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1.
Figure 4

Figure 4. From: Probing the Pathophysiology of Auditory/Verbal Hallucinations by Combining Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation.

Cortical maps of rates of improvement/worsening of AVHs associated with rTMS delivered to alternative sites for all patients with intermittent hallucinations. Left supramarginal (l. sm.) region and Wernicke’s (W) region are circled.

Ralph E. Hoffman, et al. Cereb Cortex. ;17(11):2733-2743.
2.
Figure 5

Figure 5. From: Probing the Pathophysiology of Auditory/Verbal Hallucinations by Combining Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation.

Cortical maps of rates of improvement/worsening of AVHs associated with rTMS delivered to alternative sites for all patients with continuous hallucinations. Left supramarginal (l. sm.) region and Wernicke’s (W) region are circled.

Ralph E. Hoffman, et al. Cereb Cortex. ;17(11):2733-2743.
3.
Figure 1

Figure 1. From: Probing the Pathophysiology of Auditory/Verbal Hallucinations by Combining Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation.

Diagram of the clinical trial. Most common basis for excluding prospective subjects was insufficient hallucination frequency (N = 27). Black rectangle () represents a single, 16-min, 1-Hz rTMS (or sham) session. HCS, Hallucination change score. Open-label phase not reflected in figure.

Ralph E. Hoffman, et al. Cereb Cortex. ;17(11):2733-2743.
4.
Figure 3

Figure 3. From: Probing the Pathophysiology of Auditory/Verbal Hallucinations by Combining Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation.

Representative fMRI maps of correlations relative to Wernicke’s area for 2 patients with continuous hallucinations. Left side of the brain corresponds to the right side of images. (A) Subject in the 3-site version of the protocol. As expected, a prominent (auto) correlation emerged in Wernicke’s region itself, with correlations also expressed in anterior temporal and inferior frontal regions. The 3 sites selected for rTMS were posterior superior temporal regions on the left and right (BA 22) and a site in Broca’s area (BA 45). (B) Subject in the later version of the protocol where number of sites probed varied according to functional maps and site-specific clinical response. Besides the autocorrelation in Wernicke’s area, robust correlations were detected in left and right middle temporal gyrus (BA 21), which were each targeted for rTMS. In addition, a Broca’s region at the boundary of BA 44/45 was targeted along with an orbitofrontal area (BA 8).

Ralph E. Hoffman, et al. Cereb Cortex. ;17(11):2733-2743.
5.
Figure 6

Figure 6. From: Probing the Pathophysiology of Auditory/Verbal Hallucinations by Combining Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation.

(A) Data generated under double-masked conditions averaged across all subjects receiving stimulation at designated site. Ant. Temp., anterior superior temporal regions including BA 41/42 and anterior BA 22 bilaterally; Broca’s, BA 44/45 bilaterally; l. TP, left temporoparietal region defined as Wernicke’s area (BA 22 posterior to y = −30) plus left supramarginal cortex; r. TP, homologous right temporoparietal region. If 2 rTMS sites fell within the same region for a given subject, rTMS response rates for the 2 sites were averaged. Response data for other frontal and middle temporal sites not shown because number of subjects receiving rTMS in these areas were too small to permit comparative statistics. (B) Response rates graphed according to sequential order of site that was probed. Because only 3 subjects received stimulation in 6 sites, these results were not included. Negative values on the y axis reflect reductions in hallucination severity, and numbers below bars correspond to numbers of subjects receiving rTMS to that region or order in sequence.

Ralph E. Hoffman, et al. Cereb Cortex. ;17(11):2733-2743.
6.
Figure 7

Figure 7. From: Probing the Pathophysiology of Auditory/Verbal Hallucinations by Combining Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation.

The y axis shows percent improvement in hallucination severity expressed as average hallucination change score reductions per each left temporoparietal (TP) rTMS session. Each plot represents an independent set of 6 patients. Scale of x axis in upper panel corresponds to percent increase in BOLD signal for hallucination periods relative to nonhallucination periods for intermittent hallucinators averaged over all pixels in Broca’s area (BA 44/45). The robust negative correlation suggests that higher levels of activation involving Broca’s region reinforce underlying pathophysiology in this patient group as evidenced by curtailment of effects of rTMS delivered to left temporoparietal cortex, the cortical region appearing to optimize clinical response. Scale of x axis in lower panel is z-transformed BOLD signal correlation values averaged across the right homologue of Broca’s region. The robust negative correlation suggests that higher levels of coupling between Wernicke’s area and the right homologue of Broca’s region reinforce underlying pathophysiology in continuous hallucinators as evidenced by curtailment of effects of left temporoparietal rTMS. These correlational findings, which were derived from 2 distinct patient groups, appear to partially replicate each other because both implicate inferior frontal regions in the pathophysiology of AVHs.

Ralph E. Hoffman, et al. Cereb Cortex. ;17(11):2733-2743.
7.
Figure 2

Figure 2. From: Probing the Pathophysiology of Auditory/Verbal Hallucinations by Combining Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation.

fMRI activation maps of hallucination events for 2 patients with intermittent hallucinations. Images are in the axial oblique orientation. Arrows illustrate the rTMS sites selected. Numbers next to arrows are Brodmann areas per Talairach and Tournoux (1988). Left side of the brain corresponds to the right side of images. (A) Representative subject in the 3-site version of the protocol. Activation associated with hallucination periods was focused bitemporally and in inferior frontal and prefrontal regions. Stimulation was limited to 3 sites and directed to posterior superior temporal cortex (BA 22), the right-sided homologous region, and a prefrontal region (BA 46). (B) Representative subject in the later version of the protocol where number of sites probed varied according to functional maps and site-specific clinical response. Activation in posterior temporal regions was largely absent with much more prominent involvement in frontal areas. Four sites were selected for rTMS to cover Broca’s area and right-sided homologous regions. The patient also received rTMS over primary auditory cortex and supramarginal cortex on the right side. Especially prominent temporalis muscle mass can be visualized on the right side over BA 44/45 as a thickening under the patient’s skin, which corresponds to the white rim in these images.

Ralph E. Hoffman, et al. Cereb Cortex. ;17(11):2733-2743.

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