N. Jon Shah

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.

Recognition of emotional prosody and verbal components of spoken language: an fMRI study

This study examined the neural areas involved in the recognition of both emotional prosody and phonemic components of words expressed in spoken language using echo-planar, functional magnetic resonance imaging (fMRI). Ten right-handed males were asked to discriminate words based on either expressed emotional tone (angry, happy, sad, or neutral) or phonemic characteristics, specifically, initial consonant sound (bower, dower, power, or tower). Significant bilateral activity was observed in the detection of both emotional and verbal aspects of language when compared to baseline activity. We found that the detection of emotion compared with verbal detection resulted in significant activity in the right inferior frontal lobe. Conversely, the detection of verbal stimuli compared with the detection of emotion activated left inferior frontal lobe regions most significantly. Specific analysis of the anterior auditory cortex revealed increased right hemisphere activity during the detection of emotion compared to activity during verbal detection. These findings illustrate bilateral involvement in the detection of emotion in language while concomitantly showing significantly lateralized activity in both emotional and verbal detection, in both the temporal and frontal lobes.

Being with virtual others: Neural correlates of social interaction

To characterize the neural correlates of being personally involved in social interaction as opposed to being a passive observer of social interaction between others we performed an fMRI study in which participants were gazed at by virtual characters (ME) or observed them looking at someone else (OTHER). In dynamic animations virtual characters then showed socially relevant facial expressions as they would appear in greeting and approach situations (SOC) or arbitrary facial movements (ARB). Differential neural activity associated with ME>OTHER was located in anterior medial prefrontal cortex in contrast to the precuneus for OTHER>ME. Perception of socially relevant facial expressions (SOC>ARB) led to differentially increased neural activity in ventral medial prefrontal cortex. Perception of arbitrary facial movements (ARB>SOC) differentially activated the middle temporal gyrus. The results, thus, show that activation of medial prefrontal cortex underlies both the perception of social communication indicated by facial expressions and the feeling of personal involvement indicated by eye gaze. Our data also demonstrate that distinct regions of medial prefrontal cortex contribute differentially to social cognition: whereas the ventral medial prefrontal cortex is recruited during the analysis of social content as accessible in interactionally relevant mimic gestures, differential activation of a more dorsal part of medial prefrontal cortex subserves the detection of self-relevance and may thus establish an intersubjective context in which communicative signals are evaluated.

Prefrontal involvement in imitation learning of hand actions: Effects of practice and expertise

In this event-related fMRI study, we demonstrate the effects of a single session of practising configural hand actions (guitar chords) on cortical activations during observation, motor preparation and imitative execution. During the observation of non-practised actions, the mirror neuron system (MNS), consisting of inferior parietal and ventral premotor areas, was more strongly activated than for the practised actions. This finding indicates a strong role of the MNS in the early stages of imitation learning. In addition, the left dorsolateral prefrontal cortex (DLPFC) was selectively involved during observation and motor preparation of the non-practised chords. This finding confirms Buccino et al.s [Buccino, G., Vogt, S., Ritzl, A., Fink, G.R., Zilles, K., Freund, H.-J., Rizzolatti, G., 2004a. Neural circuits underlying imitation learning of hand actions: an event-related fMRI study. Neuron 42, 323-334] model of imitation learning: for actions that are not yet part of the observers motor repertoire, DLPFC engages in operations of selection and combination of existing, elementary representations in the MNS. The pattern of prefrontal activations further supports Shallices [Shallice, T., 2004. The fractionation of supervisory control. In: Gazzaniga, M.S. (Ed.), The Cognitive Neurosciences, Third edition. MIT Press, Cambridge, MA, pp. 943-956] proposal of a dominant role of the left DLPFC in modulating lower level systems and of a dominant role of the right DLPFC in monitoring operations.

Gender differences in the cognitive control of emotion: An fMRI study.

The interaction of emotion and cognition has become a topic of major interest. However, the influence of gender on the interplay between the two processes, along with its neural correlates have not been fully analysed so far. In this functional magnetic resonance imaging (fMRI) study we induced negative emotion using negative olfactory stimulation while male (n=21) and female (n=19) participants performed an n-back verbal working memory task. Based on findings indicating increased emotional reactivity in women, we expected the female participants to exhibit stronger activation in characteristically emotion-associated areas during the interaction of emotional and cognitive processing in comparison to the male participants. Both groups were found to be significantly impaired in their working memory performance by negative emotion induction. However, fMRI analysis revealed distinct differences in neuronal activation between groups. In men, cognitive performance under negative emotion induction was associated with extended activation patterns in mainly prefrontal and superior parietal regions. In women, the interaction between emotion and working memory yielded a significantly stronger response in the amygdala and the orbitofrontal cortex (OFC) compared to their male counterparts. Our data suggest that in women the interaction of verbal working memory and negative emotion is associated with relative hyperactivation in more emotion-associated areas whereas in men regions commonly regarded as important for cognition and cognitive control are activated. These results provide new insights in gender-specific cerebral mechanisms.

Same or different? Neural correlates of happy and sad mood in healthy males

Emotional experience in healthy men has been shown to rely on a brain network including subcortical as well as cortical areas in a complex interaction, which may be substantially influenced by many internal personal and external factors such as individuality, gender, stimulus material and task instructions. The divergent results may be interpreted by taking these considerations into account. Hence, many aspects remain to be clarified in characterizing the neural correlates underlying the subjective experience of emotion. One unresolved question refers to the influence of emotion quality on the cerebral substrates. Hence, 26 male healthy subjects were investigated with functional magnetic resonance imaging during standardized sad and happy mood induction as well as a cognitive control task to explore brain responses differentially involved in positive and negative emotional experience. Sad and happy mood in contrast to the control task produced similarly significant activations in the amygdala-hippocampal area extending into the parahippocampal gyrus as well as in the prefrontal and temporal cortex, the anterior cingulate, and the precuneus. Significant valence differences emerged when comparing both tasks directly. More activation has been demonstrated in the ventrolateral prefrontal cortex (VLPFC), the anterior cingulate cortex (ACC), the transverse temporal gyrus, and the superior temporal gyrus during sadness. Happiness, on the other hand, produced stronger activations in the dorsolateral prefrontal cortex (DLPFC), the cingulate gyrus, the inferior temporal gyrus, and the cerebellum. Hence, negative and positive moods reveal distinct cortical activation foci within a common neural network, probably making the difference between qualitatively different emotional feelings.

A fronto-parietal circuit for tactile object discrimination: an event-related fMRI study.

Previous studies of somatosensory object discrimination have been focused on the primary and secondary sensorimotor cortices. However, we expected the prefrontal cortex to also become involved in sequential tactile discrimination on the basis of its role in working memory and stimulus discrimination as established in other domains. To investigate the contributions of the different cerebral structures to tactile discrimination of sequentially presented objects, we obtained event-related functional magnetic resonance images from seven healthy volunteers. Our results show that right hand object exploration involved left sensorimotor cortices, bilateral premotor, parietal and temporal cortex, putamen, thalamus, and cerebellum. Tactile exploration of parallelepipeds for subsequent object discrimination activated further areas in the dorsal and ventral portions of the premotor cortex, as well as parietal, midtemporal, and occipital areas of both cerebral hemispheres. Discriminating a parallelepiped from the preceding one involved a bilateral prefrontal-anterior cingulate-superior temporal-posterior parietal circuit. While the prefrontal cortex was active with right hemisphere dominance during discrimination, there was left hemispheric prefrontal activation during the delay period between object presentations. Delay related activity was further seen in the anterior intraparietal area and the fusiform gyrus. The results reveal a prominent role of the human prefrontal cortex for somatosensory object discrimination in correspondence with recent models on stimulus discrimination and working memory.

Emotional Processing in Male Adolescents with Childhood-Onset Conduct Disorder.

BACKGROUND Boys with early onset of conduct disorder (CD), most of whom also meet diagnostic criteria of a comorbid attention deficit hyperactivity disorder (ADHD), tend to exhibit high levels of aggression throughout development. While a number of functional neuroimaging studies on emotional processing have been performed in antisocial adults, little is known about how CD children process emotional information. METHOD Functional magnetic resonance imaging data were analyzed in 22 male adolescents aged 12 to 17 years with childhood-onset CD (16 of them with comorbid ADHD) compared to 22 age-matched male healthy controls. In order to consider the likely confounding of results through ADHD comorbidity, we performed a supplementary study including 13 adolescent subjects with pure ADHD who were compared with healthy controls. To challenge emotional processing of stimuli, a passive viewing task was applied, presenting pictures of negative, positive or neutral valence. RESULTS When comparing CD/combined disorder patients with healthy controls, we found enhanced left-sided amygdala activation in response to negative pictures as compared to neutral pictures in the patient group. In addition, these boys exhibited no reduced activation in the orbitofrontal, anterior cingulate and insular cortices. By contrast, children with pure ADHD did not show any abnormalities in amygdala activation but showed decreased neural activity in the insula only in response to negative pictures. CONCLUSIONS Increased rather than reduced amygdala activation found in our study may indicate an enhanced response to environmental cues in adolescents with early-onset CD (most of whom also met the condition of ADHD), and is not consistent with the assumption of a reduced capacity to take note of affective information in the social environment. Further studies with an emphasis on developmental aspects of affect regulation are needed to clarify the relationship between CD and adult personality pathology associated with different modes of persistent antisocial behavior.

Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study

Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After these quality-control measures had been implemented, 48 patients and 57 controls were included in the final analysis. During attention-related processes, even when the performance between patients and controls was comparable, there was a recognizable emergence of cerebral dysfunctions with hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior temporal cortex and in the thalamus. During working memory performance, parietal hypoactivations, especially in the precuneus, were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Hence, results point to a dysfunctional ventrolateral prefrontal-parietal network during working memory in patients, suggesting impairments in basic functions such as retrieval, storage and maintenance. The brain activation pattern of this large and significant sample of first-episode schizophrenia patients indicates an imbalanced system failing to adjust the amount of brain activity required in the cerebral network involved in attention and working memory.

Blood–Brain Barrier Permeability Abnormalities in Vascular Cognitive Impairment

Background and Purpose— Disruption of the blood–brain barrier has been proposed to be important in vascular cognitive impairment. Increased cerebrospinal fluid albumin and contrast-enhanced MRI provide supporting evidence, but quantification of the blood–brain barrier permeability in patients with vascular cognitive impairment is lacking. Therefore, we acquired dynamic contrast-enhanced MRI to quantify blood–brain barrier permeability in vascular cognitive impairment. Method— We studied 60 patients with suspected vascular cognitive impairment. They had neurological and neuropsychological testing, permeability measurements with dynamic contrast-enhanced MRI, and lumbar puncture to measure albumin index. Patients were separated clinically into subcortical ischemic vascular disease (SIVD), multiple and lacunar infarcts, and leukoaraiosis. Twenty volunteers were controls for the dynamic contrast-enhanced MRI studies, and control cerebrospinal fluid was obtained from 20 individuals undergoing spinal anesthesia for nonneurological problems. Results— Thirty-six patients were classified as SIVD, 8 as multiple and lacunar infarcts, and 9 as leukoaraiosis. The albumin index was significantly increased in the SIVD group compared with 20 control subjects. Permeabilities for the patients with vascular cognitive impairment measured by dynamic contrast-enhanced MRI were significantly increased over control subjects (P<0.05). Patient age did not correlate with either the blood–brain barrier permeability or albumin index. Highest albumin index values were seen in the SIVD group (P<0.05) and were significantly increased over multiple and lacunar infarcts. Ki values were elevated over control subjects in SIVD but were similar to multiple and lacunar infarcts. Conclusions— There was abnormal permeability in white matter in patients with SIVD as shown by dynamic contrast-enhanced MRI and albumin index. Future studies will be needed to determine the relationship of blood–brain barrier damage and development of white matter hyperintensities.