Subjective Cognitive Complaints in Concussion.

Studies of symptoms after concussion have been focused heavily on athletic and military populations; generalizability to "civilians" has not recently been demonstrated. We selected cognitive symptoms as an important target to assess because of impact on school and employment. We evaluated cognitive complaints in a highly symptomatic (Rivermead Post-Concussion Symptoms Questionnaire [PCSQ], mean [M] = 29.5) civilian sample (n = 100; age: M = 41.4; 36 male/64 female; days post-injury: range 14-154, M = 51.4) of consecutive referrals to a concussion specialty clinic. The Behavior Rating of Executive Functions-Adult version (BRIEF-A) was used to assess subjective cognitive symptoms. Independent variables were prior neurologic and psychiatric history, current neurological symptoms, objective neuropsychological tests and several measures of depression (Beck Depression Inventory, Second Edition [BDI2]), anxiety (Beck Anxiety Inventory), and stress (Post-Traumatic Stress Checklist-Civilian form). No demographic characteristic, injury measure, or past or current neurological history had any association with cognitive symptoms. Prior psychiatric history (57% of patients) was associated with abnormal BRIEF-A. Cognitive tests were overall in the average range, with only mild and sporadic associations with BRIEF-A elevations. All psychological measures showed significant associations with BRIEF-A elevations. Regression analyses for the BRIEF-A revealed depression was the significant contributor (BDI2, ß = 0.73) with prior psychiatric history (ß = 0.16) and age (ß = 0.14) accounting to a lesser extent. In this civilian cohort, subjective cognitive symptoms appear to be due to psychological distress (in particular, depression) and prior psychiatric history more than actual cognitive impairment or other presenting symptoms. These findings illuminate the importance of early diagnosis and treatment of mood/emotional symptoms after injury.

The effect of focal cortical frontal and posterior lesions on recollection and familiarity in recognition memory.

Recognition memory can be subdivided into two processes: recollection (a contextually rich memory) and familiarity (a sense that an item is old). The brain network supporting recognition encompasses frontal, parietal and medial temporal regions. Which specific regions within the frontal lobe are critical for recollection vs. familiarity, however, are unknown; past studies of focal lesion patients have yielded conflicting results. We examined patients with focal lesions confined to medial polar (MP), right dorsal frontal (RDF), right frontotemporal (RFT), left dorsal frontal (LDF), temporal, and parietal regions and matched controls. A series of words and their humorous definitions were presented either auditorily or visually to all participants. Recall, recognition, and source memory were tested at 30 min and 24 h delay, along with "remember/know" judgments for recognized items. The MP, RDF, temporal and parietal groups were impaired on subjectively reported recollection; their intact recognition performance was supported by familiarity. None of the groups were impaired on cued recall, recognition familiarity or source memory. These findings suggest that the MP and RDF regions, along with parietal and temporal regions, are necessary for subjectively-reported recollection, while the LDF and right frontal ventral regions, as those affected in the RTF group, are not.

Independent, Community-Based Aerobic Exercise Training for People With Moderate-to-Severe Traumatic Brain Injury.

OBJECTIVE: To determine whether people with moderate-to-severe traumatic brain injury (TBI) can adhere to a minimally supervised, community-based, vigorous aerobic exercise program. DESIGN: Prospective trial. SETTING: Young Men's Christian Association (YMCA) facilities. PARTICIPANTS: Community-dwelling volunteers (N=10; 8 men, 2 women; age range, 22-49y) 6 to 15 months after moderate-to-severe TBI. INTERVENTION: Participants received memberships to local YMCAs and brief orientations to exercise. They were then asked to independently complete ≥12 weeks of ≥3 training sessions per week, performed at 65% to 85% of maximum heart rate for ≥30 minutes per session. Participants could self-select exercise modality, provided they met intensity and duration targets. Programmable heart rate monitors captured session intensity and duration. MAIN OUTCOME MEASURES: Independence with equipment and facility use and compliance with training goals (session frequency, duration, intensity, total weeks of training). RESULTS: All participants achieved independence with equipment and facility use. All met at least 2 of 4 training goals; half met all 4 goals. Participants averaged (±SD) 3.3±0.7 sessions per week for 13 weeks (range, 6-24). Average ± SD session duration was 62±23 minutes, of which 51±22 minutes occurred at or above individuals' heart rate training targets. CONCLUSIONS: People in recovery from moderate-to-severe TBI can, with minimal guidance, perform vigorous, community-based exercise. This suggests that decentralized exercise may be logistically and economically sustainable after TBI, expanding its potential therapeutic utility and rendering longer-duration exercise studies more feasible.

Mild traumatic brain injury.

Mild traumatic brain injury (TBI) is common but accurate diagnosis and defining criteria for mild TBI and its clinical consequences have been problematic. Mild TBI causes transient neurophysiologic brain dysfunction, sometimes with structural axonal and neuronal damage. Biomarkers, such as newer imaging technologies and protein markers, are promising indicators of brain injury but are not ready for clinical use. Diagnosis relies on clinical criteria regarding depth and duration of impaired consciousness and amnesia. These criteria are particularly difficult to confirm at the least severe end of the mild TBI continuum, especially when relying on subjective, retrospective accounts. The postconcussive syndrome is a controversial concept because of varying criteria, inconsistent symptom clusters and the evidence that similar symptom profiles occur with other disorders, and even in a proportion of healthy individuals. The clinical consequences of mild TBI can be conceptualized as two multidimensional disorders: (1) a constellation of acute symptoms that might be termed early phase post-traumatic disorder (e.g., headache, dizziness, imbalance, fatigue, sleep disruption, impaired cognition), that typically resolve in days to weeks and are largely related to brain trauma and concomitant injuries; (2) a later set of symptoms, a late phase post-traumatic disorder, evolving out of the early phase in a minority of patients, with a more prolonged (months to years), sometimes worsening set of somatic, emotional, and cognitive symptoms. The later phase disorder is highly influenced by a variety of psychosocial factors and has little specificity for brain injury, although a history of multiple concussions seems to increase the risk of more severe and longer duration symptoms. Effective early phase management may prevent or limit the later phase disorder and should include education about symptoms and expectations for recovery, as well as recommendations for activity modifications. Later phase treatment should be informed by thoughtful differential diagnosis and the multiplicity of premorbid and comorbid conditions that may influence symptoms. Treatment should incorporate a hierarchical, sequential approach to symptom management, prioritizing problems with significant functional impact and effective, available interventions (e.g., headache, depression, anxiety, insomnia, vertigo).

Recovery, long-term cognitive outcome and quality of life following out-of-hospital cardiac arrest.

OBJECTIVE: Among survivors of out-of-hospital cardiac arrest (OHCA), the functional outcomes of those with rapid early or with very delayed recoveries are known. For patients between those extremes early recovery is variable, and the probability of longer-term recovery and the implications for quality of life have not been clearly defined. METHODS: Twenty-five patients of a consecutive cohort of OHCA survivors with coma duration between 12 h and 7 days and a matched group with acute coronary syndrome underwent cognitive and disability assessments 3 and 12 months after OHCA. Correlations and regression analyses of demographic, clinical arrest variables, and cognitive tests with quality of life outcomes were performed. RESULTS: The OHCA group had impairments in all cognitive domains. There was little cognitive improvement. The OHCA group reported significantly greater health impact and lower quality of life at twelve months than the controls. Longer duration of coma (4-7 versus ≤ 3 days) and greater cognitive impairment at three months, particularly memory impairment, were both associated with reduced late quality of life. CONCLUSIONS: These survivors of OHCA had persistent long-term cognitive deficits. Quality of life at one year after OHCA was reduced compared to cardiac controls. Coma duration and memory impairment at three months were harbingers of long term reduced quality of life.

Cognitive impairments due to focal cerebellar injuries in adults.

INTRODUCTION: It has been asserted that damage to the cerebellum produces a specific pattern of cognitive deficits, but clinical studies have had ambiguous results. There remains particular uncertainty about the effects of focal cerebellar injuries on cognition in adults. Clinical reports and anatomical connectivity studies have suggested a possible functional convergence of frontal lobes and cerebellum. This investigation was designed to assess whether focal cerebellar injuries in adults would cause impairment on tasks previously demonstrated to be sensitive to prefrontal lesions. METHOD: We investigated this question in 32 adults with either stroke or resection of benign tumours and 36 healthy control subjects. Patients underwent standard and experimental cognitive testing and an assessment of general health and well-being at least 3 months post onset. RESULTS: The group with right cerebellar lesions had lower performance on some tests of response control and verbal fluency than the controls and also the patients with left cerebellar lesions. On most tests, including most of the experimental tests sensitive to prefrontal lesions, the patients had no significant difference from the controls. The patient groups reported no health or functional decline. CONCLUSIONS: These results and the bulk of the clinical literature suggest that damage to some cerebellar sites may have specific cognitive consequences, but the cognitive impairment after focal cerebellar injury in adults is mild or transient. After the acute epoch, demonstration of deficits may require more demanding probes of specific domains of cognition.

Cognitive and functional outcome after out of hospital cardiac arrest.

The nature of residual cognitive deficits after out of hospital cardiac arrest (OHCA) is incompletely described and has never been defined against a cardiac control (CC) group. The objective of this study is to examine neuropsychological outcomes 3 months after OHCA in patients in a "middle range" of acute severity. Thirty prospective OHCA admissions with coma >1 day and responsive but confused at 1 week, and 30 non-OHCA coronary care admissions were administered standard tests in five cognitive domains. OHCA subjects fell into two deficit profiles. One group (N = 20) had mild memory deficits and borderline psychomotor deficits compared to the CC group; 40% had returned to work. The other group (N = 10) had severe impairments in all domains. Coma duration was associated with group. Neither group had a high prevalence of depression. For most patients within the "middle range" of acute severity of OHCA, cognitive and functional outcomes at 3 months were encouraging.

Lateralized cerebellar contributions to word generation: a phonemic and semantic fluency study.

Impairment on verbal fluency tasks has been one of the more consistently reported neuropsychological findings after cerebellar lesions, but it has not been uniformly observed and the possible underlying cognitive basis has not been investigated. We tested twenty-two patients with chronic, unilateral cerebellar lesions (12 Left, 10 Right) and thirty controls on phonemic and semantic fluency tasks. We measured total words produced, words produced in the initial 15 seconds, errors and strategy switches. In the phonemic fluency task, the right cerebellar lesion (RC) group produced significantly fewer words compared to the left cerebellar lesion (LC) group and healthy controls, particularly over the first 15 seconds of the task with no increase in errors and significantly fewer switches over the entire task. In the semantic fluency task there was only a modest decrease in total words in the RC group compared to controls. RC lesions impair fluency with many of the same performance characteristics as left prefrontal lesions. This supports the hypotheses of a prefrontal-lateral cerebellar system for modulation of attention/executive or strategy demanding tasks.

Lesion load of the corticospinal tract predicts motor impairment in chronic stroke.

BACKGROUND AND PURPOSE: Previous studies have shown motor impairment after a stroke relates to lesion size and location, but unexplained variability in recovery still exists. In this study, we used lesion-mapping techniques in combination with diffusion tensor imaging to quantitatively test the hypothesis that motor recovery in patients with chronic stroke is inversely related to the proportion of the corticospinal tract (CST) affected by the lesion. METHODS: We studied 50 patients with chronic stroke, all of whom presented with moderate to severe motor impairments in the acute stage, using high-resolution anatomic MRI. We evaluated the degree of motor impairment with the Upper Extremity module of the Fugl-Meyer Assessment. To analyze the relationship between CST damage and impairment scores, we calculated a CST-lesion load for each patient by overlaying the patient's lesion map with a probabilistic tract derived from diffusion tensor images of age-matched healthy subjects. RESULTS: CST-lesion load was a significant predictor of motor deficit. Infarct size, despite correlating with motor scores, did not significantly predict impairment. CONCLUSIONS: Our results show the degree of functional motor deficit after a stroke is highly dependent on the overlap of the lesion with the CST and not lesion size per se. In the future, automated calculation of CST-lesion load may allow more precise prediction of motor impairment after stroke.

Stroke and episodic memory disorders.

Memory impairments are common after stroke, and the anatomical basis for impairments may be quite variable. To determine the range of stroke-related memory impairment, we identified all case reports and group studies through the Medline database and the Science Citation Index. There is no hypothesis about memory that is unique to stroke, but there are several important facets of memory impairment after stroke: (1) Every node of the limbic system implicated in memory may be damaged by stroke but very rarely in isolation and the combination of amnesia with the associated deficits often illuminates additional aspects of memory functions. (2) Stroke produces amnesia by damage to critical convergence white matter connections of the limbic system, and stroke is the only etiology of amnesia that can delineate the entire pathway of memory and critical convergence points. (3) Stroke also impairs memory, without causing classical amnesia, by damaging brain regions responsible for cognitive processes, some modality specific and some more generally strategic, that are essential for normal learning and recall.

FMRI evidence of a functional network setting the criteria for withholding a response.

That the left prefrontal cortex has a critical role setting response criteria for numerous tasks has been well established, but gaps remain in our understanding of the brain mechanisms of task-setting. We aimed at (i) testing the involvement of this region in setting the criteria for a non-response and (ii) assessing functional connectivity between this and other brain regions involved in task-setting. Fourteen young participants performed a go/nogo task during functional magnetic resonance imaging. The task included two nogo visual stimuli which elicit a high (distractor) or a low (other) tendency to respond, respectively. Two task blocks were examined to assess learning the criteria. First, a multivariate Partial Least Squares (PLS) analysis identified brain regions that co-varied with task conditions, as expressed by two significant Latent Variables (LVs). One LV distinguished go and nogo stimuli. The other LV identified regions involved in the first block when the criteria not to respond to distractors were established. The left prefrontal region was prominently involved. Second, a left ventrolateral prefrontal area was selected from this LV as a seed region to perform functional connectivity using a multi-block PLS analysis. Results showed a distributed network functionally connected with the seed, including superior medial prefrontal and left superior parietal regions. These findings extend our understanding of task-setting along the following dimensions: 1) even when a task requires withholding a response, the left prefrontal cortex has a critical role in setting criteria, and 2) this region responds to the task demands within a distinctive functional network.

Contribution of prior semantic knowledge to new episodic learning in amnesia.

We evaluated whether prior semantic knowledge would enhance episodic learning in amnesia. Subjects studied prices that are either congruent or incongruent with prior price knowledge for grocery and household items and then performed a forced-choice recognition test for the studied prices. Consistent with a previous report, healthy controls' performance was enhanced by price knowledge congruency; however, only a subset of amnesic patients experienced the same benefit. Whereas patients with relatively intact semantic systems, as measured by an anatomical measure (i.e., lesion involvement of anterior and lateral temporal lobes), experienced a significant congruency benefit, patients with compromised semantic systems did not experience a congruency benefit. Our findings suggest that when prior knowledge structures are intact, they can support acquisition of new episodic information by providing frameworks into which such information can be incorporated.

Impaired list learning is not a general property of frontal lesions.

BACKGROUND: List-learning tasks are frequently used to provide measures of "executive functions" that are believed necessary for successful memory performance. Small sample sizes, confounding anomia, and incomplete representation of all frontal regions have prevented consistent demonstration of distinct regional frontal effects on this task. OBJECTIVE: To confirm specific effects of lesions in different frontal regions. SUBJECTS: Forty-one patients with chronic focal frontal lesions and 38 control subjects. There were no group differences in naming scores. METHODS: Two word lists were presented, one with unblocked words from related categories and one in a preblocked format. Standard measures of learning, recall, recognition, and strategies were obtained, first for the frontal group as a whole and then for large but defined frontal regions. For all measures with significant group differences, a lesion "hotspotting" method identified possible specific regional injury effects. RESULTS: The frontal group was impaired on almost all measures, but impairments on most measures were particularly identified with lesions in the left superior frontal lobe (approximately area 9s) and some deficits in learning processes were surprisingly more prominent on the blocked list. CONCLUSION: Difficulty with list learning is not a general property of all frontal lesions. Lesions in different frontal regions impair list learning through specific mechanisms, and these effects may be modified by manipulations of the task structure.

Mapping task switching in frontal cortex through neuropsychological group studies.

This paper considers evidence provided by large neuropsychological group studies and meta-analyses of functional imaging experiments on the location in frontal cortex of the subprocesses involved in the carrying out of task-switching paradigms. The function of the individual subprocesses is also considered in the light of analyses of the performance of normal subjects.

The multiple dimensions of sustained attention.

Sustained counting (or temporal numerosity judgements) has been one of the key means of investigating anterior attentional processes. Forty-three patients with localised lesions to the frontal lobes were assessed on two tests of the ability to count the number (8-22) of stimuli presented at either a slow (roughly one per 3 sec) or fast (roughly three per sec) rate. Patients with lesions to the Superior Medial (SM) region (particularly Brodmann areas 24, 32, and 9) were impaired both in the Slow condition and also in the Fast condition, where they underestimated the number of stimuli. Patients with Right Lateral (RL) lesions (8, 45, and 46) also had difficulties in the Fast condition, especially when the number of targets was greater than 15. The results are considered from the perspectives of alternative positions on anterior attentional processes developed by Posner and Petersen (1990) and by Stuss et al. (1995). The most plausible interpretation is in terms of energising processes which involve the SM frontal cortex and monitoring processes which involve the RL frontal cortex.