Jussi Tallus

Interaural intensity difference and ear advantage in listening to dichotic consonant-vowel syllable pairs

The right-ear advantage (REA) is typically observed in verbal dichotic listening, indicating a left hemisphere superiority for speech processing. The REA could be thought of as a bottom-up, stimulus-driven laterality effect, caused by the preponderance of the contralateral neural fibers from the right ear to the auditory/speech processing areas in the left temporal lobe. The REA can, however, be modified by explicitly requiring the listeners to focus their attention alternatively on the left or right-ear stimuli, thus either countering or enhancing the bottom-up processes through top-down attentional control. In the present study, we manipulated the strength of the bottom-up REA by inducing an intensity difference between the right-ear and left-ear speech inputs in order to make the REA either weaker (left-ear input>right-ear input) or stronger (left-ear input<right-ear input) and also examined how this manipulation affected the top-down attention modulation effects. Twenty healthy participants listened to dichotic presentations of consonant-vowel syllable pairs with different attention instructions. The results showed that the interaural intensity difference significantly affected the ear advantage in the predicted way. It also interacted with the top-down control effects, attentional control having a stronger effect when attending to the ear that had a weaker sound intensity, as compared to when the intensities were equal.

Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 as Outcome Predictors in Traumatic Brain Injury

OBJECTIVE Biomarkers ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) may help detect brain injury, assess its severity, and improve outcome prediction. This study aimed to evaluate the prognostic value of these biomarkers during the first days after brain injury. METHODS Serum UCH-L1 and GFAP were measured in 324 patients with traumatic brain injury (TBI) enrolled in a prospective study. The outcome was assessed using the Glasgow Outcome Scale (GOS) or the extended version, Glasgow Outcome Scale-Extended (GOSE). RESULTS Patients with full recovery had lower UCH-L1 concentrations on the second day and patients with favorable outcome had lower UCH-L1 concentrations during the first 2 days compared with patients with incomplete recovery and unfavorable outcome. Patients with full recovery and favorable outcome had significantly lower GFAP concentrations in the first 2 days than patients with incomplete recovery or unfavorable outcome. There was a strong negative correlation between outcome and UCH-L1 in the first 3 days and GFAP levels in the first 2 days. On arrival, both UCH-L1 and GFAP distinguished patients with GOS score 1-3 from patients with GOS score 4-5, but not patients with GOSE score 8 from patients with GOSE score 1-7. For UCH-L1 and GFAP to predict unfavorable outcome (GOS score ≤ 3), the area under the receiver operating characteristic curve was 0.727, and 0.723, respectively. Neither UCHL-1 nor GFAP was independently able to predict the outcome when age, worst Glasgow Coma Scale score, pupil reactivity, Injury Severity Score, and Marshall score were added into the multivariate logistic regression model. CONCLUSIONS GFAP and UCH-L1 are significantly associated with outcome, but they do not add predictive power to commonly used prognostic variables in a population of patients with TBI of varying severities.

Long-lasting TMS motor threshold elevation in mild traumatic brain injury

Tallus J, Lioumis P, Hämäläinen H, Kähkönen S, Tenovuo O. Long‐lasting TMS motor threshold elevation in mild traumatic brain injury. 
Acta Neurol Scand: 2012: 126: 178–182. 
© 2011 John Wiley & Sons A/S.

The Levels of Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 During the First Week After a Traumatic Brain Injury: Correlations With Clinical and Imaging Findings.

BACKGROUND Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are promising biomarkers of traumatic brain injury (TBI). OBJECTIVE We investigated the relation of the GFAP and UCH-L1 levels to the severity of TBI during the first week after injury. METHODS Plasma UCH-L1 and GFAP were measured from 324 consecutive patients with acute TBI and 81 control subject enrolled in a 2-center prospective study. The baseline measures included initial Glasgow Coma Scale (GCS), head computed tomographic (CT) scan at admission, and blood samples for protein biomarkers that were collected at admission and on days 1, 2, 3, and 7 after injury. RESULTS Plasma levels of GFAP and UCH-L1 during the first 2 days after the injury strongly correlated with the initial severity of TBI as assessed with GCS. Additionally, levels of UCH-L1 on the seventh day after the injury were significantly related to the admission GCS scores. At admission, both biomarkers were capable of distinguishing mass lesions from diffuse injuries in CT, and the area under the curve of the receiver-operating characteristic curve for prediction of any pathological finding in CT was 0.739 (95% confidence interval, 0.636-0.815) and 0.621 (95% confidence interval, 0.517-0.713) for GFAP and UCH-L1, respectively. CONCLUSION These results support the prior findings of the potential role of GFAP and UCH-L1 in acute-phase diagnostics of TBI. The novel finding is that levels of GFAP and UCH-L1 correlated with the initial severity of TBI during the first 2 days after the injury, thus enabling a window for TBI diagnostics with latency. ABBREVIATIONS AUC, area under the curveCI, confidence intervalED, emergency departmentGCS, Glasgow Coma ScaleGRAP, glial fibrillary acidic proteinIMPACT, International Mission for Prognosis and Clinical TrialROC, receiver-operating characteristicTBI, traumatic brain injuryTRACK-TBI, Transforming Research and Clinical Knowledge in Traumatic Brain InjuryUCH-L1, ubiquitin C-terminal hydrolase-L1.

Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n = 22), moderate (moTBI; n = 14) or mild TBI (mTBI; n = 108) according to Glasgow Coma Scale. The control group (n = 28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n = 23), moTBI (n = 7), mTBI (n = 37) patients and controls (n = 27). We show that two medium-chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC = 0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified ‘TBI metabotype’ in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new avenue for the development of diagnostic and prognostic markers of broad spectrum of TBIs.

Transcranial Magnetic Stimulation-Electroencephalography Responses in Recovered and Symptomatic Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) may cause diffuse damage to the brain, especially to the frontal areas, that may lead to persistent symptoms. We studied participants with past mTBI by means of navigated transcranial magnetic stimulation (nTMS) combined with electroencephalography (EEG). Eleven symptomatic and 8 recovered participants with a history of single mTBI and 9 healthy controls participated. Average time from injury to testing was 5 years. The participants did not have abnormalities or signs of injury on brain magnetic resonance imaging, and they did not use any centrally acting medication. Left primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) were stimulated with nTMS and evoked potentials measured from the corresponding areas of both hemispheres. Delayed ipsilateral P30 and contralateral N45 peak latencies to left DLPFC nTMS were found in the symptomatic group, along with higher DLPFC N100 amplitudes compared with the control or recovered group. The recovered group had shorter P200 latencies in left DLPFC nTMS compared with the other groups. Both mTBI groups had higher motor thresholds compared with the control group. In left M1 nTMS, the mTBI groups showed less P30 amplitude increase, and the symptomatic group showed longer P60 interhemispheric latency difference with higher stimulation intensities. The results suggest altered brain reactivity and connectivity in mTBI. Some of the observed differences may be related to compensatory mechanisms of recovery. nTMS-EEG is a potentially useful tool for studying the effects of mTBI.

Modulation of Auditory Attention by Training : Evidence From Dichotic Listening

We studied the effects of training on auditory attention in healthy adults with a speech perception task involving dichotically presented syllables. Training involved bottom-up manipulation (facilitating responses from the harder-to-report left ear through a decrease of right-ear stimulus intensity), top-down manipulation (focusing attention on the left-ear stimuli through instruction), or their combination. The results showed significant training-related effects for top-down training. These effects were evident as higher overall accuracy rates in the forced-left dichotic listening (DL) condition that sets demands on attentional control, as well as a response shift toward left-sided reports in the standard DL task. Moreover, a transfer effect was observed in an untrained auditory-spatial attention task involving bilateral stimulation where top-down training led to a relatively stronger focus on left-sided stimuli. Our results indicate that training of attentional control can modulate the allocation of attention in the auditory space in adults. Malleability of auditory attention in healthy adults raises the issue of potential training gains in individuals with attentional deficits.

Effects of Auditory Attention Training with the Dichotic Listening Task: Behavioural and Neurophysiological Evidence

Facilitation of general cognitive capacities such as executive functions through training has stirred considerable research interest during the last decade. Recently we demonstrated that training of auditory attention with forced attention dichotic listening not only facilitated that performance but also generalized to an untrained attentional task. In the present study, 13 participants underwent a 4-week dichotic listening training programme with instructions to report syllables presented to the left ear (FL training group). Another group (n = 13) was trained using the non-forced instruction, asked to report whichever syllable they heard the best (NF training group). The study aimed to replicate our previous behavioural results, and to explore the neurophysiological correlates of training through event-related brain potentials (ERPs). We partially replicated our previous behavioural training effects, as the FL training group tended to show more allocation of auditory spatial attention to the left ear in a standard dichotic listening task. ERP measures showed diminished N1 and enhanced P2 responses to dichotic stimuli after training in both groups, interpreted as improvement in early perceptual processing of the stimuli. Additionally, enhanced anterior N2 amplitudes were found after training, with relatively larger changes in the FL training group in the forced-left condition, suggesting improved top-down control on the trained task. These results show that top-down cognitive training can modulate the left-right allocation of auditory spatial attention, accompanied by a change in an evoked brain potential related to cognitive control.

High angular resolution diffusion-weighted imaging in mild traumatic brain injury

We sought to investigate white matter abnormalities in mild traumatic brain injury (mTBI) using diffusion-weighted magnetic resonance imaging (DW-MRI). We applied a global approach based on tract-based spatial statistics skeleton as well as constrained spherical deconvolution tractography. DW-MRI was performed on 102 patients with mTBI within two months post-injury and 30 control subjects. A robust global approach considering only the voxels with a single-fiber configuration was used in addition to global analysis of the tract skeleton and probabilistic whole-brain tractography. In addition, we assessed whether the microstructural parameters correlated with age, time from injury, patients outcome and white matter MRI hyperintensities. We found that whole-brain global approach restricted to single-fiber voxels showed significantly decreased fractional anisotropy (FA) (p = 0.002) and increased radial diffusivity (p = 0.011) in patients with mTBI compared with controls. The results restricted to single-fiber voxels were more significant and reproducible than those with the complete tract skeleton or the whole-brain tractography. FA correlated with patient outcomes, white matter hyperintensities and age. No correlation was observed between FA and time of scan post-injury. In conclusion, the global approach could be a promising imaging biomarker to detect white matter abnormalities following traumatic brain injury.

Regional brain morphometry in patients with traumatic brain injury based on acute- and chronic-phase magnetic resonance imaging

Traumatic brain injury (TBI) is caused by a sudden external force and can be very heterogeneous in its manifestation. In this work, we analyse T1-weighted magnetic resonance (MR) brain images that were prospectively acquired from patients who sustained mild to severe TBI. We investigate the potential of a recently proposed automatic segmentation method to support the outcome prediction of TBI. Specifically, we extract meaningful cross-sectional and longitudinal measurements from acute- and chronic-phase MR images. We calculate regional volume and asymmetry features at the acute/subacute stage of the injury (median: 19 days after injury), to predict the disability outcome of 67 patients at the chronic disease stage (median: 229 days after injury). Our results indicate that small structural volumes in the acute stage (e.g. of the hippocampus, accumbens, amygdala) can be strong predictors for unfavourable disease outcome. Further, group differences in atrophy are investigated. We find that patients with unfavourable outcome show increased atrophy. Among patients with severe disability outcome we observed a significantly higher mean reduction of cerebral white matter (3.1%) as compared to patients with low disability outcome (0.7%).