Alain Ptito

Neural Substrates of Symptoms of Depression Following Concussion in Male Athletes With Persisting Postconcussion Symptoms

CONTEXTnDepressed mood is frequently reported by individuals who have sustained cerebral concussion but little is known about the nature of this alteration in mood state.nnnOBJECTIVEnTo investigate whether the symptoms of depression reflect an ongoing pathophysiological change following concussion.nnnDESIGNnCohort study with male athletes using functional and structural neuroimaging.nnnSETTINGnHospital laboratory and imaging facility.nnnPARTICIPANTSnFifty-six male athletes with and without concussion were divided into (1) a no depression symptom, concussed group, (2) a mild depression symptom, concussed group, (3) a moderate depression symptom, concussed group, and (4) a healthy control group.nnnINTERVENTIONSnAll athletes filled out a postconcussive symptoms checklist and the Beck Depression Inventory II and underwent a magnetic resonance imaging session, which included T1, T2, and fluid-attenuated inversion recovery sequences, as well as functional magnetic resonance imaging (fMRI), during which they performed a working memory task.nnnMAIN OUTCOME MEASURESn(1) Behavioral: response speed and accuracy on the working memory task performed during the fMRI session; (2) functional imaging: brain activation patterns associated with the working memory task obtained using blood oxygen level-dependent fMRI; and (3) structural imaging: voxel-based morphometry examining gray matter concentration.nnnRESULTSn(1) Behavioral: there was no performance difference between the groups; and (2) imaging: athletes with concussion with depression symptoms showed reduced activation in the dorsolateral prefrontal cortex and striatum and attenuated deactivation in medial frontal and temporal regions. The severity of symptoms of depression correlated with neural responses in brain areas that are implicated in major depression. Voxel-based morphometry confirmed gray matter loss in these areas.nnnCONCLUSIONSnThe results suggest that depressed mood following a concussion may reflect an underlying pathophysiology consistent with a limbic-frontal model of depression. Given that depression is associated with considerable functional disability, this finding has important clinical implications for the management of individuals with a cerebral concussion.

A validation of the post concussion symptom scale in the assessment of complex concussion using cognitive testing and functional MRI

Background: Clinical assessment of cerebral concussion relies on the presence and duration of post concussive symptoms (PCS). Given that these PCS are subjective reports and not always specific to concussion, their usefulness remains to be validated. Objective: To evaluate the usefulness of self-reported PCS by means of cognitive tests and functional MRI (fMRI). Method: 28 male athletes with and without concussion were grouped according to their PCS score. They were then administered a computerised cognitive test battery and submitted to an fMRI session where cerebral activations associated with verbal and non-verbal working memory tasks were analysed. Results: Behaviourally, response accuracy and speed on the cognitive test battery were comparable for the control and low PCS group. The moderate PCS group showed significantly slower response times than the control group on the matching (p<0.05) and one-back tasks (p<0.05). The functional MRI study showed reduced task related activation patterns in the dorsolateral prefrontal cortex for both low and moderate PCS groups. Activation peaks outside the regions of interest, not seen in the control group, were also noted for both PCS groups. Regression analyses indicated an inverse relationship between PCS scores and performances on several CogSport subtests. Severity of PCS also predicted fMRI blood oxygen level dependent signal changes in cerebral prefrontal regions. Conclusion: Self-reported PCS is associated with an ongoing cerebral haemodynamic abnormality as well as with mild cognitive impairment. These results support the use of the PCS scale in the assessment of cerebral concussion and in monitoring recovery.

New Frontiers in Diagnostic Imaging in Concussive Head Injury

Concussed athletes may have documented incapacitating postconcussive symptoms, neuropsychological deficits, and consequent important changes in their lives and sport, yet the majority of neuroimaging attempts reveal few findings to account for these signs and symptoms. In this paper, we explore new techniques in the neuroimaging of concussion including diffusion-weighted magnetic resonance imaging and functional brain imaging technology.

Electrophysiology and Functional MRI in Post-Acute Mild Traumatic Brain Injury

Symptoms persisting beyond the acute phase (>2 months) after a mild traumatic brain injury (MTBI) are often reported, but their origin remains controversial. Some investigators evoke dysfunctional cerebral mechanisms, while others ascribe them to the psychological consequences of the injury. We address this controversy by exploring possible cerebral dysfunction with functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) in a group of patients during the post-acute phase. Fourteen MTBI symptomatic patients (5.7±2.9 months post-injury) were tested with fMRI and ERP using a visual externally ordered working memory task, and were compared with 23 control subjects. Attenuated blood oxygen level dependent (BOLD) signal changes in the left and right mid-dorsolateral prefrontal cortex (mid-DLPFC), the putamen, the body of the caudate nucleus, and the right thalamus were found in the MTBI group compared with the control group. Moreover, symptom severity and BOLD signal changes were correlated: patients with more severe symptoms had lower BOLD signal changes in the right mid-DLPFC. For ERP, a group×task interaction was observed for N350 amplitude. A larger amplitude for the working memory task than for the control task was found in control subjects, but not in MTBI subjects, who had weak amplitudes for both tasks. This study confirms that persistent symptoms after MTBI cannot be uniquely explained by psychological factors, such as depression and/or malingering, and indicates that they can be associated with cerebral dysfunction. ERP reveals decreased amplitude of the N350 component, while fMRI demonstrates that the more severe the symptoms, the lower the BOLD signal changes in the mid-DLPFC.

Effect of mild cognitive impairment on the patterns of neural activity in early Parkinson's disease

We have previously observed decreased activation of corticostriatal loops involved in planning (cognitive loop) and execution (motor loop) of a set shift in patients with early Parkinsons disease (PD) compared with control subjects. Here, we aimed to assess whether cognitive impairment in PD could drive these differences. Nondemented patients underwent a comprehensive neuropsychological evaluation and participated in our Wisconsin Card Sorting task functional magnetic resonance imaging protocol. Patients were separated into 2 groups according to the presence of mild cognitive impairment (MCI). Patients with MCI displayed reduced activity in the cognitive corticostriatal loop, which includes the caudate nucleus and prefrontal cortex while planning a set shift, whereas non-MCI patients exhibited activation patterns similar to those of healthy participants from our previous studies. Furthermore, reduced activation was observed in the premotor cortex of the MCI patients. Finally, hippocampal activity, correlated with individual memory scores, suggesting a compensatory mechanism in patients with preserved memory. These results suggest that the presence of MCI in PD affects activity in the prefrontal cortex and caudate nucleus as well as motor-related regions.

A Functional Magnetic Resonance Imaging Study of Working Memory in Youth after Sports-Related Concussion: Is It Still Working?

Abstract In children, the importance of detecting deficits after mild traumatic brain injury (mTBI) or concussion has grown with the increasing popularity of leisure physical activities and contact sports. Whereas most postconcussive symptoms (PCS) are similar for children and adults, the breadth of consequences to children remains largely unknown. To investigate the effect of mTBI on brain function, we compared working memory performance and related brain activity using blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 15 concussed youths and 15 healthy age-matched control subjects. Neuropsychological tests, self-perceived PCS, and levels of anxiety and depression were also assessed. Our results showed that, behaviorally, concussed youths had significantly worse performances on the working memory tasks, as well as on the Rey figure delayed recall and verbal fluency. fMRI results revealed that, compared to healthy children, concussed youths had significantly reduced task-related activity in bilateral dorsolateral prefrontal cortex, left premotor cortex, supplementary motor area, and left superior parietal lobule during performance of verbal and nonverbal working memory tasks. Additionally, concussed youths also showed less activation than healthy controls in the dorsal anterior cingulate cortex, left thalamus, and left caudate nucleus during the nonverbal task. Regression analysis indicated that BOLD signal changes in bilateral dorsolateral prefrontal cortex were significantly correlated with performance such that greater activities in these regions, relative to the control condition, were associated with greater accuracy. Our findings confirmed functional alterations in brain activity after concussion in youths, a result similar to that observed in adults. However, significant differences were noted. In particular, the observation of reduced working memory accuracy suggests that youths may be unable to engage compensatory strategies to maintain cognitive performance after mTBI. This has significant implications for safe return to daily activities, including competitive sport.

Visual-spatial localization by patients with frontal-lobe lesions invading or sparing area 46

Monkeys with unilateral principal sulcus (PS) lesions show a contralateral deficit in localizing remembered targets, especially as the recall interval is lengthened. We tested 20 patients with unilateral frontal-lobe excisions that invaded (FI) or spared (FS) area 46 (putative homologue of PS) and 32 normal controls (NC) on a task where subjects had to indicate the location of a light dot either immediately, or after 30s, with or without interference. The FI group was worse than the NC group following both delay conditions. NC and FS groups differed only after interference. We concluded that area 46 is involved in recalling the location of visual targets, but unlike the monkey, the deficit is not restricted to a particular part of the visual field.

Cortical areas mediating stereopsis in the human brain: a PET study

Using PET, we investigated the neural substrates of stereodepth perception in humans. The presentation of Julesz-type random-dot stereograms (RDS) produced significant rCBF elevations in Brodmann areas (BA) 18, 19 and 7, all in the right hemisphere. Activation foci were also found in both middle temporal areas (MT). These results demonstrate that, as in primates, cortical area MT and extrastriate areas are central to stereovision and that a network of predominant right hemispheric regions is recruited to meet visuo-spatial processing demands associated with horizontal binocular disparity inputs.

Evaluating the cognitive consequences of mild traumatic brain injury and concussion by using electrophysiology

OBJECTnMild traumatic brain injury (MTBI), often referred to as concussion when it occurs in sports, produces persistent cognitive problems in at least 15% of patients. Unfortunately, conventional neuropsychological tests usually yield results within normal limits in this population. The main objective of this event-related potential (ERP) study was to understand brain functioning during the performance of a working memory (WM) task in patients who have sustained an MTBI, mostly due to motor vehicle accident or sports concussion. This study also aimed for a better understanding of the association between brain functioning as measured with ERP, behavioral performance on the WM task, postconcussion symptoms, type of injury (that is, sports concussion vs other types), and time since the injury.nnnMETHODSnForty-four patients with MTBI (7.6 ± 8.4 months postinjury) were tested on a visual WM task with simultaneous recording of ERP, and were compared with 40 control volunteers who were their equivalent for age and sex. Amplitude and latency of frontal (N200 and N350) and parietal (P200 and P300) ERP waves were measured and were compared between groups. Correlation analyses were also performed between ERP characteristics, clinical variables, and behavioral performance.nnnRESULTSnA significant group difference was found for behavioral performance on the WM task, in which the MTBI group had a lower percentage of correct answers than the control group (p < 0.05). The patients with MTBI also had smaller amplitudes of both frontal N350 and parietal P300 ERP components when compared with control volunteers (p < 0.05). No changes were found for latency of ERP components. Smaller ERP amplitudes were associated with slower reaction times and worse accuracy on the WM task among patients with MTBI (p < 0.05). Types of injury (that is, sports concussion vs other mechanisms) were not associated with different ERP characteristics.nnnCONCLUSIONSnAbnormal ERP results are observed in patients after MTBI or sports concussion, even for those in the nonacute stage after their injury. Current standard clinical evaluations most often fail to detect cerebral dysfunction after MTBI, even when patients or athletes report symptoms. Clinicians should be aware that patients with MTBI, including sports concussion, probably have underlying mild but persistent cerebral dysfunctions that require further investigation.

Role of advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion: a systematic review

Objective To conduct a systematic review of published literature on advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion (SRC). Data sources Computerised searches of Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Scopus and Cochrane Library from 1 January 2000 to 31 December 2016 were done. There were 3222 articles identified. Study selection In addition to medical subject heading terms, a study was included if (1) published in English, (2) represented original research, (3) involved human research, (4) pertained to SRC and (5) involved data from neuroimaging, fluid biomarkers or genetic testing collected within 6 months of injury. Ninety-eight studies qualified for review (76 neuroimaging, 16 biomarkers and 6 genetic testing). Data extraction Separate reviews were conducted for neuroimaging, biomarkers and genetic testing. A standardised data extraction tool was used to document study design, population, tests employed and key findings. Reviewers used a modified quality assessment of studies of diagnostic accuracy studies (QUADAS-2) tool to rate the risk of bias, and a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to rate the overall level of evidence for each search. Data synthesis Results from the three respective reviews are compiled in separate tables and an interpretive summary of the findings is provided. Conclusions Advanced neuroimaging, fluid biomarkers and genetic testing are important research tools, but require further validation to determine their ultimate clinical utility in the evaluation of SRC. Future research efforts should address current gaps that limit clinical translation. Ultimately, research on neurobiological and genetic aspects of SRC is predicted to have major translational significance to evidence-based approaches to clinical management of SRC, much like applied clinical research has had over the past 20 years.