Orofacial Stereotypies Research Articles

Mommy or me? Who is the agent in a sense of agency in infant orofacial stereotypies?

That neonates imitate is an assertion that lacks supporting evidence. Orofacial stereotypies are critical to optimizing food rejection. Matching of tongue-protrusion is not imitation, but a manifestation of the infant's arousal by the modeler's exhibition of the same behavior. The support for the nativist assertion that newborn infants imitate is not compelling, and we should proceed on the assumption that they do not.

Neonatal imitation in context: Sensorimotor development in the perinatal period.

More than 35 years ago, Meltzoff and Moore (1977) published their famous article, "Imitation of facial and manual gestures by human neonates." Their central conclusion, that neonates can imitate, was and continues to be controversial. Here, we focus on an often-neglected aspect of this debate, namely, neonatal spontaneous behaviors themselves. We present a case study of a paradigmatic orofacial "gesture," namely tongue protrusion and retraction (TP/R). Against the background of new research on mammalian aerodigestive development, we ask: How does the human aerodigestive system develop, and what role does TP/R play in the neonate's emerging system of aerodigestion? We show that mammalian aerodigestion develops in two phases: (1) from the onset of isolated orofacial movements in utero to the postnatal mastery of suckling at 4 months after birth; and (2) thereafter, from preparation to the mastery of mastication and deglutition of solid foods. Like other orofacial stereotypies, TP/R emerges in the first phase and vanishes prior to the second. Based upon recent advances in activity-driven early neural development, we suggest a sequence of three developmental events in which TP/R might participate: the acquisition of tongue control, the integration of the central pattern generator (CPG) for TP/R with other aerodigestive CPGs, and the formation of connections within the cortical maps of S1 and M1. If correct, orofacial stereotypies are crucial to the maturation of aerodigestion in the neonatal period but also unlikely to co-occur with imitative behavior.

Late Onset Neurodegeneration with Brain-Iron Accumulation Presenting as Parkinsonism

Neurodegeneration with brain-iron accumulation (NBIA) encompasses a family of neurodegenerative disorders connected by evidence of abnormal brain iron deposition. Advances in imaging and genetic testing expanded the clinical spectrum of these disorders. Here, a case of parkinsonism and dystonia with orofacial stereotypies is presented. While the patient was initially diagnosed with Parkinson's disease and placed on levodopa therapy, dopamine transporter imaging via (123)I-FP-CIT SPECT (DaTSCAN) was normal. MRI brain showed “eye of the tiger” sign on T2 weighted imaging. NBIA should be considered in the differential diagnosis of atypical parkinsonism.

Palatal tremor and orofacial stereotypies within the locked‐in syndrome

Palatal tremor and orofacial stereotypies within the locked‐in syndrome

Effects of the H 3-receptor inverse agonist thioperamide on the psychomotor effects induced by acutely and repeatedly given cocaine in C57BL/6J mice

Previous studies have shown that histamine H 3 blockers potentiate the psychomotor and rewarding effects of cocaine. The present study examined the influence of thioperamide, an inverse H 3 receptor agonist, on the development of psychomotor sensitization and stereotyped activity induced by acute or intermittent cocaine in C57BL/6J mice. In the first experiment, mice were injected i.p. with saline, 10 or 20 mg/kg thioperamide and saline or 8 mg/kg cocaine, 10 min apart, before being tested for their locomotor activity (providing data on the acute effects of thioperamide on cocaine-induced activity). Subsequently, mice were treated in the same manner every other day over six additional sessions. Sensitization was assessed by the responsiveness to a cocaine challenge (8 mg/kg, i.p.) given 2 and 14 days following the intermittent treatment. In experiments 2 and 3, we tested the effects of thioperamide (10 or 20 mg/kg, i.p.) on gnawing and sniffing induced or affected by relatively high doses of cocaine (24 or 32 mg/kg, s.c.), the drugs being given 10 min apart. In the first experiment, both doses of thioperamide amplified cocaine-induced psychomotor hyperactivity almost on all experimental sessions. However, the histamine inverse agonist did not affect the induction of a psychomotor sensitization. All cocaine-treated mice showed similar levels of sensitized activity 2 and 14 days after the intermittent treatments, whether they received thioperamide or not. The second and the third experiments showed that thioperamide did not affect gnawing and sniffing induced by cocaine. Taken together, these results indicate that H 3 receptors clearly contribute to the neurobiological mechanisms of the locomotor component of cocaine-induced psychomotor activation, but less likely to those underlying the development of cocaine behavioral sensitization or the expression of cocaine-induced oro-facial stereotypies.

Effect of Methamphetamine on Cognition and Repetitive Motor Behavior of Mice Deficient for Dopamine D2 and D3 Receptors

Mice deficient for dopamine D2 and D3 receptors exhibit blunted D(1)-receptor responses to agonist stimulation. This blunted D1-receptor activity is prominent in the medial prefrontal cortex (mPFC) and results in a significantly impaired performance of the mutants in a test for spatial working memory. A single dose of methamphetamine (METH; 5 mg/kg i.p.), however, elicits a long-lasting increase in agonist-stimulated D1 receptor activity in the mPFC. In D2 mutants, this increase reaches wild-type levels, and the working memory of METH-treated mutants is completely rescued. In D3 mutants, however, the METH-induced increase in D1-receptor activity remains below wild-type levels and does not result in improved working memory performance. D2 and D3 mutants also differ in their locomotor responses to METH. Repeated administration of this drug (5 mg/kg administered three times at 2-h intervals) leads to a transition from horizontal hyperlocomotion to excessive orofacial stereotypy (taffy pulling) only in wild type and D3 mutants. In both genotypes, this transition is accompanied by a change in the relative ratios of striatal neuronal activation in two neurochemically distinct compartments, with striosomal neuronal activation exceeding that of the striatal matrix during stereotypy. Both the stereotypic response to METH and the associated predominant activation of neurons located in striosomes require D2-receptor expression. These studies indicate a differential requirement for D1- and D2-like receptor activation in mediating the effects of METH on cognitive and motor function.

P.6.034 Role of dopamine D1 receptor on dopaminergic supersensitivity induced by sleep deprivation in mice

Stereotyped behavior and striatal c-fos levels induced by chronic treatment with the D1 dopamine antagonist SCH 23390 have been investigated in rats which received subsequent subacute dopamine agonist treatment. SCH 23390 treatment (0.5 mg/kg/day) for 21 days increased both apomorphine-induced orofacial stereotypies and striatal c-fos levels. Treatment with the D1 dopamine agonist SKF 38393 (10 mg/kg/day) and the combination of SKF 38393 with the D2 dopamine agonist quinpirole (1 mg/kg/day), for 5 consecutive days, attenuated apomorphine-induced stereotypies without changing c-fos levels in rats previously treated with SCH 23390. These findings suggest that SCH 23390-induced behavioral supersensitivity and the increased striatal c-fos levels are concomitant but unrelated phenomena.

Conditioned hyperkinesia induced by cocaine in mice is dose-dependent but not correlated with the unconditioned response or the contextually-sensitized response

The aims of the study were to test whether drug dose is positively related to the magnitude of the conditioned response following sensitization to the behavioural effects of cocaine and to investigate the relationship between the conditioned response and cocaine-induced sensitization. Male mice (C57BL/6J) were first injected over seven successive days with either saline or cocaine at 2.5, 5, 10 or 20 mg/kg s.c., in the testing room. On the test day, 24 h after the last injection, mice from all conditions were challenged with saline in the testing room to test for conditioned cocaine effects. Mice were video-recorded and various behaviours were later scored using a time-sampling technique. Cocaine-elicited orofacial stereotypy was significantly sensitized at the two highest doses and dose-dependently conditioned at the three highest doses. Cocaine-increased locomotion was sensitized at the three highest doses and significantly conditioned at 10 and 20mg/kg. Cocaine-increased sniffing did not change over pretreatment at any dose, and was conditioned only at 10 mg/kg. Cocaine-decreased immobility also did not change over pretreatment at any dose, but was conditioned at 10 and 20mg/kg. Concomitantly, rearing was reduced by cocaine at 10 and 20mg/kg, without sensitization being induced, and it was reduced under saline challenge after 5 mg/kg cocaine, while cocaine-decreased grooming was sensitized at the three highest doses and conditioned at 10 and 20 mg/kg cocaine. There was a positive relation between the size of the conditioned response for orofacial stereotypy and the magnitude of the unconditioned stimulus (the doses), a result conforming to the Pavlovian account of the placebo effect. This could also be concluded from considering the behaviour patterns as components of a unique placebo effect (hyperkinetic syndrome), since orofacial stereotypy, very apparent at 20 mg/kg cocaine, interfered at that dose with the full-blown expression of locomotion and sniffing, both yielding (approximately) inverted U-shaped dose-effect curves. However, no correlation was found between the magnitude of the conditioned response and the amplitude of sensitization (the difference between the initial unconditioned non-sensitized response and the last unconditioned sensitized response), a finding which indicates that conditioned responding does not participate in the generation of the sensitized effects, contrary to the 'excitatory conditioning model of contextual sensitization'.

SCH 23390-induced behavioral supersensitivity is not related to striatal c- fos levels

Stereotyped behavior and striatal c- fos levels induced by chronic treatment with the D 1 dopamine antagonist SCH 23390 have been investigated in rats which received subsequent subacute dopamine agonist treatment. SCH 23390 treatment (0.5 mg/kg/day) for 21 days increased both apomorphine-induced orofacial stereotypies and striatal c- fos levels. Treatment with the D 1 dopamine agonist SKF 38393 (10 mg/kg/day) and the combination of SKF 38393 with the D 2 dopamine agonist quinpirole (1 mg/kg/day), for 5 consecutive days, attenuated apomorphine-induced stereotypies without changing c- fos levels in rats previously treated with SCH 23390. These findings suggest that SCH 23390-induced behavioral supersensitivity and the increased striatal c- fos levels are concomitant but unrelated phenomena.

Serotonergic stimulation of the ventrolateral striatum induces orofacial stereotypy

Dopaminergic (DA) stimulation of the ventrolateral Striatum produces a syndrome of intense orofacial stereotypies. In addition to dopaminergic projections from the substantia nigra, the Striatum receives Serotonergic (5-HT) inputs arising from the raphe nuclei. To assess the putative role of striatal 5-HT in orofacial movements, serotonin (0, 0.2, 2, 10, 20 μg/1.0 μl) was infused into the ventrolateral Striatum and behaviors were recorded using a time-sampling procedure. Serotonin produced a dose-dependent, site-specific increase in stereotyped orofacial behaviors. Infusion of selective 5-HT receptor agonists or uptake inhibitors did not produce the orofacial syndrome and pretreatment with either selective or nonselective 5-HT receptor antagonists did not block the 5-HT induced Stereotypy. In contrast, pretreatment with DA receptor antagonists completely abolished the 5-HT induced repetitive orofacial movements, providing evidence for a 5-HT/DA interaction at this site. Moreover, depletion of DA with a combination of reserpine and α-methyl- p-tyrosine markedly decreased the stereotyped behaviors induced by 5-HT microinfusion. These data provide evidence for an interaction between 5-HT and DA in the Striatum at presynaptic DA terminals. It is hypothesized that 5-HT may cause release of DA via reversal of the DA transporter. This syndrome may provide an animal model for some aspects of obsessive-compulsive disorder, because current theories of this disorder implicate 5-HT dysfunction in the basal ganglia.

Oral stereotypy induced by amphetamine microinjection into striatum: An anatomical mapping study

The ventrolateral striatum has been shown to specifically contribute to expression of psychostimulant-induced orofacial stereotypies. Adult male Sprague-Dawley rats were implanted with bilateral cannulae directed at one of eight striatal subareas, and were injected with saline or amphetamine (20 μg/0.5 /μ1/side) in a counterbalanced order. Behaviors were observed and scored using a time-sampling procedure. In the middle ventrolateral striatum, amphetamine injections produced intense stereotypy, primarily consisting of bar biting, non-injurious self-biting and repetitive paw-to-mouth movements, while having no effect on locomotion or rearing. Amphetamine injections 2 mm medial or 1 mm dorsal produced no oral stereotypy, while injections 1 mm rostral or caudal to the effective site produced only low levels of stereotypy. Injections into the surrounding sites, particularly in the ventromedial region, also had stimulatory effects on locomotion and rearing. In a separate experiment, animals were given either unilateral or bilateral injection of amphetamine into the ventrolateral striatum. The unilateral injection produced stereotypy half as intense as that observed with bilateral injections. These results suggest that the ventrolateral striatum is a discrete neuroanatomical region which is primarily responsible for expression of psychostimulant-induced orofacial stereotypies, and which is likely to be the striatal region controlling normal oral motor function. Further investigation of this area may provide valuable insights concerning the etiology and treatment of orofacial dyskinesias associated with basal ganglia dysfunction.

Excitatory amino acid receptors mediate the orofacial stereotypy elicited by dopaminergic stimulation of the ventrolateral striatum

The present experiments examined the role of excitatory amino acid receptors in the orofacial stereotypy induced by direct amphetamine microinjection into the ventrolateral striatum. In these experiments, the influence of prior intra-ventrolateral striatum treatment with various excitatory amino acid antagonists on the expression of amphetamine-stimulated oral stereotypy was observed. In all experiments, behavioral observations were conducted in the home cage using a time-sampling procedure. In the first experiment, different groups of rats received bilateral microinfusions of either kynurenic acid, 2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline or dizocilpine maleate. The excitatory amino acid antagonists were administered immediately prior to bilateral microinfusions of d-amphetamine. Both N-methyl- d-aspartate and non- N-methyl-D-aspartate antagonists dose-dependently attenuated or blocked the expression of dopamine-mediated stereotypy. 2-Amino-5-phosphonopentanoic acid was the most potent of these compounds, totally suppressing stereotypy at a dose of 0.3 μg (equivalent to 1.5 nmol). In the second experiment, the same compounds were tested for their ability to suppress physostigmine-induced mouth movements. Cholinergic stimulation of the ventrolateral striatum has previously been shown to elicit non-directed mouth movements, quite distinguishable from stimulus-directed, amphetamine-induced biting. Excitatory amino acid antagonists were administered in the same doses prior to bilateral infusion of physostigmine (2.5 μg/0.5 μl). The expression of physostigmine-induced mouth movements was for the most part not affected by excitatory amino acid antagonists, although dizocilpine maleate slightly reduced this oral behavior. In a third experiment, behavior was observed following infusion of the antagonists alone, using the same doses as in the previous experiments. No behavioral alterations were observed with the exception of a small increase in nonspecific mouth movements induced by kynurenic acid and 2-amino-5-phosphonopentanoic acid. These findings indicate that the expression of dopamine-mediated oral stereotypy, induced by amphetamine stimulation of the ventrolateral striatal region, is highly dependent on activation of striatal excitatory amino acid receptors. In contrast, oral behavior induced by cholinergic stimulation of the ventrolateral region is not mediated by glutamate input. These results are discussed in relation to the synaptic organization of neuronal elements within the striatum. Moreover, the relevance to further understanding of orofacial dyskinesias is noted.

An investigation into the role of the pedunculopontine tegmental nucleus in the mediation of locomotion and orofacial stereotypy induced by d-amphetamine and apomorphine in the rat

As the pedunculopontine tegmental nucleus has an important anatomical position as an output station for the striatum, its role in the mediation of behaviour stimulated by d-amphetamine and apomorphine was investigated. Bilateral ibotenate lesions were made in either the pedunculopontine tegmental nucleus or, as a control, in the adjacent deep mesencephalic nucleus; sham lesions were made using phosphate buffer. Over the 14 days after surgery there were no significant differences in the rats' body weight or food intake. Deep mesencephalic lesioned rats spilled more food and drank more water (never more than 5 ml more) than controls or pedunculopontine tegmental lesioned rats. Spontaneous locomotion and that elicited by d-amphetamine or apomorphine were not affected by ibotenate lesions of either the pedunculopontine tegmental nucleus or deep mesencephalic nucleus. At higher doses of d-amphetamine and apomorphine, however, excessive biting and licking were observed in the pedunculopontine tegmental nucleus, but not deep mesencephalic nucleus, lesioned rats. Such orofacial stereotypies are never observed in normal rats after systemic injection of d-amphetamine. Post mortem analysis showed that ibotenate lesions of the pedunculopontine tegmental nucleus had destroyed cholinergic and non-cholinergic neurons there but had left the deep mesencephalic nucleus intact; ibotenate lesions of the deep mesencephalic nucleus destroyed neurons in that structure but not the pedunculopontine tegmental nucleus. These data demonstrate that lesions in the pedunculopontine tegmental nucleus and deep mesencephalic nucleus have different effects, measured histologically and behaviourally; that neither spontaneous locomotion nor that stimulated by d-amphetamine or apomorphine is dependent on the integrity of the pedunculopontine tegmental nucleus; and that the pedunculopontine tegmental nucleus plays an important role in mediating orofacial activity stimulated by these drugs. The data are discussed in terms of their implications for understanding outflow from the caudate-putamen and nucleus accumbens.

Neurotensin selectively antagonizes apomorphine-induced stereotyped climbing

In order to better characterize the neuroleptic properties of neurotensin, the dose-related effects of the peptide on stereotyped climbing, sniffing and licking induced by 0.6 mg/kg apomorphine were examined. The following doses of the peptide were injected intraventricularly 30 min prior to apomorphine administration: 0.9, 3.75, 30.0 and 60 μg. Results indicate that, whereas oro-facial stereotypies remained unaffected by the peptide, stereotyped climbing was significantly decreased with the two largest doses of neurotensin. These findings indicate that the profile of neurotensin's neurobehavioral effects is more akin to that of a typical than typical neuroleptics.

A behavioral analysis of the offspring of “Haloperidol-sensitive” and “haloperidol-resistant” gerbils

The first generation (F1) offspring of haloperidol-sensitive (HS) and haloperidol-resistant (HR) gerbils were compared in a battery of motor ("catalepsy") tests, a novel cardboard-shredding (oro-facial stereotypy) test, and a holeboard (exploration) test. The F1 HS gerbils were more "cataleptic" than the F1 HR gerbils after haloperidol (1 and 3 mg/kg). The F1 HR gerbils showed more oro-facial stereotypy and more exploratory behavior than did F1 HS gerbils in undrugged tests. The F1 HS and F1 HR groups did not differ in "general activity" as measured by line crossings in an open field or by an electromagnetic monitor in the home cage. These results are preliminary behavioral evidence for a difference between HS and HR gerbils in dopaminergic or related functions.