Alterations in white matter fiber tracts may facilitate auditory hallucinations, according to Swiss researchers. During inner speech, the alterations “lead to abnormal activation in regions related to acoustical processing of external stimuli [and] may therefore account for the patients’ inability to distinguish self-generated thoughts from external stimulation,” said Daniela Hubl, MD, lead author of the study.

Dr. Hubl and colleagues at the University Hospital of Clinical Psychiatry in Bern, Switzerland, used diffusion tensor imaging “to investigate whether previously described abnormal activation patterns observed during auditory hallucinations were related to structural interconnections between the frontal and parietotemporal speech-related areas,” she explained. Their findings were published in the July Archives of General Psychiatry.

The investigators examined 13 patients with acute schizophrenia and frequent auditory hallucinations (mean age, 33; eight men), 13 patients with acute schizophrenia and no reported hallucinations (mean age, 31; eight men), and 13 healthy control subjects (mean age, 32; eight men). All subjects were right-handed.

The investigators assessed white matter connectivity in these three groups using magnetic resonance diffusion tensor imaging of anisotropy (the directionality of water diffusion). Because anisotropy is restricted by boundaries such as white matter fibers, “the amount of anisotropy correlates with the directionality and coherence of fiber tracts. Thus, a loss of white matter directionality or disruption of the microstructure is reflected in reduced anisotropy values,” she explained.

Compared to controls, fractional anisotropy values were lower in patients with schizophrenia in many parts of the white matter. There were 17 significant regions (eight clusters in the left hemisphere, nine in the right hemisphere). Significantly higher values were observed in control subjects in the long anterior-to-posterior association fibers in large parts of the arcuate fasciculus, the uncinate fasciculus, and the inferior fasciculus in both hemispheres. Higher values were also observed in the corpus callosum, Dr. Hubl said.

As compared to patients in the schizophrenia group, patients with hallucinations had significantly higher fractional anisotropy values in many parts of the white matter than did patients who had no hallucinations, the investigators said. Twelve clusters were located in the left hemisphere and five in the right hemisphere; 15 clusters had higher fractional anisotropy values in patients with auditory hallucinations. The most interesting difference was observed in the arcuate fasciculus, the researchers reported.

A subsequent comparison of patients with schizophrenia and auditory hallucinations and controls revealed 16 significant clusters, 13 of which demonstrated lower values and three of which demonstrated higher values. The regions with higher fractional anisotropy in patients with schizophrenia and hallucinations were located in the lateral left and right temporoparietal section of the arcuate fasciculus close to the posterior end of the Sylvian fissure—where the Wernicke area is located—and close to the cortical auditory regions.

“The lateral part of the arcuate fasciculus provides a pathway by which frontal speech production areas can influence auditory and speech perception areas during overt and inner speech,” Dr. Hubl said. “A disruption of the arcuate fasciculus leads to a disturbance of the neuronal connections from the frontal Broca area to the temporal Wernicke area, which results in a disturbance of the stream of speech. One link between auditory hallucinations and inner speech is the common clinical observation that the content of auditory hallucinations is often closely related to the content of the patient’s own thought and sometimes is even reported as thoughts becoming loud,” she elaborated. If—as previous studies have suggested—an increase of fractional anisotropy values is related to an increase of connectivity in white matter bundles, “it can be hypothesized that high white matter directionality in the lateral part of the arcuate fasciculus in auditory hallucinations is associated with high connectivity between distributed language and auditory areas.”

Based on this hypothesis, the white matter fibers found to be the most altered in patients who had auditory hallucinations “constitute the most important connections between language-related frontal and temporal regions,” Dr. Hubl said. “The alterations may have a developmental origin and may contribute to an understanding of how internally generated language is perceived to be generated externally. These aberrant connections may lead to the abnormal activation during hallucinations in regions that normally process external acoustical and language stimuli, which was demonstrated in a previous study by our group. Together, these results account for the patients’ inability to distinguish self-generated thoughts from external stimulation,” she concluded.

—C. Justin Romano

Suggested Reading
Hubl D, Koenig T, Strik W, et al. Pathways that make voices: white matter changes in auditory hallucinations. Arch Gen Psychiatry. 2004;61:658-668.

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