Figure 2: QEEG maps of subject A.A. at baseline and 5, 20 & 60 minutes following the CVS

1. Beneficial effects of caloric vestibular stimulation on denial of illness and manic delusions in schizoaffective disorder Levine J1‚ Doron T, Geller V, Kraus M, Grisaru N, Gauchman T , Puterman M - Departments of Psychiatry & ENT, Ben Gurion University of the Negev, Beersheva, Israel Introduction:Caloric vestibular nerve stimulation (CVS) utilizing ice water (4°C) irrigation to the left auditory canal is a safe, non-invasive and simple procedure inducing contra-lateral right hemispheric region-specific brain activation. Imaging studies have shown widespread though largely contralateral hemispheric activation following ice water CVS. PET and functional MRI studies have identified the neural structures activated following CVS. These areas include among others: a] the temporal–parietal cortex (superior temporal gyrus, inferior parietal lobe, and temporal–parietal junction); b] the anterior cingulate cortex (ACC); c] the insular cortex; and d] putamen in the basal ganglia (Tuohimaa et al., 1983; Bottini et al., 1994; Bottini et al., 1995; Vitte et al., 1996 and Wenzel et al., 1996;Bottini et al., 2001,Suzuki M et al, 2001; Kisely et al., 2002; Emri et al., 2003; Been et al, 2007; Miller & Ngo, 2007). Ice water vestibular caloric irrigation of the left ear may thus lead to activation of these key areas in the contralateral right hemisphere. Two of these structures,the ACC and the insula were repeatedly suggested to be involved in major mental disorders including bipolar illness and schizophrenia characterized by delusional thoughts and lack of insight-judgment (see Ellison-Wright &Bullmore, 2001; Kim et al, 2003; Fornito et al, 2008; Nagai et al, 2007). There is preliminary data showing immediate positive effects of left ear CVS with ice water irrigation upon neglect, anosognosia (illness denial), cognitive processes and delusions (seeSchiff & Pulver, 1999; Been et al, 2007, Rubens,1985; Vallar et al,1990; Rode et al, 1992; Geminiani a)nd Bottini, 1992; Rode and Perenin, 1994; Vallar et al., 1997; Bächtold et al (2001);Rossetti and Rode, 2002; Adair et al., 2003; Cappa et al., 1987; Ramachandran, 1994; Rode et al, 1998)and previous descriptive case report suggested a beneficial effects for CVS in mania (Dodson, 2004 ). Methods:Recently, we studied the immediate effect of left versus right ear ice water (4°C) CVS on delusions and insight of illness in a patient (A.A.) who had a manic episode due to schizoaffective disorder. This patient (A.A) had first undergone Electronystagmography (ENG) battery tests (gaze test, positional tests, saccade, pursuit and optokinetic tests and bithermal caloric test) using a VNG/ENG (videonystagmography / electronystagmography) system [Chartr 200, next generation vestibular testing, VNG/ENG G4CH (GN Otometrics- ICS Medical Corp. Shamburg, Illinois, USA)]. All these tests were within normal range except for the pursuit test. The patient was evaluated with the Delusions item of the PANSS (P1 item) , the total PANSS positive symptoms subscale (t-P-PANSS) score and the lack of insight-judgment item of the PANSS (G12 item) to assess his clinical status at baseline prior to the CVS stimulation of one ear, immediately after and at 20, 60 minutes and 24 hours later. The same method was repeated on the other ear 4 days later. Stimulation and assessment of both ears as described above will be hereafter titled a trial. Patient A.A. had 3 trials. The first one had a qualitative nature and was aimed at estimating the effect of CVS on the patient denial of illness and psychopathology. The second trial was then held to validate the stimulation of both right and left vestibular nerves with the ice water irrigation by the use of videonystagmography. This second trial was held 7 days after the first one. The same patient then had a third trial held 7 days after the second one, to demonstrate the possible effects of the CVS on brain functions by the use of quantitativeelectroencephalography(QEEG) as well as EEG LORETA (low resolution brain electromagnetic tomography)analyses before, 5, 20 and 60 minute after the CVS stimulation of either the left or right vestibular nerves. To assess whether the effect is specific to manic delusions or can be achieved in other delusions and impaired insight of illness associated with schizophrenia, we applied the same trial (a single trial) in two other patients suffering from schizophrenia and demonstrating persecutory delusions and impaired insight of illness. Discussion: The results suggest that left versus right CVS have acute beneficial effects on manic delusions and insight of illness but that such effect may also appear in other types of psychotic disorders including schizophrenia. Such effect seems to be associated with increased bilateral frontal and central alpha EEG band. Finally LORETA analyses suggest that the ACC and the insula may not be involved in such immediate clinical effect. Videonystagmography Caloric vestibular nerve stimulation (CVS) with ice water irrigation Table 1: Pre and post CVS total PANSS, its positive subscale and key items in the three trials for patient A.A. Fig 1: Vertical (red) and horizontal (blue) nistagmus following left & right ear 4 ºC CVS (as measured by videonystagmograph) Results: The manic patient as well as the two other patients suffering from schizophrenia showed a clear difference, favouring left versus right ear CVS of at least of 2 points in the PANSS P1(delusions) item, 5 points in the t-P-PANSS and at least 1 point in the PANSS G12 (lack of insight-judgment) item. This improvement was maintained for about 20 minutes and then diminished at 60 minutes. In the manic patient the stimulation of both right and left vestibular nerves was positively validated via a second trial by the use of videonystagmography. A third trial applying EEG analyses showed increased bilateral frontal and central (more pronounced at the right hemisphere) EEG alpha band activation with the left but not the right ear CVS at 5 minutes following the CVS that diminished at 20 minutes. LORETA analyses suggested no gross changes in the ACC and insula for both left and right ear CVS for theta and alpha EEG bands. Both right and left ear CVS then showed an increased activity of these two bands from 20 to 60 minutes. Figure 2: QEEG maps of subject A.A. at baseline and 5, 20 & 60 minutes following the CVS Figure 3: The Change of theta and alpha EEG band activity in the ACC as reflected by LORETA analyses . Figure 4: The Change of theta and alpha EEG band activity in the Insula as reflected by LORETA analyses