Ville Mäkinen

Serotonergic modulation of mismatch negativity

Neurochemical mechanisms mediating the interaction between emotional and cognitive processing are not yet fully understood. Here, we utilized acute tryptophan depletion (ATD) to reduce the brain synthesis of serotonin (5-HT), which is thought to have a central role in regulation of emotions and mood in humans. ATD effects on event-related potentials and magnetic fields were studied using a passive odd-ball paradigm in a randomized, double-blinded, controlled, cross-over design. Auditory responses were recorded simultaneously with high-resolution magnetoencephalography (MEG) and electroencephalography (EEG) in 14 healthy subjects, 5 h after ATD or a control condition. ATD significantly increased depressed mood and lowered plasma tryptophan concentration (total tryptophan decreased by 75%, free tryptophan decreased by 39%). As compared with the control condition, ATD increased the amplitudes of mismatch negativity (MMN) to duration and frequency changes and decreased the latencies of magnetic MMN to frequency changes in the hemisphere ipsilateral to the ear stimulated. Further, ATD modulated N1m latencies and decreased P2m source activity. ATD increased the interhemispheric latency difference of MMNm to frequency changes. No effects on P50 were observed. The present results suggest serotonergic modulation of preattentive auditory change detection, suggested to initiate involuntary attention shifting in the human brain.

Sound localization in the human brain: neuromagnetic observations

&NA; Sound location processing in the human auditory cortex was studied with magnetoencephalography (MEG) by producing spatial stimuli using a modern stimulus generation methodology utilizing head‐related transfer functions (HRTFs). The stimulus set comprised wideband noise bursts filtered through HRTFs in order to produce natural spatial sounds. Neuromagnetic responses for stimuli representing eight equally spaced sound source directions in the azimuthal plane were measured from 10 subjects. The most prominent response, the cortically generated N1m, was investigated above the left and right hemisphere. We found, firstly, that the HRTF‐based stimuli presented from different directions elicited contralaterally prominent N1m responses. Secondly, we found that cortical activity reflecting the processing of spatial sound stimuli was more pronounced in the right than in the left hemisphere.

Magnetoencephalographic (MEG) localization of the auditory N400m: effects of stimulus duration

The effects of stimulus duration on the elicitation and equivalent current dipole (ECD) localization of the auditory N400(m) were studied in two subject groups, either familiar or unfamiliar with Finnish language, using a sentence-processing paradigm with incongruent ending words of either short or long duration. Long-duration words elicited a broad response at around 400 ms, the generator location(s) of which could not be reliably determined using ECD estimation. In contrast, short-duration words elicited a sharp, strong-amplitude response at about 400 ms latency and its source location could be reliably determined as being in the vicinity of auditory cortex. Subjects unfamiliar with the Finnish language elicited no response at the 400 ms range. Thus, the use of short-duration words appears to be an important prerequisite for the elicitation and localization of N400m. The differential amplitude behaviour of the N400m between the two subject groups further suggests that comprehension of the semantic content of the speech message is also required.

Transient brain responses predict the temporal dynamics of sound detection in humans.

The neural events leading up to the conscious experience of stimulus events have remained elusive. Here we describe stimulation conditions under which activation in human auditory cortex can be used to predict the temporal dynamics of behavioral sound detection. Subjects were presented with auditory stimuli whose energy smoothly increased from a silent to a clearly audible level over either 1, 1.5, or 2 s. Magnetoencephalographic (MEG) recordings were carried out in the passive and active recording conditions. In the active condition, the subjects were instructed to attend to the auditory stimuli and to press a response key when these became audible. In both conditions, the stimuli elicited a prominent transient response whose emergence is unexplainable by changes in stimulus intensity alone. This transient response was larger in amplitude over the right hemisphere and in the active condition. Importantly, behavioral sound detection followed this brain activation with a constant delay of 180 ms, and further the latency variations of the brain response were directly carried over to behavioral reaction times. Thus, noninvasively measured transient events in the human auditory cortex can be used to predict accurately the temporal course of sound detection and may therefore turn out to be useful in clinical settings.

Disentangling the effects of phonation and articulation: Hemispheric asymmetries in the auditory N1m response of the human brain

BackgroundThe cortical activity underlying the perception of vowel identity has typically been addressed by manipulating the first and second formant frequency (F1 & F2) of the speech stimuli. These two values, originating from articulation, are already sufficient for the phonetic characterization of vowel category. In the present study, we investigated how the spectral cues caused by articulation are reflected in cortical speech processing when combined with phonation, the other major part of speech production manifested as the fundamental frequency (F0) and its harmonic integer multiples. To study the combined effects of articulation and phonation we presented vowels with either high (/a/) or low (/u/) formant frequencies which were driven by three different types of excitation: a natural periodic pulseform reflecting the vibration of the vocal folds, an aperiodic noise excitation, or a tonal waveform. The auditory N1m response was recorded with whole-head magnetoencephalography (MEG) from ten human subjects in order to resolve whether brain events reflecting articulation and phonation are specific to the left or right hemisphere of the human brain.ResultsThe N1m responses for the six stimulus types displayed a considerable dynamic range of 115–135 ms, and were elicited faster (~10 ms) by the high-formant /a/ than by the low-formant /u/, indicating an effect of articulation. While excitation type had no effect on the latency of the right-hemispheric N1m, the left-hemispheric N1m elicited by the tonally excited /a/ was some 10 ms earlier than that elicited by the periodic and the aperiodic excitation. The amplitude of the N1m in both hemispheres was systematically stronger to stimulation with natural periodic excitation. Also, stimulus type had a marked (up to 7 mm) effect on the source location of the N1m, with periodic excitation resulting in more anterior sources than aperiodic and tonal excitation.ConclusionThe auditory brain areas of the two hemispheres exhibit differential tuning to natural speech signals, observable already in the passive recording condition. The variations in the latency and strength of the auditory N1m response can be traced back to the spectral structure of the stimuli. More specifically, the combined effects of the harmonic comb structure originating from the natural voice excitation caused by the fluctuating vocal folds and the location of the formant frequencies originating from the vocal tract leads to asymmetric behaviour of the left and right hemisphere.

Visual short-term memory load affects sensory processing of irrelevant sounds in human auditory cortex.

We used whole-head magnetoencephalography (MEG) to investigate neural activity in human auditory cortex elicited by irrelevant tones while the subjects were engaged in a short-term memory task presented in the visual modality. As compared to a no-memory-task condition, memory load enhanced the amplitude of the auditory N1m response. In addition, the N1m amplitude depended on the phase of the memory task, with larger response amplitudes observed during encoding than retention. Further, these amplitude modulations were accompanied by anterior-posterior shifts in N1m source locations. The results show that a memory task for visually presented stimuli alters sensory processing in human auditory cortex, even when subjects are explicitly instructed to ignore any auditory stimuli. Thus, it appears that task demands requiring attentional allocation and short-term memory result in interaction across visual and auditory brain areas carrying out the processing of stimulus features.

Glides in speech fundamental frequency are reflected in the auditory N1m response.

The cortical dynamics underlying the perception of constant and gliding speech fundamental frequency (F0) was investigated in 10 subjects using magnetoencephalography (MEG). The stimuli comprised vowels having either constant, ascending or descending F0s and tones of corresponding frequencies, matched with the vowels in intensity or loudness. The amplitude of the N1m response was highly sensitive to F0 variation embedded in vowels and insensitive to corresponding variation in tones. The latency of the N1m elicited by the tones with respect to vowels was significantly delayed. Thus, the speech-specific behavior of the N1m arises out of cortical sensitivity to the acoustic structure of voiced speech, that is to the F0 and its harmonics, which underlie the perception of pitch and intonation in speech.

Left-hemispheric brain activity reflects formant transitions in speech sounds.

Connected speech is characterized by formant transitions whereby formant frequencies change over time. Here, using magneto-encephalography, we investigated the cortical activity in 10 participants in response to constant-formant vowels and diphthongs with formant transitions. All the stimuli elicited prominent auditory N100m responses, but the formant transitions resulted in latency modulations specific to the left hemisphere. Following the elicitation of the N100m, cortical activity shifted some 10 mm towards anterior brain areas. This late activity resembled the N400m, typically obtained with more complex utterances such as words and/or sentences. Thus, the present study demonstrates how magnetoencephalography can be used to investigate the spatiotemporal evolution in cortical activity related to the various stages of the processing of speech.

The use of stationarity and nonstationarity in the detection and analysis of neural oscillations

Using available signal (i.e., spectral and time-frequency) analysis methods, it can be difficult to detect neural oscillations because of their continuously changing properties (i.e., nonstationarities) and the noise in which they are embedded. Here, we introduce fractally scaled envelope modulation (FSEM) estimation which is sensitive specifically to the changing properties of oscillatory activity. FSEM utilizes the fractal characteristic of wavelet transforms to produce a compact, two-dimensional representation of time series data where signal components at each frequency are made directly comparable according to the spectral distribution of their envelope modulations. This allows the straightforward identification of neural oscillations and other signal components with an envelope structure different from noise. For stable oscillations, we demonstrate how partition-referenced spectral estimation (PRSE) removes the noise slope from spectral estimates, yielding a level estimate where only peaks signifying the presence of oscillatory activity remain. The functionality of these methods is demonstrated with simulations and by analyzing MEG data from human auditory brain areas. FSEM uncovered oscillations in the 9- to 12-Hz and 15- to 18-Hz ranges whereas traditional spectral estimates were able to detect oscillations only in the former range. FSEM further showed that the oscillations exhibited envelope modulations spanning 3-7 s. Thus, FSEM effectively reveals oscillations undetectable with spectral estimates and allows the use of EEG and MEG for studying cognitive processes when the common approach of stimulus time-locked averaging of the measured signal is unfeasible.

Averaged and single-trial brain responses in the assessment of human sound detection.

We investigated sound detection in humans with magnetoencephalography and behavioural measurements. Sounds with intensity increasing smoothly over 125–1000 ms elicited a transient response in auditory cortex with a peak latency in the 200–600 ms range. Importantly, peak latency accurately predicted behavioural reaction time and was unaffected by attentional engagement. Peak amplitude was augmented when the study participants attended to the stimuli and when stimulus duration was decreased. For investigating the cause of these amplitude variations in the averaged response we designed a wavelet-based method for analysing single-trial responses. We found that attention affects the amplitude of the single-trial responses whereas the intensity slope of the stimulus modifies their latency distribution. The transient response reported here holds promise for rapid, objective hearing assessment not requiring a behavioural task.