Functional Brain Imaging Studies Research Articles

Low Dopamine D2Receptor Binding in Subregions of the Thalamus in Schizophrenia

Several structural and functional brain imaging studies have pointed to a disturbance of thalamic subnuclei in patients with schizophrenia. The dopamine hypothesis of schizophrenia has, however, not been thoroughly examined in terms of this complex structure, which has connections with most brain regions of central interest in schizophrenia research. The aim of the present study was to examine dopamine D(2) receptor binding in subregions of the thalamus in patients with schizophrenia. The authors used positron emission tomography and the radioligand [(11)C]FLB457 to examine dopamine D(2) receptor binding in thalamic subregions of 10 drug-naive patients with schizophrenia. Binding potential was calculated by the reference tissue method and used as an index for dopamine D(2) receptor binding. Comparisons were made with 19 healthy subjects. Subregions of interest were defined on individual magnetic resonance images using a percentage-based operational approach. Clinical symptoms were rated by using the Brief Psychiatric Rating Scale (BPRS). The [(11)C]FLB457 binding potential was lower in the central medial and posterior subregions of the thalamus in patients with schizophrenia. At a functional level, there was a significant negative correlation between binding potential and BPRS positive symptom scores. The subregions with low D(2) receptor binding comprise primarily the dorsomedial nucleus and pulvinar, two important components in circuitries previously suggested in the pathophysiology of schizophrenia. Aberrant dopaminergic neurotransmission in thalamic subregions might be a mechanism underlying positive symptoms in schizophrenia.

Vascular parkinsonism.

Vascular parkinsonism is a highly controversial concept since its first description by Critchley in 1929. There is no doubt that cerebrovascular disease can cause elements of parkinsonism. However, the extent of the spectrum of vascular parkinsonism remains quite imprecise. Here we review recent epidemiological, clinical, electrophysiological, morphological and functional brain imaging and pathological studies on 'vascular parkinsonism'. Epidemiological studies have demonstrated that vascular parkinsonism represents 3-5% of all cases of parkinsonism. The more specific clinical features are a history of stroke, lower body parkinsonism and poor levodopa response. Vascular risk factors are dominated by arterial hypertension, whereas others have been less evaluated. Vascular lesions within or outside the basal ganglia, unique and multiple, lacunae or territorial infarcts can be demonstrated by magnetic resonance imaging. Functional imaging of the dopaminergic pathway helps to differentiate vascular parkinsonism from idiopathic Parkinson's disease. However, none of these clinical or imaging criteria taken alone are specific for the diagnosis. A combination of convergent clinical and imaging clues are therefore necessary to improve the accuracy of the diagnosis, which is only certain when the pathology excludes underlying idiopathic Parkinson's disease. At present it remains unexplained why some patients develop vascular parkinsonism and others do not with the same apparent vascular lesion load. This will need further research along with the need to develop criteria to improve the accuracy of diagnosis of vascular parkinsonism. Vascular parkinsonism is also a research field on the relationships between vascular brain lesions and neurodegenerative disorders.

Disorganised Memory after Right Dorsolateral Prefrontal Damage

Neurophysiological and functional brain imaging studies suggest the importance of dorsolateral area 9/46 for modality-independent working memory. However, the behavioural manifestations following isolated damage to this area have not been clearly outlined. Here, we describe the dramatic derangement of pragmatic memory after circumscribed lesion of the right area 9/46. A 52 year-old woman had suffered a traumatic brain injury 13 years ago and sought help for what she thought was a severe memory disorder. She regularly missed appointments and had gradually lost all her friends. She had tried different strategies to compensate for her memory problem, such as writing notes on her wrist or using electronic organizers. Intelligence, attention, verbal long-term memory, and executive functions were normal. Furthermore, experimental exploration demonstrated intact time estimation, attribution of memories to ongoing reality, and anticipation of outcomes. However, she failed to rehearse and manipulate information in working memory (n-back task), confirming the findings of functional imaging studies that the mid-dorsolateral prefrontal cortex is involved in mental manipulation of information. This case exemplifies that an isolated lesion of the right area 9/46 may induce severe failure to schedule actions and memory retrieval, a disorder leading to severely disorganised behaviour and disability.

Event-related fMRI with painful electrical stimulation of the trigeminal nerve.

Several functional brain imaging studies of pain using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have shown that painful stimulation causes activation of different brain areas. The aim of the present study was to develop and implement painful stimulation of the trigeminal nerve, which can be applied with event-related paradigms by using MRI. Twelve healthy, right-handed volunteers were examined. Painful electrical stimulation of the first trigeminal branch was performed. In an event-related setting with a 1.5 T clinical scanner with EPI capability, the following fMRI parameters were used: 20 slices, 3 mm thickness, isotropic voxel, 306 measurements with 54 randomized events. Statistical postprocessing was performed with SPM99. Activation of the ipsi- and contralateral secondary somatosensory cortex (SII), and the contralateral insular cortex was observed as well as a contralateral thalamic activation (T=4.45, extension 15 voxels). Six of the 12 volunteers revealed also activation of the cingulate cortex. The investigation demonstrates that painful stimulation of the trigeminal nerve activates the contralateral insular cortex, SII, and thalamus, as well as the ipsilateral SII. In contrast to other studies, the cingulate cortex was only activated inconsistently.

Anatomical and functional brain imaging evidence of lenticulo-insular anomalies in Smith Magenis syndrome

Smith Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion of chromosome 17p11.2. The neurobehavioral phenotype of SMS includes mental retardation, speech delay, hyperactivity, attention deficit, decreased sensitivity to pain, self-injury, aggressive behavior and sleep disturbance. Therefore, we performed anatomical and functional brain imaging studies in five SMS boys. Anatomical magnetic resonance imaging (MRI) was analyzed using optimized voxel-based morphometry (VBM). This method can detect structural anomalies not apparent on visual inspection of the scans. Two comparison groups with similar mean age were studied: Group A with 12 healthy control children and Group B with 5 children with idiopathic mental retardation. In addition, positron emission tomography (PET) and water-labeled method were used to investigate a putative localized brain dysfunction in SMS. The control group was composed of mentally retarded children (Group B). A significant bilateral decrease of grey matter concentration was detected in the insula and lenticular nucleus in SMS children. In addition, a significant hypoperfusion was found in the same regions in SMS. These anatomo-functional evidences of bilateral insulo-lenticular anomalies in SMS are consistent with neurobehavioral symptoms of the disease. The identification of localized brain anomalies in SMS may help in understanding how this well-defined genetic entity can lead to a relatively specific severe neurobehavioral syndrome.

The Curious Incident of the Dog in the Night-Time: A Novel

The Curious Incident of the Dog in the Night-Time: A Novel

Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging.

The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

Dystonia update.

Dystonia is a movement disorder with a complex and not fully understood pathophysiology. Its better understanding would enable more focused treatment for the disorder. In this review, we provide an overview of recent studies of the pathophysiology of primary and secondary dystonia, with an emphasis on functional brain imaging. Potential mechanisms underlying the beneficial effects of deep brain stimulation for dystonia are also summarized. The recognition of dysfunction at different levels of the nervous system has extended the classical notions of localized striatal abnormalities in primary dystonia. Recent biochemical studies have revealed evidence of abnormal torsion activity in DYT1 dystonia. Abnormal patterns of brain metabolism have also been identified using functional brain imaging in different dystonia genotypes. These findings, in conjunction with new electrophysiological techniques, can be utilized to help define a common mechanism for the neural dysfunction in dystonia. New insights into the pathophysiology of dystonia have been provided by recent studies using electrophysiology, biochemistry and human genetics, as well as functional brain imaging studies. These advances together may create the basis for new therapies for this disorder.

Basal ganglia systems in ritualistic social displays: reptiles and humans; function and illness

Complex, situation-specific territorial maintenance routines are similar across living terrestrial vertebrates (=amniotes). Decades ago, Paul MacLean et al., at the Laboratory of Brain Evolution and Behavior of the National Institute of Mental Health, postulated that these are evolutionarily conserved behaviors whose expression is mediated by the similarly conserved amniote basal ganglia and related brain systems (BG systems). Therefore, they undertook studies in nonhuman primates and in small social lizards (the common green anole, Anolis carolinensis) to examine this idea. MacLean et al. also postulated that when BG systems misfunction in humans, behavioral abnormalities result, some of them under the rubric of psychiatric illnesses. Obsessive–compulsive disorder (OCD) was singled out as one likely candidate. In the last dozen years, functional brain imaging studies of OCD patients have validated the contention that this is, in fact, a condition involving dysfunctioning BG systems. Inspired by the MacLean group's original investigations, my colleagues and I have now applied related functional imaging techniques in naturalistic experiments using Anolis to better understand BG systems' roles in the mediation of complex behavioral routines in healthy amniotes. Here, I will review this functional imaging work in primates (man, and a little in monkey) and in lizards. I believe the literature not only supports MacLean et al.'s contentions about BG systems and behavior in general, but also validates Paul MacLean's life-long contention that human behavioral medicine can profit from a broad comparative approach.

Alzheimer’s disease: differences in technetium-99m HMPAO SPECT scan findings between early onset and late onset dementia

Objective: To compare the HMPAO SPECT cerebral perfusion patterns in early and late onset Alzheimer’s disease. Methods: Twenty patients with early onset disease (<65 years) and 44 patients with late...

The dopaminergic system in attention deficit/hyperactivity disorder.

Numerous studies have shown the importance of the mesocorticolimbic dopamine system in the pathophysiology of attention deficit/hyperactivity disorder. However, there has been inconsistency in the findings of those studies. Varied and sometimes contradictory interpretation has been made on the basis of similar results. It is, therefore, still unclear whether the dopaminergic system is hypo- or hyperfunctioning in attention deficit/hyperactivity disorder. The majority of the functional brain imaging studies in both clinical and experimental settings support hypofunction of the basal ganglia which receive abundant dopaminergic afferent. The experimental studies, using dopamine-depleted animals, also support the hypodopaminergic hypothesis, whereas recent studies with the dopamine transporter knockout/knockdown mouse suggest hyperdopaminergic function as the underlying abnormality. In this review we attempt to clarify the issues raised by previous neuroimaging and functional neuroimaging studies. Research involving animal models with genetic traits, genetic manipulation or with brain lesions is analysed, concentrating on the significance of the dopaminergic system in the abnormal behavior of attention deficit/hyperactivity disorder. In addition, the functional state of the dopaminergic system is considered through the speculated mechanism of psychostimulant therapy of the disorder. No final conclusions have been reached regarding the pathological, biochemical and physiological mechanisms responsible for various symptoms. Inconsistency in the findings and their interpretations may indicate the heterogeneity of the pathogenesis of this syndrome.

NEURAL FOUNDATIONS FOR UNDERSTANDING SOCIAL AND MECHANICAL CONCEPTS

Motivated by neuropsychological investigations of category-specific impairments, many functional brain imaging studies have found distinct patterns of neural activity associated with different object categories. However, the extent to which these category-related activation patterns reflect differences in conceptual representation remains controversial. To investigate this issue, functional magnetic resonance imaging (fMRI) was used to record changes in neural activity while subjects interpreted animated vignettes composed of simple geometric shapes in motion. Vignettes interpreted as conveying social interactions elicited a distinct and distributed pattern of neural activity, relative to vignettes interpreted as mechanical actions. This neural system included regions in posterior temporal cortex associated with identifying human faces and other biological objects. In contrast, vignettes interpreted as conveying mechanical actions resulted in activity in posterior temporal lobe sites associated with identifying manipulable objects such as tools. Moreover, social, but not mechanical, interpretations elicited activity in regions implicated in the perception and modulation of emotion (right amygdala and ventromedial prefrontal cortex). Perceiving and understanding social and mechanical concepts depends, in part, on activity in distinct neural networks. Within the social domain, the network includes regions involved in processing and storing information about the form and motion of biological objects, and in perceiving, expressing, and regulating affective responses.

Clock Drawing in Developmental Dyslexia

Although developmental dyslexia is often defined as a language-based reading impairment not attributable to low intelligence or educational or socioeconomic limitations, the behavioral manifestations of dyslexia are not restricted to the realm of language. Functional brain imaging studies have shed light on physiological differences associated with poor reading both inside and outside the classical language areas of the brain. Concurrently, clinically useful tests that elicit these nonlinguistic deficits are few. Specifically, the integrity of the dorsal visual pathway, which predominantly projects to the parietal cortex, remains underinvestigated, lacking easily administered tests. Here we present the Clock Drawing Test (CDT), used to test the visuoconstructive ability of children with and without dyslexia and garden-variety poor readers. Compared to typically reading children, many children with dyslexia and some garden-variety poor readers showed significant left neglect, as measured by the distribution of figures drawn on the left clock face. In the poor readers with dyslexia, we observed spatial construction deficits like those of patients with acquired right-hemisphere lesions. The results suggest that in some children with dyslexia, right-hemisphere dysfunction may compound the phonological processing deficits attributed to the left hemisphere. The CDT provides an easy opportunity to assess skills known to be associated with right-hemisphere parietal function. This test can be easily administered to children for both clinical and research purposes.

Predictors of two-year follow-up in children and adolescents with schizophrenia

Deficits in working memory have been repeatedly found on a behavioural level in children with attention-deficit/hyperactivity disorder (ADHD). Functional brain imaging studies have revealed evidence for alterations in the prefrontal cortex associated with working memory. So far it remains unresolved whether object (OWM) and spatial visual working memory (SWM) are distinctly impaired in ADHD. We investigated this issue with the fist multi-channel functional near-infrared spectroscopy study of children with ADHD.We investigated 19 children with ADHD combined type (DSM-IV) and 19 controls matched for age (8–15 years), sex, handedness, and intelligence during a working memory task assessing OWM and SWM separately, and a control condition (CON). Prefrontal brain activity was measured by concentration changes of oxygenated haemoglobin.Working memory performance showed significant differences for conditions (OWM > SWM > CON), but no differences between groups. Cortical prefrontal activation was significantly higher for OWM and SWM in contrast to CON, again with no differences between groups.We found no indication for an altered prefrontal processing during OWM and SWM tasks in ADHD children compared to controls. Reviewing the existing imaging literature on working memory in ADHD and considering the present data, we discuss possible confounding factors relevant for brain activity in previous, the current, and future investigations. Thus, it is of high importance to capture developmental trajectories, task specific discrepancies, and effects of permanent medication intake in future studies.

Modified cerebral organization for language in schizophrenia: A functional magnetic resonance imaging study

The differential role of the cerebellar cortex and nuclei has rarely been addressed in human lesion and functional brain imaging studies. One important reason is the difficulty of defining the localization of the cerebellar nuclei and extent of possible lesions based on CT or MR scans. The present MRI investigation was specifically designed to study the anatomy of the deep cerebellar nuclei. In both basal ganglia and cerebellar nuclei of healthy human subjects the amount of iron is high compared to the rest of the brain. Clusters of iron are paramagnetic and, therefore, tend to cause local inhomogenities in a magnetic field. The iron-induced susceptibility artefacts were used to visualize the cerebellar nuclei as hypointensities on MR images. A three-dimensional atlas of the dentate (D), interposed (I), and fastigial (F) nuclei is presented in standard proportional stereotaxic space coordinates based on findings in a healthy 26-year-old female. A three-dimensional axial volume of the cerebellum was acquired using a T1-weighted fast low-angle shot (FLASH) sequence on a Siemens Sonata 1.5 Tesla MR. To increase the signal to noise ratio the sequence was acquired 5 times and averaged. Each volume was registered, resampled to 1.00 × 1.00 × 1.00-mm3 voxel size and spatially normalized into a standard proportional stereotaxic space (the MNI-space) using SPM99. Localization of cerebellar nuclei were confirmed by comparison with postmortem MRI and histological microsections of another brain.

Positron emission tomography in female patients with Borderline personality disorder

The pathology of Borderline personality disorder (BPD) is poorly understood and its biological basis remains largely unknown. One functional brain imaging study using [ 18F]Deoxyglucose-PET previously reported frontal and prefrontal hypometabolism. We studied brain metabolism at baseline in 12 medication-free female patients with BPD without current substance abuse or depression and 12 healthy female controls by [ 18F]Deoxyglucose-PET and statistical parametric mapping. We found significant frontal and prefrontal hypermetabolism in patients with BPD relative to controls as well as significant hypometabolism in the hippocampus and cuneus. This study demonstrated limbic and prefrontal dysfunction under resting conditions in patients with BPD by FDG-PET. Dysfunction in this network of brain regions, which has been implicated in the regulation of emotion, may underlie symptoms of BPD.

Functional Brain Imaging Study on Brain Processes Involved in Visual Awareness

Functional Brain Imaging Study on Brain Processes Involved in Visual Awareness

Visual Imagery of Famous Faces: Effects of Memory and Attention Revealed by fMRI

Complex pictorial information can be represented and retrieved from memory as mental visual images. Functional brain imaging studies have shown that visual perception and visual imagery share common neural substrates. The type of memory (short- or long-term) that mediates the generation of mental images, however, has not been addressed previously. The purpose of this study was to investigate the neural correlates underlying imagery generated from short- and long-term memory (STM and LTM). We used famous faces to localize the visual response during perception and to compare the responses during visual imagery generated from STM (subjects memorized specific pictures of celebrities before the imagery task) and imagery from LTM (subjects imagined famous faces without seeing specific pictures during the experimental session). We found that visual perception of famous faces activated the inferior occipital gyri, lateral fusiform gyri, the superior temporal sulcus, and the amygdala. Small subsets of these face-selective regions were activated during imagery. Additionally, visual imagery of famous faces activated a network of regions composed of bilateral calcarine, hippocampus, precuneus, intraparietal sulcus (IPS), and the inferior frontal gyrus (IFG). In all these regions, imagery generated from STM evoked more activation than imagery from LTM. Regardless of memory type, focusing attention on features of the imagined faces (e.g., eyes, lips, or nose) resulted in increased activation in the right IPS and right IFG. Our results suggest differential effects of memory and attention during the generation and maintenance of mental images of faces.

Attentional control of the processing of neutral and emotional stimuli

A typical scene contains many different objects that compete for neural representation due to the limited processing capacity of the visual system. At the neural level, competition among multiple stimuli is evidenced by the mutual suppression of their visually evoked responses and occurs most strongly at the level of the receptive field. The competition among multiple objects can be biased by both bottom-up sensory-driven mechanisms and top-down influences, such as selective attention. Functional brain imaging studies reveal that biasing signals due to selective attention can modulate neural activity in visual cortex not only in the presence but also in the absence of visual stimulation. Although the competition among stimuli for representation is ultimately resolved within visual cortex, the source of top-down biasing signals likely derives from a distributed network of areas in frontal and parietal cortex. Competition suggests that once attentional resources are depleted, no further processing is possible. Yet, existing data suggest that emotional stimuli activate brain regions ‘automatically,’ largely immune from attentional control. We tested the alternative possibility, namely, that the neural processing of stimuli with emotional content is not automatic and instead requires some degree of attention. Our results revealed that, contrary to the prevailing view, all brain regions responding differentially to emotional faces, including the amygdala, did so only when sufficient attentional resources were available to process the faces. Thus, similar to the processing of other stimulus categories, the processing of facial expression is under top-down control.

MRI Atlas of the Human Cerebellar Nuclei

The differential role of the cerebellar cortex and nuclei has rarely been addressed in human lesion and functional brain imaging studies. One important reason is the difficulty of defining the localization of the cerebellar nuclei and extent of possible lesions based on CT or MR scans. The present MRI investigation was specifically designed to study the anatomy of the deep cerebellar nuclei. In both basal ganglia and cerebellar nuclei of healthy human subjects the amount of iron is high compared to the rest of the brain. Clusters of iron are paramagnetic and, therefore, tend to cause local inhomogenities in a magnetic field. The iron-induced susceptibility artefacts were used to visualize the cerebellar nuclei as hypointensities on MR images. A three-dimensional atlas of the dentate (D), interposed (I), and fastigial (F) nuclei is presented in standard proportional stereotaxic space coordinates based on findings in a healthy 26-year-old female. A three-dimensional axial volume of the cerebellum was acquired using a T1-weighted fast low-angle shot (FLASH) sequence on a Siemens Sonata 1.5 Tesla MR. To increase the signal to noise ratio the sequence was acquired 5 times and averaged. Each volume was registered, resampled to 1.00 × 1.00 × 1.00-mm 3 voxel size and spatially normalized into a standard proportional stereotaxic space (the MNI-space) using SPM99. Localization of cerebellar nuclei were confirmed by comparison with postmortem MRI and histological microsections of another brain.