Tonotopic control of auditory thalamus frequency tuning by reticular thalamic neurons

GABAergic cells of the thalamic reticular nucleus (TRN) can potentially exert strong control over transmission of information through thalamus to the cerebral cortex. Anatomical studies have shown that the reticulo-thalamic connections are spatially organized in the visual, somatosensory, and auditory systems. However, the issue of how inhibitory input from TRN controls the functional properties of thalamic relay cells and whether this control follows topographic rules remains largely unknown. Here we assessed the consequences of increasing or decreasing the activity of small ensembles of TRN neurons on the receptive field properties of medial geniculate (MG) neurons. For each MG cell, the frequency tuning curve and the rate-level function were tested before, during, and after microiontophoretic applications of GABA, or of glutamate, in the auditory sector of the TRN. For 66 MG cells tested during potent pharmacological control of TRN activity, group data did not reveal any significant effects. However, for a population of 20/66 cells (all but 1 recorded in the ventral, tonotopic, division), the breadth of tuning, the frequency selectivity and the acoustic threshold were significantly modified in the directions expected from removing, or reinforcing, a dominant inhibitory input onto MG cells. Such effects occurred only when the distance between the characteristic frequency of the recorded ventral MG cell and that of the TRN cells at the ejection site was <0.25 octaves; they never occurred for larger distances. This relationship indicates that the functional interactions between TRN cells and ventral MG cells rely on precise topographic connections.     

Tonotopic and heterotopic projection systems in physiologically defined auditory cortex

Combined physiological and connectional studies show significant non-topographic extrinsic projections to frequency-specific domains in the cat auditory cortex. These frequency-mismatched loci in the thalamus, ipsilateral cortex, and commissural system complement the predicted topographic and tonotopic projections. Two tonotopic areas, the primary auditory cortex (AI) and the anterior auditory field (AAF), were electrophysiologically characterized by their frequency organization. Next, either cholera toxin beta subunit or cholera toxin beta subunit gold conjugate was injected into frequency-matched locations in each area to reveal the projection pattern from the thalamus and cortex. Most retrograde labeling was found at tonotopically appropriate locations within a 1 mm-wide strip in the thalamus and a 2-3 mm-wide expanse of cortex (approximately 85%). However, approximately 13-30% of the neurons originated from frequency-mismatched locations far from their predicted positions in thalamic nuclei and cortical areas, respectively. We propose that these heterotopic projections satisfy at least three criteria that may be necessary to support the magnitude and character of plastic changes in physiological studies. First, they are found in the thalamus, ipsilateral and commissural cortex; since this reorganization could arise from any of these routes and may involve each, such projections ought to occur in them. Second, they originate from nuclei and areas with or without tonotopy; it is likely that plasticity is not exclusively shaped by spectral influences and not limited to cochleotopic regions. Finally, the projections are appropriate in magnitude and sign to plausibly support such rearrangements; given the rapidity of some aspects of plastic changes, they should be mediated by substantial existing connections. Alternative roles for these heterotopic projections are also considered.     

Somatotopic organization of the human somatosensory cortex revealed by neuromagnetic measurements

Summary The primary projection areas in the human somatosensory cortex activated by electrical stimulation of the digits of the hand and the ankle were localized by measuring the magnetic field outside the head contralateral to the side of stimulation. Most of the spatial variation in the amplitude of the field component normal to the scalp could be accounted for by representing each source as a single current dipole in a spherical conducting medium with solely concentric variations in electrical conductivity, although the fit of this model to the data showed some statistically significant deviations. Based on the best-fitting parameter values of the model, we found that the projection areas of the thumb, the index finger, the little finger and the ankle were located at successively more medial positions along the primary somatosensory cortex, at an average depth of 2.2 cm from the scalp surface.This research was supported in part by ONR grant N00014-76-C-0568The preliminary results from the present study were reported at the Sixth Conference on Slow Potentials in the Human Brain held in 1981 (Kaufman et al. 1984) and at the Fourth Workshop on Biomagnetism held in 1982 (Okada 1983)     

Large-scale organization of ferret auditory cortex revealed using continuous acquisition of intrinsic optical signals

We have adapted a new approach for intrinsic optical imaging, in which images were acquired continuously while stimuli were delivered in a series of continually repeated sequences, to provide the first demonstration of the large-scale tonotopic organization of both primary and nonprimary areas of the ferret auditory cortex. Optical responses were collected during continuous stimulation by repeated sequences of sounds with varying frequency. The optical signal was averaged as a function of time during the sequence, to produce reflectance modulation functions (RMFs). We examined the stability and properties of the RMFs and show that their zero-crossing points provide the best temporal reference points for quantifying the relationship between the stimulus parameter values and optical responses. Sequences of different duration and direction of frequency change gave rise to comparable results, although in some cases discrepancies were observed, mostly between upward- and downward-frequency sequences. We demonstrated frequency maps, consistent with previous data, in primary auditory cortex and in the anterior auditory field, which were verified with electrophysiological recordings. In addition to these tonotopic gradients, we demonstrated at least 2 new acoustically responsive areas on the anterior and posterior ectosylvian gyri, which have not previously been described. Although responsive to pure tones, these areas exhibit less tonotopic order than the primary fields.     

Processing of complex sounds in the human auditory cortex as revealed by magnetic brain responses

Processing of simple and complex sounds in the human brain was compared by recording extracranial magnetic mismatch responses (MMNm; the magnetic counterpart of the mismatch negativity, or MMN) to frequency changes in these sounds. Generator sources, modeled as equivalent current dipoles (ECDs), of MMNm responses to a change in one frequency element of complex sounds (a chord and a serial tone pattern) were located in supratemporal auditory cortex, on average, 10 mm medially to the source of an MMNm elicited by an identical frequency change in a simple tone. These results suggest that at least partially different supratemporal neuron populations are invovled in processing changes in simple and complex sounds and that sensory-memory representations for these sounds may be located in different fields of the auditory cortex.     

Temporal coherence sensitivity in auditory cortex

Natural sounds often contain energy over a broad spectral range and consequently overlap in frequency when they occur simultaneously; however, such sounds under normal circumstances can be distinguished perceptually (e.g., the cocktail party effect). Sound components arising from different sources have distinct (i.e., incoherent) modulations, and incoherence appears to be one important cue used by the auditory system to segregate sounds into separately perceived acoustic objects. Here we show that, in the primary auditory cortex of awake marmoset monkeys, many neurons responsive to amplitude- or frequency-modulated tones at a particular carrier frequency [the characteristic frequency (CF)] also demonstrate sensitivity to the relative modulation phase between two otherwise identically modulated tones: one at CF and one at a different carrier frequency. Changes in relative modulation phase reflect alterations in temporal coherence between the two tones, and the most common neuronal response was found to be a maximum of suppression for the coherent condition. Coherence sensitivity was generally found in a narrow frequency range in the inhibitory portions of the frequency response areas (FRA), indicating that only some off-CF neuronal inputs into these cortical neurons interact with on-CF inputs on the same time scales. Over the population of neurons studied, carrier frequencies showing coherence sensitivity were found to coincide with the carrier frequencies of inhibition, implying that inhibitory inputs create the effect. The lack of strong coherence-induced facilitation also supports this interpretation. Coherence sensitivity was found to be greatest for modulation frequencies of 16-128 Hz, which is higher than the phase-locking capability of most cortical neurons, implying that subcortical neurons could play a role in the phenomenon. Collectively, these results reveal that auditory cortical neurons receive some off-CF inputs temporally matched and some temporally unmatched to the on-CF input(s) and respond in a fashion that could be utilized by the auditory system to segregate natural sounds containing similar spectral components (such as vocalizations from multiple conspecifics) based on stimulus coherence.     

Responses of auditory cortex to complex stimuli: functional organization revealed using intrinsic optical signals

We used optical imaging of intrinsic signals to study the large-scale organization of ferret auditory cortex in response to complex sounds. Cortical responses were collected during continuous stimulation by sequences of sounds with varying frequency, period, or interaural level differences. We used a set of stimuli that differ in spectral structure, but have the same periodicity and therefore evoke the same pitch percept (click trains, sinusoidally amplitude modulated tones, and iterated ripple noise). These stimuli failed to reveal a consistent periodotopic map across the auditory fields imaged. Rather, gradients of period sensitivity differed for the different types of periodic stimuli. Binaural interactions were studied both with single contralateral, ipsilateral, and diotic broadband noise bursts and with sequences of broadband noise bursts with varying level presented contralaterally, ipsilaterally, or in opposite phase to both ears. Contralateral responses were generally largest and ipsilateral responses were smallest when using single noise bursts, but the extent of the activated area was large and comparable in all three aural configurations. Modulating the amplitude in counter phase to the two ears generally produced weaker modulation of the optical signals than the modulation produced by the monaural stimuli. These results suggest that binaural interactions seen in cortex are most likely predominantly due to subcortical processing. Thus our optical imaging data do not support the theory that the primary or nonprimary cortical fields imaged are topographically organized to form consistent maps of systematically varying sensitivity either to stimulus pitch or to simple binaural properties of the acoustic stimuli.     

Tonotopic auditory cortex and the magnetoencephalographic (MEG) equivalent of the mismatch negativity

Two tone stimuli, one frequent (standard) and the other infrequent (a slightly higher, deviant tone), were presented in random order and at short intervals to subjects reading texts they had selected. In different blocks, standards were either 250, 1,000, or 4,000 Hz, with the deviants always being 10% higher in frequency than the standards of the same blocks. Magnetic responses elicited by the standard and deviant tones included N1m, the magnetoencephalographic equivalent of the electrical N1 (its supratemporal component). In addition, deviant stimuli elicited MMNm, the magnetic equivalent of the electrical mismatch negativity, MMN. The equivalent dipole sources of the two responses were located in supratemporal auditory cortex, with the MMNm source being anterior to that of N1m. The dipole orientations of both sources in the sagittal plane depended on stimulus frequency, suggesting that the responses are generated by tonotopically organized neuronal populations. The tonotopy reflected by the frequency dependence of the MMNm source might be that of the neural trace system underlying frequency representation of auditory stimuli in sensory memory.     

Chemoarchitectonic organization of the cat primary auditory cortex

Summary Acetylcholinesterase (AChE) activity, demonstrated histochemically, defines an area of cortex on the middle ectosylvian gyrus that appears to correspond to the cytoarchitectonically defined area 41 and the physiologically defined primary auditory area (AI). In this area there are high levels of AChE in layers III, IV and VI while in the surrounding areas there are comparatively low levels of enzyme in these layers. The monoclonal antibody CAT 301, which was raised against a cell surface proteoglycan, also defines this area. There are high levels of CAT 301 immunoreactivity in cell bodies and the neuropil of layer III and an absence of very large immunoreactive neurons in layer V. Furthermore there are higher levels of the calcium binding protein, parvalbumin and the metabolic enzyme, cytochrome oxidase, in layers III and IV of AI, than in most of the surrounding cortex. By contrast the distribution of the calcium binding protein, calbindin and the distribution of myelinated fibers are similar in area 41 and the surrounding areas.     

Concurrent encoding of frequency and amplitude modulation in human auditory cortex: MEG evidence

A natural sound can be described by dynamic changes in envelope (amplitude) and carrier (frequency), corresponding to amplitude modulation (AM) and frequency modulation (FM), respectively. Although the neural responses to both AM and FM sounds are extensively studied in both animals and humans, it is uncertain how they are corepresented when changed simultaneously but independently, as is typical for ecologically natural signals. This study elucidates the neural coding of such sounds in human auditory cortex using magnetoencephalography (MEG). Using stimuli with both sinusoidal modulated envelope (f(AM), 37 Hz) and carrier frequency (f(FM), 0.3-8 Hz), it is demonstrated that AM and FM stimulus dynamics are corepresented in the neural code of human auditory cortex. The stimulus AM dynamics are represented neurally with AM encoding, by the auditory steady-state response (aSSR) at f(AM). For sounds with slowly changing carrier frequency (f(FM) <5 Hz), it is shown that the stimulus FM dynamics are tracked by the phase of the aSSR, demonstrating neural phase modulation (PM) encoding of the stimulus carrier frequency. For sounds with faster carrier frequency change (f(FM) > or = 5 Hz), it is shown that modulation encoding of stimulus FM dynamics persists, but the neural encoding is no longer purely PM. This result is consistent with the recruitment of additional neural AM encoding over and above the original neural PM encoding, indicating that both the amplitude and phase of the aSSR at f(AM) track the stimulus FM dynamics. A neural model is suggested to account for these observations.     

Spatial sensitivity in field PAF of cat auditory cortex

We compared the spatial tuning properties of neurons in two fields [primary auditory cortex (A1) and posterior auditory field (PAF)] of cat auditory cortex. Broadband noise bursts of 80-ms duration were presented from loudspeakers throughout 360 degrees in the horizontal plane (azimuth) or 260 degrees in the vertical median plane (elevation). Sound levels varied from 20 to 40 dB above units' thresholds. We recorded neural spike activity simultaneously from 16 sites in field PAF and/or A1 of alpha-chloralose-anesthetized cats. We assessed spatial sensitivity by examining the dependence of spike count and response latency on stimulus location. In addition, we used an artificial neural network (ANN) to assess the information about stimulus location carried by spike patterns of single units and of ensembles of 2-32 units. The results indicate increased spatial sensitivity, more uniform distributions of preferred locations, and greater tolerance to changes in stimulus intensity among PAF units relative to A1 units. Compared to A1 units, PAF units responded at significantly longer latencies, and latencies varied more strongly with stimulus location. ANN analysis revealed significantly greater information transmission by spike patterns of PAF than A1 units, primarily reflecting the information transmitted by latency variation in PAF. Finally, information rates grew more rapidly with the number of units included in neural ensembles for PAF than A1. The latter finding suggests more accurate population coding of space in PAF, made possible by a more diverse population of neural response types.     

Concurrent encoding of frequency and amplitude modulation in human auditory cortex: encoding transition

Complex natural sounds (e.g., animal vocalizations or speech) can be characterized by specific spectrotemporal patterns the components of which change in both frequency (FM) and amplitude (AM). The neural coding of AM and FM has been widely studied in humans and animals but typically with either pure AM or pure FM stimuli. The neural mechanisms employed to perceptually unify AM and FM acoustic features remain unclear. Using stimuli with simultaneous sinusoidal AM (at rate f(AM) = 37 Hz) and FM (with varying rates f(FM)), magnetoencephalography (MEG) is used to investigate the elicited auditory steady-state response (aSSR) at relevant frequencies (f(AM), f(FM), f(AM) + f(FM)). Previous work demonstrated that for sounds with slower FM dynamics (f(FM) < 5 Hz), the phase of the aSSR at f(AM) tracked the FM; in other words, AM and FM features were co-tracked and co-represented by "phase modulation" encoding. This study explores the neural coding mechanism for stimuli with faster FM dynamics (< or =30 Hz), demonstrating that at faster rates (f(FM) > 5 Hz), there is a transition from pure phase modulation encoding to a single-upper-sideband (SSB) response (at frequency f(AM) + f(FM)) pattern. We propose that this unexpected SSB response can be explained by the additional involvement of subsidiary AM encoding responses simultaneously to, and in quadrature with, the ongoing phase modulation. These results, using MEG to reveal a possible neural encoding of specific acoustic properties, demonstrate more generally that physiological tests of encoding hypotheses can be performed noninvasively on human subjects, complementing invasive, single-unit recordings in animals.     

New field with tonotopic organization in guinea pig auditory cortex

In guinea pig auditory cortex, two core areas, a primary area (AI) and a dorsocaudal field (DC), and two belt regions ventral to AI and DC (VRB and VCB) with an intermediate zone (T) in between, together with a small field (S) rostral to AI, have been reported in single-electrode studies although field S and zone T have not been observed in imaging studies. Using a high-resolution in vivo optical-imaging system with the voltage-sensitive dye RH-795, we report here the successful imaging of a rostral small field and zone T and a ventral-to-dorsal frequency gradient in zone T. Further, we found that VRB can be subdivided into two areas, a ventrorostral field (VR) with properties similar to those reported for VRB, and a ventrocaudal field (VC) with novel properties. With increasing stimulus tone frequency, activation in VR shifted caudally while activation in VC shifted rostrally. Thus we have newly identified field VC that has mirror-symmetric tonotopy to that of VR.     

Fine frequency tuning in monkey auditory cortex and thalamus

The frequency resolution of neurons throughout the ascending auditory pathway is important for understanding how sounds are processed. In many animal studies, the frequency tuning widths are about 1/5th octave wide in auditory nerve fibers and much wider in auditory cortex neurons. Psychophysical studies show that humans are capable of discriminating far finer frequency differences. A recent study suggested that this is perhaps attributable to fine frequency tuning of neurons in human auditory cortex (Bitterman Y, Mukamel R, Malach R, Fried I, Nelken I. Nature 451: 197-201, 2008). We investigated whether such fine frequency tuning was restricted to human auditory cortex by examining the frequency tuning width in the awake common marmoset monkey. We show that 27% of neurons in the primary auditory cortex exhibit frequency tuning that is finer than the typical frequency tuning of the auditory nerve and substantially finer than previously reported cortical data obtained from anesthetized animals. Fine frequency tuning is also present in 76% of neurons of the auditory thalamus in awake marmosets. Frequency tuning was narrower during the sustained response compared to the onset response in auditory cortex neurons but not in thalamic neurons, suggesting that thalamocortical or intracortical dynamics shape time-dependent frequency tuning in cortex. These findings challenge the notion that the fine frequency tuning of auditory cortex is unique to human auditory cortex and that it is a de novo cortical property, suggesting that the broader tuning observed in previous animal studies may arise from the use of anesthesia during physiological recordings or from species differences.     

Sound-level-dependent representation of frequency modulations in human auditory cortex: a low-noise fMRI study.

Recognition of sound patterns must be largely independent of level and of masking or jamming background sounds. Auditory patterns of relevance in numerous environmental sounds, species-specific vocalizations and speech are frequency modulations (FM). Level-dependent activation of the human auditory cortex (AC) in response to a large set of upward and downward FM tones was studied with low-noise (48 dB) functional magnetic resonance imaging at 3 Tesla. Separate analysis in four territories of AC was performed in each individual brain using a combination of anatomical landmarks and spatial activation criteria for their distinction. Activation of territory T1b (including primary AC) showed the most robust level dependence over the large range of 48-102 dB in terms of activated volume and blood oxygen level dependent contrast (BOLD) signal intensity. The left nonprimary territory T2 also showed a good correlation of level with activated volume but, in contrast to T1b, not with BOLD signal intensity. These findings are compatible with level coding mechanisms observed in animal AC. A systematic increase of activation with level was not observed for T1a (anterior of Heschl's gyrus) and T3 (on the planum temporale). Thus these areas might not be specifically involved in processing of the overall intensity of FM. The rostral territory T1a of the left hemisphere exhibited highest activation when the FM sound level fell 12 dB below scanner noise. This supports the previously suggested special involvement of this territory in foreground-background decomposition tasks. Overall, AC of the left hemisphere showed a stronger level-dependence of signal intensity and activated volume than the right hemisphere. But any side differences of signal intensity at given levels were lateralized to right AC. This might point to an involvement of the right hemisphere in more specific aspects of FM processing than level coding.     

Processing of novel sounds and frequency changes in the human auditory cortex: Magnetoencephalographic recordings

Whole-head magnetoencephalographic (MEG) responses to repeating standard tones and to infrequent slightly higher deviant tones and complex novel sounds were recorded together with event-related brain potentials (ERPs). Deviant tones and novel sounds elicited the mismatch negativity (MMN) component of the ERP and its MEG counterpart (MMNm) both when the auditory stimuli were attended to and when they were ignored. MMNm generators were located bilateral to the superior planes of the temporal lobes where preattentive auditory discrimination appears to occur. A subsequent positive P3a component was elicited by deviant tones and with a larger amplitude by novel sounds even when the sounds were to be ignored. Source localization for the MEG counterpart of P3a (P3am) suggested that the auditory cortex in the superior temporal plane is involved in the neural network of involuntary attention switching to changes in the acoustic environment.