Longitudinal study of a NoGo-P3 event-related potential component following mild traumatic brain injury in adults.

BACKGROUND: Event-related potentials have repeatedly revealed electrophysiological markers of cognitive dysfunction associated with Mild Traumatic Brain Injury (MTBI) and may represent a sensitive tool to guide cognitive rehabilitative interventions. We previously found patients with symptomatic MTBI characterized by smaller P300 (or P3) wave amplitudes in a NoGo-P3 subcomponent in the acute phase of the injury. The goal of this longitudinal study was to investigate whether this early NoGo-P3 subcomponent differs over time in symptomatic MTBI patients and healthy controls. METHODS: We included adults with a diagnosis of MTBI and individually matched healthy controls tested at 1 week, 3 months, and 1 year after the MTBI. Symptoms were assessed by the Rivermead Post-Concussion Symptoms Questionnaire. NoGo-P3 was collected by using a cued Go/NoGo task and the relevant subcomponent was extracted by independent component analysis. RESULTS: Among 53 adults with a diagnosis of MTBI and 53 controls, we included 35 with symptomatic MTBI and 35 matched healthy controls (18 females each group; mean age 34.06±13.15 and 34.26±12.98 years). Amplitudes for the early NoGo-P3 subcomponent were lower for symptomatic MTBI patients than controls (P<0.05) at 1 week post-injury. Furthermore, mixed ANOVA revealed a significant time by group interaction (P<0.05), so the effect of time differed for symptomatic MTBI patients and healthy controls. The amplitudes for MTBI patients normalized from 1 week to 3 months post-injury and were comparable to those of controls from 3 months to 1 year post-injury. However, amplitudes for 3 MTBI patients with particularly severe complaints 1 year post-injury did not normalize and were lower than those for the remaining MTBI sample (P<0.05). CONCLUSIONS: Selected event-related potentials can be used as a sensitive and objective tool to illustrate the cognitive consequences of and recovery after MTBI.

Prefrontal Cortical Thickening after Mild Traumatic Brain Injury: A One-Year Magnetic Resonance Imaging Study.

The objective of this study was to evaluate group-by-time interactions between gray matter morphology of healthy controls and that of patients with mild traumatic brain injury (mTBI) as they transitioned from acute to chronic stages, and to relate these findings to long-term cognitive alterations to identify distinct recovery trajectories between good outcome (GO) and poor outcome (PO). High-resolution T1-weighted magnetic resonance images were acquired in 49 mTBI patients within 7 days and 1 year post-injury and at equivalent times in 49 healthy controls. Using linear mixed-effects models, we performed mass-univariate analyses and associated the results of the interaction with changes in cognitive performance. Morphological alterations indexed by increased or decreased cortical thickness have been expected mainly in frontal, parietal, and temporal brain regions. A significant interaction was found in cortical thickness, spatially restricted to bilateral structures of the prefrontal cortex, showing thickening in mTBI and normal developmental thinning in controls. A discrete thickness increase that can interpreted as the absence of cortical thinning typically seen in the healthy population was associated with cognitive recovery in the GO subgroup, while the exaggerated cortical thickening in the PO patients was linked to worsening cognitive performance. Thickness of the prefrontal cortex is subject to structural alterations during the first year after mTBI. Beside beneficial neuroplasticity, a prolonged state of neuroinflammation for symptomatic patients (maladaptive neuroplasticity) cannot be excluded. If the underlying cellular processes responsible for cortical thickening following mTBI have been determined, brain stimulation or even pharmacological intervention targeting the prefrontal cortex might promote endogenous neural restoration.

Functional and Structural Network Recovery after Mild Traumatic Brain Injury: A 1-Year Longitudinal Study.

Brain connectivity after mild traumatic brain injury (mTBI) has not been investigated longitudinally with respect to both functional and structural networks together within the same patients, crucial to capture the multifaceted neuropathology of the injury and to comprehensively monitor the course of recovery and compensatory reorganizations at macro-level. We performed a prospective study with 49 mTBI patients at an average of 5 days and 1 year post-injury and 49 healthy controls. Neuropsychological assessments as well as resting-state functional and diffusion-weighted magnetic resonance imaging were obtained. Functional and structural connectome analyses were performed using network-based statistics. They included a cross-sectional group comparison and a longitudinal analysis with the factors group and time. The latter tracked the subnetworks altered at the early phase and, in addition, included a whole-brain group × time interaction analysis. Finally, we explored associations between the evolution of connectivity and changes in cognitive performance. The early phase of mTBI was characterized by a functional hypoconnectivity in a subnetwork with a large overlap of regions involved within the classical default mode network. In addition, structural hyperconnectivity in a subnetwork including central hub areas such as the cingulate cortex was found. The impaired functional and structural subnetworks were strongly correlated and revealed a large anatomical overlap. One year after trauma and compared to healthy controls we observed a partial normalization of both subnetworks along with a considerable compensation of functional and structural connectivity subsequent to the acute phase. Connectivity changes over time were correlated with improvements in working memory, divided attention, and verbal recall. Neuroplasticity-induced recovery or compensatory processes following mTBI differ between brain regions with respect to their time course and are not fully completed 1 year after trauma.

Connectomic and Surface-Based Morphometric Correlates of Acute Mild Traumatic Brain Injury.

Reduced integrity of white matter (WM) pathways and subtle anomalies in gray matter (GM) morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI). However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare. Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected subnetwork suggests that mTBI can be conceptualized as a dysconnection syndrome. It remains unclear whether reduced WM integrity is the trigger for changes in cortical surface area or whether tissue deformations are the direct result of mechanical forces acting on the brain. The findings suggest that rapid identification of high-risk patients with the use of clinical scales should be assessed acutely as part of the mTBI protocol.

Altered cognitive processes in the acute phase of mTBI: an analysis of independent components of event-related potentials.

Mild traumatic brain injuries (mTBI) generate acute disruptions of brain function and a subset of patients shows persisting cognitive, affective, and somatic symptoms. Deficits in the executive function domain are among the more frequent cognitive impairments reported by mTBI patients. By means of independent component analysis, event-related potential components from a visual cued go/nogo task, namely contingent negative variation (CNV) and NoGo-P3, were decomposed into distinct independent components that have been shown to be associated with the executive processes of energization, monitoring, and task setting. A group of symptomatic mTBI patients was compared with a group of controls matched for sex, age, and education. Patients showed reduced amplitudes in the late CNV as well as in the early NoGo-P3 subcomponents. Whereas the decreased CNVlate component indicates an impaired ability to generate representations of stimulus-response associations and to energize the maintenance of response patterns, the reduced P3NOGOearly component suggests a deficient ability to invest attentional effort in the initiation of response patterns in mTBI patients. Besides indicating the effects of mTBI on cognitive brain processing, the results may open up the possibility for assessing individual mTBI profiles and facilitate personalized rehabilitative measures.

OXA-48 carbapenemase-producing Salmonella enterica serovar Kentucky isolate of sequence type 198 in a patient transferred from Libya to Switzerland.

Here, we report a case of OXA-48-producing Salmonella enterica serovar Kentucky of sequence type 198 (ST198) from perianal screening cultures of a patient transferred from Libya to Switzerland. The blaOXA-48 gene was carried by Tn1999.2 and located on an ∼60-kb IncL/M plasmid. This Salmonella strain also possessed the blaVEB-8, aac(6)-Ib, tet(A), sul1, and mphA resistance genes and substitutions in GyrA (Ser83Phe and Asp87Asn) and ParC (Ser80Ile). This finding emphasizes that prompt screening strategies are essential to prevent the dissemination of carbapenemase producers imported from countries where they are endemic.

Physiotherapy after traumatic brain injury: a systematic review of the literature.

PRIMARY OBJECTIVES: At present there are no standardized recommendations concerning physiotherapy of individuals with traumatic brain injury (TBI) resulting in a high variability of methods and intensity. The aim of this literature review is to develop recommendations concerning physiotherapy in the post-acute phase after TBI on the basis of scientific evidence. METHOD: literature review: data bases: PubMed, PEDro, OT-Seeker, Cochrane and Cinahl. KEYWORDS: brain injury (in PEDro, OT-Seeker, Cochrane), brain injury AND physical therapy (in PubMed and Cinahl). RESULTS: Fourteen studies met the inclusion criteria and were grouped into sub-groups: sensory stimulation, therapy intensity, casting/splinting, exercise or aerobic training and functional skill training. While for sensory stimulation evidence could not be proven, a strong evidence exists that more intensive rehabilitation programmes lead to earlier functional abilities. The recommendation due to casting for the improvement of passive range of motion is a grade B, while only a C recommendation is appropriate concerning tonus reduction. Strong evidence exists that intensive task-orientated rehabilitation programmes lead to earlier and better functional abilities. CONCLUSION: Although some recommendations for the effectiveness of physical therapy interventions could be expressed, there are many questions concerning the treatment of humans with TBI which have not been investigated so far. Especially on the level of activity and participation only a few studies exist.

Semantic, syntactic, and phonological processing of written words in adult developmental dyslexic readers: an event-related brain potential study.

BACKGROUND: The present study used event-related brain potentials to investigate semantic, phonological and syntactic processes in adult German dyslexic and normal readers in a word reading task. Pairs of German words were presented one word at a time. Subjects had to perform a semantic judgment task (house-window; are they semantically related?), a rhyme judgment task (house-mouse; do they rhyme?) and a gender judgment task (das-Haus [the-house]; is the gender correct? [in German, house has a neutral gender: das Haus]). RESULTS: Normal readers responded faster compared to dyslexic readers in all three tasks. Onset latencies of the N400 component were delayed in dyslexic readers in the rhyme judgment and in the gender judgment task, but not in the semantic judgment task. N400 and the anterior negativity peak amplitudes did not differ between the two groups. However, the N400 persisted longer in the dyslexic group in the rhyme judgment and in the semantic judgment tasks. CONCLUSION: These findings indicate that dyslexics are phonologically impaired (delayed N400 in the rhyme judgment task) but that they also have difficulties in other, non-phonological aspects of reading (longer response times, longer persistence of the N400). Specifically, semantic and syntactic integration seem to require more effort for dyslexic readers and take longer irrespective of the reading task that has to be performed.

Lateralized irrelevant speech alters visuospatial selective attention mechanisms.

Recent studies indicate that the coordination of spatial attention across modalities may in part be mediated by a supramodal attentional system. We try to extend the concept of a supramodal system and hypothesized that involuntary modulations of auditory attentional processes by irrelevant speech signals influence visuospatial attention, suggesting crossmodal links between vision and speech. In order to test this we recorded event-related brain potentials (ERPs) of 12 healthy subjects in a visuospatial selective attention task. The task to identify target stimuli appearing at lateral visual field locations caused the expected enhancements of the early P1 and N1 ERP components to attended visual stimuli. Understandable and ununderstandable task irrelevant speech was presented either at the visually attended position or in the opposite visual field location. Speech contralateral to unattended visual stimuli led to a decreased N1 amplitude. This effect was stronger for understandable speech. Thus, speech influences the allocation of visual spatial attention if it is presented in the unattended location. The results suggest crossmodal links of speech and visuospatial attention mechanisms at a very early stage of human perception.

Disturbed egocentric space representation in cervical dystonia.

In addition to visual spatial input, vestibular and proprioceptive signals are used in judging the egocentric space. We asked whether the abnormal head posture of patients with cervical dystonia (CD) is associated with distortions of their internal spatial reference frame. The perception of subjective straight-ahead (SSA) was tested under various conditions in 28 CD patients and in matched controls. They were asked to direct a laser pointer to the position that they believed to be "straight ahead" relative to their bodies' orientation (body-centered spatial perception). Body-independent visual spatial perception was assessed with different neuropsychological tests. CD patients had a greater deviation of the subjective straight ahead, indicating body-centered visual spatial perception, than controls. No effects were seen in body-independent visual spatial perception. Patients with CD are impaired in body-centered, egocentric spatial perception, but not in body-independent, allocentric spatial perception.

Brain potentials index executive functions during random number generation.

The generation of random sequences is considered to tax different executive functions. To explore the involvement of these functions further, brain potentials were recorded in 16 healthy young adults while either engaging in random number generation (RNG) by pressing the number keys on a computer keyboard in a random sequence or in ordered number generation (ONG) necessitating key presses in the canonical order. Key presses were paced by an external auditory stimulus to yield either fast (1 press/800 ms) or slow (1 press/1300 ms) sequences in separate runs. Attentional demands of random and ordered tasks were assessed by the introduction of a secondary task (key-press to a target tone). The P3 amplitude to the target tone of this secondary task was reduced during RNG, reflecting the greater consumption of attentional resources during RNG. Moreover, RNG led to a left frontal negativity peaking 140 ms after the onset of the pacing stimulus, whenever the subjects produced a true random response. This negativity could be attributed to the left dorsolateral prefrontal cortex and was absent when numbers were repeated. This negativity was interpreted as an index for the inhibition of habitual responses. Finally, in response locked ERPs a negative component was apparent peaking about 50 ms after the key-press that was more prominent during RNG. Source localization suggested a medial frontal source. This effect was tentatively interpreted as a reflection of the greater monitoring demands during random sequence generation.

Transcranial magnetic stimulation to the parietal lobes reduces detection of contralateral somatosensory stimuli.

OBJECTIVES: Neglect has been described in patients with lesions of the parietal cortex and has been interpreted as a disorder of the allocation of spatial attention. The persistence of neglect has been linked to poor rehabilitation outcome in patients suffering from acute stroke. Transcranial magnetic stimulation (TMS) applied to the parietal cortex has been shown to induce changes in the perception of stimuli including tactile stimulation of the fingers contra- and ipsilateral to the stimulated hemisphere. MATERIAL AND METHODS: In the current study, eleven normal young subjects performed a detection task for cutaneous electrical stimuli to the left or right forearm that had been precued by a preceding visual warning stimulus. To investigate the role of the parietal cortical areas for attentional processes TMS was applied to frontal and parietal scalp sites of each hemisphere in the cue-target interval before the somatosensory stimulus. RESULTS: Right and left parietal stimulation led to reduced detection sensitivity for near threshold stimuli to the forearm contralateral to the stimulated hemisphere without hemispheric differences. Ipsilateral tactile perception was not influenced by parietal TMS and there was no change in perception after frontal stimulation to left or right scalp sites. CONCLUSION: This pattern of results is consistent with a role of the right and left parietal lobe in the distribution of spatial attention and provides an experimental basis for possible therapeutical application of TMS to improve attentional deficits in stroke patients.

Target evaluation processing and serum levels of nerve tissue protein S100B in patients with remitted major depression.

Selective attention processes (N2 and P3 components of event-related potentials (ERPs)) have been shown to be impaired in depressed patients but findings have been mixed. Part of this variability might be explained by neurobiological factors. ERPs (Go/Nogo paradigm) were investigated in patients with remitted major depression in relation to S100B. S100B, an astroglial protein with neuroplastic properties, has been shown to be increased in depression. Its pathophysiologic role in depression, however, is not yet sufficiently understood. Patients with increased S100B serum levels (n=6) showed a normal N2- and P3-amplitude in contrast to a reduced N2- and P3-amplitude in patients with normal S100B serum levels (n=6). These findings provide evidence of a correlation between S100B levels and attentional processes in patients with recurrent depression and further substantiate S100B's role as a marker in the course of affective disorders.

Recognition memory for high- and low-frequency words in adult normal and dyslexic readers: an event-related brain potential study.

Differences in word processing between adult developmental dyslexic (n = 12) and normal readers (n = 12) were studied using event-related brain potentials recorded while subjects performed a recognition memory task. During the first part of the experiment, words were presented consecutively, and within this phase one third of the words were repeated. Subjects had to indicate whether a given word had previously been seen or not. After a delay of 1 hr, a second phase was administered. Here, another list containing 33% old words (presented in Phase 1) and 66% new words was shown and an old/new decision was required. In both categories, half of the words presented in either phase were of high normative frequency, and the other half were of low-frequency in the German language. Recognition performance was superior in normal readers for both high- and low-frequency words. In Phase 1, a fronto-centrally distributed N400 repetition effect discriminated between correctly identified old and new words (new words more negative). This effect was present for dyslexic as well as normal readers and for high- and low-frequency words. Between 450 and 800 ms, a 'P600 old/new effect' emerged (ERPs evoked by old words were more positive than those for new words). This effect was larger for low-frequency words. In Phase 2, an old/new effect was obtained for normal readers only. These findings are discussed in relation to current concepts of dyslexia and of semantic processing.

Recognition memory for unfamiliar faces does not differ for adult normal and dyslexic readers: an event-related brain potential study.

OBJECTIVE: Differences in recognition memory for unfamiliar faces between adult developmental dyslexic (n=12) and normal readers (n=12) were studied by means of event-related brain potentials. METHODS: Subjects performed a continuous face recognition task, in which 240 unfamiliar faces were presented on a computer screen, 100 of which were repetitions. For each face, subjects had to indicate whether it was presented before or not. Performance did not differ between normal and dyslexic readers. Old/repeated faces elicited more positive event-related potentials (ERPs) starting 250 ms poststimulus. These were analyzed in two time-windows encompassing the early (250-450 ms) and the late phase (450-750 ms) of the old/new effect. RESULTS: No group difference in amplitude or topography of the old/new effect emerged. However, ERPs for all faces were more positive for normal compared with those of dyslexic readers. CONCLUSIONS: These results show that a previously described recognition memory deficit for words in dyslexic readers is likely to be specific for verbal material.

Disturbed monitoring and response inhibition in patients with Gilles de la Tourette syndrome and co-morbid obsessive compulsive disorder.

OBJECTIVE: Fronto-striatal dysfunction has been discussed as underlying symptoms of Tourette syndrome (TS) with co-morbid Obsessive Compulsive Disorder (OCD). This suggests possible impairments of executive functions in this disorder, which were therefore targeted in the present study. METHODS: A comprehensive series of neuropsychological tests examining attention, memory and executive functions was performed in a group of 14 TS/OCD in co-occurrence with OCD patients and a matched control group. RESULTS: While attentional and memory mechanisms were not altered, TS/OCS patients showed deficits in executive functions predominantly in the areas of response inhibition and action monitoring. CONCLUSIONS: These findings provide further evidence for a substantial impairment of the frontal-striatal-thalamic-frontal circuit. We propose that the deficits in monitoring, error detection and response inhibition constitute the major impairment of TS/OCD patients in the cognitive domain.

Tourette syndrome and obsessive-compulsive disorder: event-related brain potentials show similar mechanisms [correction of mechansims] of frontal inhibition but dissimilar target evaluation processes.

OBJECTIVES: Tourette Syndrome (TS) and Obsessive-Compulsive Disorders (OCD) share many clinical similarities and show a strong comorbidity. Current theories view a frontal-striatal dysfunction as the underlying cause of many clinical aspects of both disorders. This study sought to investigate mechanisms of conceptual integration and attention in both disorders. We hypothesized that the processing of stimuli with interfering aspects would be altered in a similar way while attentional mechanisms could differ. METHODS: Event-related brain potentials (ERPs) were recorded in a modified STROOP-paradigm in groups of TS and OCD patients and in a control group. The paradigm involved the presentation of color words in a range of different colors. The subjects had to respond to words of matching word content and color and to ignore mismatching stimuli. RESULTS: Incongruent stimuli elicited a frontal negative component ("N450") which was enhanced in amplitude and prolonged in latency in both patient groups. Matching stimuli evoked enhanced N2 and P3b components representing target evaluation mechanisms. The OCD group alone displayed a larger P3b amplitude in comparison to both other groups. CONCLUSIONS: The data are interpreted to indicate that frontal inhibitory mechanisms are altered alike in TS and OCD. In contrast, only the OCD group showed evidence for aberrant target evaluation.

Cognitive brain potentials to novel acoustic stimuli in adult dyslexic readers.

Event-related brain potentials were recorded in two three-stimulus oddball tasks in 13 adult dyslexic and 13 age- and IQ-matched normal readers. The stimuli consisted of a random series of frequent (80%) and non-frequent tones (10%) as well as occasionally inserted novel sounds (10%). The experiment comprised an active (response to the rare target tone) and a passive listening condition. No performance differences were found for dyslexic and normal readers in the active task. In both conditions, novel sounds evoked a centrally distributed P3a-component followed by a P3b-component most prominent at parietal electrodes for target and novel sounds. Additionally, a slow negativity emerged after presentation of novel sounds at frontal electrodes. In the active condition only, peak amplitude of the P3a and the frontal slow negativity to novel stimuli were slightly enlarged for dyslexic readers. These findings indicate a larger distractability of dyslexic readers (enhancement of P3a to novel tones). Furthermore, we propose that dyslexics need to employ more cognitive resources to refocus on the task at hand (as indicated by the enlarged slow frontal negativity).

Excessive action monitoring in Tourette syndrome.

Tourette Syndrome (TS) has been related to hyperactive basal-ganglia thalamocortical pathways. This suggests that action monitoring might also be hyperactive. The present study used the event-related brain potential (ERP) technique to investigate this hypothesis. A simple "oddball" reaction time experiment was administered to a group of TS patients and a matched control group. In order to investigate variations in attentional allocation separate experimental runs were undertaken with target frequencies of 50% and 80%. The P3b component to targets was taken as an indicator of the target evaluation process and the response locked error-related negativity (ERN) served as an indicator of action monitoring. We hypothesized that the amplitudes of ERN and P3b would vary with respect to target frequency. The TS group would show an overall enhanced ERN but an unchanged P3b.ERN and P3b amplitudes were lower in the 80% target condition than in the 50% condition. In comparison with control subjects TS patients displayed an ERN of overall higher amplitude but with similar variations between target conditions. P3b amplitudes did not differ between groups. The data are interpreted to support the assumption of an abnormal action monitoring system in TS. A number of similarities to Obsessive-Compulsive Disorder are outlined and it is argued that the findings could be related to a hyperactive frontal-striatal-thalamic-frontal circuit.