Habituation: Theories, Characteristics and Biological Mechanisms

As already mentioned, this book was one of the books I read last week. I gave it two stars on goodreads.

The book did not have a goodreads profile, so I had to add one. When books don’t have goodreads profiles and/or I’m unable to find an amazon rating, I usually end up (cautiously) assuming that the book probably has not been read by, well, let’s use the words ‘a lot of people’. As you may be able to tell from the goodreads book description which I included in the profile at the link above, it’s a book which deals with some slightly obscure stuff: “Topics include the important roles for matrix metalloproteinases and cell adhesion molecules in long-term potentiation (LTP)” and “a mathematical description of habituation and recovery of the head-shake response in rats“. The description at the link is a quote from the book – it’s the first paragraph of the preface. Some of the stuff in here is fairly technical and really quite difficult to blog also on account of being somewhat difficult to summarize – for these reasons there was some stuff in the book which I decided against covering here despite it being interesting, including most of the first chapter. The stuff I decided to exclude includes the stuff about ‘important roles for matrix metalloproteinases and cell adhesion molecules’ but I also decided to exclude the coverage of the drug addiction stuff in that chapter, however for a different reason; I’ve dealt with this kind of stuff before, and Clark et al.’s coverage go into much more detail than does this book.

Below I have added some observations from the book and a few remarks of my own.

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“Nonassociative learning is considered to be the simplest form of learning and includes the phenomena of habituation, dishabituation, and sensitization. Of these phenomena, habituation is the most frequently studied and refers to a decrease in responding, as related to frequency, magnitude, or intensity to a stimulus repeatedly presented, or presented for a prolonged period of time […] Habituation has been documented across many species and response systems ranging from the gill-withdrawal reflex in Aplysia [sea slugs] […] and tap withdrawal or chemotaxic response in the nematode Caenorhabditis elegans [a ~1 mm long roundworm] […], to acoustic startle response in rats and mice […], schedules of reinforcement in operant conditioning […] and feeding in humans (Myers and Epstein, 2002).”

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“From the viewpoint of neuroscience, tinnitus has been defined as (i) the perception of a sound in the ear in the absence of external stimulation […]; (ii) an ongoing conscious perception of a sound in the absence of any external sound source […]; (iii) the conscious perception of a sound that is not generated by any source outside the body […]; (iv) a phantom auditory perception or the perception of abnormal activity not induced by any combination of external sounds […]. As documented almost thirty years ago by Coles (1984), approximately 14-18 per cent of the population included in an epidemiological study in Great Britain reported tinnitus. Findings from a community survey conducted in Gothenburg, Sweden showed that 14.2 per cent suffer “always” or “often”, and it has been estimated that 1-2 per cent perceive tinnitus as a plague all day or as a threat towards quality of life […]. More recent epidemiological surveys from China (Xu et al. 2011) and Egypt (Khedr et al. 2010) demonstrate that tinnitus can be a significant problem for the inhabitants in the eastern part of the world as well. Overall prevalence of tinnitus in a population of 6333 inhabitants in a province (Jiangsu) in China was 12.4 per cent and standardized rates for China was calculated to be 11.4 per cent. […] In a survey in Assiut, Egypt including 4848 inhabitants prevalence rate of tinnitus was 5.17 per cent. […] Along with these results, earlier epidemiological studies also disclosed that a large proportion of individuals do not seek help for having tinnitus, so a clinically relevant question to rise was, and still is, why some patients are plagued by tinnitus, while others seem to be able to cope. In one of the first larger tinnitus populations studies Meikle et al. (1983) investigated the relationship between tinnitus loudness obtained by a loudness balance procedure and tinnitus severity ratings in 1800 patients attending a tinnitus clinic. No significant correlation was found between tinnitus loudness and severity. Neither was the severity ratings associated to type, quality and the pitch of tinnitus.”

I thought prevalence was significantly lower than that, but I must admit that i did not have good reasons for assuming this. Tinnitus seems to be yet another one of those sneaky health problems which are both reasonably hard to observe when other people suffer from them (you can’t tell if someone has tinnitus or not unless the individual in question tells you that he or she does) and actually quite common. The chapter has a lot of stuff, much of which are critical remarks towards current therapeutic approaches and the interpretive frameworks (there are two relevant models, a ‘psychological model’ and a ‘neurophysiological model’) on which they are based. The reason why this condition is included in the book is that a habituation process often occurs in people who are affected by this condition – most people with tinnitus adjust to some extent to the condition. However: “To date, habituation to tinnitus remains an unexplained process [and] it is not legitimate to state that tolerance to tinnitus is a natural process”. Habituation is the common outcome, but sometimes it fails and they don’t really seem to have a good explanatory model of what goes wrong when it does. It should be noted that a few of the people who do not habituate to tinnitus end up killing themselves – so figuring out more about this stuff is most certainly not unimportant to some of the people who are affected. Some of the details which are clear at this point is that the habituation process relates to a lot of stuff besides what’s going on in the ear, and that some treatment-relevant patient heterogeneities do not seem to be taken into account in the current treatment modalities on offer (or for that matter in the theoretical models on which the treatment modalities are based). Incidentally it may be a mistake to think of the neurological research into these things as only being relevant to the organism’s ‘response to tinnitus’, as such processes may well also be implicated in the pathophysiology more broadly defined – at least this is how I interpret some of the findings. For example they point out in chapter 5 of the book that: “recent auditory neuroscience research has suggested that an imbalance of excitatory and inhibitory neural interactions within the auditory cortex could lead to the perception of tinnitus”.

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“The model of orientation and habituation that will be discussed is derived from the work of Sokolov (1975). Sokolov postulated that production of an orienting response is dependent on incongruity between incoming stimulus and existing neural templates that are created by previously stored memory traces of environmental stimuli. The neural template or model encodes all aspects of the stimulus including duration, interstimulus interval and the relationship between several stimuli across time. If there is a mismatch between the new stimuli and the neuronal template, sensitization to the stimulus occurs and a response will be generated. If the new stimulus matches the neural template, habituation occurs (i.e., decrease in responding to repeated presentations of the same stimuli). […] If a stimulus differs in any way from the original stimulus presented (i.e. higher or lower pitch), the orienting response will reappear to a previously habituated stimulus because of the change. Sokolov termed the reappearance of the orienting response dishabituation. […] It is argued that Sokolov’s model captures the organism’s ability to modulate internal memory traces and compare these traces to external stimuli to determine the importance or irrelevance of stimuli in the environment. However, it does not directly address the activation or suppression of the motor system in orienting to novelty or inhibiting responding to irrelevant stimuli. Orienting must involve two interactive channels of information processing: automatic and conscious. These two channels must be integrated by feedforward and feedback interconnections that involve many functional brain systems. The widespread involvement of different brain regions is further implicated by the research finding of cingulotomy patients. […] damage to the cingulate can produce attentional impairments.”

“It is proposed that orientation and habituation occur through the modulation of both internal and external states. The modulation of information occurs in three separate levels as follows: (1) memory comparator level, (2) value-appraisal level, and (3) behavioral-response/decision-making level […]. All of these levels are processing the information simultaneously through synchronized connections of neural circuits between the functional areas involved. The memory comparator level is composed of the hippocampus.
The value-appraisal system is composed of the amygdala, orbitofrontal cortex and peripheral nervous system. The peripheral nervous system is important in controlling the organism’s arousal system. One division expends energy (sympathetic) and the other division conserves energy (parasympathetic). The behavioral-response/decision-making level is composed of the cerebellum, basal ganglia, premotor, motor cortex and anterior cingulate. It is proposed that the cerebellum is the key structure involved in linking the temporal properties of signals especially with regard to the basal ganglia and the anterior cingulate.
It is also proposed that the anterior cingulate plays an important role in coordinating internal and external influences on stimuli processing and response monitoring. The anterior cingulate receives initial information as well as feedback; it determines priorities in selecting which stimuli to attend and respond to. There is considerable agreement in the literature indicating that the role of the anterior cingulate cortex is to assist in bringing together the influences of internal and external stimuli with behavioral goals and plans for activation […] Evidence from animal, clinical and neuroimaging studies indicates that the anterior cingulate cortex is involved in directing attention and action by modulating cognitive and affective states […] The anterior cingulate cortex may be involved in processing competing inputs and inhibiting competing actions (Pardo, Pardo, Janer and Raichle, 1990) or directing attentional responses when there are multiple or competing inputs and action (Pardo, Fox, and Raichle, 1991). In this sense the anterior cingulate has several roles but its most important role may be in optimizing behavioral stability. […] The proposed three levels of modulation are highly dependent on the diffuse and broadly distributed neuronal circuits in the brain.”

“The NE [neurotransmitter norepinephrine] system serves a very specific function; it maintains the basic level of excitability, arousal, and attentiveness.
The NE system plays an important modulatory role in learning, memory, and retrieval. Norepinephrine also appears to be more inhibitory than excitatory. Over activity can lead to hypervigilance and anxiety and under activity can lead to depression. Norepinephrine is known to be involved in behavioral arousal due to the affects of certain drugs. Amphetamine and cocaine act on NE and are both potent brain stimulants. Several studies have provided evidence that effects of stimulus significance and stimulus repetition are a function of noradrenergic control originating in the pontine nucleus LC.” [Yes, I noticed the spelling errors and they were part of the reason why I included this paragraph in the coverage – to illustrate this aspect of the coverage. Sloppiness like this is part of why I gave the book two stars. The chapter from which this quote is taken is not that terrible, but chapter five – written by a couple of Italian researchers – is quite bad.]

“Neurons do not operate in isolation; each neuron affects the activation of another neuron. The connections between neurons can be excitatory (the firing of one neuron makes the other more likely to send its own signal), or inhibitory (the firing of one neuron makes the other less likely to send its own signal). The excitatory or inhibitory effects neurons have on each other are an important construct in the present model. Connections between neurons (or neural circuits) are determined by the strength between them, or in other words, the degree to which the activation of one affects the activation of another. Too little strength between the neurons or an imbalance in neural synchronization can cause a disruption in processing. The efficient processing of neural circuits can also become weakened when other circuits interfere with their functioning. Of additional importance is the fact that neural connections can be made stronger or weaker through learning. […] In the proposed model sensory information from the environment is received in the amplifying system (thalamus, reticular activating system), which is responsible for arousal, amplification and relay of signals. Information is then forwarded to the memory comparator system (hippocampus), the value-appraisal system (amygdala, orbitofrontal cortex), and behavioral-response/decision-making system (cerebellum, basal ganglia, anterior cingulate, and motor areas). In processing information for decisional action, the organism will habituate if there is a memory trace in the hippocampus (event memory with affect) and cerebellum (motor response memories) from prior experience. If the organism habituates to irrelevant information, the RAS [reticular activating system] is tonically inhibited by the hippocampus and cerebellum. If there are no memory traces, the organism is aroused to process the sensory signal for its affective/motivational salience by the amygdala and orbitofrontal cortex. The cerebellum initiates a motor response (“what is it”) at which time the basal ganglia and anterior cingulate become activated for further processing. After the initial stimulus is processed in these regions, information is sent back to sensory areas thus creating a feedback loop. As information in the environment is being refined and updated, sensory areas continue to receive new input and the feedback from the monitored response as well. In this sense, a dynamic and complex process that is cyclical in nature is proposed. Stimulus perception, selection, and response initiation is being fed forward and fed back at each stage in processing and the influences of these processes are sorted for priority by the anterior cingulate cortex. Thus orientation and habituation is a continuous process that enables the organism the flexibility to adapt to changes in the internal and external environment.”

“Habituation is not only a gating mechanism that is extremely critical in attentional processes but it also dampens arousal (e.g., reticular activating system) and motor behavior […]. Thus habituation is a process that also involves inhibitory control. Stated differently, the same mechanisms of habituation would be recruited to sustain willed attention to an activity (e.g., habituating to environmental distractors in order to read a book) and to automatically capture attention if the demands of the environment change (e.g., sound of a fire alarm that pulls our attention from reading). Overall, research findings indicate that habituation processes are impaired in ADHD […], ASD [autism spectrum disorder] […] and TBI [traumatic brain injury] […]. Moreover, the deficits in habituation facilitate the explanation of the characteristic symptoms of these disorders […] At the present time however, the underlying neural correlates of habituation can only be speculated”.

There isn’t a lot of research supporting the ‘research findings’ part above (the ASD part is only supported by one “unpublished manuscript”…), but this seems to be the kind of stuff some people are looking into these days.

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“Habituation is a reduction in responsiveness to repeated or prolonged stimulation; that allows nervous system filters to identify biologically less relevant input in the flow of sensory information, and in turn devote more attention and processing energy toward more relevant or dynamic stimuli. This form of non-associative learning enables an animal to perceptually deemphasize persistent o[r] static stimuli in favour of novel of changing stimuli. Habituation has been described experimentally in multiple sensory modalities within various invertebrate and vertebrate species including sea slugs, fruit flies, nematodes, birds and mammals [1]. The observed decrements in responding in reflexive behavior are not mediated by motor fatigue or adaptation at the level of sensory receptors. The distinction between fatigue and habituation is commonly made by demonstrating that the response decrement is specific to the repeated stimulus [2], [3]. Change in stimulation, such as introduction of an intense stimulus, allows a return of responsiveness (dishabituation) or heightened responsiveness (sensitization). […] Habituation reflects an intact central nervous system (CNS) with normal functioning [10]; habituation can be detected before birth [11–13] and can be used to evaluate the maturation of the fetal CNS [14].”

“Habituation in olfaction allows the olfactory system to maintain equilibrium with the odorant concentrations in the ambient environment, yet respond appropriately to the appearance of novel odors or changes in odorant concentration. Olfactory habituation can be induced by multiple paradigms that differ in timescale and are thought to be mediated by distinct mechanisms within different regions of the olfactory system […] Some studies have revealed that the odors are processed differently in relation to their valence: chemosensory evoked potentials towards pleasant and unpleasant odors change with repeated presentation [47], in particular unpleasant odor produced earlier response, as for fulfil their warning function about potential threats [48].”

“The traditional definition of motion sickness has been the onset of vomiting or nausea experienced by the land, air, sea, or space traveler that results in impaired function. Motion sickness can be induced […] by either physical motion or stimuli that result in perceived motion […] Manifestations of motion sickness may include visual and postural instability, pallor, diaphoresis, excess salivation, sweating, dizziness, malaise, headaches , anxiety, hyperventilation, nausea and vomiting. All of them are attributable to activation of the autonomic system in response to vestibular stimuli [50], as if motion sickness itself could have evolved from a system designed to protect from potential ingestion of neurotoxins, by inducing vomiting when unexpected central nervous system inputs are detected (the “toxin detector” hypothesis)[51]. Less popular alternatives to the toxin detector hypothesis propose that motion sickness could be the result of aberrant activation of vestibular-cardiovascular reflexes [52], or that motion sickness is a unfortunate consequence of the physical proximity of the motion detector (vestibular) and vomiting circuitry in the brainstem [53]. […] a conflict between visual and vestibular information regarding spatial orientation has been identified as the primary causal factor for motion sickness [56]. […] The principles of habituation have been applied with varying success to reduce or prevent motion sickness in pilots and astronauts [57–59]. Habituation programs pioneered by military are effective but time consuming. […] Research on habituation training has focused on the use of visual or vestibular stimuli, and results support the concept that habituation is stimuli-specific [62]: tolerance to car travel may have no effect on susceptibility to seasickness.”