Applause sign

The applause sign can indicate frontal lobe dysfunction[3] because deliberate movement functions are localised to the brain's frontal lobe, meaning all control of deliberate movement like clapping is the responsibility of frontal lobe structures.[7] Hence, when the frontal lobe functions abnormally, an inability to execute movement according to intention[8] results.

Ability to stop actions as and when intended is a process key to the applause sign, and to which voluntary movement control is integral. The inferior frontal gyrus is the specific part of the frontal lobe[9] responsible for generating stop processes.[10][11][12] Hence, when a patient experiences frontal lobe dysfunction, the inferior frontal gyrus is impacted, resulting in movement perseveration (an abnormal prolongation of current activity),[13] and appearance of the applause sign.

Higher frequency of the applause sign in severe than mild and moderate Alzheimer's[4] evidences this mechanism, with frontal lobe dysfunction only a feature of severe cases.[14][15] FMRI studies in healthy participants also show increased activity in the frontal lobe during stop-signal tasks similar to the TCT.[16]

The applause sign can also reflect dysfunction of the subthalamic nucleus (STN) and pallidum,[5] two structures involved in function of the basal ganglia (a small group of brain structures involved in voluntary movement control networks).

The basal ganglia and its relevant substructures

Normal function of the STN prevents unwanted movement through its influence in the basal ganglia. It stimulates the pallidum to decrease activity in the thalamus, another structure implicated in movement control, which decreases movement.[17] Hence, when the STN is dysfunctional, unwanted movements such as additional claps go unprevented,[18] and we see appearance of the applause sign.

This mechanism is supported by correlation between TCT scores and high scores from a test of basal ganglia dysfunction (UPDRS part III).[5][19]

One study[2] proposes a combined mechanism, involving both the basal ganglia and the inferior frontal gyrus.

When basal ganglia pathways are dysfunctioning, the inferior frontal gyrus and other motor preparation areas stop receiving normal input from the basal ganglia about when to stop preparing and executing observed actions.[20] This results in continuous activity in this imitation processing circuitry.[20] Hence, we observe an inability to stop imitation of claps when desired during the TCT.

This mechanism may reflect increased prevalence of the sign in PSP patients,[2] since PSP is associated with damage to both the frontal lobe and basal ganglia structures simultaneously. It may also explain why the sign appears regardless of if the individual's condition is predominantly frontal or predominantly subcortical (the level of the basal ganglia).

The Applause Sign has been able to identify patients with neurodegenerative conditions from healthy controls at 100% success rate.[1][3][5]

Separating PSP patients and healthy controls using the sign had a mean success rate of 64.7% across 4 known studies, effectiveness as high as 85% in one.[5][21][22][24]

Appearance of the sign, when used in conjunction with 4 classical parkinsonian disease findings, enables highly accurate PSP diagnosis .[25]

One study reported the sign as present in 80% of patients with the disinhibited subtype of the behavioral variant of FTD (bvFTD).[24]

TCT scores show correlation with Stroop Test scores[24] and performance on the Initiation/Preservation task of the Dementia rating scale results,[26] which are both common measures of executive function.

A Rapid Cognitive Screen Test (RCS-T) combined with a triple test of the applause and two other signs appears effective in identifying specific cognitive impairment.[27]

The applause sign is detectable in any condition impacting the frontal lobe,[3] so it often fails to discriminate between neurodegenerative conditions, including PSP from Parkisnonian disorders, and CBD from MSA.[21] The applause sign is also present in 72% of patients with any form of cognitive impairment, regardless of whether this is mild cognitive impairment (MCI) or dementia.[28]

Additionally, it may also reflect only certain condition subtypes, rather than all forms: in one study, prevalence of applause sign was 63% in atypical parkinsonism and only 29% in typical PD.[20] Another reported the occurrence of the sign in cortical dementias patients as 10%, but a much higher 39% in cortico-subcortical dementia patients.[23]

The applause sign also fails to discriminate between individuals who clap more and individuals who clap less[24] than 3 times, sometimes called a non-applause sign. Both of these demonstrate an applause sign, but which of these response categories they fall into changes the dysfunctional motor initiative responsible for failure.[24]

The applause sign's non-specificity may make it more appropriate as part of wider diagnostic framework, or as an observational clue, similar to glabellar, masseter, and palmomental signs in Parkinsonian disorders.[2]

One study finds no correlation between results of a test of motor behaviour (Luria motor sequence) and the applause sign.[4] If the applause sign demonstrates motor disruption as theorised,[5] then this presents significant opposition to that claim.

This criticism has been downplayed on the basis that applause sign exclusively reflects motor perseveration and therefore association to performance in motor planning and execution tests is unlikely.[4]

22 distinct studies exist[2] on the applause sign and its effectiveness. Within this, only 129 PSP patients have been examined across 6 studies, including one sample of only 5.[2] Relation to CBD is based on 2 studies sampling 2 and 9 participants.[2] Small sample sizes hugely reduce generalisability of findings. Further studies about the diagnostic properties of the applause sign must come forward to clarify its practical value and specific role as a sign of frontostriatal disconnection.[2]