Martin Andermann

Reduced volume of Heschl's gyrus in tinnitus.

The neural basis of tinnitus is unknown. Recent neuroimaging studies point towards involvement of several cortical and subcortical regions. Here we demonstrate that tinnitus may be associated with structural changes in the auditory cortex. Using individual morphological segmentation, the medial partition of Heschls gyrus (mHG) was studied in individuals with and without chronic tinnitus using magnetic resonance imaging. Both the tinnitus and the non-tinnitus group included musicians and non-musicians. Patients exhibited significantly smaller mHG gray matter volumes than controls. In unilateral tinnitus, this effect was almost exclusively seen in the hemisphere ipsilateral to the affected ear. In bilateral tinnitus, mHG volume was substantially reduced in both hemispheres. The tinnitus-related volume reduction was found across the full extent of mHG, not only in the high-frequency part usually most affected by hearing loss-induced deafferentation. However, there was also evidence for a relationship between volume reduction and hearing loss. Correlations between volume and hearing level depended on the subject group as well as the asymmetry of the hearing loss. The volume changes observed may represent antecedents or consequences of tinnitus and tinnitus-associated hearing loss and also raise the possibility that small cortical volume constitutes a vulnerability factor.

Cortical Representation of Afferent Bodily Signals in Borderline Personality Disorder: Neural Correlates and Relationship to Emotional Dysregulation

IMPORTANCE The ability to perceive and regulate ones own emotions has been tightly linked to the processing of afferent bodily signals (interoception). Thus, disturbed interoception might contribute to the core feature of emotional dysregulation in borderline personality disorder (BPD), as increased levels of depersonalization, body image disturbances, and reduced sensitivity to physical pain suggest poor body awareness in BPD. OBJECTIVE To determine neural correlates of disturbed body awareness in BPD and its associations with emotional dysregulation and to explore improvements in body awareness with BPD symptom remission. DESIGN, SETTING, AND PARTICIPANTS Case-control study performed at Heidelberg University Hospital, Heidelberg, Germany. Heartbeat evoked potentials (HEPs), an indicator of the cortical representation of afferent signals from the cardiovascular system, were investigated in 34 medication-free patients with BPD, 31 healthy volunteers, and 17 medication-free patients with BPD in remission. The HEPs were assessed using 5-minute resting-state electroencephalograms and parallel electrocardiograms. Core BPD symptoms, history of childhood traumatization, and psychiatric disorders were assessed by means of self-reports and structured interviews. To measure neural correlates of disturbed body awareness, high-resolution T1-weighted structural magnetic resonance imaging scans were collected and analyzed using voxel-based morphometry and region-of-interest-based approaches. The study was performed between 2012 and 2014, and data analysis was performed in 2014. MAIN OUTCOMES AND MEASURES Mean HEP amplitudes in resting-state electroencephalograms and their correlation with self-reported emotional dysregulation, as well as with gray matter volume. RESULTS Patients with BPD had significantly reduced mean HEP amplitudes compared with healthy volunteers (F1,61 = 11.32, P = .001), whereas the mean HEP amplitudes of patients with BDP in remission lie somewhere in between these 2 groups of participants (P > .05). The HEP amplitudes were negatively correlated with emotional dysregulation (R = -0.30, P = .01) and positively associated with gray matter volume in the left anterior insula (R = 0.53, P < .05) and the bilateral dorsal anterior cingulate cortex (R = 0.47, P < .05), 2 structures that have been identified as core regions for interoception. CONCLUSIONS AND RELEVANCE The results indicate state-dependent deficits in the cortical processing of bodily signals in patients with BPD, which appear to be associated with core features of BPD. The analysis of patients with BPD in remission suggests an improvement in cortical representation of bodily signals with symptom remission. Results recommend the integration of techniques to strengthen bodily awareness in psychotherapeutic interventions of BPD.

Interaction among the components of multiple auditory steady-state responses: enhancement in tinnitus patients, inhibition in controls

Amplitude and phase of steady-state signals recorded in response to amplitude-modulated (AM) sine tones vary over time, suggesting that the steady-state response (SSR) reflects not only stimulus input but also its interaction with other input streams or internally generated signals. Alterations of the interaction between simultaneous SSRs associated with tinnitus were studied by recording the magnetic field evoked by AM-tones with one of three carrier and one of three modulation frequencies. Single AM-tones were presented in single presentation mode and superpositions of three AM-tones differing in carrier and modulation frequency in multiple presentation mode. Modulation frequency-specific SSR components were recovered by bandpass filtering. Compared with single mode, in multiple mode SSR amplitude was reduced in healthy controls, but increased in tinnitus patients. Thus, while in controls multiple response components seem to reciprocally inhibit one another, in tinnitus reciprocal facilitation seems to predominate. Reciprocal inhibition was unrelated to the phase coherence among SSR components, but was correlated with the frequency of phase slips, indicating that the lateral interaction among SSR components acts in a quasi-paroxysmal manner and manifests itself in terms of a random train of phase reset events. Phase slips were more frequent in patients than controls both in single and multiple mode. Together, these findings indicate that lateral or surround inhibition of single units in auditory cortex is reduced and suggest that in-field inhibition is increased in tinnitus.

Evidence for a magnocellular disadvantage in early-onset schizophrenic patients: A source analysis of the N80 visual-evoked component

BACKGROUND Visual impairments in schizophrenia have been suggested to be partly caused by early processing deficits of the magnocellular (M) pathway. This might include disturbed interactions between the M and parvocellular (P) pathways and especially impaired M priming, which can disturb highlighting of relevant information. Such disorders may result from neurodevelopmental irregularities, which are assumed to be substantially involved in schizophrenia. This study sought to test the hypothesis that M priming is impaired in schizophrenia. In order to elucidate this neurodevelopmental aspect, we investigated patients with different ages of schizophrenia onset. This provided a useful design to integrate visual information processing in a neurodevelopmental model of schizophrenia. METHOD Nine stimulus conditions were used to investigate the M- and P-pathways and their interaction in a pattern reversal VEP paradigm. N80 generators were analyzed using source localization (Brain Electrical Source Analysis software: BESA). Forty schizophrenia patients (early-onset=19; adult-onset=21) were compared with age- and gender-matched healthy controls (early-onset controls=19; adult-onset controls=21). Hypotheses were tested using a bootstrap resampling procedure. RESULTS The N80 component was represented by a single dipole located in the occipital visual cortex. The bootstrap analysis yielded significant differences between early-onset schizophrenia patients and controls. We found lower amplitudes in response to mixed M-P conditions and normal amplitudes in response to isolated P- and M-biased stimulation. Concerning the latencies, significant differences were found between adult-onset subjects and their controls, with prolonged latencies for schizophrenia patients. CONCLUSIONS The early VEP component N80 evoked by mixed M-P conditions is assumed to be a correlate of M priming and showed reduced amplitude in early-onset schizophrenic patients but not in adult-onset patients. These findings point towards an M priming deficit in early-onset patients and are compatible with a neurodevelopmental hypothesis of schizophrenia, probably reflecting asynchronies in brain maturational abnormalities occurring at different ages of illness onset.

Duifhuis pitch: neuromagnetic representation and auditory modeling

When a high harmonic is removed from a cosine-phase harmonic complex, we hear a sine tone pop out of the perception; the sine tone has the pitch of the high harmonic, while the tone complex has the pitch of its fundamental frequency, f0. This phenomenon is commonly referred to as Duifhuis Pitch (DP). This paper describes, for the first time, the cortical representation of DP observed with magnetoencephalography. In experiment 1, conditions that produce the perception of a DP were observed to elicit a classic onset response in auditory cortex (P1m, N1m, P2m), and an increment in the sustained field (SF) established in response to the tone complex. Experiment 2 examined the effect of the phase spectrum of the complex tone on the DP activity: Schroeder-phase negative waves elicited a transient DP complex with a similar shape to that observed with cosine-phase waves but with much longer latencies. Following the transient DP activity, the responses of the negative and positive Schroeder-phase waves converged, and the increment in the SF slowly died away. In the absence of DP, the two Schroeder-phase conditions with low peak factors both produced larger SFs than cosine-phase waves with large peak factors. A model of the auditory periphery that includes coupling between adjacent frequency channels is used to explain the early neuromagnetic activity observed in auditory cortex.

Neuromagnetic Representation of Musical Register Information in HumaN Auditory Cortex

Pulse-resonance sounds like vowels or instrumental tones contain acoustic information about the physical size of the sound source (pulse rate) and body resonators (resonance scale). Previous research has revealed correlates of these variables in humans using functional neuroimaging. Here, we report two experiments that use magnetoencephalography to study the neuromagnetic representations of pulse rate and resonance scale in human auditory cortex. In Experiment 1, auditory evoked fields were recorded from nineteen subjects presented with French horn tones, the pulse rate and resonance scale of which had been manipulated independently using a mucoder. In Experiment 2, fifteen subjects listened to French horn tones which differed in resonance scale but which lacked pulse rate cues. The resulting cortical activity was evaluated by spatio-temporal source analysis. Changes in pulse rate elicited a well-defined N1m component with cortical generators located at the border between Heschls gyrus and planum temporale. Changes in resonance scale elicited a second, independent, N1m component located in planum temporale. Our results demonstrate that resonance scale can be distinguished in its neuromagnetic representation from cortical activity related to the sounds pulse rate. Moreover, the existence of two separate components in the N1m sensitive to register information highlights the importance of this time window for the processing of frequency information in human auditory cortex.

Neuromagnetic correlates of the vocal characteristics of vowels in auditory cortex

As a child grows up the formants of their vowels move down in frequency and the spacing of the harmonics that determines voice pitch decreases. Perceptually, these variables determine who listeners hear speaking (child, woman or man). In a logarithmic-frequency spectrum, the envelope with its formant peaks, moves toward the origin as a unit, without changing shape as a child grows up. Similarly, the harmonics, which constitute the fine structure of the spectrum, move toward the origin as a unit without changing shape, but at a different rate. This paper describes neuromagnetic studies which show that the generator associated with voice pitch is in Heschls gyrus just lateral to primary auditory cortex, while the generator associated spectral envelope position is in planum temporale, some distance behind the pitch activity generator. The posterior generator is close to the location of the large N1m that typically accompanies the onset of acoustic energy of any sort. The pitch processing component of the N1...

Brain imaging the activity associated with pitch intervals in a melody

Early attempts to locate brain regions involved in pitch processing employed sequences of notes with no pitch, fixed pitch, and melodic pitch. They revealed a region of Heschl’s gyrus lateral to primary auditory cortex where sequences with pitch produced more activity than noise, and regions where melody produced more activation than fixed pitch (in planum polare and the superior temporal sulcus). Subsequent research has focused on the fixed pitch region in Heschl’s gyrus and the degree to which the activity is pitch specific. Recently, MEG techniques have been developed to compare the responses to sequences of notes as they occur within bars of music, and to separate current sources associated with attention to melody. This paper illustrates how the techniques can be used to investigate the hierarchy of pitch and melody processing as it occurs in four bar phrases with brass instruments. The experiments show that a given note elicits a larger response when it is part of a melody and the increment is assoc...

Neuromagnetic correlates of voice pitch, vowel type, and speaker size in auditory cortex

Vowel recognition is largely immune to differences in speaker size despite the waveform differences associated with variation in speaker size. This has led to the suggestion that voice pitch and mean formant frequency (MFF) are extracted early in the hierarchy of hearing/speech processing and used to normalize the internal representation of vowel sounds. This paper presents a magnetoencephalographic (MEG) experiment designed to locate and compare neuromagnetic activity associated with voice pitch, MFF and vowel type in human auditory cortex. Sequences of six sustained vowels were used to contrast changes in the three components of vowel perception, and MEG responses to the changes were recorded from 25 participants. A staged procedure was employed to fit the MEG data with a source model having one bilateral pair of dipoles for each component of vowel perception. This dipole model showed that the activity associated with the three perceptual changes was functionally separable; the pitch source was located in Heschls gyrus (bilaterally), while the vowel-type and formant-frequency sources were located (bilaterally) just behind Heschls gyrus in planum temporale. The results confirm that vowel normalization begins in auditory cortex at an early point in the hierarchy of speech processing.