Synnöve Carlson

The mismatch negativity (MMN) - A unique window to disturbed central auditory processing in ageing and different clinical conditions

In this article, we review clinical research using the mismatch negativity (MMN), a change-detection response of the brain elicited even in the absence of attention or behavioural task. In these studies, the MMN was usually elicited by employing occasional frequency, duration or speech-sound changes in repetitive background stimulation while the patient was reading or watching videos. It was found that in a large number of different neuropsychiatric, neurological and neurodevelopmental disorders, as well as in normal ageing, the MMN amplitude was attenuated and peak latency prolonged. Besides indexing decreased discrimination accuracy, these effects may also reflect, depending on the specific stimulus paradigm used, decreased sensory-memory duration, abnormal perception or attention control or, most importantly, cognitive decline. In fact, MMN deficiency appears to index cognitive decline irrespective of the specific symptomatologies and aetiologies of the different disorders involved.

Cognitive and motor loops of the human cerebro-cerebellar system

We applied fMRI and diffusion-weighted MRI to study the segregation of cognitive and motor functions in the human cerebro-cerebellar system. Our fMRI results show that a load increase in a nonverbal auditory working memory task is associated with enhanced brain activity in the parietal, dorsal premotor, and lateral prefrontal cortices and in lobules VII–VIII of the posterior cerebellum, whereas a sensory-motor control task activated the motor/somatosensory, medial prefrontal, and posterior cingulate cortices and lobules V/VI of the anterior cerebellum. The load-dependent activity in the crus I/II had a specific relationship with cognitive performance: This activity correlated negatively with load-dependent increase in RTs. This correlation between brain activity and RTs was not observed in the sensory-motor task in the activated cerebellar regions. Furthermore, probabilistic tractography analysis of the diffusion-weighted MRI data suggests that the tracts between the cerebral and the cerebellar areas exhibiting cognitive load-dependent and sensory-motor activity are mainly projected via separated pontine (feed-forward tracts) and thalamic (feedback tracts) nuclei. The tractography results also indicate that the crus I/II in the posterior cerebellum is linked with the lateral prefrontal areas activated by cognitive load increase, whereas the anterior cerebellar lobe is not. The current results support the view that cognitive and motor functions are segregated in the cerebellum. On the basis of these results and theories of the function of the cerebellum, we suggest that the posterior cerebellar activity during a demanding cognitive task is involved with optimization of the response speed.

The mismatch negativity: an index of cognitive decline in neuropsychiatric and neurological diseases and in ageing

Cognitive impairment is a core element shared by a large number of different neurological and neuropsychiatric diseases. Irrespective of their different aetiologies and symptomatologies, most appear to converge at the functional deficiency of the auditory-frontal cortex network of auditory discrimination, which indexes cognitive impairment shared by these abnormalities. This auditory-frontal cortical deficiency, and hence cognitive decline, can now be objectively measured with the mismatch negativity and its magnetic equivalent. The auditory-frontal cortical network involved seems, therefore, to play a pivotal, unifying role in the different abnormalities. It is, however, more likely that the dysfunction that can be detected with the mismatch negativity and its magnetoencephalographic equivalent manifests a more widespread brain disorder, namely, a deficient N-methyl-D-aspartate receptor function, shared by these abnormalities and accounting for most of the cognitive decline.

Working memory, psychiatric symptoms, and academic performance at school

Previous studies of the relationship among working memory function, academic performance, and behavior in children have focused mainly on clinical populations. In the present study, the associations of the performance in audio- and visuospatial working memory tasks to teacher reported academic achievement and psychiatric symptoms were evaluated in a sample of fifty-five 6-13-year-old school children. Working memory function was measured by visual and auditory n-back tasks. Information on incorrect responses, reaction times, and multiple and missed responses were collected during the tasks. The childrens academic performance and behavioral and emotional status were evaluated by the Teacher Report Form. The results showed that good spatial working memory performance was associated with academic success at school. Children with low working memory performance, especially audiospatial memory, were reported to have more academic and attentional/behavioral difficulties at school than children with good working memory performance. An increased number of multiple and missed responses in the auditory and visual tasks was associated with teacher reported attentional/behavioral problems and in visual tasks with teacher reported anxiety/depressive symptoms. The results suggest that working memory deficits may underlie some learning difficulties and behavioral problems related to impulsivity, difficulties in concentration, and hyperactivity. On the other hand, it is possible that anxiety/depressive symptoms affect working memory function, as well as the ability to concentrate, leading to a lower level of academic performance at school.

Preserved functional specialization for spatial processing in the middle occipital gyrus of the early blind

The occipital cortex (OC) of early-blind humans is activated during various nonvisual perceptual and cognitive tasks, but little is known about its modular organization. Using functional MRI we tested whether processing of auditory versus tactile and spatial versus nonspatial information was dissociated in the OC of the early blind. No modality-specific OC activation was observed. However, the right middle occipital gyrus (MOG) showed a preference for spatial over nonspatial processing of both auditory and tactile stimuli. Furthermore, MOG activity was correlated with accuracy of individual sound localization performance. In sighted controls, most of extrastriate OC, including the MOG, was deactivated during auditory and tactile conditions, but the right MOG was more activated during spatial than nonspatial visual tasks. Thus, although the sensory modalities driving the neurons in the reorganized OC of blind individuals are altered, the functional specialization of extrastriate cortex is retained regardless of visual experience.

Early visual deprivation alters modality of neuronal responses in area 19 of monkey cortex

Monkeys deprived on vision during the first year of life by lid suture appear functionally blind after the opening of the eyes, but move actively in familiar surroundings using somesthetic cues. Microelectrode recordings of multiple unit activity in the associative visual cortical area 19 of deprived monkeys indicated that 20% of the neuron groups studies responded only during active somatic exploration. In normal animals all neuron groups studied responses exclusively to visual stimuli, but in the deprived animals only 40% of them did. Visual deprivation alters the synaptic pathways to visual associative cortex enhancing the efficiency of those inputs that can mediate somatic information to this region.

Cognitive Control in Auditory Working Memory Is Enhanced in Musicians

Musical competence may confer cognitive advantages that extend beyond processing of familiar musical sounds. Behavioural evidence indicates a general enhancement of both working memory and attention in musicians. It is possible that musicians, due to their training, are better able to maintain focus on task-relevant stimuli, a skill which is crucial to working memory. We measured the blood oxygenation-level dependent (BOLD) activation signal in musicians and non-musicians during working memory of musical sounds to determine the relation among performance, musical competence and generally enhanced cognition. All participants easily distinguished the stimuli. We tested the hypothesis that musicians nonetheless would perform better, and that differential brain activity would mainly be present in cortical areas involved in cognitive control such as the lateral prefrontal cortex. The musicians performed better as reflected in reaction times and error rates. Musicians also had larger BOLD responses than non-musicians in neuronal networks that sustain attention and cognitive control, including regions of the lateral prefrontal cortex, lateral parietal cortex, insula, and putamen in the right hemisphere, and bilaterally in the posterior dorsal prefrontal cortex and anterior cingulate gyrus. The relationship between the task performance and the magnitude of the BOLD response was more positive in musicians than in non-musicians, particularly during the most difficult working memory task. The results confirm previous findings that neural activity increases during enhanced working memory performance. The results also suggest that superior working memory task performance in musicians rely on an enhanced ability to exert sustained cognitive control. This cognitive benefit in musicians may be a consequence of focused musical training.

Effects of an NMDA-receptor antagonist MK-801 on an MMN-like response recorded in anesthetized rats.

In the human brain, auditory sensory memory has been extensively studied using a well-defined component of event-related potential named the mismatch negativity (MMN). The MMN is generated in the auditory and frontal cortices in response to deviant stimuli. In monkeys, cortical N-methyl-d-aspartate (NMDA) receptors have a central role in the generation of the MMN. MMN-like responses have also been recorded in other animals, including rats. The present study aimed at determining whether the MMN-like response in rats depends on an intact NMDA-receptor system. We recorded auditory evoked responses during an oddball paradigm epidurally in anesthetized rats that had received intraperitoneal injections of saline or an NMDA-receptor antagonist MK-801. An MMN-like response was recorded in the oddball paradigm in saline-treated rats. Further, this response was dose-dependently blocked by MK-801. These results suggest that the MMN-like response in rats depends on an intact NMDA-receptor system.

Working Memory of Identification of Emotional Vocal Expressions: An fMRI Study

The distribution of brain activation during working memory processing of emotional vocal expressions was studied using functional magnetic resonance imaging (fMRI) in eight female subjects performing n-back tasks with three load levels (0-back, 1-back, and 2-back tasks). The stimuli in the n-back tasks were the Finnish female name [Saara] uttered in an astonished, angry, frightened, commanding, and scornful mode, and the subjects were instructed to memorize the emotional connotation of the stimuli. Subregions in the prefrontal, parietal, and visual association areas were load-dependently activated during the performance of the n-back tasks. The most consistently activated areas in the prefrontal region were detected in the inferior frontal gyrus corresponding to Brodmanns areas (BAs) 44 and 45 and in the middle and superior frontal gyri (BAs 6/8). Activation was also found in the inferior parietal lobe and intraparietal sulcus (BAs 40/7) and visual association areas including the lingual and fusiform gyri. The results suggest that a distributed neuronal network in occipital, parietal, and frontal areas is involved in working memory processing of emotional content of aurally presented information.

Acute opioid effects on human brain as revealed by functional magnetic resonance imaging

Functional magnetic resonance imaging has been widely used to study brain activation induced either by specific sensory stimulation or motor or cognitive task performance. We demonstrate that functional magnetic resonance imaging can provide information of brain regions involved in opioid-induced central nervous system effects. The reproducibility of the responses in the predefined regions of interest was confirmed by repeated boluses of ultra-short acting mu-opioid receptor agonist remifentanil and saline. We report spatially and temporally detailed information after remifentanil administration. Areas rich in mu-opioid receptors showed strong activations, whereas primary somatosensory cortex that has the lowest density of mu-opioid receptors showed negligible activation. The cingulate, orbitofrontal, posterior parietal and insular cortices, and amygdala showed activation, which was temporally closely related to most subjective sensations that were strongest at 80 to 90 s after drug administration. These areas belong to a circuitry that modulates the affective experience of sensory stimuli.