarized during the depolarizing oscillations. The depolarizations occur simultaneously with large surface positive potentials of the cortical after-discharge. 7. 7. Possible mechanisms relating EEG waves to cellular potentials are discussed within the framework of transcortical and soma-apical dendrite potential distributions during different phases of physiological and pathological cortical activity.

An intracellular analysis of visual cortical neurones to moving stimuli: Responses in a co-operative neuronal network

Summary1.Responses of cortical cells from the foveal and perifoveal visual field representation in area 17 to moving contrasts were analyzed with intracellular records in anesthetized cats. These intracellularly recorded responses were normal in so far as the cells showed typical orientation/direction sensitivity and only short phasic or no responses to diffuse illumination.2.With slowly moving bright or dark bars, two types of responses were seen: those with a small excitatory peak and those with a wider excitatory peak. Inhibitory regions outside the excitatory peak were only seen in cells with a small excitatory area. Only very few cells showed inhibitory “flanks” preceding and following the excitation; often inhibition followed the excitation in both the forward and backward direction; sometimes it preceded it in both directions. The inhibition outside the excitatory zone practically always had “dynamic” properties, i.e. was smaller or larger in the two opposite directions of movements.3.All cells showed strong inhibition (IPSPs) mixed with excitation while the stimulus moved over the excitatory response field. The degree of inhibition was clearly sensitive to the direction of movement (forward or backward) of an optimally oriented moving stimulus, and could also be different at different orientation/ directions. However, the orientation dependence of intracortical inhibition was often less clear than the differences found between the two opposite directions of an optimally oriented stimulus. Inhibition was more marked during binocular than during monocular stimulation.4.The excitatory areas of cortical cells were mostly slightly elongated, but not systematically along the axis of optimal orientation. The diameters of the excitatory fields were similar along the optimal and the non-optimal orientation axes (mean 1.9±0.78 vs. 2.2±0.92°).5.It is proposed that the orientation/direction sensitivity of cortical cells is a function of intracortical inhibitory connections with direction/orientation sensitivity rather than only due to the spatial arrangement of excitatory and inhibitory on- or off-center fields. A hypothetical retino-cortical projection map is proposed and it is assumed that direction/orientation sensitive intracortical inhibition is essential for the functional properties of cortical neurones.

Physiologic and anatomic investigation of a visual cortical area situated in the ventral bank of the anterior ectosylvian sulcus of the cat

SummaryIn this paper a cortical area is described that covers approximately the posterior two-thirds of the ventral bank of the anterior ectosylvian sulcus of the cat and is called anterior ectosylvian visual area (AEV).In cats anesthetized with a combination of N2O and barbiturate we explored this area by recording extracellularly the responses of AEV neurons to visual and electric stimulation as well as by injecting HRP into physiologically verified points. AEV neurons were found to be highly sensitive to small light stimuli moving rapidly in a particular direction through their large receptive fields. The properties of 74 neurons were quantitatively analyzed. Increasing the length of the stimulus within the receptive field to more than 2 deg strongly inhibited the responses, whereas increasing the speed of the stimulus movement up to 72–120 deg/s enhanced the neuronal responsiveness. Although the majority of neurons responded to a wide range of possible directions, one clearly preferred direction could usually be found for each neuron. There was a predominance of preferred directions toward the contralateral hemifield. Anatomic and electrophysiologic connectivity studies showed that AEV receives its main afferent inputs from the lateral suprasylvian visual area (LS) and from the tecto-recipient zone of the nucleus lateralis posterior (LP)-pulvinar complex.Although these studies suggested some topographical organization within the projection from LS to AEV, the large receptive fields in AEV, the great majority of which included the central area, did not reveal a clear retinotopic order. It is concluded that AEV is a specific visual area and that functionally the extrageniculate inputs predominate.

Functional organization of the corticofugal system from visual cortex to lateral geniculate nucleus in the cat

Summary1.In the cat visual cortex (VC), electrophoretic glutamate application at a depth corresponding to layer VI may have excitatory or inhibitory effects on relay cells of the lateral geniculate nucleus (LGN). Corticofugal excitation was seen, if the receptive field centers (RFCs) of the VC neurons recorded at the application site were within 2.3 ° of the RFCs of the LGN neurons under test. Inhibitory effects were seen if the RFCs of both cells were further apart up to 3.1 °. Glutamate application at more superficial cortical sites had no effect on LGN-neuron activity.2.Cross-correlation analysis between spontaneous activities of simultaneously recorded VC and LGN neurons revealed excitatory cortico-geniculate connections in 18 pairs with RFCs separated by less than 1.7 °. In 15 pairs the peak latency of the excitation was 2–5 msec (3.4 msec in the average), 3 pairs showed long cortico-geniculate latencies (13–18 msec). The existence of a fast and slow cortico-geniculate system is suggested.3.Inhibitory cortico-geniculate interaction was demonstrated with cross-correlation analysis in 8 pairs of which 4 had RFCs separated by more than 1.7 °. The onset latency of the inhibition was 2–7 msec except for 2 pairs with about 20 msec latency.4.Most of the LGN neurons which were affected by cortical glutamate application or which showed an excitatory or inhibitory connection with a VC neuron were sustained cells, while the majority of VC neurons which were recorded in the effective glutamate application sites or which showed a significant interaction with LGN neurons in the cross-correlogram were binocularly driven and complex, with mostly large RFCs (mean diameter 3.5 °). They responded briskly to moving small spots as well as to moving slits.5.It is concluded that the corticofugal excitatory effect is transmitted through monosynaptic links from VC neurons located in layer VI (complex cell) to LGN relay neurons (mostly sustained-cell) and this system is organized in a precise topographical manner.6.In an Appendix neuron pairs which showed a positive correlation in the geniculo-cortical direction were described. The findings may support the view that complex as well as simple cells are driven monosynaptically from geniculo-cortical afferents of the sustained or transient type.

Generality of the functional structure of the neocortex.

The fundamental similarities between various neocortical areas are elaborated by pointing out the common principles of its afferent, intrinsic, and efferent organization, with special emphasis on the generality of thalamocortical circuits. Interareal differences in morphology and function can be considered as accidental, i.e., depending on the circuit in which a given cortical area is involved. The neocortex is a link in the chain of afferent-efferent signal processing, and can be understood as a cooperative network that acts as a non-linear spatiotemporal filter with adaptive properties (memory) and that transforms afferent signal flow. It is assumed that these filter properties are identical for all neocortical areas. The functional role of a circumscribed cortical area depends exclusively on its position within a certain functional circuit and is defined by it.

Crosscorrelation between the activity of septal units and hippocampal EEG during arousal

Summary EEG potentials of the septum and dorsal hippocampus, as well as the septal unit activity and hippocampus EEG, were simultaneously recorded in 44 unanaesthetized, curarized rabbits. (1) The cross- and autocorrelation of EEG potentials of the septum and dorsal hippocampus during arousal, both spontaneous and induced by sensory or reticular stimulation, was studied. The correlation curves obtained showed a phase difference that was constant in each rabbit but that varied in different rabbits by between 1 and 2 msec. The EEGs from the dorsal hippocampus always followed the EEGs from the septum. The largest delay (2 msec) was recorded between the ‘nucleus of the diagonal band’ and the dorsal hippocampus. (2) Three types of septal units (A, B, C) were differentiated on the basis of their firing rates and interspike intervals. (3) The firing characteristics of septal units in relation to the hippocampal EEG were studied, and the following conclusions were drawn. (a) For each C unit the spike activity always bears a constant phase relation to the corresponding hippocampal EEG, but the phase relationship varies from cell to cell. (b) There is no constant phase relation between B unit activity and the hippocampal EEG. (4) Changes in membrane potential of C units were observed as EPSPs which occur during a particular phase with hippocampal EEG. Spontaneous firing, as well as evoked, occurred in two distinct patterns: (a) solitary spikes, and (b) repetitive firing.