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Right prefrontal rTMS treatment for refractory auditory command hallucinations – a neuroSPECT assisted case study
Psychiatry Research Neuroimaging 116 (2002) 113–117
Case reports
Right prefrontal rTMS treatment for refractory auditory command hallucinations – a neuroSPECT assisted case study Shaul Schreibera,*, Pinhas N. Dannonb, Elinor Goshenc, Revital Amiazb, Tzila S. Zwasc, Leon Grunhausb a
Department of Psychiatry, Tel Aviv Sourasky Medical Center and Tel Aviv University Sackler School of Medicine, 6 Weismann Street, IL-64239 Tel Aviv, Israel b Department of Psychiatry, Chaim Sheba Medical Center Tel-HaShomer and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel c Department of Nuclear Medicine, Chaim Sheba Medical Center Tel-HaShomer and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel Received 19 December 2001; received in revised form 1 July 2002; accepted 11 July 2002
Abstract Auditory command hallucinations probably arise from the patient’s failure to monitor hisyher own ‘inner speech’, which is connected to activation of speech perception areas of the left cerebral cortex and to various degrees of dysfunction of cortical circuits involved in schizophrenia as supported by functional brain imaging. We hypothesized that rapid transcranial magnetic stimulation (rTMS), by increasing cortical activation of the right prefrontal brain region, would bring about a reduction of the hallucinations. We report our first schizophrenic patient affected with refractory command hallucinations treated with 10 Hz rTMS. Treatment was performed over the right dorsolateral prefrontal cortex, with 1200 magnetic stimulations administered daily for 20 days at 90% motor threshold. Regional cerebral blood flow changes were monitored with neuroSPECT. Clinical evaluation and scores on the Positive and Negative Symptoms Scale and the Brief Psychiatric Rating Scale demonstrated a global improvement in the patient’s condition, with no change in the intensity and frequency of the hallucinations. NeuroSPECT performed at intervals during and after treatment indicated a general improvement in cerebral perfusion. We conclude that right prefrontal rTMS may induce a general clinical improvement of schizophrenic brain function, without directly influencing the mechanism involved in auditory command hallucinations. 䊚 2002 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Auditory command hallucinations; Cerebral cortex; Rapid transcranial magnetic stimulation; Schizophrenia; Single photon emission computed tomography
*Corresponding author. Tel.: q972-3-697-4707; fax: q972-3-697-4586. E-mail address: [email protected] (S. Schreiber). 0925-4927/02/$ - see front matter 䊚 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 9 2 5 - 4 9 2 7 Ž 0 2 . 0 0 0 6 5 - 3
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S. Schreiber et al. / Psychiatry Research Neuroimaging 116 (2002) 113–117
1. Introduction Imperative command hallucinations, once thought to be a source of divine inspiration or of demonic possession, are recognized as complex symptoms in neuropsychiatric disorders (du Feu and McKenna, 1999; Ohayon et al., 1996) and, within special contexts such as bereavement, as culturally bound manifestations. Functional neuroimaging allows the in vivo assessment of neural function of the hallucinating patient, before and after treatment (for review, see Weiss and Heckers, 1999). Musalek et al. (1988, 1989), using 99mTc-HMPAO-SPECT during periods of active hallucinations, demonstrated that auditory hallucinations were associated with increased activity bilaterally in the basal ganglia and the hippocampus as well as decreased activity in the lateral frontal lobes bilaterally. McGuire et al. (1993) demonstrated that the hallucinating state is associated with increased blood flow in Broca’s area, the left anterior cingulate gyrus, and the left temporal lobe. These findings support the idea that auditory hallucinations arise from the patient’s failure to monitor hisyher own thoughts and ‘inner speech’, which is therefore regarded as alien and perceived as emanating from others (Lishman, 1997). Repetitive transcranial magnetic stimulation (rTMS), administered at a frequency of 10 Hz, has been shown to increase cortical activation and has generated interest as a probe and potential treatment in several neuropsychiatric disorders (George et al., 1996). A recent report described the use of low-frequency (1 Hz) TMS of left temporoparietal cortex (Hoffman et al., 1999). Using Tc-99m-ECD-SPECT, we evaluated the effect of 4 weeks of right prefrontal rTMS treatment on treatment-resistant command hallucinations in a patient with chronic schizophrenia. 2. Methods M.S. is a right-handed, 49-year-old male, unmarried and unemployed patient, with a diagnosis of paranoid schizophrenia. He reported a 20-year history of auditory command hallucinations and was responding poorly to conventional and novel
neuroleptics. Upon admission, he was unkempt, oriented to time, place and person, and gave a coherent account of his past and current life. He was not depressed or anxious and had constricted affect. He was convinced that his neighbors were trying to kill him, and heard voices of strangers scorning him and telling him ‘you are a dead person’, but was without active suicidal ideation. Trials with clozapine and olanzapine had to be interrupted following exacerbation of his noninsulin-dependent diabetes mellitus. A full course of bilateral electroconvulsive therapy failed to affect the hallucinations. As a last resort, a trial with rTMS was offered to the patient. The patient was maintained on his psychotropic medication (haloperidol, 20 mgyday, which he had been taking for more then 3 months) with no change in dose, and he had routine laboratory evaluations. After both the patient’s voluntary informed consent and the approval of the hospital’s ethics committee had been obtained, rTMS was performed using MAGSTIM rapid equipment with four booster modules, according to a method described in detail elsewhere (Grunhaus et al., 2000). Briefly, rTMS was administered to the right dorsolateral prefrontal cortex (RDLPFC), with 1200 magnetic stimulations being administered daily for 20 days at 90% motor threshold, 5 days a week for 4 weeks – a total of 20 daily sessions. Each session consisted of 20 trains of 6-s duration, at 10-Hz frequency, separated by 1 min each. Motor threshold was measured before each session. The coil placement over the RDLPFC was decided following documentation of right hypofrontality in pre-treatment single photon emission computed tomography (SPECT), and the intensity of 10 Hz was chosen because we wanted excitatory pulses. NeuroSPECT studies were performed four times: at baseline (before 1st treatment), after 5 treatments and again at the end of 20 treatments. A follow-up neuroSPECT was performed 6 weeks after the rTMS treatment course ended. Each neuroSPECT was performed 15 min following i.v. injection of 30 mCi (740 MBq) Tc-99m-ECD, using a dual-headed gamma camera equipped with fan-beam collinators. The data were acquired over 3608 in 38 angular steps in a 128=128 matrix, attenuation-corrected and reconstructed using a
S. Schreiber et al. / Psychiatry Research Neuroimaging 116 (2002) 113–117 Table 1 Psychiatric rating scale evaluations before, during and after the rTMS treatment course Rating scale Scores Baseline 1 week End of treatment Follow-up PANSS BPRS 17-Ham-D MMSE GDR PSQI
76 49 13 23 1 4
72 41 13 23 1 5
64 34 11 26 0 6
66 47 13 24 1 4
Metz back-projection filter. All studies were normalized to cerebellar activity. Psychiatric evaluation included a 100-mm visual analogue scale for daily monitoring of the intensity of the auditory command hallucinations, the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Symptoms Scale (PANSS), the 17-item Hamilton Psychiatric Rating Scale for Depression (17-Ham-D), the Global Depression Scale (GDR), the Pittsburgh Sleep Quality Index (PSQI), and the Mini Mental State Examination (MMSE). 3. Results 3.1. Clinical findings Clinically, the patient’s global condition at the end of the 20 rTMS treatments was improved: he was more cooperative, better groomed, and much more willing to participate in the occupational therapy program. However, as far as he could tell, there was no change in the content, intensity or frequency of his hallucinations. Both BPRS and PANSS scores improved (PANSS from 76 to 64, BPRS from 49 to 34) during the treatment course; however, changes in other rating scales were minor and non-significant. At follow-up 6 weeks after the rTMS treatment ended, all scores but the PANSS returned to pre-rTMS treatment baseline (Table 1). 3.2. SPECT findings Pre-treatment baseline brain SPECT with Tc99m-ECD demonstrated decreased perfusion in the
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left cerebellar and right temporal regions and slightly decreased perfusion in bilateral inferofrontal regions, more prominent on the right, as well as mild, non-homogeneous uptake in the caudate nuclei. The second neuroSPECT, performed after five treatments, showed an overall improvement in cerebral perfusion, including temporal and cerebellar regions, as well as the basal ganglia. The third neuroSPECT evaluation, performed at the end of the 20-treatment course of rTMS, demonstrated a slight further improvement in the general cortical perfusion, as well as in subcortical regions. A fourth neuroSPECT, performed 6 weeks after rTMS treatment ended, indicated a general improvement in perfusion, primarily in frontal, infero-frontal and temporal regions, more prominent on the right, and an increased uptake in the left thalamus (Figs. 1 and 2). 4. Discussion The neural systems involved in the perception of hallucinations appear to involve the same modality-specific cerebral structures implicated in ‘normal’ perception, including mental imagery. In the case of verbal auditory hallucinations, increased activity in both primary and secondary auditory cortex appears consistently throughout the literature, occasionally associated with activity in the striatum, hippocampusyamygdala, andyor anterior cingulate cortex. Studies investigating the perception of external stimuli in hallucinating patients have found decreased activation in brain areas processing sensory input, perhaps due to tonic baseline hyperactivity (David, 1999). Rollnik et al. (2000) used 2 weeks of highfrequency rTMS of the left DLPFC and 2 weeks of sham treatment in 12 schizophrenic patients and noted a significant decrease of the BPRS scores under active rTMS (P-0.05), whereas depressive symptoms (BDI) and anxiety (STAI) did not change significantly. We postulated that high-frequency rTMS would activate the right, ipsilateral to the auditory-linguistic cortex, hypofunctional areas, and induce a reduction of auditory hallucinations. This did not happen: the content, frequency and intensity of the auditory command
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S. Schreiber et al. / Psychiatry Research Neuroimaging 116 (2002) 113–117
Fig. 1. Top row: Representative consecutive transaxial slices at the level of the basal ganglia parallel to the cantho-meatal line of pre-rTMS treatment neuroSPECT. The pre-treatment study demonstrates decreased perfusion in the right temporal and bilateral infero-frontal regions, as well as non-homogeneous uptake in the caudate nuclei. Bottom row: Representative consecutive transaxial slices at the same level of the basal ganglia as the previous study of post-rTMS treatment neuroSPECT. Following treatment, the neuroSPECT study demonstrates marked, general improvement in brain perfusion, including frontal, infero-frontal, and temporal regions, and an increased uptake in the left thalamus.
hallucinations were unaffected by the rTMS treatment. It is possible that a different placement of the coil (i.e. on the left DLPFC) would have brought about a different result. However, following the paradigm we used, an impressive clinical change was evident regarding both the patient’s behavioral patterns (mostly those regarding the negative signs), and his subjective feelings of general well-being.
Several lines of evidence have converged to implicate dysfunction in the prefrontal cortex and its subcortical reciprocal projections in the emergence of aberrant source monitoring (Johnson et al., 1993). Recent studies have indicated that rTMS is able to produce activation, not only at the site stimulated, but also in a network of interconnected areas, likely by means of transsynaptic spread. One possible reason for the overall clinical improve-
Fig. 2. Computer subtracted activity difference map (CSADM) indicates the semi-quantitative changes in perfusion between the two studies, most likely attributable to the treatment. Post-treatment minus pre-treatment yielded diffused increased activity of 20%.
S. Schreiber et al. / Psychiatry Research Neuroimaging 116 (2002) 113–117
ment of our patient is the rTMS-induced activation of non-hallucination-associated cortical circuits involved in schizophrenia. Further controlled studies, with large numbers of patients, are needed to establish the possible benefit of rTMS in schizophrenic patients, and the recommended coil placements. References David, A.S., 1999. Auditory hallucinations: phenomenology, neuropsychology, and neuroimaging update. Acta Psychiatrica Scandinavica 99, 95–104. du Feu, M., McKenna, P.J., 1999. Prelingually profoundly deaf schizophrenic patients who hear voices: a phenomenological analysis. Acta Psychiatrica Scandinavica 99, 453–459. George, M.S., Wassermann, E.M., Post, R.M., 1996. Transcranial magnetic stimulation: a neuropsychiatric tool for the 21st century. Journal of Neuropsychiatry and Clinical Neuroscience 8, 373–382. Grunhaus, L., Dannon, P.N., Schreiber, S., Dolberg, O.T., Amiaz, R., Ziv, R., Lepkifker, E., 2000. Repetitive transcranial magnetic stimulation is as effective as ECT in the treatment of non-delusional major depressive disorder: an open study. Biological Psychiatry 47, 314–324. Hoffman, R.E., Boutros, N.N., Berman, R.M., Roessler, E., Belger, A., Krystal, J.H., Charney, D.S., 1999. Transcranial magnetic stimulation of left temporoparietal cortex in three patients reporting hallucinated ‘voices’. Biological Psychiatry 46, 130–132.
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Johnson, M.K., Hashtroudi, S., Lindsay, D.S., 1993. Source monitoring. Psychological Bulletin 114, 3–28. Lishman, W.A., 1997. Symptoms and syndromes with regional affiliations Organic Psychiatry. The Psychological Consequences of Cerebral Disorder, 3rd ed. Blackwell Science, Oxford and Northampton, pp. 88. McGuire, P.K., Shah, G.M.S., Murray, R.M., 1993. Increased blood flow in Broca’s area during auditory hallucinations in schizophrenia. Lancet 342, 703–706. Musalek, M., Podreka, I., Suess, E., Nutzinger, D., Passweg, V., Strobl, R., Walter, H., Baumgartner, C., Lesch, O.M., 1988. Neurophysiological aspects of auditory hallucinations. Psychopathology 21, 275–280. Musalek, M., Podreka, I., Walter, H., Suess, E., Passweg, V., Nutzinger, D., Strobl, R., Lesch, O.M., 1989. Regional brain function in hallucinations: a study of regional cerebral blood flow with 99m-Tc-HMPAO-SPECT in patients with auditory hallucinations, tactile hallucinations, and normal controls. Comprehensive Psychiatry 30, 99–108. Ohayon, M.M., Priest, R.G., Caulet, M., Guilleminault, C., 1996. Hypnagogic and hypnapompic hallucinations: pathological phenomena? British Journal of Psychiatry 169, 459–467. Rollnik, J.D., Huber, T.J., Mogk, H., Siggelkow, S., Kropp, S., Dengler, S., Emrich, H.M., Schneider, U., 2000. High frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in schizophrenic patients. Neuroreport 11, 4013–4015. Weiss, A.P., Heckers, U.S., 1999. Neuroimaging of hallucinations: a review of the literature. Psychiatry Research: Neuroimaging 92, 61–74.
Case reports
Right prefrontal rTMS treatment for refractory auditory command hallucinations – a neuroSPECT assisted case study Shaul Schreibera,*, Pinhas N. Dannonb, Elinor Goshenc, Revital Amiazb, Tzila S. Zwasc, Leon Grunhausb a
Department of Psychiatry, Tel Aviv Sourasky Medical Center and Tel Aviv University Sackler School of Medicine, 6 Weismann Street, IL-64239 Tel Aviv, Israel b Department of Psychiatry, Chaim Sheba Medical Center Tel-HaShomer and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel c Department of Nuclear Medicine, Chaim Sheba Medical Center Tel-HaShomer and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel Received 19 December 2001; received in revised form 1 July 2002; accepted 11 July 2002
Abstract Auditory command hallucinations probably arise from the patient’s failure to monitor hisyher own ‘inner speech’, which is connected to activation of speech perception areas of the left cerebral cortex and to various degrees of dysfunction of cortical circuits involved in schizophrenia as supported by functional brain imaging. We hypothesized that rapid transcranial magnetic stimulation (rTMS), by increasing cortical activation of the right prefrontal brain region, would bring about a reduction of the hallucinations. We report our first schizophrenic patient affected with refractory command hallucinations treated with 10 Hz rTMS. Treatment was performed over the right dorsolateral prefrontal cortex, with 1200 magnetic stimulations administered daily for 20 days at 90% motor threshold. Regional cerebral blood flow changes were monitored with neuroSPECT. Clinical evaluation and scores on the Positive and Negative Symptoms Scale and the Brief Psychiatric Rating Scale demonstrated a global improvement in the patient’s condition, with no change in the intensity and frequency of the hallucinations. NeuroSPECT performed at intervals during and after treatment indicated a general improvement in cerebral perfusion. We conclude that right prefrontal rTMS may induce a general clinical improvement of schizophrenic brain function, without directly influencing the mechanism involved in auditory command hallucinations. 䊚 2002 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Auditory command hallucinations; Cerebral cortex; Rapid transcranial magnetic stimulation; Schizophrenia; Single photon emission computed tomography
*Corresponding author. Tel.: q972-3-697-4707; fax: q972-3-697-4586. E-mail address: [email protected] (S. Schreiber). 0925-4927/02/$ - see front matter 䊚 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 9 2 5 - 4 9 2 7 Ž 0 2 . 0 0 0 6 5 - 3
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S. Schreiber et al. / Psychiatry Research Neuroimaging 116 (2002) 113–117
1. Introduction Imperative command hallucinations, once thought to be a source of divine inspiration or of demonic possession, are recognized as complex symptoms in neuropsychiatric disorders (du Feu and McKenna, 1999; Ohayon et al., 1996) and, within special contexts such as bereavement, as culturally bound manifestations. Functional neuroimaging allows the in vivo assessment of neural function of the hallucinating patient, before and after treatment (for review, see Weiss and Heckers, 1999). Musalek et al. (1988, 1989), using 99mTc-HMPAO-SPECT during periods of active hallucinations, demonstrated that auditory hallucinations were associated with increased activity bilaterally in the basal ganglia and the hippocampus as well as decreased activity in the lateral frontal lobes bilaterally. McGuire et al. (1993) demonstrated that the hallucinating state is associated with increased blood flow in Broca’s area, the left anterior cingulate gyrus, and the left temporal lobe. These findings support the idea that auditory hallucinations arise from the patient’s failure to monitor hisyher own thoughts and ‘inner speech’, which is therefore regarded as alien and perceived as emanating from others (Lishman, 1997). Repetitive transcranial magnetic stimulation (rTMS), administered at a frequency of 10 Hz, has been shown to increase cortical activation and has generated interest as a probe and potential treatment in several neuropsychiatric disorders (George et al., 1996). A recent report described the use of low-frequency (1 Hz) TMS of left temporoparietal cortex (Hoffman et al., 1999). Using Tc-99m-ECD-SPECT, we evaluated the effect of 4 weeks of right prefrontal rTMS treatment on treatment-resistant command hallucinations in a patient with chronic schizophrenia. 2. Methods M.S. is a right-handed, 49-year-old male, unmarried and unemployed patient, with a diagnosis of paranoid schizophrenia. He reported a 20-year history of auditory command hallucinations and was responding poorly to conventional and novel
neuroleptics. Upon admission, he was unkempt, oriented to time, place and person, and gave a coherent account of his past and current life. He was not depressed or anxious and had constricted affect. He was convinced that his neighbors were trying to kill him, and heard voices of strangers scorning him and telling him ‘you are a dead person’, but was without active suicidal ideation. Trials with clozapine and olanzapine had to be interrupted following exacerbation of his noninsulin-dependent diabetes mellitus. A full course of bilateral electroconvulsive therapy failed to affect the hallucinations. As a last resort, a trial with rTMS was offered to the patient. The patient was maintained on his psychotropic medication (haloperidol, 20 mgyday, which he had been taking for more then 3 months) with no change in dose, and he had routine laboratory evaluations. After both the patient’s voluntary informed consent and the approval of the hospital’s ethics committee had been obtained, rTMS was performed using MAGSTIM rapid equipment with four booster modules, according to a method described in detail elsewhere (Grunhaus et al., 2000). Briefly, rTMS was administered to the right dorsolateral prefrontal cortex (RDLPFC), with 1200 magnetic stimulations being administered daily for 20 days at 90% motor threshold, 5 days a week for 4 weeks – a total of 20 daily sessions. Each session consisted of 20 trains of 6-s duration, at 10-Hz frequency, separated by 1 min each. Motor threshold was measured before each session. The coil placement over the RDLPFC was decided following documentation of right hypofrontality in pre-treatment single photon emission computed tomography (SPECT), and the intensity of 10 Hz was chosen because we wanted excitatory pulses. NeuroSPECT studies were performed four times: at baseline (before 1st treatment), after 5 treatments and again at the end of 20 treatments. A follow-up neuroSPECT was performed 6 weeks after the rTMS treatment course ended. Each neuroSPECT was performed 15 min following i.v. injection of 30 mCi (740 MBq) Tc-99m-ECD, using a dual-headed gamma camera equipped with fan-beam collinators. The data were acquired over 3608 in 38 angular steps in a 128=128 matrix, attenuation-corrected and reconstructed using a
S. Schreiber et al. / Psychiatry Research Neuroimaging 116 (2002) 113–117 Table 1 Psychiatric rating scale evaluations before, during and after the rTMS treatment course Rating scale Scores Baseline 1 week End of treatment Follow-up PANSS BPRS 17-Ham-D MMSE GDR PSQI
76 49 13 23 1 4
72 41 13 23 1 5
64 34 11 26 0 6
66 47 13 24 1 4
Metz back-projection filter. All studies were normalized to cerebellar activity. Psychiatric evaluation included a 100-mm visual analogue scale for daily monitoring of the intensity of the auditory command hallucinations, the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Symptoms Scale (PANSS), the 17-item Hamilton Psychiatric Rating Scale for Depression (17-Ham-D), the Global Depression Scale (GDR), the Pittsburgh Sleep Quality Index (PSQI), and the Mini Mental State Examination (MMSE). 3. Results 3.1. Clinical findings Clinically, the patient’s global condition at the end of the 20 rTMS treatments was improved: he was more cooperative, better groomed, and much more willing to participate in the occupational therapy program. However, as far as he could tell, there was no change in the content, intensity or frequency of his hallucinations. Both BPRS and PANSS scores improved (PANSS from 76 to 64, BPRS from 49 to 34) during the treatment course; however, changes in other rating scales were minor and non-significant. At follow-up 6 weeks after the rTMS treatment ended, all scores but the PANSS returned to pre-rTMS treatment baseline (Table 1). 3.2. SPECT findings Pre-treatment baseline brain SPECT with Tc99m-ECD demonstrated decreased perfusion in the
115
left cerebellar and right temporal regions and slightly decreased perfusion in bilateral inferofrontal regions, more prominent on the right, as well as mild, non-homogeneous uptake in the caudate nuclei. The second neuroSPECT, performed after five treatments, showed an overall improvement in cerebral perfusion, including temporal and cerebellar regions, as well as the basal ganglia. The third neuroSPECT evaluation, performed at the end of the 20-treatment course of rTMS, demonstrated a slight further improvement in the general cortical perfusion, as well as in subcortical regions. A fourth neuroSPECT, performed 6 weeks after rTMS treatment ended, indicated a general improvement in perfusion, primarily in frontal, infero-frontal and temporal regions, more prominent on the right, and an increased uptake in the left thalamus (Figs. 1 and 2). 4. Discussion The neural systems involved in the perception of hallucinations appear to involve the same modality-specific cerebral structures implicated in ‘normal’ perception, including mental imagery. In the case of verbal auditory hallucinations, increased activity in both primary and secondary auditory cortex appears consistently throughout the literature, occasionally associated with activity in the striatum, hippocampusyamygdala, andyor anterior cingulate cortex. Studies investigating the perception of external stimuli in hallucinating patients have found decreased activation in brain areas processing sensory input, perhaps due to tonic baseline hyperactivity (David, 1999). Rollnik et al. (2000) used 2 weeks of highfrequency rTMS of the left DLPFC and 2 weeks of sham treatment in 12 schizophrenic patients and noted a significant decrease of the BPRS scores under active rTMS (P-0.05), whereas depressive symptoms (BDI) and anxiety (STAI) did not change significantly. We postulated that high-frequency rTMS would activate the right, ipsilateral to the auditory-linguistic cortex, hypofunctional areas, and induce a reduction of auditory hallucinations. This did not happen: the content, frequency and intensity of the auditory command
116
S. Schreiber et al. / Psychiatry Research Neuroimaging 116 (2002) 113–117
Fig. 1. Top row: Representative consecutive transaxial slices at the level of the basal ganglia parallel to the cantho-meatal line of pre-rTMS treatment neuroSPECT. The pre-treatment study demonstrates decreased perfusion in the right temporal and bilateral infero-frontal regions, as well as non-homogeneous uptake in the caudate nuclei. Bottom row: Representative consecutive transaxial slices at the same level of the basal ganglia as the previous study of post-rTMS treatment neuroSPECT. Following treatment, the neuroSPECT study demonstrates marked, general improvement in brain perfusion, including frontal, infero-frontal, and temporal regions, and an increased uptake in the left thalamus.
hallucinations were unaffected by the rTMS treatment. It is possible that a different placement of the coil (i.e. on the left DLPFC) would have brought about a different result. However, following the paradigm we used, an impressive clinical change was evident regarding both the patient’s behavioral patterns (mostly those regarding the negative signs), and his subjective feelings of general well-being.
Several lines of evidence have converged to implicate dysfunction in the prefrontal cortex and its subcortical reciprocal projections in the emergence of aberrant source monitoring (Johnson et al., 1993). Recent studies have indicated that rTMS is able to produce activation, not only at the site stimulated, but also in a network of interconnected areas, likely by means of transsynaptic spread. One possible reason for the overall clinical improve-
Fig. 2. Computer subtracted activity difference map (CSADM) indicates the semi-quantitative changes in perfusion between the two studies, most likely attributable to the treatment. Post-treatment minus pre-treatment yielded diffused increased activity of 20%.
S. Schreiber et al. / Psychiatry Research Neuroimaging 116 (2002) 113–117
ment of our patient is the rTMS-induced activation of non-hallucination-associated cortical circuits involved in schizophrenia. Further controlled studies, with large numbers of patients, are needed to establish the possible benefit of rTMS in schizophrenic patients, and the recommended coil placements. References David, A.S., 1999. Auditory hallucinations: phenomenology, neuropsychology, and neuroimaging update. Acta Psychiatrica Scandinavica 99, 95–104. du Feu, M., McKenna, P.J., 1999. Prelingually profoundly deaf schizophrenic patients who hear voices: a phenomenological analysis. Acta Psychiatrica Scandinavica 99, 453–459. George, M.S., Wassermann, E.M., Post, R.M., 1996. Transcranial magnetic stimulation: a neuropsychiatric tool for the 21st century. Journal of Neuropsychiatry and Clinical Neuroscience 8, 373–382. Grunhaus, L., Dannon, P.N., Schreiber, S., Dolberg, O.T., Amiaz, R., Ziv, R., Lepkifker, E., 2000. Repetitive transcranial magnetic stimulation is as effective as ECT in the treatment of non-delusional major depressive disorder: an open study. Biological Psychiatry 47, 314–324. Hoffman, R.E., Boutros, N.N., Berman, R.M., Roessler, E., Belger, A., Krystal, J.H., Charney, D.S., 1999. Transcranial magnetic stimulation of left temporoparietal cortex in three patients reporting hallucinated ‘voices’. Biological Psychiatry 46, 130–132.
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Johnson, M.K., Hashtroudi, S., Lindsay, D.S., 1993. Source monitoring. Psychological Bulletin 114, 3–28. Lishman, W.A., 1997. Symptoms and syndromes with regional affiliations Organic Psychiatry. The Psychological Consequences of Cerebral Disorder, 3rd ed. Blackwell Science, Oxford and Northampton, pp. 88. McGuire, P.K., Shah, G.M.S., Murray, R.M., 1993. Increased blood flow in Broca’s area during auditory hallucinations in schizophrenia. Lancet 342, 703–706. Musalek, M., Podreka, I., Suess, E., Nutzinger, D., Passweg, V., Strobl, R., Walter, H., Baumgartner, C., Lesch, O.M., 1988. Neurophysiological aspects of auditory hallucinations. Psychopathology 21, 275–280. Musalek, M., Podreka, I., Walter, H., Suess, E., Passweg, V., Nutzinger, D., Strobl, R., Lesch, O.M., 1989. Regional brain function in hallucinations: a study of regional cerebral blood flow with 99m-Tc-HMPAO-SPECT in patients with auditory hallucinations, tactile hallucinations, and normal controls. Comprehensive Psychiatry 30, 99–108. Ohayon, M.M., Priest, R.G., Caulet, M., Guilleminault, C., 1996. Hypnagogic and hypnapompic hallucinations: pathological phenomena? British Journal of Psychiatry 169, 459–467. Rollnik, J.D., Huber, T.J., Mogk, H., Siggelkow, S., Kropp, S., Dengler, S., Emrich, H.M., Schneider, U., 2000. High frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in schizophrenic patients. Neuroreport 11, 4013–4015. Weiss, A.P., Heckers, U.S., 1999. Neuroimaging of hallucinations: a review of the literature. Psychiatry Research: Neuroimaging 92, 61–74.