Functional Brain Imaging Studies Research Articles

The cognitive burden in Huntington's disease: Pathology, phenotype, and mechanisms of compensation

Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder. The most prominent sign of HD is the presence of involuntary motor movements. However, HD is also characterized by marked cognitive decline, which often precedes the onset of motor symptoms and is generally considered to be more debilitating to the patients and their families, compared to motor symptoms. Cognitive decline is widespread across most faculties of cognition in later stages of the disease, but seems to be selective in preclinical and early stages of the disease, with deficits in the HD patients' ability to multitask, their speed of processing, and executive function. It is now well established that preceding clinical diagnosis there is a preclinical stage, during which HD gene mutation carriers are relatively symptom free, despite disease pathological onset and the presence of neurodegeneration. Evidence from functional brain imaging studies suggests the presence of neural compensation in preclinical stages of HD, whereby the brain undergoes functional reorganization in response to neurodegeneration to preserve motor and cognitive performance. In this review, we will describe the underlying HD pathology with a focus on how it links to the cognitive phenotype. We will also present evidence regarding the presence of neural compensation in HD and the possible mechanisms supporting it. Finally, we will discuss current research in the field of cognitive interventions that aim to support and enhance neural compensation in HD. These research efforts could, one day, prolong the preclinical stage and assist with symptom management of those affected with HD.

28. Modulation of cerebral sensorimotor circuits during botulinum toxin treatment of cervical dystonia

Objective Neurophysiological and lately also functional brain imaging studies in cervical dystonia (CD) patients indicate a disorder of sensorimotor integration within extensive cortico-subcortical brain networks. Intramuscular botulinum toxin type A (BoNT-A) application has a proven clinical effect on pathological muscle activation in CD but recently has also been shown to modulate sensorimotor networks. To clarify cervical dystonia pathophysiology through functional magnetic resonance imaging of sensorimotor network changes associated with first-time botulinum toxin treatment. Methods We have studied 12 BoNT-A naive CD patients using functional MRI during specific hand motor task performance. Clinical and imaging examinations were performed before the first BoNT-A application and subsequently 4 weeks after application, at the time of maximal clinical effect of BoNT-A. Clinical treatment response was evaluated with the Tsui score, functional MRI data were analyzed with a general linear model implemented in FSL software, treatment effects were tested in pair-wise linear contrasts. Results First BoNT-A injection, although it had a good clinical effect, did not lead to any significant changes in activation of cortex or basal ganglia in our group of CD patients. Discussions Within the context of previously described sensorimotor network hypoactivation during motor task performance in CD, our observed effect of no significant change in sensorimotor cortex activation would suggest the hypothesis that robust central changes develop after long-term regular BoNT-A treatment, although even the first BoNT-A application is clinically effective. Acknowledgment Research supported by Grant IGA MH CR NT13575.

The neural correlates of agrammatism: Evidence from aphasic and healthy speakers performing an overt picture description task

Functional brain imaging studies have improved our knowledge of the neural localization of language functions and the functional reorganization after a lesion. However, the neural correlates of agrammatic symptoms in aphasia remain largely unknown. The present fMRI study examined the neural correlates of morpho-syntactic encoding and agrammatic errors in continuous language production by combining three approaches. First, the neural mechanisms underlying natural morpho-syntactic processing in a picture description task were analyzed in 15 healthy speakers. Second, agrammatic-like speech behavior was induced in the same group of healthy speakers to study the underlying functional processes by limiting the utterance length. In a third approach, five agrammatic participants performed the picture description task to gain insights in the neural correlates of agrammatism and the functional reorganization of language processing after stroke. In all approaches, utterances were analyzed for syntactic completeness, complexity, and morphology. Event-related data analysis was conducted by defining every clause-like unit (CLU) as an event with its onset-time and duration. Agrammatic and correct CLUs were contrasted. Due to the small sample size as well as heterogeneous lesion sizes and sites with lesion foci in the insula lobe, inferior frontal, superior temporal and inferior parietal areas the activation patterns in the agrammatic speakers were analyzed on a single subject level. In the group of healthy speakers, posterior temporal and inferior parietal areas were associated with greater morpho-syntactic demands in complete and complex CLUs. The intentional manipulation of morpho-syntactic structures and the omission of function words were associated with additional inferior frontal activation. Overall, the results revealed that the investigation of the neural correlates of agrammatic language production can be reasonably conducted with an overt language production paradigm.

Subclinical cognitive decline in middle‐age is associated with reduced task‐induced deactivation of the brain's default mode network

Cognitive abilities decline with age, but with considerable individual variation. The neurobiological correlate of this variation is not well described. Functional brain imaging studies have demonstrated reduced task-induced deactivation (TID) of the brain's default mode network (DMN) in a wide range of neurodegenerative diseases involving cognitive symptoms, in conditions with increased risk of Alzheimer's disease, and even in advanced but healthy aging. Here, we investigated brain activation and deactivation during a visual-motor task in 185 clinically healthy males from a Danish birth cohort, whose cognitive function was assessed in youth and midlife. Using each individual as his own control, we defined a group with a large degree of cognitive decline, and a control group. When correcting for effects of total cerebral blood flow and hemoglobin level, we found reduced TID in the posterior region of the DMN in the cognitive decline group compared to the control group. Furthermore, increased visual activation response was found in the cognitive decline group, indicating that the TID reduction was not exclusively due to overall impaired vascular reactivity. These results suggest a neurobiological basis for subclinical cognitive decline in late midlife, which includes TID alterations similar to the pattern seen in patients with AD and mild cognitive impairment. Hence, TID reduction might be suggested as an early marker for subtle cognitive decline in aging.

Indigestion Leads to Depression: Avicenna's Point of View

Dear Editor, Depression is a common mental disorder and leading cause of disability worldwide (1). As a definition, depression may be a mood state, a syndrome or a specific disorder that may be secondary to various medical illnesses (2, 3). Avicenna (980-1037 AD), a scholar in traditional medicine, believed that indigestion can lead to depression (4). Indigestion is a common gastrointestinal problem that consists of nausea, vomiting, heartburn, regurgitation and dyspepsia (5). Functional dyspepsia is one of the most common causes of indigestion (6). In the modern medicine the effect of psychological factors on indigestion has been confirmed (2). In the current study we have demonstrated evidences of the effects of indigestion on depression. A recent prospective study in 2012 has stated that people with Functional gastrointestinal disorders (FGIDs) such as functional dyspepsia who had not suffered from anxiety and depression at baseline significantly developed signs and symptoms of anxiety and depression over 12-year follow-up (7). The probable mechanisms for the relationship between depression and dyspepsia have also been studies. Functional brain imaging study has shown neurobiological link between psychological abnormalities and visceral hypersensitivity in FGIDs (8). Another study has approved the role of serotonin and noradrenalin, the two main neurotransmitters involved in the pathophysiology of depression, in indigestion (9). On the other hand, from the Avicenna's point of view the absorbable part of food converts to in the stomach that absorbs via the mesenteric vessels to the liver. Then chylous is converted to chymous in the liver. Chymous is composed of four humors including blood, phlegm, yellow bile and black bile. The body is also composed of these four humors. Humors enter to the blood circulation and supply food and energy for different organs. Abnormal humors cause functional disturbances in all organs including brain. Therefore the development of depression may be explained by the presence of the abnormal humors in the blood circulation. Production of normal humors requires appropriate composition of the gastric chylous that is delivered to the liver. Some etiological factors affect composition of the gastric chylous including: type of food consumed, the quality of gastric digestion, and also the quality of post-feeding conditions. Hence, indigestion can leads to depression with the following mechanism (4, 10) The preventive methods have a crucial importance in Iranian Traditional Medicine (ITM). To this end, some items have been considered in association with the three mentioned etiological factors for indigestion as follows: Dietary habits that cause indigestion Over eating, low eating, inappropriate time of eating like eating when stomach is full, eating slow-digesting foods before fast-digesting ones and also eating some foods like milk, watermelon, peach and mushroom Gastric Disorders that cause indigestion Primary gastric disorders like gastric impairments or secondary gastric disorders like ones due to accumulation of excessive gas in stomach or entering of post nasal discharge to it. Post-feeding conditions that cause indigestion Lack of sleep, excessive movement, intercourse, taking a shower, exposure to hot or cold weather, and also little or too much drinking after meal (4). If the Avicenna’s perspective would be considered alongside with further complementary investigations especially through observational studies, the prevention of indigestion may lead to significance decrease in the prevalence of depression.

Unconscious influences on decision making: Neuroimaging and neuroevolutionary perspectives

Newell and Shanks provide a useful critique on unconscious decision making. However, they do not consider an important set of functional brain imaging studies of unconscious processes. Here we review briefly the relevant brain imaging and psychobiological literature and its implications for understanding unconscious decision making.

Imaging and neurobiological changes in late-life depression

Depression was previously thought of as a ‘functional’ illness, without demonstrable pathology, but the advent of sophisticated neuroimaging techniques has changed this perspective. This article reviews the latest structural and functional brain imaging studies, describing the neurobiological changes which underlie this common condition.

The Cerebellum and Premenstrual Dysphoric Disorder.

The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.

Synaptic Plasticity and the Warburg Effect

Functional brain imaging studies show that in certain brain regions glucose utilization exceeds oxygen consumption, indicating the predominance of aerobic glycolysis. In this issue, Goyal et al. (2014) report that this metabolic profile is associated with an enrichment in the expression of genes involved in synaptic plasticity and remodeling processes.

Functional brain imaging studies of youth depression: A systematic review

BackgroundThere is growing interest in understanding the neurobiology of major depressive disorder (MDD) in youth, particularly in the context of neuroimaging studies. This systematic review provides a timely comprehensive account of the available functional magnetic resonance imaging (fMRI) literature in youth MDD.MethodsA literature search was conducted using PubMED, PsycINFO and Science Direct databases, to identify fMRI studies in younger and older youth with MDD, spanning 13–18 and 19–25 years of age, respectively.ResultsTwenty-eight studies focusing on 5 functional imaging domains were identified, namely emotion processing, cognitive control, affective cognition, reward processing and resting-state functional connectivity. Elevated activity in “extended medial network” regions including the anterior cingulate, ventromedial and orbitofrontal cortices, as well as the amygdala was most consistently implicated across these five domains. For the most part, findings in younger adolescents did not differ from those in older youth; however a general comparison of findings in both groups compared to adults indicated differences in the domains of cognitive control and affective cognition.ConclusionsYouth MDD is characterized by abnormal activations in ventromedial frontal regions, the anterior cingulate and amygdala, which are broadly consistent with the implicated role of medial network regions in the pathophysiology of depression. Future longitudinal studies examining the effects of neurodevelopmental changes and pubertal maturation on brain systems implicated in youth MDD will provide a more comprehensive neurobiological model of youth depression.

Effectiveness of temporary deafferentation of the arm on somatosensory and motor functions following stroke: a systematic review protocol

Effectiveness of temporary deafferentation of the arm on somatosensory and motor functions following stroke: a systematic review protocol

RTMS in the management of auditory hallucinations in patients with schizophrenia.

rTMS in the management of auditory hallucinations in patients with schizophrenia.

PL1 * FOUR DECADES OF RESEARCH ON THE LEVEL OF RESPONSE TO ALCOHOL AS A RISK FACTOR FOR ALCOHOLISM: FROM IDEA TO PREVENTION

PL1 * FOUR DECADES OF RESEARCH ON THE LEVEL OF RESPONSE TO ALCOHOL AS A RISK FACTOR FOR ALCOHOLISM: FROM IDEA TO PREVENTION

Brain Signature Characterizing the Body-Brain-Mind Axis of Transsexuals

Individuals with gender identity disorder (GID), who are commonly referred to as transsexuals (TXs), are afflicted by negative psychosocial stressors. Central to the psychological complex of TXs is the conviction of belonging to the opposite sex. Neuroanatomical and functional brain imaging studies have demonstrated that the GID is associated with brain alterations. In this study, we found that TXs identify, when viewing male-female couples in erotic or non-erotic (“neutral”) interactions, with the couple member of the desired gender in both situations. By means of functional magnetic resonance imaging, we found that the TXs, as opposed to controls (CONs), displayed an increased functional connectivity between the ventral tegmental area, which is associated with dimorphic genital representation, and anterior cingulate cortex subregions, which play a key role in social exclusion, conflict monitoring and punishment adjustment. The neural connectivity pattern suggests a brain signature of the psychosocial distress for the gender-sex incongruity of TXs.

Dynamic topographical pattern classification of multichannel prefrontal NIRS signals

Objective. Near-infrared spectroscopy (NIRS) is an optical imaging technique that has recently been considered for brain–computer interface (BCI) applications. To date, NIRS-BCI studies have primarily made use of temporal features of brain activity, derived from the time-course of optical signals measured from discrete locations, to differentiate mental states. However, functional brain imaging studies have indicated that the spatial distribution of haemodynamic activity is also rich in information. Thus, the progression of a response over both time and space may be valuable to brain state classification. In this paper, we investigate the implication of including spatiotemporal features in the single-trial classification of haemodynamic events for a two-class problem by exploiting this information from dynamic NIR topograms. Approach. The value of spatiotemporal information was explored through a comparative analysis of four different classification schemes performed on multichannel NIRS data collected from the prefrontal cortex during a mental arithmetic activation task and rest. Employing a linear discriminant classifier, data were analysed using spatiotemporal features, temporal features, and a collective pool of spatiotemporal and temporal features. We also considered a majority vote combination of three classifiers; each established using one of the above feature sets. Lastly, two separate task durations (20 and 10 s) were considered for feature extraction. Main results. With features from the longer task interval, the highest overall classification accuracy was achieved using the majority voting classifier (76.1 ± 8.4%), which was greater than the accuracy obtained using temporal features alone (73.5 ± 8.5%) (F3,144 = 7.04, p = 0.0002). While results from the shorter task duration were lower overall, the classifier employing only spatiotemporal features (with an average accuracy of 67.9 ± 9.3%) achieved a higher average accuracy than the rate obtained using only temporal features (64.4 ± 8.4%) (F3,144 = 18.58, p < 10−4). Significance. Collectively, these results suggest that spatiotemporal information can be of value in the analysis of functional NIRS data, and improved classification rates may be obtained in future NIRS-BCI applications with the inclusion of this information.

Human Retrosplenial Cortex Displays Transient Theta Phase Locking with Medial Temporal Cortex Prior to Activation during Autobiographical Memory Retrieval

The involvement of retrosplenial cortex (RSC) in human autobiographical memory retrieval has been confirmed by functional brain imaging studies, and is supported by anatomical evidence of strong connectivity between the RSC and memory structures within the medial temporal lobe (MTL). However, electrophysiological investigations of the RSC and its interaction with the MTL have mostly remained limited to the rodent brain. Recently, we reported a selective increase of high-frequency broadband (HFB; 70-180 Hz) power within the human RSC during autobiographical retrieval, and a predominance of 3-5 Hz theta band oscillations within the RSC during the resting state. In the current study, we aimed to explore the temporal dynamics of theta band interaction between human RSC and MTL during autobiographical retrieval. Toward this aim, we obtained simultaneous recordings from the RSC and MTL in human subjects undergoing invasive electrophysiological monitoring, and quantified the strength of RSC-MTL theta band phase locking. We observed significant phase locking in the 3-4 Hz theta range between the RSC and the MTL during autobiographical retrieval. This theta band phase coupling was transient and peaked at a consistent latency before the peak of RSC HFB power across subjects. Control analyses confirmed that theta phase coupling between the RSC and MTL was not seen for other conditions studied, other sites of recording, or other frequency ranges of interest (1-20 Hz). Our findings provide the first evidence of theta band interaction between the human RSC and MTL during conditions of autobiographical retrieval.

Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates

Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum.

Brain areas associated with sentence processing: A functional MRI study and a lesion study

Abstract The aim of this study was to identify the location associated with primitive sentence processing. Processing related to generation and comprehension of sentences (“sentence processing”) is postulated to be largely divided into syntactic processing (processing related to the formation of sentences and to verb reflection and particles) and verb information (argument structure and thematic role). Numerous lesion studies and functional brain imaging studies on unimpaired individuals have suggested that the left inferior frontal gyrus (IFG) is involved in syntactic processing. In addition, some studies have reported that the area from the left parietal lobe to the posterior superior temporal gyrus is involved in processing information such as argument structure and thematic role. However, studies on sentence processing using functional brain imaging have used complex sentences as tasks, raising the possibility that the results show the demands on not only language processing, but also on working memory. To clarify the brain areas involved in basic sentence processing in human language, there is a need to examine tasks involved in sentence processing that assume more primitive processing with minimal demands on working memory. The present study used sentence-completion tasks in the Japanese language that include basic sentence processing. The results showed activation in the left IFG and left parietal lobe, suggesting that these areas are involved in sentence processing. We then investigated the proportion of patients showing impaired sentence processing from among patients with aphasia and a lesion in the left IFG or from the parietal lobe to the posterior superior temporal gyrus. Four of 5 patients (80%) with lesions mostly in the left IFG showed impaired sentence processing, suggesting that this site plays a critical role in sentence processing. Of the 4 patients with lesions mostly in the area from the left parietal lobe to the posterior superior temporal gyrus, 1 patient (25%) showed impaired sentence processing. Unlike the other 3 subjects, this subject exhibited impaired recalling of verbs. This area is mainly involved in lexical-semantics and the present results suggest that verb information within that field became impaired, in turn causing impaired sentence processing.

The role of psychosocial factors and psychiatric disorders in functional dyspepsia

In this Review, after a brief historical introduction, we first provide an overview of epidemiological studies that demonstrate an association between functional dyspepsia and psychological traits, states or psychiatric disorders. These studies suggest an important intrinsic role for psychosocial factors and psychiatric disorders, especially anxiety and depression, in the aetiopathogenesis of functional dyspepsia, in addition to their putative influence on health-care-seeking behaviour. Second, we describe pathophysiological evidence on how psychosocial factors and psychiatric disorders might exert their role in functional dyspepsia. Novel insights from functional brain imaging studies regarding the integration of gut-brain signals, processed in homeostatic-interoceptive brain regions, with input from the exteroceptive system, the reward system and affective and cognitive circuits, help to clarify the important role of psychological processes and psychiatric morbidity. We therefore propose an integrated model of functional dyspepsia as a disorder of gut-brain signalling, supporting a biopsychosocial approach to the diagnosis and management of this disorder.

Erratum: A genome-wide survey and functional brain imaging study identify CTNNBL1 as a memory-related gene

Erratum: A genome-wide survey and functional brain imaging study identify CTNNBL1 as a memory-related gene