Errors on the Trail Making Test Are Associated with Right Hemispheric Frontal Lobe Damage in Stroke Patients.

Measures of performance on the Trail Making Test (TMT) are among the most popular neuropsychological assessment techniques. Completion time on TMT-A is considered to provide a measure of processing speed, whereas completion time on TMT-B is considered to constitute a behavioral measure of the ability to shift between cognitive sets (cognitive flexibility), commonly attributed to the frontal lobes. However, empirical evidence linking performance on the TMT-B to localized frontal lesions is mostly lacking. Here, we examined the association of frontal lesions following stroke with TMT-B performance measures (i.e., completion time and completion accuracy measures) using voxel-based lesion-behavior mapping, with a focus on right hemispheric frontal lobe lesions. Our results suggest that the number of errors, but not completion time on the TMT-B, is associated with right hemispheric frontal lesions. This finding contradicts common clinical practice-the use of completion time on the TMT-B to measure cognitive flexibility, and it underscores the need for additional research on the association between cognitive flexibility and the frontal lobes. Further work in a larger sample, including left frontal lobe damage and with more power to detect effects of right posterior brain injury, is necessary to determine whether our observation is specific for right frontal lesions.

Disorganized behavior on Link's cube test is sensitive to right hemispheric frontal lobe damage in stroke patients.

One of Luria's favorite neuropsychological tasks for challenging frontal lobe functions was Link's cube test (LCT). The LCT is a cube construction task in which the subject must assemble 27 small cubes into one large cube in such a manner that only the painted surfaces of the small cubes are visible. We computed two new LCT composite scores, the constructive plan composite score, reflecting the capability to envisage a cubical-shaped volume, and the behavioral (dis-) organization composite score, reflecting the goal-directedness of cube construction. Voxel-based lesion-behavior mapping (VLBM) was used to test the relationship between performance on the LCT and brain injury in a sample of stroke patients with right hemisphere damage (N = 32), concentrated in the frontal lobe. We observed a relationship between the measure of behavioral (dis-) organization on the LCT and right frontal lesions. Further work in a larger sample, including left frontal lobe damage and with more power to detect effects of right posterior brain injury, is necessary to determine whether this observation is specific for right frontal lesions.

Performance on the Frontal Assessment Battery is sensitive to frontal lobe damage in stroke patients.

BACKGROUND: The Frontal Assessment Battery (FAB) is a brief battery of six neuropsychological tasks designed to assess frontal lobe function at bedside [Neurology 55:1621-1626, 2000]. The six FAB tasks explore cognitive and behavioral domains that are thought to be under the control of the frontal lobes, most notably conceptualization and abstract reasoning, lexical verbal fluency and mental flexibility, motor programming and executive control of action, self-regulation and resistance to interference, inhibitory control, and environmental autonomy. METHODS: We examined the sensitivity of performance on the FAB to frontal lobe damage in right-hemisphere-damaged first-ever stroke patients based on voxel-based lesion-behavior mapping. RESULTS: Voxel-based lesion-behavior mapping of FAB performance revealed that the integrity of the right anterior insula (BA13) is crucial for the FAB global composite score, for the FAB conceptualization score, as well as for the FAB inhibitory control score. Furthermore, the FAB conceptualization and mental flexibility scores were sensitive to damage of the right middle frontal gyrus (MFG; BA9). Finally, the FAB inhibitory control score was sensitive to damage of the right inferior frontal gyrus (IFG; BA44/45). CONCLUSIONS: These findings indicate that several FAB scores (including composite and item scores) provide valid measures of right hemispheric lateral frontal lobe dysfunction, specifically of focal lesions near the anterior insula, in the MFG and in the IFG.

Motor cortex preactivation by standing facilitates word retrieval in aphasia.

BACKGROUND AND OBJECTIVES: A tight link between linguistic functions and activation of motor areas has been consistently reported, indicating that the 2 systems share functional neural resources. Few efforts have been made to explore whether this knowledge could aid the rehabilitation of aphasia. METHODS: The authors assessed whether preactivation of the leg motor cortex during standing, compared with sitting, can facilitate language production in patients with chronic aphasia. In a cross-over within-subject design, the authors assessed performance on a picture naming task and controlled for effects on processing speed and simple verbal reaction time. RESULTS: They found that standing compared with sitting had a beneficial effect on the number of semantic self-corrections that resulted in correct naming. In the absence of effects on motor or general processing speed, this points to a specific effect on lexical retrieval and selection. This was further corroborated by an error pattern analysis. Successful semantic self-corrections during standing were only found when there was already partial activation of the target semantic network-that is, when self-corrections were preceded by an incorrect but semantically associated naming response. DISCUSSION: These findings show that preactivation of the motor system, which extends beyond the intrinsic link between manual gestures and language, can facilitate lexical access in chronic aphasia and may open new directions in aphasia rehabilitation.

Levodopa improves procedural motor learning in chronic stroke patients.

OBJECTIVE: To test the hypothesis that administration of dopamine precursor levodopa improves procedural motor learning (defined as the ability to acquire novel movement patterns gradually through practice) in patients with residual motor deficits in the chronic phase after stroke (> or =1 y after stroke). DESIGN: A double-blind, placebo-controlled, randomized crossover design. SETTING: Neurology department in a German university. PARTICIPANTS: Eighteen patients with chronic motor dysfunction because of stroke (13 men, 5 women; age range, 53-78 y; mean time poststroke +/- SD, 3.3+/-2.1 y). INTERVENTION: Patients received 3 doses of levodopa (100mg of levodopa plus 25mg of carbidopa) or placebo before 1 session of procedural motor learning. MAIN OUTCOME MEASURES: Procedural motor learning performed by using the paretic hand assessed by using a modified version of the serial reaction time task with a probabilistic sequence. The primary outcome measure was the difference in reaction times between random and sequential elements. RESULTS: Levodopa significantly improved our primary outcome measure, procedural motor learning, compared with placebo (P<.05). Reaction times to random elements, analysis of error rates, psychophysical assessments, and performance in a simple motor task were comparable between conditions, indicating that better learning under levodopa was not caused by differences in response styles, arousal, mood, or motor reaction times but that levodopa modulated learning. CONCLUSIONS: Our results show that levodopa may improve procedural motor learning in patients with chronic stroke, in line with our hypothesis. These findings suggest that this interventional strategy in combination with customary rehabilitative treatments could significantly improve the outcome of neurorehabilitation in the chronic stage after stroke. (Clinicaltrials.gov identifier NCT00126087.)

Pharmacological enhancement of motor recovery in subacute and chronic stroke.

Pharmacological agents, known to modulate practice-dependent plasticity in animal models of brain damage, have recently received increased interest for treatment of motor recovery after stroke. The present paper gives an overview of agents that are currently available. Amphetamines have been repeatedly shown to promote recovery of function in animals, but clinical data remain inconclusive. Other pharmacological agents evaluated for motor recovery include selective norepinephrine re-uptake inhibitors, dopamine, dopamine agonists, cholinergic substances, serotonin re-uptake inhibitors, and granulocyte-colony stimulating factor. Although preliminary data from animal and human experimental studies on these agents are promising, larger clinical trials are needed before any of the available agents may be recommended for routine use.

Noninvasive brain stimulation improves language learning.

Anodal transcranial direct current stimulation (tDCS) is a reliable technique to improve motor learning. We here wanted to test its potential to enhance associative verbal learning, a skill crucial for both acquiring new languages in healthy individuals and for language reacquisition after stroke-induced aphasia. We applied tDCS (20 min, 1 mA) over the posterior part of the left peri-sylvian area of 19 young right-handed individuals while subjects acquired a miniature lexicon of 30 novel object names. Every subject participated in one session of anodal tDCS, one session of cathodal tDCS, and one sham session in a randomized and double-blinded design with three parallel versions of the miniature lexicon. Outcome measures were learning speed and learning success at the end of each session, and the transfer to the subjects' native language after the respective stimulation. With anodal stimulation, subjects showed faster and better associative learning as compared to sham stimulation. Mood ratings, reaction times, and response styles were comparable between stimulation conditions. Our results demonstrate that anodal tDCS is a promising technique to enhance language learning in healthy adults and may also have the potential to improve language reacquisition after stroke.

Lack of improvement in odor identification by levodopa in humans.

Several animal studies demonstrated that olfaction is modulated by dopamine (DA). We examined if such results could be replicated in humans. Thus, we tested olfaction in elderly healthy humans before and after external administration of levodopa in a double-blind, placebo-controlled, randomized cross-over study. Main outcome measure was the sum of correctly identified odors in an odor identification paradigm. In contrast to what had been demonstrated in rats, levodopa did not improve olfaction. We even noted a trend for the reverse. Blood pressure, mood ratings, as well as performance in a simple motor task were comparable between conditions, indicating that levodopa did not induce differences in general arousal, mood, attention, or reaction time. Our findings may be explained by differences in the distribution of dopaminergic receptor subtypes in the olfactory system in animals and humans, by relative differences in dosing regimes, or by subtle differences in the respective paradigms. These hypotheses have to be tested in future experiments, but our study demonstrates that results from animal studies cannot be directly transferred to the human situation.

Psychometric characteristics and practice effects of the Brunswick Trail Making Test.

Three trail-making tasks were designed to yield measures of visuomotor speed, efficiency of visual search, and cognitive flexibility (attentional switching). Scores on paper-and-pencil trail-making performance tasks were analyzed in 54 neurologically nonimpaired participants (21 men, 33 women; M=40 yr., SD=15 yr.). In Study 1, a 5-item 3-task format of the new trail-making test was developed by selecting items based on psychometric characteristics. The tasks were visuomotor trail-making (one item), visual search (two items), and cognitive flexibility (two items). Estimates of internal consistency of the resulting test scores of the Brunswick Trail Making Test yielded acceptable values (.91 and .90). In Study 2, the effects of repeated practice on trail-making tasks were analyzed. Task repetition affected the performance in the three trail-making tasks differentially. On the visuomotor task, effects of repeated task practice were completely carried over to similar trails. Evidence for transfer of learning was obtained neither for the visual search task nor for the cognitive flexibility task. It is concluded that training effects of perceptual-motor and cognitive skills are highly specific. Implications of these findings for cognitive neurorehabilitation are discussed.