Examining the neural impact of pediatric concussion: a scoping review of multimodal and integrative approaches using functional and structural MRI techniques.

PURPOSE OF REVIEW: This study presents the findings from a scoping review of recent, original research investigating changes in brain structure and/or function following pediatric concussion or mild traumatic brain injury (mTBI) using MRI and functional MRI techniques. RECENT FINDINGS: Our scoping review identified only five studies, two of which were focused specifically on sports-related concussion. A common finding across studies was that traditional structural methods such as anatomical T1, T2, and even susceptibility-weighted MRI failed to reveal abnormalities in brain structure following pediatric concussion/mTBI. Although data suggest alterations in brain function associated with concussion, correlation with changes in performance is inconsistently found, possibly because of the use of compensatory cerebral mechanisms or alternate pathways while the brain is still dysfunctional. SUMMARY: In conclusion, the literature describing neuroimaging investigations of pediatric concussion is too scarce to allow the formulation of definitive conclusions regarding the impact of concussion on the developing brain. There is a dire need for longitudinal, multisite investigations focused on a wider age range and recovery period.

Contributions of neuroimaging, balance testing, electrophysiology and blood markers to the assessment of sport-related concussion.

OBJECTIVE: To review the diagnostic tests and investigations used in the management of sports concussion, in the adult and paediatric populations, to (a) monitor the severity of symptoms and deficits, (b) track recovery and (c) advance knowledge relating to the natural history and neurobiology of the injury. DESIGN: Qualitative literature review of the neuroimaging, balance testing, electrophysiology, blood marker and concussion literature. INTERVENTION: PubMed and Medline databases were reviewed for investigations used in the management of adult and paediatric concussion, including structural imaging (computerised tomography, magnetic resonance imaging, diffusion tensor imaging), functional imaging (single photon emission computerised tomography, positron emission tomography, functional magnetic resonance imaging), spectroscopy (magnetic resonance spectroscopy, near infrared spectroscopy), balance testing (Balance Error Scoring System, Sensory Organization Test, gait testing, virtual reality), electrophysiological tests (electroencephalography, evoked potentials, event related potentials, magnetoencephalography, heart rate variability), genetics (apolipoprotein E4, channelopathies) and blood markers (S100, neuron-specific enolase, cleaved Tau protein, glutamate). RESULTS: For the adult and paediatric populations, each test has been classified as being: (1) clinically useful, (2) a research tool only or (3) not useful in sports-related concussion. CONCLUSIONS: The current status of the diagnostic tests and investigations is analysed, and potential directions for future research are provided. Currently, all tests and investigations, with the exception of clinical balance testing, remain experimental. There is accumulating research, however, that shows promise for the future clinical application of functional magnetic resonance imaging in sport concussion assessment and management.

Local morphology informs location of activation during navigation within the parahippocampal region of the human brain.

The relationship between the local morphological features that define the entorhinal and parahippocampal cortex in the medial temporal region of the human brain and activation as measured during a navigation task with functional magnetic resonance imaging was examined individually in healthy participants. Two functional activation clusters were identified one within the caudal end of the collateral sulcus proper and the other in the parahippocampal extension of the collateral sulcus, clearly establishing the activation in the posterior parahippocampal cortex. A third activation cluster was identified where the anterior segment of the collateral sulcus proper gives way to the posterior segment, demonstrating also activation within the middle parahippocampal cortex. No activation was observed in the entorhinal cortex that lies medial to the rhinal sulcus or in the anterior part of the parahippocampal cortex along the anterior branch of the collateral sulcus proper. The activations could also be clearly differentiated from the cortex of the fusiform and lingual gyri that lie laterally and posteriorly. These findings demonstrated specific activation in the middle and posterior part of the parahippocampal cortex when information necessary for navigation was retrieved from a previously established cognitive map and demonstrate that the sulci that comprise the collateral sulcal complex represent important landmarks that can provide an accurate localization of activation foci along the parahippocampal cortex and allow identification of subdivisions involved in the processing of spatial information.

Feedback and cognition in arm motor skill reacquisition after stroke.

BACKGROUND AND PURPOSE: A debated subject in stroke rehabilitation relates to the best type of training approach for motor recovery. First, we analyzed the effects of repetitive movement practice in 2 feedback conditions (knowledge of results [KR]; knowledge of performance, [KP]) on reacquisition of reaching. Second, we evaluated the impact of cognitive impairment on motor relearning ability. METHODS: A randomized controlled clinical trial was conducted in Montreal-area rehabilitation centers between 1998 and 2003 with 37 patients with chronic hemiparesis. Patients were randomly assigned to 3 groups: (1) KR (n=14) practiced a reaching task involving 75 repetitions per day, 5 days per week for 2 weeks, with 20% KR about movement precision; (2) KP (n=14) trained on the same task and schedule as KR but with faded KP about joint motions; and (3) control (C; n=9) practiced a nonreaching task. Physical (motor impairment, function) and kinematic (movement time, precision, segmentation, variability) variables were assessed before and after (immediately, 1 month) practice. Cognitive functions (memory, attention, mental flexibility, planning) were also evaluated. RESULTS: Kinematic gains in KR (precision) and KP (time, variability) exceeded those in C and depended on memory and mental flexibility deficits. In KP, more severely impaired patients made the most clinical gains (>2xC), which were related to memory and planning abilities. CONCLUSIONS: Use of KP during repetitive movement practice resulted in better motor outcomes. Stroke severity together with cognitive impairments are important factors for choosing motor rehabilitation interventions after stroke.

Tactile functions after cerebral hemispherectomy.

Patients that were hemispherectomized due to brain lesions early in life sometimes have remarkably well-preserved tactile functions on their paretic body half. This has been attributed to developmental neuroplasticity. However, the tactile examinations generally have been fairly crude, and subtle deficits may not have been revealed. We investigated monofilament detection and three types of tactile directional sensibility in four hemispherectomized patients and six healthy controls. Patients were examined bilaterally on the face, forearm and lower leg. Normal subjects were examined unilaterally. Following each test of directional sensibility, subjects were asked to rate the intensity of the stimulation. On the nonparetic side, results were almost always in the normal range. On the paretic side, the patients' capacity for monofilament detection was less impaired than their directional sensibility. Despite the disturbed directional sensibility on their paretic side the patients rated tactile sensations evoked by the stimuli, on both their paretic and nonparetic body halves, as more intense than normals. Thus, mechanisms of plasticity seem adequate for tactile detection and intensity coding but not for more complex tactile functions such as directional sensibility. The reason for the high vulnerability of tactile directional sensibility may be that it depends on spatially and temporally precise afferent information processed in a distributed cortical network.

Impaired stereoscopic detection thresholds after left or right temporal lobectomy.

The present study assessed global stereopsis as measured by random dot stereograms (RDS). Single stimuli were presented in order of increasing binocular correlation (40-100%) making it progressively easier to perceive the figures in depth, and then the same set of stimuli was presented in reverse order. The subjects tested included 50 patients with unilateral temporal-lobe lesions, 11 patients with right frontal-lobe lesions and 18 normal control subjects. Results indicate that either right or left temporal lobectomy leads to a higher than normal detection threshold for RDS. In contrast, right frontal lobectomy did not have a significant effect compared to the normal control subjects. All subjects were able to perceive correctly the figures at 100% binocular correlation. The results are interpreted in terms of a possible contribution of the inferior temporal cortex to global stereopsis.

Residual vision with awareness in the field contralateral to a partial or complete functional hemispherectomy.

Two patients with unilateral disconnection or removal of the entire occipital lobe were tested for residual vision in their blind field. Using image stabilization to eliminate eye motion artifacts, the central portion of each subject's visual field was tested, beginning 1 degree from fixation and extending outward to 13.5 degrees. A narrow zone of residual vision was identified along the retinal vertical meridian of each patient. The lateral edge of this zone was generally within 3.5 degrees of the vertical meridian, though extended farther outward (but not beyond 6 degrees) at one field location for each subject. In one patient, it was present in both superior and inferior quadrants; in the other, it was confined to the superior quadrant. Within their zones of residual vision, both patients could detect stimuli and perform simple shape discriminations, but could not name complex line drawings. The patients were aware of their vision within this zone. No residual vision, with or without awareness, was found in areas tested outside these zones. Given the complete absence of visual cortex contralateral to the observed residual vision, alternate structures must be mediating these abilities.

REM sleep dream mentation in right hemispherectomized patients.

Investigations of dream mentation in brain damaged patients have shed some light on the controversial issue of cerebral lateralization of dreaming. To examine further the relationships between brain function and dreaming, we studied REM sleep dream recall and content in four patients having undergone right functional or anatomical hemispherectomy and eight matched control subjects. Patients were found to have the capacity to report dreams to much the same extent as control subjects. Further, the patients' dream content was overall similar to that of the control subjects. The results provide strong evidence that dreaming is not a right-hemisphere function, and that the left hemisphere may be more critical for the generation of dreams. In addition, some characteristics of hemispherectomized patients' dream content (characters, smells) are consistent with the possibility that a history of epilepsy may influence REM sleep imagery over the long term.

'Seeing' in the blind hemifield following hemispherectomy.

Destruction of the striate cortex has traditionally been thought to lead to permanent blindness in the contralateral visual field and to the dogma that this region is indispensable for vision in primates. For over 25 years now, evidence has been accumulating that hemianopic human subjects and monkeys possess wide-ranging residual visual capacities or 'blindsight' in the blind part of their visual field. For some researchers, isolated islands of the striate cortex have been associated with patches of degraded vision and made responsible for blindisight. Artefacts such as light scatter, criterion effects, macular sparing, eccentric fixation and minute eye movements have also been linked with the residual vision. For others, the fact that certain aspects of the visual information can be processed without the geniculostriate pathway suggests mediation by the visual subsystems such as extrastriate visual cortical areas which receive visual information via subcortical pathways, that escaped the cortical damage. Subjects who have had a whole cerebral hemisphere removed or disconnected (for the treatment of uncontrollable epilepsy) and who show residual vision in their blind field offer a remarkable opportunity to help clear the controversy regarding the neural substrate of blindsight. Because it is certain that no functional striate or extrastriate cortex remains on the ablated side, these subjects have contributed significantly to identifying the critical pathways involved in blindsight.

Neural bases of residual vision in hemicorticectomized monkeys.

In this series of studies, we have attempted to characterize anatomically the organization of the retinofugal pathways in monkeys that underwent the surgical removal in infancy of the entire left cerebral hemisphere. Hemidecordication in baby monkeys produced a transneuronal retrograde degeneration of the retinal ganglion cells (RGCs) that affected mainly the foveal rim. Although the density of RGCs in this region was drastically diminished, the soma sizes of the surviving cells remained normal. The lateral geniculate nucleus (dLGN) ipsilateral to the removed cortex was dramatically reduced in size although it still showed normal layering. There was a marked reduction in the number of neurons in both the parvocellular and magnocellular layers and a heavy gliosis. By contrast, the superior colliculus ipsilateral to the lesion was remarkably well preserved: although slightly reduced in volume, it showed little gliosis and a metabolic activity, as revealed by cytochrome oxidase histochemistry, similar to the superior colliculus contralateral to the lesion. Behavioral perimetry indicated a partial sparing of vision up to 45 degrees in the 'blind' hemifield. We argue that the preservation of the retino-tectal pathway mediates most of the residual visual functions found in the 'blind field' of hemispherectomized human subjects.

Extrageniculostriate vision in humans: investigations with hemispherectomy patients.

Residual vision was assessed in the blind hemifield of one hemispherectomized and one partially hemispherectomized patient, using an interval two alternative forced choice detection task. Fixation instabilities were controlled by retinal stabilization. In both patients, residual vision was found in the hemianopic field close to the vertical meridian. This residual vision is largely confined to a band not wider the 3 degrees, but there is a local region in each patient where it extends more than 3 degrees from the meridian. However, more than 6 degrees from the vertical meridian we found no indication of residual function in either patient. Within the band of spared vision, subjects are aware of stimuli and can perform simple shape discriminations. Visual acuity profiles argue against an explanation based on eccentric fixation. Explanations based on the retino-tectal pathway or on retinal naso-temporal overlap are possible.

Temperature during cardiopulmonary bypass for coronary artery operations does not influence postoperative cognitive function: a prospective, randomized trial.

OBJECTIVE: The objective was to examine the effect of temperature (28 degrees vs 36 degrees C) during cardiopulmonary bypass on postoperative cognitive functions in a prospective, double-blind, and randomized manner. METHODS: Sixty-two patients scheduled for coronary operations were randomized to warm or cold cardiopulmonary bypass. Preoperative and postoperative (7 days) neuropsychologic evaluations were performed by an observer unaware of cardiopulmonary bypass temperature. RESULTS: Fifty-four patients completed the study (cold bypass, n = 24; warm bypass, n = 30). Significant (p < 0.01) postoperative deterioration for tests of psychomotor coordination and verbal memory was noted in both warm and cold groups, but no differences were observed between groups. CONCLUSION: Temperature during cardiopulmonary bypass for coronary operations does not influence postoperative cognitive function.

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 30 s, 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.

No blindsight following hemidecortication in human subjects?

Using a guessing paradigm we measured visual sensitivity in the blind and normal half-fields of four cerebrally hemidecorticated patients. In the blind field, sensitivity was reduced by approximately 3 long units. Stimuli which produced significant detection also evoked conscious sensations of light and colour. Control experiments showed that although sensitivity in the blind field depended in a normal fashion on background luminance it was independent of the luminance of a local platform, and showed no spatial summation. This residual vision can be explained by intraocular light diffusion and reflection.

Localization and lateralization of stereoscopic processing in the human brain.

Positron emission tomography was used to investigate the neural substrate of stereopsis. Changes in cerebral blood flow were measured in nine volunteers while they judged the orientation of a rectangular cyclopean shape in random dot stereograms. This experimental condition was compared with two control conditions, one having a two-dimensional shape but no cyclopean stimulus, the other having neither shape nor cyclopean stimulus. Blood flow increases were observed in areas 17 and 18 in the right hemisphere when comparing experimental with control conditions; blood flow decreases occurred in the right inferotemporal cortex. Results indicate that stereopsis begins in posterior visual areas in the right cerebral hemisphere. Under ambiguous stereoscopic conditions, participation of more anterior areas in the temporal lobe may be elicited.

Stereoscopic processing in the human brain as a function of binocular luminance rivalry.

We investigated the neural substrates of a recent model of human stereodepth perception by obtaining measurements of regional cerebral blood flow (rCBF) using PET. Subjects experienced the perceptual properties of stereopsis by viewing rival-luminance stereograms displaying an identical random-dot pattern in their central portion while the backgrounds exhibited correspondent dots contrasting in black/white luminance. The stereoscopic vision induced by retinal luminance rivalry coincided with a significant elevation of rCBF in the dorsal visual pathway. Area V5 (MT) was activated bilaterally by the experimental condition while the remaining active loci were restricted to the right hemisphere. The neural sites that responded to this novel stereoscopic stimulus are similar to those activated by traditional stereograms containing horizontal disparities.

Perception of motion-in-depth in patients with partial or complete cerebral hemispherectomy.

Four patients with functional hemispherectomy, one patient with a complete anatomical hemispherectomy, and one patient with unilateral removal of the temporal, parietal and occipital lobes took part in two sets of experiments designed to investigate their residual sensitivity to motion-in-depth in the hemianopic visual field. Two types of computer-generated visual displays were used; in the first set of experiments, a dot pattern and in the second, a circular checkerboard. These simulated either convergent, divergent or reversed rotational motion. Each set of experiments consisted of two parts; in the first part, electrodermal responses were monitored during stimulus presentation while the subjects performed a simple distracting task. In the second part, subjects were asked to state verbally the direction of stimulus motion. Contrary to expectations, no reliable changes in skin conductance were elicited from any of the subjects by changes in the direction of motion of the component parts of either the dot pattern display or the circular checkerboard display. Furthermore, none of the subjects were able to discriminate the direction of motion of the target patterns when presented in the hemianopic field. The most parsimonious explanation is that the subcortical visual pathways which survive hemispherectomy are unable to process visual information relating to motion in depth.

Central pain in a hemispherectomized patient.

We have examined a hemispherectomized patient who complained of touch-evoked pricking and burning pain in her paretic hand, especially when the hand was cold. Psychophysical examination showed that for the paretic side she confused cool and warm temperatures, and confirmed that she had a robust allodynia to brush stroking that was enhanced at a cold ambient temperature. Functional magnetic resonance imaging (fMRI) showed that during brush-evoked allodynia, brain structures implicated in normal pain processing (viz. posterior part of the anterior cingulate cortex, secondary somatosensory cortex, and prefrontal cortices) were activated. The fMRI findings thus indicate that the central pain in this patient was served by brain structures implicated in normal pain processing. Possible pathophysiological mechanisms include plasticity as well as thalamic disinhibition.

Sleep in right hemispherectomized patients: evidence of electrophysiological compensation.

OBJECTIVES: The goal of this study is to provide a better understanding of the role of the cortex in sleep's macro- and microstructure modulation. METHODS: Sleep architecture and phasic events were investigated in 4 patients having undergone right functional or anatomical hemispherectomy and 8 control subjects. Between-groups differences were assessed using the Wilcoxon-Mann-Whitney test. RESULTS: Findings provide evidence for overall similarity between patients' and control subjects' left hemispheric sleep architecture. In addition, results clearly indicate that it is possible to detect electrical activity over the operated side of a hemispherectomized patient's brain, even when resection of the hemi-cortex has been complete. Finally, findings provide evidence for similar left and right hemispheric relative spectral activities and for an increase in fast activity bands over the intact hemisphere in anatomical hemispherectomized patients. CONCLUSIONS: This study provides evidence that right hemispherectomy does not produce significant sleep architecture alterations as recorded over the intact hemisphere. In addition, residual activity detected over the operated side in anatomical hemispherectomized patients is interpreted as resulting from volume conduction originating from generators located in the intact hemisphere. Finally, there is strong evidence for electrophysiological compensation in the intact hemisphere following complete resection of the contralateral hemi-cortex.

Retained language in dysgenic cortex: case report.

Since the advent of magnetic resonance imaging, there has been renewed interest in disorders of cortical migration in the cause of focal epilepsy. The function of dysplastic cortex is poorly understood. We report a 46-year-old woman in whom this was assessed by intraoperative stimulation. This left-handed patient had a 30-year history of complex partial seizures with secondary generalization. Prolonged electroencephalographic recordings documented an epileptic focus in the right lateral and inferomesiotemporal lobe. Computed tomographic scanning and angiography suggested a right posterotemporal hamartoma. Amytal testing showed major speech representation in the right hemisphere. At craniotomy, an ivory-colored, posterotemporal lesion originating 5 cm from the temporal tip and 4 cm in diameter occupied the posterotemporal region. Electrical stimulation of this lesion produced speech interference. A histological examination of the resected anterotemporal lobe, amygdala, and hippocampus and biopsy specimens of the lesion showed extensive multifocal cortical microdysgenesis and gliovascular and cortical hamartoma. This case shows that grossly dysplastic cortex can remain functional. Cortical mapping under local anesthesia should be performed before resection of dysplastic lesions in putatively functional areas in patients with intractable epilepsy.