Toward a more precise, clinically—informed pathophysiology of pathological laughing and crying

Lauterbach, Edward C.; Cummings, Jeffrey L.; Kuppuswamy, Preetha Sharone

doi:10.1016/j.neubiorev.2013.03.002

Cited by 83 publications

(70 citation statements)

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“…34,36 In the hypothesis proposed by Parvizi et al 9 to explain PBA, inputs from the frontal and association cortex to the cerebellum are used to modulate the duration and intensity of facio-respiratory muscle activation in emotional expression. Our imaging data support this hypothesis, and suggest that PBA can be considered a "dysmetria" of emotional expression 1,8 that results from loss of corticopontine inputs. However, it is important to note that diffusion changes were also seen in white matter tracts from the motor cortex.…”

Section: Statistical Analysis Of Clinical Data Continuous Demographicsupporting

confidence: 78%

“…32 Functional imaging studies suggest that the network for emotional processing includes the prefrontal and orbitofrontal cortex, insula, anterior cingulate cortex, and regions of the cerebellum. 1,33,34 Clinical observations of stroke patients who developed emotional facial paresis in the setting of preserved volitional expression also implicate the frontal cortex. 7,35 The cerebellum has been shown to have a modulatory role in behavioral and cognitive control, receiving input from frontal and paralimbic cortex through pontine relay nuclei.…”

Section: Statistical Analysis Of Clinical Data Continuous Demographicmentioning

confidence: 99%

“…1 It occurs in several neurologic disorders, including amyotrophic lateral sclerosis (ALS). 2,3 In one retrospective series, PBA occurred in 50% of patients with ALS.…”

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confidence: 99%

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Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders

et al. 2014

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Objective: The objectives of the study were (1) to determine the prevalence and characteristics of pseudobulbar affect (PBA) in patients with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) in an outpatient clinic population, and (2) to test the hypothesis that damage of inputs to the cerebellum, leading to cerebellar dysmodulation, is associated with PBA.Methods: Chart review of all patients with PLS and ALS seen between 2000 and 2013. The examining neurologist documented the presence or absence of PBA in 87 patients. Fortyseven patients also had diffusion tensor imaging (DTI) studies. Tract-based spatial statistics were used to compare DTI of patients with and without PBA to identify altered white matter tracts associated with PBA.Results: Thirty-one of 50 patients with PLS and 12 of 37 patients with ALS had PBA. Psychiatric/emotional assessment found congruence between mood and affect during episodes, but excessive magnitude of the response. DTI studies of 25 PLS and 22 ALS patient brains showed reduced fractional anisotropy of the corticospinal and callosal white matter tracts in all patients. Patients with PBA additionally had increased mean diffusivity of white matter tracts underlying the frontotemporal cortex, the transverse pontine fibers, and the middle cerebellar peduncle.Conclusions: PBA is common in PLS. Imaging findings showing disruption of corticopontocerebellar pathways support the hypothesis that PBA can be viewed as a "dysmetria" of emotional expression resulting from cerebellar dysmodulation. Neurology ® 2014;83:620-627 GLOSSARY ALS 5 amyotrophic lateral sclerosis; ALSbi 5 amyotrophic lateral sclerosis with mild behavioral impairment; ALSci 5 amyotrophic lateral sclerosis with mild cognitive impairment; ALSFRS-R 5 Amyotrophic Lateral Sclerosis Functional Rating Scale-revised; BDI-II 5 Beck Depression Inventory-II; DRS-2 5 Mattis Dementia Rating Scale-2; DTI 5 diffusion tensor imaging; FA 5 fractional anisotropy; FSL 5 FMRIB's Software Library; PBA 5 pseudobulbar affect; PLS 5 primary lateral sclerosis; TFCE 5 threshold-free cluster enhancement; UCLA 5 University of California Los Angeles.Pseudobulbar affect (PBA) is a syndrome of involuntary emotional expression dissociated from one's true emotional experience.1 It occurs in several neurologic disorders, including amyotrophic lateral sclerosis (ALS).2,3 In one retrospective series, PBA occurred in 50% of patients with ALS. 4 There have been case reports of PBA in patients with primary lateral sclerosis (PLS), a motor neuron disorder variant with relatively selective degeneration of upper motor neurons. However, the prevalence of PBA in PLS has not been evaluated in a large patient series. 2,6 To assess the occurrence of PBA in PLS, we reviewed the charts of all patients seen in an upper motor neuron disorder clinic.Two hypotheses have been proposed regarding the neural circuits that produce PBA. Wilson 7 proposed that brainstem centers controlling laughter and crying were separately controlled by volitional a...

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Section: Statistical Analysis Of Clinical Data Continuous Demographicsupporting

confidence: 78%

Section: Statistical Analysis Of Clinical Data Continuous Demographicmentioning

confidence: 99%

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Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders

et al. 2014

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“…It has been suggested that pathological laughter is a manifestation of seizure activity in the brain (39). It is possible that the abnormal EEGs, the enhanced response to acoustic stimuli, and the failure to suppress USV production, reflect a common neural abnormality, possibly a defect in inhibition.…”

Section: Discussionmentioning

confidence: 99%

Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated by reducing Arc expression

Mandel‐Brehm

Salogiannis

Dhamne

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Angelman syndrome (AS) is a neurodevelopmental disorder arising from loss-of-function mutations in the maternally inherited copy of the UBE3A gene, and is characterized by an absence of speech, excessive laughter, cognitive delay, motor deficits, and seizures. Despite the fact that the symptoms of AS occur in early childhood, behavioral characterization of AS mouse models has focused primarily on adult phenotypes. In this report we describe juvenile behaviors in AS mice that are strain-independent and clinically relevant. We find that young AS mice, compared with their wild-type littermates, produce an increased number of ultrasonic vocalizations. In addition, young AS mice have defects in motor coordination, as well as abnormal brain activity that results in an enhanced seizure-like response to an audiogenic challenge. The enhanced seizure-like activity, but not the increased ultrasonic vocalizations or motor deficits, is rescued in juvenile AS mice by genetically reducing the expression level of the activity-regulated cytoskeleton-associated protein, Arc. These findings suggest that therapeutic interventions that reduce the level of Arc expression have the potential to reverse the seizures associated with AS. In addition, the identification of aberrant behaviors in young AS mice may provide clues regarding the neural circuit defects that occur in AS and ultimately allow new approaches for treating this disorder.Angelman syndrome | ARC | EPHEXIN5 | ultrasonic vocalizations | EEG

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“…As a relay station in the limbic vocalization-control pathway, it serves a gating function in the initiation of involuntarily produced vocalisations ( [18,30]; research mainly in monkeys). Although the exact mechanisms remain elusive, the PAG appears to play a role in the production of human laughter [12,[31][32][33]. Functional magnetic resonance imaging has revealed PAG-activity to occur in conjunction with involuntarily produced laughter [19].…”

Section: Introductionmentioning

confidence: 99%

Reduction in 50-kHz call-numbers and suppression of tickling-associated positive affective behaviour after lesioning of the lateral hypothalamic parvafox nucleus in rats

Roccaro-Waldmeyer

Babalian

Müller

et al. 2016

Behavioural Brain Research

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h i g h l i g h t s• Wistar rats were tickled before and after excitotoxic lesioning of the lateral hypothalamic parvafox nucleus.• Ultrasonic vocalisations (USVs) that were emitted during the tickling of rats and their tendency to approach and follow the experimenter's hand were analysed.• Lesioning was considered successful if the number of parvalbuminimmunoreactive (PV-ir) cells in the area of the parvafox nucleus was reduced beyond a threshold level.• Rats with bilaterally successful lesions manifested the most profound surgery-associated reduction in the number of 50-kHz USVs and in the tendency to approach and follow the experimenter's hand.• Positive correlations were found between each of the four investigated parameters. g r a p h i c a l a b s t r a c tThe parvafox nucleus is located ventrolaterally in the lateral hypothalamic area (LHA). Its core and shell are composed of neurons expressing the calcium-binding protein parvalbumin (PV) and the transcription factor Foxb1, respectively. Given the known functions of the LHA and that the parvafox nucleus receives afferents from the lateral orbitofrontal cortex and projects to the periaqueductal gray matter, a functional role of this entity in the expression of positive emotions has been postulated.The purpose of the present study was to ascertain whether the deletion of neurons in the parvafox nucleus influenced the tickling-induced 50-kHz calls, which are thought to reflect positive affective states, in rats. To this end, tickling of the animals (heterospecific play) was combined with intracerebral injections of the excitotoxin kainic acid into the parvafox nucleus.The most pronounced surgery-associated reduction in 50-kHz call-numbers was observed in the group of rats in which, on the basis of PV-immunoreactive-cell counts in the parvafox nucleus, bilateral lesions had been successfully produced. Two other parameters that were implemented to quantify positive affective behaviour, namely, an approach towards and a following of the hand of the tickling * Corresponding author at: Institute of Anatomy, University of Fribourg, Rte A. Gockel 1, CH-1700 Fribourg, Switzerland.E-mail address: marco.celio@unifr.ch (M.R. Celio). 1Published in which should be cited to refer to this work.http://doc.rero.ch experimenter, were likewise most markedly suppressed in the group of rats with bilaterally successful lesions. Furthermore, positive correlations were found between each of the investigated parameters. Our data afford evidence that the parvafox nucleus plays a role in the production of 50-kHz calls in rats, and, more generally, in the expression of positive emotions.

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Toward a more precise, clinically—informed pathophysiology of pathological laughing and crying

Cited by 83 publications

References 235 publications

Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders

Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders

Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated by reducing Arc expression

Reduction in 50-kHz call-numbers and suppression of tickling-associated positive affective behaviour after lesioning of the lateral hypothalamic parvafox nucleus in rats

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