Shahram Mirzazade

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.

A parametric analysis of the 'rate effect' in the sensorimotor cortex : a functional magnetic resonance imaging analysis in human subjects

We studied the effects of different movement speeds of unimanual right hand movements on functional magnetic resonance signal changes in the sensorimotor cortex using echo planar imaging (EPI). Six healthy right-handed subjects were scanned at rest and while executing a finger tapping task with their right index finger. Movement frequency was visually paced at rates ranging from 0.5 to 5 Hz, separated by 0.5 Hz steps. The blood oxygen level dependent (BOLD) response within the left sensorimotor cortex was linearly and positively related to movement frequency. However, this relation holds (r2 = 0.91) only for movement frequencies faster than 1 Hz (1.5-5 Hz). For the slower frequencies there was an initial sharp increase of the BOLD response from 0.5 to 1 Hz followed by an activity drop for 1.5 Hz. These results are compatible with the idea that two different motor control modes are operative during slow or fast movements. During slow movements a computational demanding on-line feedback control mode is operative resulting in strong BOLD signals indicating extensive neural activity. During faster movements on the other hand a program-like motor control mode is operative resulting in less demanding neural computations. The amount of neural computation for the latter control mode increases with increasing movement speed.

The effect of finger-movement speed of the dominant and the subdominant hand on cerebellar activation: A functional magnetic resonance imaging study.

We studied the effects of different speeds of unimanual and bimanual movements on functional magnetic resonance signal changes in the cerebellum. Six healthy consistently right-handed subjects were scanned at rest and while executing a sequential finger-to-thumb-opposition task either unimanually (left or right hand) or bimanually. Movement frequency was paced by an auditory signal at rates of either 1 or 3 Hz. Significant frequency-dependent blood oxygen level-dependent signal increases were demonstrated ipsilaterally and contralaterally in the intermediate and lateral portions of the anterior cerebellum for bimanual movements and for unimanual movements with the subdominant hand. There was only a weak frequency-dependent effect for unimanual movements performed with the dominant hand. In addition, signals were stronger on the right intermediate zone of the anterior cerebellum for movements involving the right (dominant) hand while there was stronger activity on the left cerebellar hemisphere for movements involving the left (subdominant) hand. Taken together, these results suggest that rate and movement task effects on cerebellar activation are differentially sensitive to subdominant and dominant hand movements.

Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6

Spinocerebellar ataxias are dominantly inherited disorders that are associated with progressive brain degeneration, mainly affecting the cerebellum and brainstem. As part of the multicentre European integrated project on spinocerebellar ataxias study, 37 patients with spinocerebellar ataxia-1, 19 with spinocerebellar ataxia-3 and seven with spinocerebellar ataxia-6 were clinically examined and underwent magnetic resonance imaging at baseline and after a 2-year follow-up. All patients were compared with age-matched and gender-matched healthy control subjects. Magnetic resonance imaging analysis included three-dimensional volumetry and observer-independent longitudinal voxel-based morphometry. Volumetry revealed loss of brainstem, cerebellar and basal ganglia volume in all genotypes. Most sensitive to change was the pontine volume in spinocerebellar ataxia-1, striatal volume in spinocerebellar ataxia-3 and caudate volume in spinocerebellar ataxia-6. Sensitivity to change, as measured by standard response mean, of the respective MRI measures was greater than that of the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia. Longitudinal voxel-based morphometry revealed greatest grey matter loss in the cerebellum and brainstem in spinocerebellar ataxia-1, in the putamen and pallidum in spinocerebellar ataxia-3 and in the cerebellum, thalamus, putamen and pallidum in spinocerebellar ataxia-6. There was a mild correlation between CAG repeat length and volume loss of the bilateral cerebellum and the pons in spinocerebellar ataxia-1. Quantitative volumetry and voxel-based morphometry imaging demonstrated genotype-specific patterns of atrophy progression in spinocerebellar ataxias-1, 3 and 6, and they showed a high sensitivity to detect change that was superior to clinical scales. These structural magnetic resonance imaging findings have the potential to serve as surrogate markers, which might help to delineate quantifiable endpoints and non-invasive methods for rapid and reliable data acquisition, encouraging their use in clinical trials.

Ageing-related changes of neural activity associated with spatial contextual memory.

Neuropsychological studies provide evidence for an ageing-related decline of memory for contextual information related to remembered items. Using event-related fMRI we investigated the neural correlates of ageing-related changes during encoding and retrieval of spatial contextual memory. Eighteen young and 17 older subjects were included in the analysis (mean age 24 and 60 years, respectively). Although young and older subjects recognised the same amount of items during retrieval, spatial context memory for remembered items was superior in younger subjects. In both groups, left parahippocampal activity during encoding predicted contextual memory performance during retrieval. During encoding, an interaction between age and success of spatial context encoding was found in the left fusiform gyrus. During retrieval, the left hippocampal formation showed higher activity for successful than for unsuccessful spatial context retrieval as well as an interaction between age and spatial context judgement. Both findings are likely to underlie the contextual memory deficit observed in older subjects.

Altered Resting-State Connectivity in Huntington's Disease

Huntingtons disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Using resting‐state fMRI (rs‐fMRI) we investigated the functional integrity of resting‐state networks (RSN) in HD. 17 HD and 19 matched control participants were examined at a 3 Tesla MR scanner. After controlling for structural degeneration by means of voxel‐based morphometry, task‐free rs‐fMRI data were analyzed using Independent Component Analysis (ICA) and a dual‐regression approach in the context of genetic and clinical parameters. Further, we evaluated HD‐related differences in interregional connectivity between networks. RSN analysis showed a significant increase in intrinsic functional connectivity in the HD sample compared with controls, including the thalamus, striatum, prefrontal, premotor, and parietal maps. A subset of the Default Mode Network (DMN) was also affected. In the HD cohort, motor impairment correlated with higher network connectivity in mainly motor and parietal cortices. Deteriorating total functional capacity was additionally associated with higher connectivity in the striatum, thalamus, insular and frontal areas. This pattern of increased activity in intrinsic functional networks might suggest a reduced ability of intra‐network differentiation with clinical disease progression in HD. Finally, results showed reduced long‐range connectivity between parietal ICA components in HD compared to controls, indicating impaired functional coupling between interregional networks in HD. Our data demonstrates that functional connectivity is profoundly altered in HD, both within and between RSN. Rs‐fMRI analysis may provide additional valuable insights into neuronal dysfunctions beyond HD‐related structural degeneration and disruptions of functional circuits in HD. Hum Brain Mapp 35:2582–2593, 2014.

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.

Neural correlates of impaired emotion processing in manifest Huntington’s disease

The complex phenotype of Huntingtons disease (HD) encompasses motor, psychiatric and cognitive dysfunctions, including early impairments in emotion recognition. In this first functional magnetic resonance imaging study, we investigated emotion-processing deficits in 14 manifest HD patients and matched controls. An emotion recognition task comprised short video clips displaying one of six basic facial expressions (sadness, happiness, disgust, fear, anger and neutral). Structural changes between patients and controls were assessed by means of voxel-based morphometry. Along with deficient recognition of negative emotions, patients exhibited predominantly lower neural response to stimuli of negative valences in the amygdala, hippocampus, striatum, insula, cingulate and prefrontal cortices, as well as in sensorimotor, temporal and visual areas. Most of the observed reduced activity patterns could not be explained merely by regional volume loss. Reduced activity in the thalamus during fear correlated with lower thalamic volumes. During the processing of sadness, patients exhibited enhanced amygdala and hippocampal activity along with reduced recruitment of the medial prefrontal cortex. Higher amygdala activity was related to more pronounced amygdala atrophy and disease burden. Overall, the observed emotion-related dysfunctions in the context of structural neurodegeneration suggest both disruptions of striatal-thalamo-cortical loops and potential compensation mechanism with greater disease severity in manifest HD.

Differential activation of memory-relevant brain regions during a dialysis cycle

Cognitive impairment is a common and largely undiagnosed finding in a significant number of dialysis patients. These alterations may result from concomitant cerebrovascular disease, hemodynamic instability, the uremic milieu, or changes induced by the dialysis process. In order to gain further insight into this, we recruited 12 stable chronic hemodialysis patients (without clinical neurological disease) and an age- and gender-matched cohort of 12 control individuals (without renal or neurological problems) in a prospective, single-center study. In order to disentangle the influence of dialysis itself on memory function, each dialysis patient was tested twice: once immediately before dialysis following a long weekend (t1) and again the day after this dialysis (t2). The control individuals were tested in the same time frame. Neuropsychological testing found that the control individuals performed significantly better in verbal learning, motor speed, task switching, verbal comprehension, word fluency, spatial visualization, spatial perception, and reasoning; all independent of the time point. Functional magnetic resonance imaging of the whole brain in seven hemodialysis patients found significantly more bilateral activation of the hippocampus during the verbal working memory task at t2 relative to t1 compared with their seven matched control counterparts. Thus, our study found differential and task-specific activation of memory-relevant brain areas during a dialysis cycle.

Attention Modulates the Blood Oxygen Level Dependent Response in the Primary Visual Cortex measured with Functional Magnetic Resonance Imaging

Attention is a basic mechanism which enables the processing of incoming stimuli to be enhanced or attenuated. In the auditory modality, for example, a person can attend selectively to a particular speaker’s voice while turning off other, simultaneous, conversations (“cocktail party phenomenon”). Although this process has been the target of extensive research, even a few years ago it would not have been possible even in preliminary form to outline a functional anatomy of the human attentional system. New developments and techniques in neuroscience (positron emission tomography, magneto-encephalography, and functional magnetic resonance imaging) have opened the possibility of studying the anatomical basis of higher cognitive functions, including attentional processes. These new techniques have made possible the delineation of attentional systems that control alertness [1, 2], consciousness [3], spatial visual attention [4], and higher cognitive functions [5]. However, controversy continues as to whether attentional processes modulate neuronal activity within primary sensory areas [6]. Most researchers believe that attentional modulation is related to activity in secondary sensory areas [7]. We report here data supporting the notion that there is indeed modulation of neuronal activity within the primary visual cortex due to attentional processes.