Impaired Subcortical Detection of Auditory Changes in Schizophrenia but Not in Major Depression.

The mismatch negativity is a cortical response to auditory changes and its reduction is a consistent finding in schizophrenia. Recent evidence revealed that the human brain detects auditory changes already at subcortical stages of the auditory pathway. This finding, however, raises the question where in the auditory hierarchy the schizophrenic deficit first evolves and whether the well-known cortical deficit may be a consequence of dysfunction at lower hierarchical levels. Finally, it should be resolved whether mismatch profiles differ between schizophrenia and affective disorders which exhibit auditory processing deficits as well. We used functional magnetic resonance imaging to assess auditory mismatch processing in 29 patients with schizophrenia, 27 patients with major depression, and 31 healthy control subjects. Analysis included whole-brain activation, region of interest, path and connectivity analysis. In schizophrenia, mismatch deficits emerged at all stages of the auditory pathway including the inferior colliculus, thalamus, auditory, and prefrontal cortex. In depression, deficits were observed in the prefrontal cortex only. Path analysis revealed that activation deficits propagated from subcortical to cortical nodes in a feed-forward mechanism. Finally, both patient groups exhibited reduced connectivity along this processing stream. Auditory mismatch impairments in schizophrenia already manifest at the subcortical level. Moreover, subcortical deficits contribute to the well-known cortical deficits and show specificity for schizophrenia. In contrast, depression is associated with cortical dysfunction only. Hence, schizophrenia and major depression exhibit different neural profiles of sensory processing deficits. Our findings add to a converging body of evidence for brainstem and thalamic dysfunction as a hallmark of schizophrenia.

The organization of frequency and binaural cues in the gerbil inferior colliculus.

The inferior colliculus (IC) is the common target of separate pathways that transmit different types of auditory information. Beyond tonotopy, little is known about the organization of response properties within the 3-dimensional layout of the auditory midbrain in most species. Through study of interaural time difference (ITD) processing, the functional properties of neurons can be readily characterized and related to specific pathways. To characterize the representation of ITDs relative to the frequency and hodological organization of the IC, the properties of neurons were recorded and the sites recovered histologically. Subdivisions of the IC were identified based on cytochrome oxidase (CO) histochemistry. The results were plotted within a framework formed by an MRI atlas of the gerbil brain. The central nucleus was composed of two parts, and lateral and dorsal cortical areas were identified. The lateral part of the central nucleus had the highest CO activity in the IC and a high proportion of neurons sensitive to ITDs. The medial portion had lower CO activity and fewer ITD-sensitive neurons. A common tonotopy with a dorsolateral to ventromedial gradient of low to high frequencies spanned the two regions. The distribution of physiological responses was in close agreement with known patterns of ascending inputs. An understanding of the 3-dimensional organization of the IC is needed to specify how the single tonotopic representation in the IC central nucleus leads to the multiple tonotopic representations in core areas of the auditory cortex.

[Manganese enhanced magnetic resonance imaging investigation in the central auditory pathway of the cat].

OBJECTIVE: To compare enhancement of the central auditory pathway in cats receiving auditory stimulation between manganese enhanced magnetic resonance imaging (MEMRI) with intraperitoneal manganese injection route and MEMRI with intratympanic manganese injection route, and investigate the optimal method for displaying enhancement of the central auditory pathway. METHODS: Twenty-seven normal hearing adult cats were randomly divided into three groups, receiving intraperitoneal manganese injection, left intratympanic manganese injection or left intratympanic gadolinium injection respectively.All cats received white noise stimulation of 80 dB in twenty-four hours after injection.Three dimensionally coronal T1-weighted imaging of the cat brain was obtained with an animal dedicated MRI scanner.The signal noise ratios (SNRs) of bilateral cochlear nuclei (CN), dorsal nuclei of the trapezoid bodies (DNTB), caudal colliculi (CC) and auditory cortices (AC) were measured on reconstructed images and compared. RESULTS: Obvious increased SNRs on both sides were shown in intraperitoneal mangasese injection group while left predilection was shown in intratympanic manganese injection group: left CN 45.7±6.0, 37.4±11.9, 23.9±2.7, F=17.694, P=0.000; left DNTB 50.5±11.2, 37.1±11.2, 27.6±7.3, F=11.781, P=0.000; left CC 37.6±3.9, 22.6±3.1, 17.9±0.7, F=111.898, P=0.000; left AC 27.7±2.5, 17.3±2.3, 14.5±1.0, F=105.132, P=0.000; right CN 42.7±8.3, 23.9±3.0, 22.7±2.1, F=41.492, P=0.000; right DNTB 44.1±8.3, 21.9±3.0, 23.9±4.0, F=27.862, P=0.000; right CC 38.0±4.0, 21.9±3.0, 17.6±0.9, F=120.032, P=0.000; right AC 26.7±3.4, 17.1±2.9, 14.9±1.3, F=64.587, P=0.000.Compared with the left intratympanic gadolinium injection group, the intraperitoneal manganese injection group showed higher SNRs in bilateral CN and CC (P<0.05), and the left intratympanic manganese injection group showed higher SNRs in left CN, AC and bilateral CC.The SNRs of right CN, bilateral DNTB, CC and AC were significantly higher in the intraperitoneal manganese injection group than those in the left intratympanic manganese injection group (P<0.05). CONCLUSION: MEMRI with intraperitoneal manganese injection might be the optimal method for displaying enhancement of the central auditory pathway in cats receiving auditory stimulation.

An animal model of central auditory pathway imaging in the rat brain by high resolution small animal positron emission tomography.

CONCLUSIONS: Our study demonstrated that high resolution animal positron emission tomography (PET) can non-invasively assess the change in glucose metabolism of the central auditory pathway including the inferior colliculus and auditory cortex in the rat. OBJECTIVES: The traditional in vitro approach with immunohistochemical staining or autoradiography to assess chronological changes or topographic arrangement of central auditory pathway required sacrificing a large number of animals. Inter-individual difference is also a major concern. Therefore, development of an in vivo animal model using PET imaging would be a rational method to overcome these shortcomings. MATERIALS AND METHODS: Small animal PET scan using (18)F-fluorodeoxyglucose (FDG) as a functional marker was performed in rats. Each animal was serially scanned before and after unilateral cochlear ablation, with and without acoustic stimulation. The images were analyzed by the region of interest (ROI) method. Ratios of radioactivity at the inferior colliculus and auditory cortex and a referenced cerebral cortex between bilateral hemispheres were measured. RESULTS: These scans demonstrated several brain structures including the inferior colliculus (IC) and cortex (B). Moreover, unilateral cochlear ablation decreased the radioactivity at contralateral IC and auditory cortex (C) areas. Differences may reach 33% in IC and 27% in C, and average radioactivity ratios were 1.24+/-0.08 and 1.18+/-0.07 in selected adjacent sections, respectively.

The frequency organization of the inferior colliculus of the guinea pig: A [14C]-2-deoxyglucose study.

The [14C]-2-deoxyglucose (2-DG) technique was used to study the frequency organization of the inferior colliculus (IC) of the guinea pig. Discrete regions of heightened 2-DG labelling were observed in the ICs of animals exposed to a variety of pure-tone stimuli. Regions associated with 1, 4, 10 and 19 kHz pure tones were described and displayed in three-dimensional representations. The IC of the guinea pig was found to be arranged as a series of sheet-like, iso-frequency planes that extend throughout the nucleus from its caudal to its rostral pole. Iso-frequency planes associated with low frequencies are located dorsolaterally in the nucleus and those associated with higher frequencies are located progressively more ventromedially. The predominant orientation, in the frontal plane, of all iso-frequency planes is oblique from dorsomedial to ventrolateral. Most planes, however, twist about their caudal-to-rostral axis in a caudal-to-rostral, horizontal-to-vertical direction. The extent to which each plane twists is frequency-dependent; planes associated with low frequencies twist most and those associated with high frequencies do not twist at all.

Observations on tonotopic organization within the rat inferior colliculus using 2-deoxy-D[1-3H] glucose.

Tonotopic organization is a major feature of central auditory structures. The tritiated 2-deoxyglucose metabolic marking technique is demonstrated to be useful for visualizing isofrequency contours in the rat inferior colliculus. Following pure-tone stimulation, the central nucleus of the inferior colliculus shows discrete, prominent banding patterns and a well-organized tonotopic arrangement.