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Connections between thalamic structures of the auditory system and subcortical areas (amygdala, hippocampus, hypothalamus) had been hypothesized to act as a fast reacting "memory chain" establishing and enhancing adverse excitations during noise exposure.
Recent studies prove that the lateral amygdala is an important part of a second separate pathway to the telencephalic projections of the auditory system.
This fast, monosynaptic thalamo-amygdala tract is responsible for full-blown "fear responses" evoked by auditory stimuli as shownd by several conditioning experiments in animals: A fear memory system.
The appertaining basic processes of plasticity in the amygdala are reductions of latencies of neuronal excitations and recruiting of more elements with shorter latency, long-term potentiation causing enhancement of auditory- evoked responses by repeated stimulation, as well as sharpening of primary broad tuning curves of elements.
Very recently a study using Functional-Magnetic-Resonance-Imaging (fMRI) demonstrated that an amygdalar contribution to conditioned fear learning can be revealed in normal human subjects too. These findings were supported by Positron-Emission-Tomography (PET) studies in depressive persons showing that amygdala metabolic abnormality predicted the cortisol concentration in blood.
Using connections via central amygdala, lateral and medial hypothalamus to parts named nuclei paraventriculares and regio arcuata, the sound evoked excitations reach two essential components of endocrine functioning: a) the well-known hypothalamic-pituitary-adrenal (HPA) system with a subsequent rise (via Corticotropin-Releasing Hormone: CRH) in Corticotropin (Adreno-CorticoTropin Hormone: ACTH) and the corticosterone levels; b) the synthesis of ACTH and beta-endorphine-like substances in the arcuate region being axonally transported to extrahypothalamic brain regions.
Longer-lasting activation of the HPA-axis, especially abnormally increased or periodically elevated levels of cortisol and the widespread extrahypothalamically distributed CRF/ACTH may lead to disturbed hormonal balance and even to severe diseases. Keywords: Noise, amygdala, plasticity, fear memory, extrahypothalamic ACTH, cortisol
How to cite this article:
Spreng M. Central nervous system activation by noise. Noise Health 2000;2:49-57 |
| Introduction | |  |
The ability to respond to adverse environmental cues, for instance a noise signalling danger, is present in all organisms. In the same way as the information flow from sensation to motoric action is not exclusively based on cortico-cortical connections, but involves subcortical regions, the bridge between sensation and emotion is given to a great extent by subcortical emotional-processing pathways.
They include limbic and hypothalamic mechanisms quickly controlling the autonomic nervous system and especially hormonal stress-responses. Those mechanisms often react with poor introspective knowledge of the situational origin of emotional responses or even without conscious awareness as during sleep.
Which parts of the central nervous system are involved in the presence of uncontrollable noise signals or signals with a higher dynamic and intensity than the background noise? Both conditions have adverse aspects.
Important facts of the auditory system
Considering an updated simple sketch of the auditory system (Spreng 1985), three main facts should be emphasized [Figure - 1]:
a) The overshooting excitation behind the sensory cells and therefore within the complete peripheral auditory system depending on the dynamic of the onset of the sound.
b) The quick, paucisynaptic processing of the excitation reaching the inferior colliculus (IC) after 5 ms and the geniculate body (GB) after 7 ms as shown in brainstem recordings and single cell recordings of an awake free moving cat (Spreng et al., 1984).
c) The involvement of the processing chain hippocampus, amygdala and hypothalamus.
The connection between thalamic structures of the auditory processing system (GB) and the subcortical areas of amygdala, hippocampus and hypothalamus had been hypothesized to act as some kind of quickly reacting "memory chain" establishing and enhancing adverse excitations during noisy sounds (Spreng, 1985).
Amygdala as part of auditory system and fear memory
Meanwhile studies of LeDoux, 1990 and Masterton, 1996 proved that the lateral amygdala is an important part of the auditory system. It acts as a second separate pathway to its telencephalic projections. On the other side the amygdala is closely connected with the autonomic nervous system, as shown in [Figure - 2]. Furthermore a large and growing body of evidence points to the amygdala as a critical structure in the neural system reponsible for fear and emotional learning.
Therefore the quick, monosynaptic thalamo-amygdala tract is responsible for full-blown "fear responses" evoked by auditory stimuli as shown by several conditioning experiments in animals: Fear memory system. The same seems to be true for human subjects, because recently a study (LaBar et al., 1998) using echoplanar functional magnetic resonance (fMRI) demonstrated that an amygdalar contribution to conditioned fear learning can be revealed in normal human subjects too. To a certain degree those findings were supported by PET studies in depressive persons (Drevets, 1998) showing that amygdala metabolic abnormality predicted the cortisol concentration in blood.
What are the basic processes enabling plasticity in the thalamo-amygdala tract and causing for instance increased excitations in noisy environments which give rise to emotional memory processes as learned aversions, or even fear of certain types of noise signals?
Enhanced short-latency auditory responses of amygdala neurons
Among all the elements of the anatomical circuits through which information about the incoming sounds flow into and through the amygdala, the region of lateral amygdala (LA) has the shortest response latency to acoustic stimuli. In the dorsal part of the LA, Quirk et al. (1995) found that the portion of cells exhibiting early tone response was increased from 56% to 69% following training. The additionally observed increased number of short-latency responses after conditioning ([Figure - 3], middle part) was due to two factors: the addition of newly tone responsive neurons and a decrease in the latency of tone-responsive neurons responding with longer latencies prior to conditioning.
Additionally some increase of short-latency (1-4 ms) direct coupling of LA cells was observed using cross-correlation techniques, suggesting long-term changes of synaptic strength in the network by training.
The hypothesis that the LA and/or long-term potentiation (LTP) in the direct transmission from the auditory thalamus to the amygdala are responsible for plasticity is supported by the fact that those effects occuring in the latency range 12 to 17 ms while cortical activation of the amygdala involves latencies greater 20 ms.
Enhancement of amygdala auditory-evoked response properties
Experience-dependent neural plasticity based on increased synaptic efficacy in the pathways involved is a result of repeated stimulation resulting in a long-term potentiation (LTP) or hetero-synaptic facilitation. This is an example of use-dependent plasticity.
For the thalamo-amygdala pathways under consideration this has been proved by Rogan and LeDoux (1995) measuring auditory-evoked potentials in the LA with latencies around 18.5 ms after preceding electrical high frequency stimulation of the relevant pathways beginning in the medial geniculate body (MGB). They found a commensurate long-lasting enhancement of slopes (129%) and amplitudes (55%) of the evoked responses in the lateral amygdala, as shown in figure 3 (top right). Based upon these results it appears that the thalamo-amygdala pathway has the capacity to alter its response to acoustic stimuli for long periods of time as a consequence of brief stimulation episodes.
This finding is of special significance since this pathway -as mentioned above- is involved in the formation of long-lasting memories of an acoustic stimulus.
Furthermore these findings throw some new light upon earlier results gained with auditory evoked brainstem responses in human beings (Spreng, 1985). Components generated mostly in the inferior colliculus and/or the medial geniculate body evoked after a 10 minute series of quickly repeated (1s mean interval) regular and irregular impulsive noise stimulation (artificial impulses: 10 ms rise, 100 ms exponential decay, 96 dB peak, 80 dB Leq,10min) were evaluated. Whereas very early components (cochlear nucleus) remained unchanged, enhancements of amplitudes were observed as a sign of increased efficacy of the thalamic part of the auditory system caused by the preceding stressing series of noise ([Figure - 3], bottom right).
Retuning in the thalamic sources of input to amygdala
This is very important with respect to annoyance or adverse effects. Typical reactions to noise signals with special frequency content are based on the plasticity processes in the thalamic source of input to the amygdala. These effects are clear and specific modifications of information processing rather than only increased excitability after sensitization.
Weinberger and his coworkers (Edeline and Weinberger, 1992, Lennartz and Weinberger, 1992) found that, after training, the MGB serves as an "adaptive filter" and that it binds diverse components of a memory. They reported fascinating frequency learning effects on frequency receptive fields (comparable to inverted tuning curves) of single elements in the MGB of the guinea pig.
During conditioning the generally broadly tuned elements of the MGB rapidly changed their behaviour: i.e. increased response at the frequency used for conditioning with decreased responses at the other frequencies, even for the best frequency. In addition sharpening of the broad tuning curves was observed and therefore increased selectivity for special frequencies as shown in the sketch [Figure - 4].
Consequences of neural plasticity for amygdala excitation
During exposure to a noise stimulus all the effects mentioned above will have considerable influence upon the amount of excitation of the total amygdala. Although the effects had been observed during conditioning experiments they may occur during repeated and/or longer lasting adverse sounds (noise) with great probability.
Regarding the connections between LA and cortical areas, processing particular perceptual features, as well as hippocampal areas [Figure - 2], (the latter is known to be involved in complex cognitive processing,) reveals the LA as a sensory-cognitive gateway to the whole amygdala. Thus annoyance and even fear may result when the amygdala is activated by the summation of the sensory inputs from the thalamus and/or the cortex.
As a result of "learning" the thalamo-amygdala pathway serves as a "quick and dirty" processing of complex stimulus situation with direct and rapid access to emotional circuits and without the need of time to contemplate the full semantic ramification (LeDoux, 1990) and/or the cognitive (mnemonic and attentional) meaning of the sounds.
Especially the retuning of neurons, in the beginning with broad tuning, transmitting all frequency components; then enhancing the responsivity to special frequencies, suggests a mechanism that could contribute to the creation and modification of emotional feature detectors.
Amygdala connections to thalamo-pituitary-adrenal (HPA) axis
Recent data indicate that the amygdala has an excitatory effect on the hypothalamo-pituitary-adrenocortical (HPA) axis. This is demonstrated by the increase in corticosterone levels following amygdala stimulation, as well as by an inhibition of HPA responses to a variety of stressful stimuli in animals with amygdala lesions (Grey, 1991).
Which hypothalamic mechanisms are involved in the facilitatory effects of the amygdala on the HPA axis?
Recently Feldman and Weinfeld (1998) clearly showed that electrical stimulation of the central amygdala [Figure - 2] caused a depletion of hypothalamic corticotropin-releasing factor (CRF-41) and a subsequent rise in plasma adrenocorticotropic hormone (ACTH) and corticosterone levels.
Direct, topographically organized projections exist from the amygdala to the parvocellular division of the paraventricular nucleus (PNV) with terminals which directly contact CRF-41 cells in the PNV of the hypothalamus. CRF-41 is released into the portal circulation, stimulating ACTH secretion formed by enzymatic processes in the pro-opiomelanocortine (POMC) cells of the pituitary gland [Figure - 2]. ACTH itself stimulates the adrenal gland and thus increases release of cortisol as well as other substances. These effects in the hypothalamus are mediated by the hypothalamic norepinephrine and serotonin in the sense of inhibition if there is a lack of both neurotransmitters.
Amygdala connections to hypothalamic/extrahypothalamic regions
Although the major site of POMC synthesis is the pituitary gland, POMC-producing cell bodies have also been identified in the arcuate region of the hypothalamus and the medulla oblongata. These POMC positive neurons especially of the arcuate nucleus innervate a wide array of brain regions.
The mapping of the brain-born POMC-derived peptides, especially ACTH and Beta-E, have been described in detail by Khachaturian et al. (1985). Barna et al. (1997) showed by cuts around the medial hypothalamus of rats that the ACTH and Beta-E substances are axonally transported by very large neuronal pathways to extrahypothalamic brain regions e.g. septum, thalamus, hippocampus, amygdala, and medulla oblongata.
Gomes-Sanches et al. (1997) reported synthesis of corticosterone and aldosterone from endogenous precursors in these brain areas, indicating an enzymatic machinery for the production of adrenal corticosteroids and aldosteron in the brain.
These facts open a wide range of relations of perceived stress-dependent cortisol values to perturbation of other endocrine axes especially in the case of long term overactivation by factors such as environmental stress.
Thus noise signals activating the auditory system and the part amygdala as key component in a network being linked with the ability of an organism to react to potentially threatening stimuli in the environment may lead to alterations in the homeostatic balance with pathogenetic consequences.[18]
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Correspondence Address:
M Spreng
Dept. Physiology and Experimental Pathophysiology, University of Erlangen, Universitaetsstrasse 17, D-91054 Erlangen
Germany
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 12689471 
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4] |
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