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The development of different methods of brain stimulation provides a promising therapeutic tool with potentially beneficial effects on subjects with impaired cognitive functions. We performed a systematic review of the studies published in the field of neurostimulation in Alzheimer's disease (AD), from basic research to clinical applications. The main methods of non-invasive brain stimulation are repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Preliminary findings have suggested that both techniques can enhance performances on several cognitive functions impaired in AD. Another non-invasive emerging neuromodulatory approach, the transcranial electromagnetic treatment, was found to reverse cognitive impairment in AD transgenic mice and even improves cognitive performance in normal mice. Experimental studies suggest that high-frequency electromagnetic fields may be critically important in AD prevention and treatment through their action at mitochondrial level. Finally, the application of a widely known invasive technique, the deep brain stimulation (DBS), has increasingly been considered as a therapeutic option also for patients with AD; it has been demonstrated that DBS of fornix/hypothalamus and nucleus basalis of Meynert might improve or at least stabilize cognitive functioning in AD. Initial encouraging results provide support for continuing to investigate non-invasive and invasive brain stimulation approaches as an adjuvant treatment for AD patients.

The intrinsic connectivity of the default mode network has been associated with the level of consciousness in patients with severe brain injury. Especially medial parietal regions are considered to be highly involved in impaired consciousness. To better understand what aspect of this intrinsic architecture is linked to consciousness, we applied spectral dynamic causal modeling to assess effective connectivity within the default mode network in patients with disorders of consciousness. We included 12 controls, 12 patients in minimally conscious state and 13 in vegetative state in this study. For each subject, we first defined the four key regions of the default mode network employing a subject-specific independent component analysis approach. The resulting regions were then included as nodes in a spectral dynamic causal modeling analysis in order to assess how the causal interactions across these regions as well as the characteristics of neuronal fluctuations change with the level of consciousness. The resulting pattern of interaction in controls identified the posterior cingulate cortex as the main driven hub with positive afferent but negative efferent connections. In patients, this pattern appears to be disrupted. Moreover, the vegetative state patients exhibit significantly reduced self-inhibition and increased oscillations in the posterior cingulate cortex compared to minimally conscious state and controls. Finally, the degree of self-inhibition and strength of oscillation in this region is correlated with the level of consciousness. These findings indicate that the equilibrium between excitatory connectivity towards posterior cingulate cortex and its feedback projections is a key aspect of the relationship between alterations in consciousness after severe brain injury and the intrinsic functional architecture of the default mode network. This impairment might be principally due to the disruption of the mechanisms underlying self-inhibition and neuronal oscillations in the posterior cingulate cortex., (Copyright © 2015. Published by Elsevier Inc.)

Changes in descending serotonergic innervation of spinal neural activity have been implicated in symptoms of paralysis, spasticity, sensory disturbances and pain following spinal cord injury (SCI). Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury, including SCI. Current research suggests that serotonine (5-HT) release within the ventral horn of the spinal cord plays a critical role in motor function, and activation of 5-HT receptors mediates locomotor control. 5-HT originating from the brain stem inhibits sensory afferent transmission and associated spinal reflexes; by abolishing 5-HT innervation SCI leads to a disinhibition of sensory transmission. 5-HT denervation supersensitivity is one of the key mechanisms underlying the increased motoneuron excitability that occurs after SCI, and this hyperexcitability has been demonstrated to underlie the pathogenesis of spasticity after SCI. Moreover, emerging evidence implicates serotonergic descending facilitatory pathways from the brainstem to the spinal cord in the maintenance of pathologic pain. There are functional relevant connections between the descending serotonergic system from the rostral ventromedial medulla in the brainstem, the 5-HT receptors in the spinal dorsal horn, and the descending pain facilitation after tissue and nerve injury. This narrative review focussed on the most important studies that have investigated the above-mentioned effects of impaired 5-HT-transmission in humans after SCI. We also briefly discussed the promising therapeutical approaches with serotonergic drugs, monoclonal antibodies and intraspinal cell transplantation.

Short-latency afferent inhibition (SAI) technique gives the opportunity to non-invasively test an inhibitory circuit in the human cerebral motor cortex that depends mainly on central cholinergic activity. Important SAI abnormalities have been reported in both patients with Alzheimer disease (AD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a model of "pure" vascular dementia (VD). Interestingly, a normalization of SAI was observed in AD after levo-dopa (L-dopa) administration. We aimed to determine whether the pharmacological manipulation of the dopaminergic system can also interfere with SAI test in CADASIL patients, compared with AD patients and healthy controls. SAI was found to be significantly reduced in both patient groups. L-Dopa significantly increased SAI in the AD patients, while it failed to restore SAI abnormality in CADASIL patients. Therefore, L-dopa-mediated changes on SAI in AD patients seem to be a specific effect. The present study supports the notion that relationship between acetylcholine and dopamine systems may be specifically abnormal in AD. L-Dopa challenge may thus be able to differentiate the patients with AD or a mixed form of dementia from those with "pure" VD.

Objective: In the present study, we searched for resting-EEG biomarkers that distinguish different levels of consciousness on a single subject level with an accuracy that is significantly above chance., Methods: We assessed 44 biomarkers extracted from the resting EEG with respect to their discriminative value between groups of minimally conscious (MCS, N=22) patients, vegetative state patients (VS, N=27), and - for a proof of concept - healthy participants (N=23). We applied classification with support vector machines., Results: Partial coherence, directed transfer function, and generalized partial directed coherence yielded accuracies that were significantly above chance for the group distinction of MCS vs. VS (.88, .80, and .78, respectively), as well as healthy participants vs. MCS (.96, .87, and .93, respectively) and VS (.98, .84, and .96, respectively) patients., Conclusions: The concept of connectivity is crucial for determining the level of consciousness, supporting the view that assessing brain networks in the resting state is the golden way to examine brain functions such as consciousness., Significance: The present results directly show that it is possible to distinguish patients with different levels of consciousness on the basis of resting-state EEG., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Temporal lobe epilepsy (TLE) and mild cognitive impairment (MCI) are both subject to intensive memory research. Memory problems are a core characteristic of both conditions and we wonder if there are analogies which would enrich the two distinct research communities. In this review we focus on memory decline in both conditions, that is, the most feared psychosocial effect. While it is clear that memory decline in MCI is highly likely and would lead to the more severe diagnosis of Alzheimer's disease, it is a debate if TLE is a dementing disease or not. As such, like for MCI, one can differentiate progressive from stable TLE subtypes, mainly depending on the age of onset. Neuroimaging techniques such as volumetric analysis of the hippocampus, entorhinal, and perirhinal cortex show evidence of pathological changes in TLE and are predictive for memory decline in MCI. Several studies emphasize that it is necessary to extend the region of interest-even whole-brain characteristics can be predictive for conversion from MCI to Alzheimer's disease. Electroencephalography is increasingly subject to computational neuroscience, revealing new approaches for analyzing frequency, spatial synchronization, and information content of the signals. These methods together with event-related designs that assess memory functions are highly promising for understanding the mechanisms of memory decline in both TLE and MCI populations. Finally, there is evidence that the potential of such markers for memory decline is far from being exhausted. Similar structural and neurophysiological characteristics are linked to memory decline in TLE and MCI. We raise the hope that interdisciplinary research and cross-talk between fields such as research on epilepsy and dementia, will shed further light on the dementing characteristics of the pathological basis of MCI and TLE and support the development of new memory enhancing treatment strategies.

A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases; this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic shunt. Hepatic myelopathy (HM) is characterized by progressive weakness and spasticity of the lower extremities, while sensory and sphincter disturbances have rarely been described and are usually less important. The diagnosis is assigned in the appropriate clinical setting on clinical grounds after the exclusion of other clinical entities leading to spastic paraparesis. Magnetic resonance imaging is often unremarkable; however, also intracerebral corticospinal tract abnormalities have been reported recently. The study of motor evoked potentials may disclose central conduction abnormalities even before HM is clinically manifest. HM responds poorly to blood ammonia-lowering and other conservative medical therapy. Liver transplantation represents a potentially definitive treatment for HM in patients with decompensated cirrhosis of Child-Pugh B and C grades. Other surgical treatment options in HM include surgical ligation, shunt reduction, or occlusion by interventional procedures.

Amongst the impulse-control disorders (ICDs) associated with dopamine-replacement therapy in patients with Parkinson's disease (PD) is a repetitive, complex, stereotyped behaviour called punding. Disruption of the reciprocal loops between the striatum and structures in the prefrontal cortex (PFC) following dopamine depletion may predispose patients with PD to these behavioural disorders. The purpose of the present study was to assess the effects of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral PFC (DLPFC) on punding in PD. We used low-frequency (LF) rTMS in four PD patients presenting with punding. Punding was transiently reversed by LF-rTMS over the DLPFC without enhancing motor impairment. The effect was more sustained after right DLPFC rTMS. Therefore, LF-rTMS produced a transient beneficial effect in PD patients with punding, similar to that reported in PD patients with levodopa-induced dyskinesias. rTMS might have therapeutic potential for the treatment of punding and perhaps other ICDs in PD.

Context: Past evidence has shown that invasive and non-invasive brain stimulation may be effective for relieving central pain., Objective: To perform a topical review of the literature on brain neurostimulation techniques in patients with chronic neuropathic pain due to traumatic spinal cord injury (SCI) and to assess the current evidence for their therapeutic efficacy., Methods: A MEDLINE search was performed using following terms: "Spinal cord injury", "Neuropathic pain", "Brain stimulation", "Deep brain stimulation" (DBS), "Motor cortex stimulation" (MCS), "Transcranial magnetic stimulation" (TMS), "Transcranial direct current stimulation" (tDCS), "Cranial electrotherapy stimulation" (CES)., Results: Invasive neurostimulation therapies, in particular DBS and epidural MCS, have shown promise as treatments for neuropathic and phantom limb pain. However, the long-term efficacy of DBS is low, while MCS has a relatively higher potential with lesser complications that DBS. Among the non-invasive techniques, there is accumulating evidence that repetitive TMS can produce analgesic effects in healthy subjects undergoing laboratory-induced pain and in chronic pain conditions of various etiologies, at least partially and transiently. Another very safe technique of non-invasive brain stimulation - tDCS - applied over the sensory-motor cortex has been reported to decrease pain sensation and increase pain threshold in healthy subjects. CES has also proved to be effective in managing some types of pain, including neuropathic pain in subjects with SCI., Conclusion: A number of studies have begun to use non-invasive neuromodulatory techniques therapeutically to relieve neuropathic pain and phantom phenomena in patients with SCI. However, further studies are warranted to corroborate the early findings and confirm different targets and stimulation paradigms. The utility of these protocols in combination with pharmacological approaches should also be explored.

Recovery of consciousness has been associated with connectivity in the frontal cortex and parietal regions modulated by the thalamus. To examine this model and to relate alterations to deficits in cognitive functioning and conscious processing, we investigated topological network properties in patients with chronic disorders of consciousness recovered from coma. Resting state fMRI data of 34 patients with unresponsive wakefulness syndrome and 25 in minimally conscious state were compared to 28 healthy controls. We investigated global and local network characteristics. Additionally, behavioral measures were correlated with the local metrics of 28 regions within the fronto-parietal network and the thalamus. In chronic disorders of consciousness, modularity at the global level was reduced suggesting a disturbance in the optimal balance between segregation and integration. Moreover, network properties were altered in several regions which are associated with conscious processing (particularly, in medial parietal, and frontal regions, as well as in the thalamus). Between minimally conscious and unconscious patients the local efficiency of medial parietal regions differed. Alterations in the thalamus were particularly evident in non-conscious patients. Most of the regions affected in patients with impaired consciousness belong to the so-called 'rich club' of highly interconnected central nodes. Disturbances in their topological characteristics have severe impact on information integration and are reflected in deficits in cognitive functioning probably leading to a total breakdown of consciousness.

Current research aims at identifying voluntary brain activation in patients who are behaviorally diagnosed as being unconscious, but are able to perform commands by modulating their brain activity patterns. This involves machine learning techniques and feature extraction methods such as applied in brain computer interfaces. In this study, we try to answer the question if features/classification methods which show advantages in healthy participants are also accurate when applied to data of patients with disorders of consciousness. A sample of healthy participants (N = 22), patients in a minimally conscious state (MCS; N = 5), and with unresponsive wakefulness syndrome (UWS; N = 9) was examined with a motor imagery task which involved imagery of moving both hands and an instruction to hold both hands firm. We extracted a set of 20 features from the electroencephalogram and used linear discriminant analysis, k-nearest neighbor classification, and support vector machines (SVM) as classification methods. In healthy participants, the best classification accuracies were seen with coherences (mean = .79; range = .53-.94) and power spectra (mean = .69; range = .40-.85). The coherence patterns in healthy participants did not match the expectation of central modulated [Formula: see text]-rhythm. Instead, coherence involved mainly frontal regions. In healthy participants, the best classification tool was SVM. Five patients had at least one feature-classifier outcome with p[Formula: see text]0.05 (none of which were coherence or power spectra), though none remained significant after false-discovery rate correction for multiple comparisons. The present work suggests the use of coherences in patients with disorders of consciousness because they show high reliability among healthy subjects and patient groups. However, feature extraction and classification is a challenging task in unresponsive patients because there is no ground truth to validate the results.

The neural mechanisms underlying the development of the most common intrinsic sleep disorders are not completely known. Therefore, there is a great need for noninvasive tools which can be used to better understand the pathophysiology of these diseases. Transcranial magnetic stimulation (TMS) offers a method to noninvasively investigate the functional integrity of the motor cortex and its corticospinal projections in neurologic and psychiatric diseases. To date, TMS studies have revealed cortical and corticospinal dysfunction in several sleep disorders, with cortical hyperexcitability being a characteristic feature in some disorders (i.e., the restless legs syndrome) and cortical hypoexcitability being a well-established finding in others (i.e., obstructive sleep apnea syndrome narcolepsy). Several research groups also have applied TMS to evaluate the effects of pharmacologic agents, such as dopaminergic agent or wake-promoting substances. Our review will focus on the mechanisms underlying the generation of abnormal TMS measures in the different types of sleep disorders, the contribution of TMS in enhancing the understanding of their pathophysiology, and the potential diagnostic utility of TMS techniques. We also briefly discussed the possible future implications for improving therapeutic approaches., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans.

To further investigate the mechanisms of exercise-induced cortical plasticity after spinal cord injury (SCI), the cortical silent period (CoSP) evoked by transcranial magnetic stimulation (TMS) during a fatiguing muscle contraction was evaluated in 5 patients with incomplete cervical SCI and in 5 healthy subjects. The physiological lengthening of CoSP end latency during fatigue was not observed in the SCI patients. This reduced intracortical inhibition, probably secondary to decreased activity of the GABAergic inhibitory interneurons that modulate the corticomotoneuronal output, could represent a 'positive' neuroplastic response in an attempt to compensate for the loss of corticospinal axons. The investigation of motor cortex excitability during fatiguing exercise may shed light on the role of exercise therapy in promoting brain reorganization and functional recovery in humans., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Previous neuroimaging studies raised the hypothesis that enhanced activity in the ipsilateral motor cortex (M1) plays a contributing role in the compensation for the motor deficits resulting from a spinal cord injury (SCI). However, it is still unknown whether the activity in the ipsilateral M1 directly contributes to movement performance after SCI. To address this question, we evaluated in five subjects with chronic incomplete cervical SCI the effects of suprathreshold transcranial magnetic stimulation (TMS) to both hemispheres when a movement of the right and left hand was performed separately in the setting of a simple reaction time. We found that stimulation of each hemisphere resulted in delayed simple reaction times in the contralateral but not in the ipsilateral hand. These observations provide the first direct evidence in humans that the ipsilateral M1 did not contribute significantly to motor task performance after SCI., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The active oddball paradigm is a candidate task for voluntary brain activation. Previous research has focused on group effects, and has largely overlooked the potential problem of interindividual differences. Interindividual variance causes problems with the interpretation of group-level results. In this study we want to demonstrate the degree of consistency in the active oddball task across subjects, in order to answer the question of whether this task is able to reliably detect conscious target processing in unresponsive patients. We asked 18 subjects to count rare targets and to ignore frequent standards and rare distractors in an auditory active oddball task. Event-related-potentials (ERPs) and time-frequency data were analyzed with permutation-t-tests on a single subject level. We plotted the group-average ERPs and time-frequency data, and evaluated the numbers of subjects showing significant differences between targets and distractors in certain time-ranges. The distinction between targets/distractors and standards was found to be significant in the time-range of the P300 in all participants. In contrast, significant differences between targets and distractors in the time-range of the P3a/b were found in 8 subjects, only. By including effects in the N1 and in a late negative component there remained 2 subjects who did not show a distinction between targets and distractors in the ERP. While time-frequency data showed prominent effects for target/distractor vs. standard, significant differences between targets and distractors were found in 2 subjects, only. The results suggest that time-frequency- and ERP-analysis of the active oddball task may not be sensitive enough to detect voluntary brain activation in unresponsive patients. In addition, we found that time-frequency analysis was even less informative than ERPs about the subject's task performance. Despite suggesting the use of more sensitive paradigms and/or analysis techniques, the present results give further evidence that electroencephalographic research should rely more strongly on single-subject analysis because interpretations of group-effects may be misleading.

Self-related stimuli activate anterior parts of cortical midline regions, which normally show task-induced deactivation. Deactivation in medial posterior and frontal regions is associated with the ability to focus attention on the demands of the task, and therefore, with consciousness. Studies investigating patients with impaired consciousness, that is, patients in minimally conscious state and patients with unresponsive wakefulness syndrome (formerly vegetative state), demonstrate that these patients show responses to self-related content in the anterior cingulate cortex. However, it remains unclear if these responses are an indication for conscious processing of stimuli or are due to automatic processing. To shed further light on this issue, we investigated responses of cortical midline regions to the own and another name in 27 patients with a disorder of consciousness and compared them to task-induced deactivation. While almost all of the control subjects responding to the own name demonstrated higher activation due to the self-related content in anterior midline regions and additional deactivation, none of the responding patients did so. Differences between groups showed a similar pattern of findings. Despite the relation between behavioral responsiveness in patients and activation in response to the own name, the findings of this study do not provide evidence for a direct association of activation in anterior midline regions and conscious processing. The deficits in processing of self-referential content in anterior midline regions may rather be due to general impairments in cognitive processing and not particularly linked to impaired consciousness.

Specific phobia of vomiting (SPOV) is a clinical condition with early onset, chronic course and substantial psychosocial impairment due to a rigorous avoidance behavior. A primary symptom which drives patients to consult a medical practitioner is nausea. In this study our aim was to further analyze this symptom of SPOV and examined its role in the development and manifestation of the phobia. We conducted an internet survey in the german SPOV-internet-forum. We calculated a nausea score and grouped participants in a high-and low-nausea group to examine the relationship between nausea and characteristics of the fear of vomiting. In this sample (N = 131), nausea was fairly common in most participants with fear of vomiting. Participants in the high-nausea group had significantly higher ratings of subjective fear and significantly longer duration of fear of vomiting. Additionally, the high-nausea group contained more participants with a body mass index below 19 than the low-nausea group. The present findings suggest that nausea is a core symptom in SPOV which is closely related to intensity of the fear, duration of the fear, and body weight. Future research should investigate if nausea-specific design of treatment could improve therapy outcome.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a clinical condition characterized by an intermittent or complete loss of muscle atonia and an increase of phasic muscular activity during REM sleep (or Stage R), leading to complex nocturnal motor behaviors. Correct and early diagnosis is important because RBD may lead to serious injuries and is a well-treatable disorder. Since the characteristic electrophysiologic finding in patients with RBD is the increased electromyographic tone during REM sleep/Stage R, simultaneous video/polysomnography recording is essential for diagnosing this parasomnia. Moreover, several neurophysiological techniques have been used to improve our knowledge and understanding of this troubling sleep disorder. We reviewed the most important studies employing quantitative electroencephalography, event-related potentials, transcranial magnetic stimulation, brainstem reflexes and cortico-muscular coherence analysis. All these neurophysiological techniques have proven to provide a valuable tool to gain insight into the pathophysiological mechanisms underlying RBD. The review concludes with a brief discussion on the possible future implications for improving therapeutic approaches., (Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Plastic changes of neural circuits occur after spinal cord injury (SCI) at various level of the central nervous system. In this review we will focus on delineating the pathophysiological mechanisms of the brain plasticity changes following SCI, based on the existing neuroimaging and neurophysiological evidence in experimental models and humans. In animal experiments, reorganization of the sensory topography as well as of the topographical map of primary motor and premotor cortices have been reported in several studies. Brain imaging revealed that cortical representation in response to spared forelimb stimulation early enlarges and invades adjacent sensory-deprived hind limb territory. Electrophysiological studies demonstrated that the deafferentation due to SCI can immediately change the state of large cortical networks within 1h, and that these changes play a critical role in the functional reorganization after SCI. In humans neuroimaging also showed shifts of functional motor and sensory cortical representations that relate to the severity of SCI. In patients with cervical SCI, cortical forearm motor representations, as assessed by means of transcranial magnetic stimulation, may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm. Excessive or aberrant reorganisation of cerebral cortex may also have pathological consequences, such as phantom sensations or neuropathic pain. Integrated neuroimaging and neurophysiological approaches may also lead to the development of new therapeutic strategies, which have the potential of enhancing sensorimotor recovery in patients with SCI., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Motor imagery tasks are well established procedures in brain computer interfaces, but are also used in the assessment of patients with disorders of consciousness. For testing awareness in unresponsive patients it is necessary to know the natural variance of brain responses to motor imagery in healthy subjects. We examined 22 healthy subjects using EEG in three conditions: movement of both hands, imagery of the same movement, and an instruction to hold both hands still. Single-subject non-parametric statistics were applied to the fast-Fourier transformed data. Most effects were found in the α- and β-frequency ranges over central electrodes, that is, in the μ-rhythm. We found significant power changes in 18 subjects during movement and in 11 subjects during motor imagery. In 8 subjects these changes were consistent over both conditions. The significant power changes during movement were a decrease of μ-rhythm. There were 2 subjects with an increase and 9 subjects with a decrease of μ-rhythm during imagery. α and β are the most responsive frequency ranges, but there is a minor number of subjects who show a synchronization instead of the more common desynchronization during motor imagery. A (de)synchronization of μ-rhythm can be considered to be a normal response., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Music is a stimulus which may give rise to a wide range of emotional and cognitive responses. Therefore, brain reactivity to music has become a focus of interest in cognitive neuroscience. It is possible that individual preference moderates the effectof music on the brain. In the present study we examined whether there are common effects of listening to music even if each subject in a sample chooses their own piece of music. We invited 18 subjects to bring along their favorite relaxing music, and their favourite stimulating music. Additionally, a condition with tactile stimulation on the foot and a baseline condition (rest) without stimulation were used. The tactile stimulation was chosen to provide a simple, non-auditory condition which would be identical for all subjects. The electroencephalogram was recorded for each of the 3 conditions and during rest. We found responses in the alpha range mainly on parietal and occipital sites that were significant compared to baseline in 13 subjects during relaxing music, 15 subjects during activating music, and 16 subjects during tactile stimulation. Most subjects showed an alpha desynchronization in a lower alpha range followed by a synchronization in an upper frequency range. However, some subjects showed an increase in this area, whereas others showed a decrease only. In addition, many subjects showed reactivity in the beta range. Beta activity was especially increased while listening to activating music and during tactile stimulation in most subjects. We found interindividual differences in the response patterns even though the stimuli provoked comparable subjective emotions (relaxation, activation), and even if the stimulus was the same for all subjects (somatosensory stimulation). We suggest that brain responsivity to music should be examined individually by considering individual characteristics., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Functional brain imaging in mild cognitive impairment (MCI) reveals differences in activation of task-relevant brain areas between patients and age-matched healthy controls. However, some studies reported hyperactivation and others hypoactivation in MCI compared with controls. The inconsistencies may be explained by compensatory mechanisms due to high complexity of the applied tasks. The oddball task is a simple paradigm that is known to activate a widespread network in the brain, involving attentional and monitoring mechanisms. In the present study, we examined amnestic or amnestic multidomain MCI patients (n = 12) and healthy controls (n = 13) in an auditory oddball task. Participants had to respond to infrequent targets and inhibit response to infrequent novel-nontarget stimuli. Lower stimulus related activation was found in MCI patients compared with healthy controls in parts of the middle temporal gyrus, the temporal pole, regions along the superior temporal sulcus, in the left cuneus, the left supramarginal gyrus, the anterior cingulated cortex and in the left inferior and middle frontal gyrus. Activation for oddball stimuli is assumed to reflect an automatic reflexive engagement of many brain regions in response to potentially important changes in the environment as well as cognitive control to monitor responses. The mechanisms of attention and cognitive control may be severely impaired in MCI and thus, underlie the cognitive deficits of this clinical group., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Distortion correction is applied to endoscopic duodenal imagery to improve automated classification of celiac disease affected mucosa patches. In a set of six edge- and shape-related feature extraction techniques, only a single one is able to consistently benefit from distortion correction, while for others, even a decrease of classification accuracy is observed. Different types of distortion correction do not lead to significantly different behaviour in the observed application scenario.

There has been little investigation on the association between cognitive impairment and the microbleeds (MBs) frequently seen in subcortical vascular dementia (SVaD). One possible mechanism of cognitive decline in individuals with SVaD could be disruption of cholinergic fibers by vascular lesions. Central cholinergic circuits in human brain can be tested non-invasively by means of a transcranial magnetic stimulation (TMS) protocol named short latency afferent inhibition (SAI) of motor cortex. In the present study, we used this test in SvaD patients with and without MBs. SAI was evaluated in 13 SVaD patients with MBs (MB-positive group) and the data were compared with those from a group of 15 SVaD patients without MBs (MB-negative group) and with those from 20 healthy subjects. Moreover, we studied covariation of individual SAI values with the Mini-Mental State Examination (MMSE) total score and subscores. SAI was significantly reduced in the MB-positive group when compared with the MB-negative group and the control subjects. Total MMSE score, "attention and calculation" and "orientation" subscores were significantly lower in the MB-positive group than in the MB-negative group; SAI showed a positive correlation with total MMSE score. Adjustment for age, gender, education, presence of lacunae, severe white matter hyperintensities or severe periventricular hyperintensities did not affect these findings. This study provides novel physiological evidence that MBs have an impact on central cholinergic function that is independent of the extent of associated white matter changes and ischaemic stroke. This finding shows that TMS have potential diagnostic and therapeutic implications. TMS studies may help in evaluating the causes of cognitive impairment in cerebrovascular diseases.

Objective: The diagnostic validity of non-phase-locked oscillations (NPLOs) and mismatch negativity (MMN) in an oddball task for assessing attentional reactivity in patients with disordered consciousness was examined., Methods: Patients in a minimally conscious (MCS, n = 6) or vegetative (VS, n = 16) state and healthy controls (n = 15) were assessed. MMN and NPLOs were analyzed with single-subject, non-parametric statistics., Results: In 11 healthy controls and 2 VS patients, MMN was detected. More subjects showed NPLO differences in the alpha than in the theta or beta frequency ranges. In 14 healthy controls, 4 MCS patients, and 5 VS patients, lower amplitudes after deviants were found in the alpha frequency range. One healthy subject and one VS patient showed higher amplitudes after deviants., Conclusions: Neither ERPs nor NPLOs could reliably distinguish MCS from VS patients. However, NPLOs were more sensitive than ERPs for detecting significantly different activity, and they possibly identified preserved processing better than ERPs., Significance: Intact neurophysiological attentional responses observed in the NPLOs of VS patients may indicate a need for other diagnostic techniques. Inter-individual differences in the direction of the effect should be considered as normal variance., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

In previous studies event-related potentials and oscillations in response to subject's own name have been analyzed extensively on group-level in healthy subjects and in patients with a disorder of consciousness. Subject's own name as a deviant produces a P3. With equiprobable stimuli, non-phase-locked alpha oscillations are smaller in response to subject's own name compared to other names or subject's own name backwards. However, little is known about replicability on a single-subject level. Seventeen healthy subjects were assessed in an own-name paradigm with equiprobable stimuli of subject's own name, another name, and subject's own name backwards. Event-related potentials and non-phase locked oscillations were analyzed with single-subject, non-parametric statistics. No consistent results were found either for ERPs or for the non-phase locked changes of oscillatory activities. Only 4 subjects showed a robust effect as expected, that is, a lower activity in the alpha-beta range to subject's own name compared to other conditions. Four subjects elicited a higher activity for subject's own name. Thus, analyzing the EEG reactivity in the own-name paradigm with equiprobable stimuli on a single-subject level yields a high variance between subjects. In future research, single-subject statistics should be applied for examining the validity of physiologic measurements in other paradigms and for examining the pattern of reactivity in patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: The neuronal response to hearing a subject's own (SON) compared with other names has been examined in healthy subjects as well as in patients with disorders of consciousness. So far, on electroencephalographic data, only event-related potentials (ERPs) were considered. In this study, we examined the frequency properties of SON., Methods: Data of 17 healthy subjects were processed for equiprobable stimuli of SON, other- and own-name backwards by calculating ERPs, evoked and induced activity for a period of 2000 ms from stimulus onset in the delta, theta, lower and upper alpha bands and averaging for four consequent temporal segments of 500 ms each., Results: For SON, the N1 component's amplitude was larger, while induced activity in the alpha band decreased in the second temporal segment (of 500-1000 ms). No differences between other- and own-name backwards were found., Conclusions: The late reactivity may indicate responses to a stimulus after having recognised it. Alpha is known to play a role in attention and alertness. The results may reflect the fact that the SON stimulus enhances alertness., Significance: The findings correlate previous work about alertness and alpha activity with those about attention capturing of the SON stimulus. We suggest using frequency analysis in research on disorders of consciousness., (Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Diagnosis of patients with a disorder of consciousness is very challenging. Previous studies investigating resting state networks demonstrate that 2 main features of the so-called default mode network (DMN), metabolism and functional connectivity, are impaired in patients with a disorder of consciousness. However, task-induced deactivation--a third main feature of the DMN--has not been explored in a group of patients. Deactivation of the DMN is supposed to reflect interruptions of introspective processes. Seventeen patients with unresponsive wakefulness syndrome (UWS, former vegetative state), 8 patients in minimally conscious state (MCS), and 25 healthy controls were investigated with functional magnetic resonance imaging during a passive sentence listening task. Results show that deactivation in medial regions is reduced in MCS and absent in UWS patients compared to healthy controls. Moreover, behavioral scores assessing the level of consciousness correlate with deactivation in patients. On single-subject level, all control subjects but only 2 patients in MCS and 6 with UWS exposed deactivation. Interestingly, all patients who deactivated during speech processing (except for one) showed activation in left frontal regions which are associated with conscious processing. Our results indicate that deactivation of the DMN can be associated with the level of consciousness by selecting those who are able to interrupt ongoing introspective processes. In consequence, deactivation of the DMN may function as a marker of consciousness.

Functional magnetic resonance imaging (fMRI) has been shown to be a very useful tool to do research on psychiatric disorders, validating psychotherapeutical interventions, medication as well as disorder-specific deficits. The field of fMRI-research is examining the potential of identifying differences of activity between brains of clinical, subclinical and healthy subjects. The design of such research is drawn to evaluate the average activation to different conditions. We remark that there are still some methodological problems to face, i.e. choosing the sample with special considerations on comorbidity and medication, accounting individual differences in brain activation, complex statistical calculations etc. When evaluating therapeutical interventions it is necessary to take the placebo-effect into account. However, fMRI is a highly promising research method. For future application of fMRI in clinical practice it would be worth building standard paradigms. Then, valid diagnostics of impaired functionality may be possible. Furthermore, fMRI should be combined with other neurodiagnostical technologies and with genetics. The cooperation of different fields in brain research with fMRI may provide further knowledge about psychiatric disorders.

The present study attempts to demonstrate functional similarities between the P1 component of event-related potentials and alpha oscillations that are predicted by the 'alpha inhibition-timing' hypothesis. On the basis of findings showing that the frequency characteristic of the P1 component lies in the alpha range and that alpha oscillation is functionally associated with inhibition, we predict that the P1 component also reflects inhibitory processes. This hypothesis is tested in two experiments, a spatial-cuing task and a visual-semantic categorization task. The results of the cuing task demonstrate that in a similar way as alpha power, the P1 component is larger over task-irrelevant ipsilateral sites. For the categorization task, we found that the P1 component, in a similar way to alpha oscillations, is larger for task-irrelevant, distorted pictures. We conclude that the P1 component may be generated at least in part by evoked alpha oscillations and reflects inhibition in the sense of suppressing task-irrelevant processes.

We tested the hypothesis whether images of real objects elicit stronger gamma (>25 Hz) synchronization, when compared with scrambled objects. The background of this study is a recent debate about the functional meaning of evoked and induced gamma oscillations. Brain electrical source analysis (BESA) and low resolution electromagnetic tomography analysis (LORETA) was performed on the basis of the event-related potential (ERP) data. A component at around 230 ms (termed C230) showed strongest differences between objects and scrambled objects. Time-frequency analyses were run across electrodes and within the dipole sources. We found increased gamma event-related synchronization (ERS) between 200 and 300 ms for real objects. This effect was strongest in a fronto-medial source. Induced gamma, as also shown in previous studies, reflects the more task-relevant mechanism where object representations become activated.