Spatiotemporal properties of auditory intensity processing in multisensor MEG.

Loudness dependence of auditory evoked potentials (LDAEP) evaluates loudness processing in the human auditory system and is often altered in patients with psychiatric disorders. Previous research has suggested that this measure may be used as an indicator of the central serotonergic system through the highly serotonergic innervation of the auditory cortex. However, differences among the commonly used analysis approaches (such as source analysis and single electrode estimation) may lead to different results. Putatively due to discrepancies of the underlying structures being measured. Therefore, it is important to learn more about how and where in the brain loudness variation is processed. We conducted a detailed investigation of the LDAEP generators and their temporal dynamics by means of multichannel magnetoencephalography (MEG). Evoked responses to brief tones of five different intensities were recorded from 19 healthy participants. We used magnetic field tomography in order to appropriately localize superficial as well as deep source generators of which we conducted a time series analysis. The results showed that apart from the auditory cortex other cortical sources exhibited activation during the N1/P2 time window. Analysis of time courses in the regions of interest revealed a sequential cortical activation from primary sensory areas, particularly the auditory and somatosensory cortex to posterior cingulate cortex (PCC) and to premotor cortex (PMC). The additional activation within the PCC and PMC has implications on the analysis approaches used in LDAEP research.

Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

BACKGROUND: Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. AIMS: To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. METHODS: Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. RESULTS: The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. CONCLUSIONS: The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier.

fMRI reveals cognitive and emotional processing in a long-term comatose patient.

We report on a 41-year old woman with prolonged comatose unresponsiveness following traumatic head injury. Structural MRI showed bilateral midbrain damage and ventriculomegalia. Functional MRI revealed robust cortical responses to visual, auditory and tactile stimulation. Speech stimuli moreover consistently elicited activation in Broca's and Wernicke's areas. Familiar speakers and direct addressing evoked significantly stronger amygdala activation than unfamiliar speakers and neutral phrases. This study hence demonstrates the potential of functional neuroimaging in the investigation of residual higher cortical functions in unresponsive comatose patients.

The neural correlates of person familiarity. A functional magnetic resonance imaging study with clinical implications.

Neural activity was measured in 10 healthy volunteers by functional MRI while they viewed familiar and unfamiliar faces and listened to familiar and unfamiliar voices. The familiar faces and voices were those of people personally known to the subjects; they were not people who are more widely famous in the media. Changes in neural activity associated with stimulus modality irrespective of familiarity were observed in modules previously demonstrated to be activated by faces (fusiform gyrus bilaterally) and voices (superior temporal gyrus bilaterally). Irrespective of stimulus modality, familiarity of faces and voices (relative to unfamiliar faces and voices) was associated with increased neural activity in the posterior cingulate cortex, including the retrosplenial cortex. Our results suggest that recognizing a person involves information flow from modality-specific modules in the temporal cortex to the retrosplenial cortex. The latter area has recently been implicated in episodic memory and emotional salience, and now seems to be a key area involved in assessing the familiarity of a person. We propose that disturbances in the information flow described may underlie neurological and psychiatric disorders of the recognition of familiar faces, voices and persons (prosopagnosia, phonagnosia and Capgras delusion, respectively).

The transfer of a timing pattern to the untrained human hand investigated with functional magnetic resonance imaging.

The study investigates cortical hemodynamic responses during continuation tapping using auditory pacing stimuli in five healthy right-handed subjects using functional magnetic resonance imaging. The tasks required the use of either the same finger for synchronization of the tapping movement and for continuation, or to use the contralateral finger for continuation. Results show, that using the contralateral finger increases regional cerebral blood flow in motor areas such as the anterior cerebellar hemispheres and vermis, in the cingulate motor area, but also in the posterior cingulum, when compared to using the same finger. The complementary comparison shows increased regional blood flow in the left hippocampus. The results suggest that in addition to pure executive functions, higher cognitive functions localized in these areas are involved in the transfer of interval timing.

The role of the inferior parietal cortex in linking the tactile perception and manual construction of object shapes.

We employed functional magnetic resonance imaging (fMRI) in 12 healthy subjects to measure cerebral activation related to a set of higher order manual sensorimotor tasks performed in the absence of visual guidance. Purposeless manipulation of meaningless plasticine lumps served as a reference against which we contrasted two tasks where manual manipulation served a meaningful purpose, either the perception and recognition of three-dimensional shapes or the construction of such shapes out of an amorphous plasticine lump. These tasks were compared with the corresponding mental imagery of the modelling process which evokes the constructive concept but lacks concomitant sensorimotor input and output. Neural overlap was found in a bilateral activity increase in the posterior and anterior intraparietal sulcus area (IPS and AIP). Differential activation was seen in the supplementary and cingulate motor areas, the left M1 and the superior parietal lobe for modelling and in the left angular and ventral premotor cortex for imagery. Our data thus point to a congruent neural substrate for both perceptive and constructive object-oriented sensorimotor cognition in the AIP and posterior IPS. The leftward asymmetry of the inferior parietal activations, including the angular gyrus, during imagery of modelling along with the ventral premotor activations emphasize the close vicinity of the circuitry for cognitive manipulative motor behaviour and language.

Polymodal motion processing in posterior parietal and premotor cortex: a human fMRI study strongly implies equivalencies between humans and monkeys.

In monkeys, posterior parietal and premotor cortex play an important integrative role in polymodal motion processing. In contrast, our understanding of the convergence of senses in humans is only at its beginning. To test for equivalencies between macaque and human polymodal motion processing, we used functional MRI in normals while presenting moving visual, tactile, or auditory stimuli. Increased neural activity evoked by all three stimulus modalities was found in the depth of the intraparietal sulcus (IPS), ventral premotor, and lateral inferior postcentral cortex. The observed activations strongly suggest that polymodal motion processing in humans and monkeys is supported by equivalent areas. The activations in the depth of IPS imply that this area constitutes the human equivalent of macaque area VIP.

Cortical activations during paced finger-tapping applying visual and auditory pacing stimuli.

In order to study neural systems which are involved in motor timing we used whole-brain functional resonance imaging while subjects performed a paced finger-tapping task (PFT) with their right index finger. During one condition, subjects were imaged while tapping in synchrony with tones separated by a constant interval (auditory synchronisation, AS), followed by tapping without the pacing stimulus (auditory continuation, AC). In another condition, subjects were imaged while tapping in synchrony with a visual stimulus presented at the same frequency as the tones (visual synchronisation, VS) followed by a tapping sequence without visual pacing (visual continuation, VC). The following main results were obtained: (1) tapping in the context of visual pacing was generally more variable than tapping in the context of auditory stimuli; (2) during all conditions, a fronto-parietal network was active including the dorsal lateral premotor cortex (dPMC), M1, S1, inferior parietal lobule (LPi), supplementary motor cortex (SMA), the right cerebellar hemisphere, and the paravermial region; (3) stronger activation in the bilateral ventral premotor cortex (vPMC), the left LPi, the SMA, the right inferior cerebellum, and the left thalamus during both auditory conditions (AS and AC) compared to the visual conditions (VS and VC); (4) stronger activation in the right superior cerebellum, the vermis, and the right LPi during the visual conditions (VS and VC); (5) similar activations for the AS and AC conditions; but (6) marked differences between the VS and VC conditions especially in the dorsal premotor cortex (dPMC) and LPi areas; and (7) finally, there were no activations in the auditory and visual cortices when the pacing stimuli were absent. These findings were taken as evidence for a general difference between the motor control modes operative during the auditory and visual conditions. Paced finger tapping in the context of auditory pacing stimuli relies more on brain structures subserving internal motor control while paced finger-tapping in the context of visual pacing stimuli relies on brain structures relying on the subserving processing or imagination of visual pacing stimuli.

The time course of the BOLD response in the human auditory cortex to acoustic stimuli of different duration.

The relationship between activity within the human auditory cortices and the duration of heard tones was investigated by measuring the hemodynamic response with functional magnetic resonance imaging. We demonstrate that there is no significant influence of stimulus duration as used here on the intensity and spatial extent of the hemodynamic response in the auditory cortices. We found however, that the time course of the hemodynamic response to the repeated stimulus presentation exhibited a characteristic decline after the first stimulus exposure during the activation period. The possible reasons for this time course are currently unknown, however, several factors may be involved, including top-down mechanisms and/or the interplay of tissue perfusion and oxygen consumption.

Attention modulates activity in the primary and the secondary auditory cortex: a functional magnetic resonance imaging study in human subjects.

Using functional magnetic resonance imaging, ten healthy subjects were scanned whilst listening to consonant-vowel syllables under three different conditions: (i) a 'no-attention' condition required subjects to ignore the stimuli; (ii) an 'attend' condition requiring attentive listening to stimuli; (iii) a 'detect' condition requiring detection of a specific target syllable. Hemodynamic responses were measured in the primary and secondary auditory cortex. These three conditions were associated with significantly different activations in the primary and secondary auditory cortex. The strongest activations were found for the 'detect' condition, followed by the 'attend' condition. The weakest activation was evident during the 'no-attention' condition. There were also stronger activations in the left hemisphere and within the primary auditory cortex. These results suggest that the primary and secondary auditory cortex play a main role in the selective attention.

Influence of acoustic masking noise in fMRI of the auditory cortex during phonetic discrimination.

The application of functional magnetic resonance imaging (fMRI) to study activation of auditory cortex suffers from one significant confounding factor, namely, that of the acoustic noise generated by the gradient system, which is an integral part of the imaging process. Earlier work has shown that it is indeed possible to distinguish cortical activation resulting from presentation of auditory stimuli despite the presence of background noise from the gradient system. The influence of acoustic noise from the gradient system of the MRI scanner on the blood oxygen level-dependent (BOLD) response during functional activation of the auditory cortex has been investigated in six healthy subjects with no hearing difficulties. Experiments were performed using gradient-echo echoplanar imaging (EPI) and a verbal, auditory discrimination paradigm, presented in a block-wise manner, in which carefully aligned consonant-vowel syllables were presented at a rate of 1 Hz. For each volunteer the experiment was repeated three times with all parameters fixed, except slice number, which was 4, 16, or 64. The positioning of the central four slices in each experiment was common. Thus, the fraction of TR during which the stimulus is on but no imaging is being performed, varies from almost zero, in the case of 64 slices, to over 8 seconds, in the case of four slices. Only the central four slices were of interest; additional slices simply generated acoustic noise and were discarded. During the four-slice experiment, all subjects showed a robust BOLD response in the superior temporal gyrus covering the primary and secondary auditory cortex. The spatial extent and the z-scores of the activated regions decreased with longer duration of gradient noise from the scanner. For a phonetic discrimination task, the results indicate that presentation of the stimulus during periods free from scanner noise leads to a more pronounced BOLD response.

A three stage model of awareness: formulation and initial experimental support.

The various components which together make up the complex state of consciousness require neural support involving a connected network of many brain areas at differing levels. At the lowest level is non-aware processing, of which there is not direct awareness. There are also modules involved in processing with awareness but without focussed attention. Finally there must be a set of modules involved in directing attention in a controlled manner. We expect to be able to dissociate the various components of the three-stage network by using different levels of attention. The results of an auditory experiment performed under three different levels of awareness and attention are analysed to show support for the three-stage model of awareness. The relevant auditory areas are delineated.