The eligibility of advanced non-small-cell lung cancer patients for targeted therapy clinical trials.

BACKGROUND: The selection criteria for phase III trials are often stringent. We aimed to determine how many advanced non-small-cell lung cancer (NSCLC) patients would have been eligible for phase III targeted therapy trials and the proportion receiving anticancer treatment. PATIENTS AND METHODS: From March 2007 to May 2008, all advanced NSCLC patients presented at our lung cancer multidisciplinary team meeting were included to assess eligibility for the targeted therapy trials: ECOG-4599, AVAiL, FLEX, TALENT, INTACT-1, INTACT-2, ESCAPE, NEXUS and MONET1. Medical records were examined to determine treatment utilisation and overall survival. RESULTS: A total of 62 patients were registered: 63% male; median age 71 years; 61% stage IIIB disease. Percentages that met criteria were: ECOG-4599 31%, AVAiL 24%, FLEX 69%, TALENT 27%, INTACT-1 50%, INTACT-2 42%, ESCAPE 39%, NEXUS 63% and MONET1 34%. Common reasons for ineligibility were insufficient life expectancy, poor performance status, abnormal bloods, proteinuria and associated cancer problems. Systemic therapies were received by 66% of patients and median survival was 10.3 months. CONCLUSION: Only 24%-69% were eligible for targeted therapy trials but 66% received anticancer treatment. Clinical trials in patients with advanced NSCLC need to be more representative of the majority of patients.

Spontaneous and stimulus-evoked intrinsic optical signals in primary auditory cortex of the cat.

Spontaneous and tone-evoked changes in light reflectance were recorded from primary auditory cortex (A1) of anesthetized cats (barbiturate induction, ketamine maintenance). Spontaneous 0.1-Hz oscillations of reflectance of 540- and 690-nm light were recorded in quiet. Stimulation with tone pips evoked localized reflectance decreases at 540 nm in 3/10 cats. The distribution of patches "activated" by tones of different frequencies reflected the known tonotopic organization of auditory cortex. Stimulus-evoked reflectance changes at 690 nm were observed in 9/10 cats but lacked stimulus-dependent topography. In two experiments, stimulus-evoked optical signals at 540 nm were compared with multiunit responses to the same stimuli recorded at multiple sites. A significant correlation (P < 0.05) between magnitude of reflectance decrease and multiunit response strength was evident in only one of five stimulus conditions in each experiment. There was no significant correlation when data were pooled across all stimulus conditions in either experiment. In one experiment, the spatial distribution of activated patches, evident in records of spontaneous activity at 540 nm, was similar to that of patches activated by tonal stimuli. These results suggest that local cerebral blood volume changes reflect the gross tonotopic organization of A1 but are not restricted to the sites of spiking neurons.

Directionality derived from differential sensitivity to monaural and binaural cues in the cat's medial geniculate body.

Azimuth tuning of high-frequency neurons in the primary auditory cortex (AI) is known to depend on binaural disparity and monaural spectral (pinna) cues present in broadband noise bursts. Single-unit response patterns differ according to binaural interactions, strength of monaural excitatory input from each ear, and azimuth sensitivity to monaural stimulation. The latter characteristic has been used as a gauge of neural sensitivity to monaural spectral directional cues. Azimuth sensitivity may depend predominantly on binaural disparity cues, exclusively on monaural spectral cues, or on both. The primary goal of this study was to determine whether each cortical response pattern corresponds to a similar pattern in the medial geniculate body (MGB) or whether some patterns are unique to the cortex. Single-unit responses were recorded from the ventral nucleus (Vn) and lateral part of the posterior group of thalamic nuclei (Po), tonotopic subdivisions of the MGB. Responses to free-field presentation of noise bursts that varied in azimuth and sound pressure level were obtained using methods identical to those used previously in field AI. Many units were azimuth sensitive, i.e., they responded well at some azimuths, and poorly, if at all, at others. These were studied further by obtaining responses to monaural noise stimulation, approximated by reversible plugging of one ear. Monaural directional (MD) cells were sensitive to the azimuth of monaural noise stimulation, whereas binaural directional (BD) cells were either insensitive to its azimuth or monaurally unresponsive. Thus BD and MD cells show differential sensitivity to monaural spectral cues. Monaural azimuth sensitivity could not be used to interpret the spectral sensitivity of predominantly binaural cells that exhibited strong binaural facilitation because they were either unresponsive or poorly responsive to monaural stimulation. The available evidence suggests that some such cells are sensitive to spectral cues. The results do not indicate the presence of any response types in AI that are not present in the MGB. Vn and Po contain similar classes of MD and BD cells. Because Po neurons project to the anterior auditory field, neurons in this cortical area also are likely to exhibit differential sensitivity to binaural disparity and monaural spectral cues. Comparison of these MGB data with a published report of cochlear nucleus (CN) single-unit azimuth tuning shows that MGB sensitivity to spectral cues is considerably stronger than CN sensitivity.

Organization of somatosensory cortex in three species of marsupials, Dasyurus hallucatus, Dactylopsila trivirgata, and Monodelphis domestica: neural correlates of morphological specializations.

The organization of somatosensory neocortex was investigated in three species of marsupials, the northern quoll (Dasyurus hallucatus), the striped possum (Dactylopsila trivirgata), and the short-tailed opossum (Monodelphis domestica). In these species, multiunit microelectrode mapping techniques were used to determine the detailed organization of the primary somatosensory area (SI). In the striped possum and quoll, the topography of somatosensory regions rostral (R), and caudal (C) to SI were described as well. Lateral to SI, two fields were identified in the striped possum, the second somatosensory area (SII) and the parietal ventral area (PV); in the quoll, there appeared to be only one additional lateral field which we term SII/PV. Visual and auditory cortices adjacent to somatosensory cortex were also explored, but the details of organization of these regions were not ascertained. In these animals, electrophysiological recording results were related to cortical myeloarchitecture and/or cytochrome oxidase staining. In one additional species, the fat-tailed dunnart (Sminthopsis crassicaudata), an architectonic analysis alone was carried out, and compared with the cortical architecture and electrophysiological recording results in the other three species. We discuss our results on the internal organization of SI in relation to the morphological specializations that each animal possesses. In addition, we discuss the differences in the organization of SI, and how evolutionary processes and developmental and adult neocortical plasticity may contribute to the observed variations in SI.

Interhemispheric connections of somatosensory cortex in the flying fox.

The interhemispheric connections of somatosensory cortex in the gray-headed flying fox (Pteropus poliocephalus) were examined. Injections of anatomical tracers were placed into five electrophysiologically identified somatosensory areas: the primary somatosensory area (SI or area 3b), the anterior parietal areas 3a and 1/2, and the lateral somatosensory areas SII (the secondary somatosensory area) and PV (pairetal ventral area). In two animals, the hemisphere opposite to that containing the injection sites was explored electrophysiologically to allow the details of the topography of interconnections to be assessed. Examination of the areal distribution of labeled cell bodies and/or axon terminals in cortex sectioned tangential to the pial surface revealed several consistent findings. First, the density of connections varied as a function of the body part representation injected. For example, the area 3b representation of the trunk and structures of the face are more densely interconnected than the representation of distal body parts (e.g., digit 1, D1). Second, callosal connections appear to be both matched and mismatched to the body part representations injected in the opposite hemisphere. For example, an injection of retrograde tracer into the trunk representation of area 3b revealed connections from the trunk representation in the opposite hemisphere, as well as from shoulder and forelimb/wing representations. Third, the same body part is differentially connected in different fields via the corpus callosum. For example, the D1 representation in area 3b in one hemisphere had no connections with the area 3b D1 representation in the opposite hemisphere, whereas the D1 representation in area 1/2 had relatively dense reciprocal connections with area 1/2 in the opposite hemisphere. Finally, there are callosal projections to fields other than the homotopic, contralateral field. For example, the D1 representation in area 1/2 projects to contralateral area 1/2, and also to area 3b and SII.

Cortical synthesis of azimuth-sensitive single-unit responses with nonmonotonic level tuning: a thalamocortical comparison in the cat.

1. Azimuth and sound pressure level (SPL) tuning to noise stimulation was characterized in single-unit samples obtained from primary auditory cortex (AI) and in areas of the medial geniculate body (MGB) that project to AI. The primary aim of the study was to test the hypothesis that AI is an important site of synthesis of single-unit responses that exhibit both azimuth sensitivity (tendency for directionally restricted responsiveness) and nonmonotonic (NM) level tuning (tendency for decreased responsiveness with increasing SPL). This was accomplished by comparing the proportions of such responses in AI and MGB. 2. Samples consisted of high-best-frequency (BF) single units located in MGB (n = 217) and AI (n = 216) of barbiturate-anesthetized cats. The MGB sample was obtained mainly from recording sites located in two nuclei that project to AI, the ventral nucleus (VN, n = 118) and the lateral part of the posterior group of thalamic nuclei (Po, n = 84). In addition, a few MGB units were obtained from the medial division (n = 8) or uncertain locations (n = 7). Each unit's responses were studied using noise bursts presented from azimuthal sound directions distributed throughout 180 degrees of the frontal hemifield at 0 degrees elevation. SPL was varied over an 80-dB range in steps of < or = 20 dB at each location. Similarities and differences in azimuth and level tuning were evaluated statistically by comparing the AI sample with the entire MGB sample. If they were found to differ, the AI, VN, and Po samples were compared. 3. Azimuth function modulation was used as a measure of azimuth sensitivity, and its mean was greater in AI than in MGB. NM strength was defined as the percentage reduction in level function value at 75 dB SPL and its mean was greater in AI (showing a greater tendency for decreased responsiveness) than in MGB. Azimuth-sensitive (AS) NM units were identified by jointly categorizing each sample according to both azimuth sensitivity (sensitive and insensitive categories) and NM strength (NM and monotonic categories). AS NM units were much more common in the AI sample than in any of the MGB samples, suggesting that some such responses are synthesized in AI. 4. A vast majority of AI NM units have been reported to be AS, showing a preferential association (linkage) between these two response properties. This finding was confirmed in AI, but was not found to be the case in MGB. This suggests that a linkage between these response properties emerges in the cortex, presumably as a result of synthesis of NM AS responses. Although the functional significance of the linkage is unknown, NM responses may reflect excitatory/inhibitory antagonism that provides AS AI neurons with sensitivity to stimulus features beyond that which is present in MGB. 5. Breadth of azimuth tuning of AS cells was measured as the portion of the frontal hemifield over which azimuth function values were > 75% of maximum (preferred azimuth range, PAR). PARs were broadly distributed in each structure, and mean PAR was narrower in AI than in MGB. A preferred level range (PLR) was defined for NM level functions as the range over which values were > 75% of maximum, and mean PLRs were similar in each sample. There was a weak, but significant, positive correlation between PARs and PLRs in AI but not in MGB. This further suggests a linkage between azimuth and level tuning in AI that does not exist in MGB. 6. Best azimuth (midpoint of the PAR) was used to classify cells as contralateral preferring, ipsilateral preferring, midline preferring, or multipeaked. Samples from AI and MGB exhibited similar distributions of these categories. Contralateral-preferring cells represented a majority of each sample, whereass midline-preferring, ipsilateral-preferring, and multipeaked cells each represented smaller proportions. This suggests that the azimuth preference distribution in AI largely reflects that in MGB. 7. A best SPL was defined as the midpoint of the PLR. This wa

Interhemispheric modulation of somatosensory receptive fields: evidence for plasticity in primary somatosensory cortex.

Extracellular recordings were made from single and multiple neurons in primary somatosensory cortex (area 3b) of macaque monkeys and flying foxes. When a small region of area 3b (or adjacent area 1) in the opposite hemisphere was cooled, thereby blocking activity that is normally transferred via the corpus callosum, larger receptive fields (RFs) were immediately unmasked for most neurons. RF expansion presumably reflects the expression of afferent inputs that are normally inhibited, suggesting that callosal inputs provide a source of tonic inhibition that contributes to the shaping of neuronal RFs. Quantitative analyses of single neuron responses revealed other effects that were consistent with a release from inhibition, such as increases in response magnitude to stimulation of points within the original RF and decreases in response latency. An unexpected finding was the reversal of these unmasking effects with extended periods of cooling: RFs returned to their original dimensions and within-field response magnitude decreased. In contrast to the initial effects, this reversal of disinhibition cannot be readily explained by an unmasking of previously unexpressed inputs. Any explanation for the reversal requires an increase in the efficacy of interneuron-mediated inhibition, and presumably occurs in response to ongoing, altered patterns of activity.

Comparison of noise and tone azimuth tuning of neurons in cat primary auditory cortex and medical geniculate body.

1. A comparison of the azimuth tuning of single neurons to broadband noise and to best frequency (BF) tone bursts was made in primary auditory cortex (AI: n = 173) and the medial geniculate body (MGB: n = 52) of barbiturate-anesthetized cats. Observations were largely restricted to cells located within the tonotopically organized divisions of the MGB (i.e., the ventral nucleus and the lateral division of the posterior nuclear group) and the middle layers of AI. All cells studied had BFs > or = 4 kHz. 2. The responses of each cell to sounds presented from seven frontal azimuthal locations (-90 to +90 degrees in 30 degrees steps; 0 degree elevation) and at five sound pressure levels (SPLs: 0-80 dB or 5-85 dB in 20-dB steps) provided an azimuth-level data set. Responses were averaged over SPL to obtain an azimuth function, and a number of features of this function were used to describe azimuth tuning to noise and to tone stimulation. Azimuth function modulation was used to assess azimuth sensitivity, and cells were categorized as sensitive or insensitive depending on whether modulation was > or = 75% or < 75% of maximum, respectively. The majority (88%) of cells in the sample were azimuth sensitive to noise stimulation, and statistical analyses were restricted to these cells, which are presumably best suited to encode sound source azimuth. Azimuth selectivity was assessed by a preferred azimuth range (PAR) over which azimuth function values exceeded 75% (PAR75) or 50% of maximum response. Cells were categorized according to the location and extent of their noise PARs. Unbounded cells had laterally located PARs that extended to the lateral pole (+/- 90 degrees); bounded cells had PARs that were contained entirely within the frontal hemifield, and a subset of these had PARs centered on the midline (+/- 15 degrees). A final group of cells exhibited multipeaked azimuth functions to noise stimulation. 3. Azimuth functions to noise were generally more selective and/or more sensitive than those to tones. Statistical analyses showed that these differences were significant for cells in each azimuth function category, and for the thalamic and cortical samples. With the exception of multipeaked cells, responsiveness to noise was significantly lower than that to tones in all categories, and for the thalamic and cortical samples.(ABSTRACT TRUNCATED AT 400 WORDS)

A redefinition of somatosensory areas in the lateral sulcus of macaque monkeys.

The present investigation was designed to determine the organization of somatosensory fields in the lateral sulcus of macaque monkeys using standard microelectrode recording techniques. Our results provide evidence for two complete representations of the body surface. We term these fields the second somatosensory area (SII) and the parietal ventral area (PV) because of their similarities in position, internal organization, and relationship to anterior parietal fields, as described for SII and PV in other mammals. Areas SII and PV are mirror-symmetrical representations of the body surface, sharing a common boundary at the representations of the digits of the hand and foot, lips, and mouth. These fields are located adjacent to the face representations of anterior parietal fields (areas 3b, 1, and 2), and are bounded ventrally and caudally by other regions of cortex in which neurons are responsive to somatic or multimodal stimulation. The finding of a double representation of the body surface in the region of cortex traditionally designated as SII may explain conflicting descriptions of SII organization in macaque monkeys. In addition, the present study raises some questions regarding the designation of serial processing pathways in Old World monkeys, by suggesting that fields may have been confused in studies demonstrating such pathways. We propose that SII and PV are components of a common plan of organization, and are present in many eutherian mammals.

Functional organization of sound direction and sound pressure level in primary auditory cortex of the cat.

1. The functional organization of neuronal tuning to the azimuthal location and sound pressure level (SPL) of noise bursts was studied in high-frequency primary auditory cortex (AI) of barbiturate-anesthetized cats. Three data collection strategies were used to map neural responses: 1) electrode penetrations oriented normal to the cortical surface provided information on the radial organization of neurons' responses; 2) neurons' responses were examined at a few points in the middle cortical layers in multiple normal penetrations across AI to produce fine-grain maps of azimuth and level selectivity; and 3) electrode penetrations oriented tangential to the cortical surface provided information on neurons' responses along the isofrequency dimension. 2. An azimuth-level data set was obtained for each single- or multiple- (multi-) unit recording; this consisted of responses to noise bursts at five SPLs (0-80 dB in 20-dB steps) from seven azimuthal locations in the frontal hemifield (-90 to +90 degrees in 30 degrees steps; 0 degree elevation). An azimuth function was derived from these data by averaging response magnitude over all SPLs at each azimuth tested. A preferred azimuth range (PAR; range of azimuths over which the response was > or = 75% of maximum) was calculated from the azimuth function and provided a level-independent measure of azimuth selectivity. Each PAR was assigned to one of four azimuth preference categories (contralateral-, midline-, ipsilateral-preferring, or broad/multipeaked) according to its location and extent. A level function obtained from the data set (responsiveness averaged over all azimuths) was classified as monotonic if it showed a decrease of < or = 25% (relative to maximum) at the highest SPL tested (usually 80 dB), and nonmonotonic if it showed a decrease of > 25%. The percentage reduction in responsiveness, relative to maximum, at the highest level tested (termed nonmonotonic strength) and the preferred level range (PLR; range of SPLs over which responsiveness was > or = 75% of maximum) of each response was also determined. 3. Normal penetrations typically showed a predominance of one azimuth preference category and/or level function type. The majority of penetrations (26/36: 72.2%) showed statistically significant azimuth preference homogeneity, and approximately one-half (17/36: 47.2%) showed significant level function type homogeneity. Over one-third (13/36) showed significant homogeneity for both azimuth preference and level function type. 4. Mapping experiments (n = 4) sampled the azimuth and level response functions at two or more depths in closely spaced normal penetrations that covered several square millimeters of AI.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of ear plugging on single-unit azimuth sensitivity in cat primary auditory cortex. II. Azimuth tuning dependent upon binaural stimulation.

1. Single-unit recordings were carried out in primary auditory cortex (AI) of barbiturate-anesthetized cats. Observations were based on a sample of 131 high-best-frequency (> 5 kHz), azimuth-sensitive neurons. These were identified by their responses to a set of noise bursts, presented in the free field, that varied in azimuth and sound-pressure level (SPL). Each azimuth-sensitive neuron responded well to some levels at certain azimuths, but did not respond well to any level at other azimuths. 2. Unilateral ear plugging was used to infer each neuron's response to monaural stimulation. Ear plugs, produced by injecting a plastic ear mold compound into the external ear, attenuated sound reaching the tympanic membrane by 25-70 dB. The azimuth tuning of a large proportion of the sample (62/131), referred to as binaural directional (BD), was completely dependent upon binaural stimulation because with one ear plugged, these cells were insensitive to azimuth (either responded well at all azimuths or failed to respond at any azimuth) or in a few cases exhibited striking changes in location of azimuth function peaks. This report describes patterns of monaural responses and binaural interactions exhibited by BD neurons and relates them to each cell's azimuth and level tuning. The response of BD cells to ear plugging is consistent with the hypothesis that they derive azimuth tuning from interaural level differences present in noise bursts. Another component of the sample consisted of monaural directional (27/131) cells that derived azimuth tuning in part or entirely from monaural spectral cues. Cells in the remaining portion of the sample (42/131) responded too unreliably to permit specific conclusions. 3. Binaural interactions were inferred by statistical comparison of a cell's responses to monaural (unilateral plug) and binaural (no plug) stimulation. A larger binaural response than either monaural response was taken as evidence for binaural facilitation. A smaller binaural than monaural response was taken as evidence for binaural inhibition. Binaural facilitation was exhibited by 65% (40/62) of the BD sample (facilitatory cells). Many of these exhibited mixed interactions, i.e., binaural facilitation occurred in response to some azimuth-level combinations, and binaural inhibition to others. Binaural inhibition in the absence of binaural facilitation occurred in 35% (22/62) of the BD sample, a majority of which were EI cells, so called because they received excitatory (E) input from one ear (excitatory ear) and inhibitory (I) input from the other (inhibitory ear). One cell that exhibited binaural inhibition received excitatory input from each ear.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of ear plugging on single-unit azimuth sensitivity in cat primary auditory cortex. I. Evidence for monaural directional cues.

1. Single-unit recordings were carried out in primary auditory cortex (AI) of barbiturate-anesthetized cats. Neurons, sensitive to sound direction in the horizontal plane (azimuth), were identified by their responses to noise bursts, presented in the free field, that varied in azimuth and sound pressure level (SPL). SPLs typically varied between 0 and 80 dB and were presented at each azimuth that was tested. Each azimuth-sensitive neuron responded well to some SPLs at certain azimuths and did not respond well to any SPL at other azimuths. This report describes AI neurons that were sensitive to the azimuth of monaurally presented noise bursts. 2. Unilateral ear plugging was used to test each azimuth-sensitive neuron's response to monaural stimulation. Ear plugs, produced by injecting a plastic ear mold compound into the concha and ear canal, attenuated sound reaching the tympanic membrane by 25-70 dB. Binaural interactions were inferred by comparing responses obtained under binaural (no plug) and monaural (ear plug) conditions. 3. Of the total sample of 131 azimuth-sensitive cells whose responses to ear plugging were studied, 27 were sensitive to the azimuth of monaurally presented noise bursts. We refer to these as monaural directional (MD) cells, and this report describes their properties. The remainder of the sample consisted of cells that either required binaural stimulation for azimuth sensitivity (63/131), because they were insensitive to azimuth under unilateral ear plug conditions or responded too unreliably to permit detailed conclusions regarding the effect of ear plugging (41/131). 4. Most (25/27) MD cells received either monaural input (MD-E0) or binaural excitatory/inhibitory input (MD-EI), as inferred from ear plugging. Two MD cells showed other characteristics. The contralateral ear was excitatory for 25/27 MD cells. 5. MD-E0 cells (22%, 6/27) were monaural. They were unaffected by unilateral ear plugging, showing that they received excitatory input from one ear, and that stimulation of the other ear was without apparent effect. On the other hand, some monaural cells in AI were insensitive to the azimuth of noise bursts, showing that sensitivity to monaural directional cues is not a property of all monaural cells in AI. 6. MD-EI cells (70%, 19/27) exhibited an increase in responsiveness on the side of the plugged ear, showing that they received excitatory drive from one ear and inhibitory drive from the other. MD-EI cells remained azimuth sensitive with the inhibitory ear plugged, showing that they were sensitive to monaural directional cues at the excitatory ear.(ABSTRACT TRUNCATED AT 400 WORDS)

The anterior ectosylvian sulcal auditory field in the cat: I. An electrophysiological study of its relationship to surrounding auditory cortical fields.

The extent of a region containing acoustically responsive neurons within the anterior ectosylvian sulcus and its relationship to surrounding gyral auditory cortical fields was examined in chloralose-anaesthetized cats. Multiple microelectrode penetrations were made orthogonal to the middle and anterior ectosylvian gyral surfaces, and longer penetrations were made into the dorsal and ventral banks and fundus of the anterior ectosylvian sulcus. The quantitative and qualitative auditory response characteristics of neurons and neuron clusters in the sulcal banks and surrounding regions were mapped in detail, and the degree of overlap of auditory and visual neurons within the sulcus was determined by routinely testing for responsiveness to a gross light flash. The detailed results from three animals and a summary of all penetrations into the sulcus are presented. The anterior ectosylvian sulcal field (Field AES) lay deep within the banks and fundus of the posterior three quarters of the sulcus. A combination of changes in the auditory response characteristics of neurons (i.e., in optimal stimulus, latency, and frequency tuning), and the presence of visually responsive cells, distinguished this field from surrounding fields. The distinction between the anterior ectosylvian field and extensions of the nearby tonotopic fields (i.e., primary and anterior auditory fields) into the dorsal and ventral banks of the dorsoposterior sector of the sulcus was readily made on the basis of these characteristics. The distinction between the anterior ectosylvian field and extensions of the second auditory field into the ventral bank of the middle sector of the sulcus was more difficult and there were differences between animals in the transition between these fields. Anterior ectosylvian sulcal field responses did not extend into the dorsal bank in anterior parts of the sulcus but were restricted to fundal regions, an observation consistent with the presence of the fourth somatosensory field in the dorsal bank of this sector of the sulcus. The majority of penetrations into the sulcus revealed coextensive auditory and visual activity, an observation apparently at variance with the identification of a purely visual field in this region. Barbiturate anaesthesia, which has been used in experiments demonstrating an anterior ectosylvian visual area, was found to have a depressing effect on auditory responses within the anterior ectosylvian sulcal field.

The anterior ectosylvian sulcal auditory field in the cat: II. A horseradish peroxidase study of its thalamic and cortical connections.

The thalamic and cortical projections to acoustically responsive regions of the anterior ectosylvian sulcus were determined by identifying retrogradely labelled cells after physiologically guided iontophoretic injections of horseradish peroxidase. The medial division of the medial geniculate nucleus, the intermediate division of the posterior nuclear group, the principal division of the ventromedial nucleus, and the lateroposterior complex were consistently labelled after these injections, although each animal showed slightly different patterns of labelling. The suprageniculate nucleus and the lateral and medial divisions of the posterior nuclear group were also labelled in most experiments. The cortex of the suprasylvian sulcus was the most consistently and densely labelled cortical region; each experiment showed a slightly different pattern of labelling throughout the suprasylvian sulcus, with an overall tendency for greater labelling in the ventral (lateral) bank of the middle region of the sulcus. Other cortical regions labelled less consistently included the anterior ectosylvian sulcus itself, the insular cortex of the anterior sylvian gyrus, and the posterior rhinal sulcus. In three experiments the contralateral cortex was examined and a small number of labelled cells was located in the anterior ectosylvian and suprasylvian sulci. Input from extralemniscal auditory thalamus is compatible with previously described auditory response properties of anterior ectosylvian sulcus neurons. The results also confirm the presence of input from visual and multimodal regions of thalamus and cortex, and therefore support claims of overlap of modalities within the sulcus. This overlap, as well as input from motor regions, suggests that the anterior ectosylvian sulcal field serves a sensorimotor role.

Auditory response properties of neurons in the anterior ectosylvian sulcus of the cat.

The auditory response properties of single neurons in the fundus and banks of the anterior ectosylvian sulcus (AES) were studied with simple dichotic stimuli (viz. noise- and tone-bursts) in cats anaesthetized with alpha-chloralose. Neurons within AES showed simple onset responses, were most commonly excited by stimulation of both ears, and showed either broad tuning or multiple high best frequencies. Some neurons were also tested for visual responsiveness and it was found that auditory cells and visual cells were intermingled within the sulcus. A small percentage of cells responded to both auditory and visual stimulation. Overall, the response properties of AES neurons differed from those of nearby auditory cortical fields. The region of AES studied appears to be outside the recently defined fourth somatosensory area (SIV), but overlaps para-SIV found deeper in the sulcus. It appears that deep within the sulcus and along most of its length there is a population of auditory, somatosensory and visual cells; to delineate this auditory population from the surrounding auditory cortical fields this region has been designated Field AES.

Frequency representation in auditory cortex of the common marmoset (Callithrix jacchus jacchus).

The location and characteristics of the primary auditory cortex of the common marmoset, Callithrix jacchus jacchus, were determined in five anesthetized male adult animals by mapping the responses of cortical units and unit clusters to pure tone stimuli presented to the contralateral ear. The primary auditory cortex lies largely ventral to the lateral sulcus, the only major fissure on the lateral cortex of this smooth-brained primate, but in some animals it may extend significantly down the ventral bank of this sulcus. Responses are distributed such that low best frequencies are found rostroventrally whereas high best frequencies occur caudally. The disposition of frequency-band contours is fan-shaped, with contours separating low-frequency octaves nearly parallel to the lateral sulcus and high-frequency (greater than 8 kHz) contours perpendicular to that sulcus. Best frequencies range from 0.6 to 30 kHz across the primary field, but there is a disproportionate representation of the three octaves between 2 and 16 kHz. The most sensitive thresholds (as low as -2 dB SPL) are found between 7 and 9 kHz. The primary auditory cortex is similar in cytoarchitecture to that reported for the cat, showing a blurring of lamination in the middle layers (II-IV) and a preponderance of small cells in these merged layers, giving a highly granular appearance. The accessibility of the cochlear representation on the gyral surface makes the marmoset an attractive animal for studies of primate auditory cortex.

Frequency representation in the auditory midbrain and forebrain of a marsupial, the northern native cat (Dasyurus hallucatus).

The representation of sound frequency was examined in the auditory cortex and inferior colliculus of anaesthetized marsupial native cats (Dasyurus hallucatus) using microelectrode mapping techniques. The tonotopic organizations of these two auditory regions are grossly similar to those described in brush-tailed possums and in Eutheria. There appears to exist a biased representation of high frequencies (greater than 10kHz) in native cats and a paucity of frequencies below 1 kHz. Unit threshold audiograms indicate minimum thresholds between 7 and 12kHz and high thresholds above 30kHz.

Auditory response properties of neurons in the claustrum and putamen of the cat.

The auditory response properties of single neurons in claustrum and putamen were studied in response to simple dichotic stimuli (viz. noise-and tone-bursts) in chloralose-anaesthetized cats. Neurons in claustrum were commonly weakly driven with long latency, were broadly tuned and were excited by stimulation of either ear (EE). Putamen neurons, in contrast, were securely driven with short latency, showed irregular tuning with a preference for low frequencies and were either EE or excited only by the contralateral ear (EO). The differences between claustrum and putamen responses can be related to differences in connections with the auditory cortical fields and with auditory thalamus. Some neurons were also tested for visual responsiveness: auditory and visual cells were intermingled in both nuclei and only a small percentage of cells were bimodal. In contrast to the visual and somatosensory input to claustrum, which are derived from primary cortical fields, the auditory input to claustrum is apparently derived from non-primary cortical regions, suggesting a fundamentally different role for processing of auditory information in claustrum.

Masking by internally generated noise and protection by middle ear muscle activity.

Gross auditory nerve action potentials to high-frequency clicks were recorded bilaterally from awake cats with unilaterally tenotomized middle ear muscles (MEM) during eating and during control quiet periods. Masking by internally generated noise associated with eating increased with decreases in click intensity, but did not differ in ears with intact and tenotomized MEM. Under the conditions of this study, non-reflex MEM activity does not appear to provide protection against masking by internally generated noise.