Polymer stability plays an important role in the positional regulation of FtsZ.

We conducted a series of experiments examining the effect of polymer stability on FtsZ localization dynamics in Bacillus subtilis. A loss-of-function mutation in ezrA, a putative polymer-destabilizing factor, suppresses the defects in FtsZ polymer stability associated with minCD overexpression. In addition, a mutation that is predicted to stabilize the FtsZ polymer leads to the formation of polar FtsZ rings. These data support the hypothesis that carefully balanced polymer stability is important for the assembly and localization of FtsZ during the bacterial cell cycle.

Effects of bromocriptine in a patient with crossed nonfluent aphasia: a case report.

OBJECTIVE: Because studies have shown some positive effects of the dopaminergic agent bromocriptine for improving verbal production in patients with nonfluent aphasia, we examined its effect in a patient with an atypical form of crossed nonfluent aphasia from a right hemisphere lesion. DESIGN: Open-label single-subject experimental ABAB withdrawal design. PATIENT: A right-handed man who, after a right frontal stroke, developed nonfluent aphasia, emotional aprosodia, and limb apraxia. INTERVENTION: Escalating doses up to 20mg of bromocriptine in 2 separate phases. MAIN OUTCOME MEASURES: We measured verbal fluency (words/min in discourse, Thurstone letter fluency), expression of emotional prosody, and gesture production. RESULTS: The patient showed substantial improvement in both verbal fluency measures and no significant improvement in gesture or emotional prosody. Verbal fluency improvements continued in withdrawal phases. CONCLUSIONS: Our results are less likely caused by practice or spontaneous recovery because we observed little improvement in emotional prosody and gesture tasks. Verbal fluency improvements during treatment and withdrawal phases suggest that the effects of bromocriptine may be long-lasting in its influence on the neural networks subserving verbal initiation.

Emotional conversations in Parkinson's disease.

OBJECTIVE: To learn how PD influences verbal description of emotional events. BACKGROUND: Individuals with PD exhibit emotional processing deficits. Emotional experience likely involves several dimensions (e.g., valence, arousal, motor activation) subserved by a distributed modular network involving cortical, limbic, basal ganglia, diencephalic, and mesencephalic regions. Although the neurodegeneration in PD likely affects components in this network, little is known about how PD influences emotional processing. Because PD is associated with activation deficits, one could predict that the discourse of emotional experiences involving high activation would be reduced in patients with PD compared to control subjects. Alternatively, because patients with PD exhibit paradoxical sensitivity to externally evoked motor activation (kinesia paradoxica), it is possible that emotional stimuli may facilitate verbal emotional expression more so in patients with PD than in control subjects. METHODS: The authors measured verbal descriptions of personal emotional experiences in subjects with PD and normal controls. RESULTS: Compared with control subjects, individuals with PD showed a relative increase in the number of words spoken and in discourse duration when talking about emotional experiences that are usually associated with high levels of arousal and motor activation. Although the authors did not measure arousal or activation, prior research has shown that, when asked to recall an emotional experience, people will often re-experience the emotion previously experienced during that episode. CONCLUSIONS: Recalling emotional episodes induces verbal kinesia paradoxica in patients with PD. Although recall of these emotional episodes may have been associated with increased arousal and activation, the mechanism underlying emotional verbal kinesia paradoxica is unclear.

Conceptual apraxia in probable Alzheimer's disease as demonstrated by the Florida Action Recall Test.

Patients with probable Alzheimer's disease (AD) often have difficulties associated with semantic knowledge. Therefore, conceptual apraxia, a defect of action semantics and mechanical knowledge, may be an early sign of this disease. The Florida Action Recall Test (FLART), developed to assess conceptual apraxia, consists of 45 line drawings of objects or scenes. The subject must imagine the proper tool to apply to each pictured object or scene and then pantomime its use. Twelve participants with Alzheimer's disease (NINCDS-ADRDA criteria) and 21 age- and education-matched controls were tested. Nine Alzheimer's disease participants scored below a 2-standard-deviation cutoff on conceptual accuracy, and the three who scored above the cutoff were beyond a 2-standard-deviation cutoff on completion time. The FLART appears to be a sensitive measure of conceptual apraxia in the early stages of Alzheimer's disease.

Testing memory for self-generated items in dementia: method makes a difference.

OBJECTIVE: To learn how pAD (probable Alzheimer's disease), PD+ ("Parkinson's Plus" syndrome), and control subjects remember internally generated material under different conditions. BACKGROUND: "Self-discovered," or internally generated knowledge, prized by educators and therapists, can bring about considerable behavioral change. Both parietal-temporal-limbic (pAD) and frontal-subcortical dementia (e.g. PD+) cause dysmemory, but may cause different internal-external memory bias. pAD subjects, confusing internal and external information (confabulation) and reporting internal information during memory testing (intrusions), may be biased to remember internal material. PD+ subjects, impaired at generative tests, may be externally biased. METHODS: Ten pAD, 5 PD+, and 10 control subjects generated words in a category without instruction to remember (INR), and took a list-learning test of incidental memory for internally and externally generated words. To test how INR influences memory, subjects then generated and attempted to recall four more words. RESULTS: All three subject groups remembered more internally generated than externally provided words without INR. Recall versus recognition of internally generated words differed by group, with PD+ subjects showing greatest improvement with recognition. The pAD subjects performed worse with INR than without INR, had the most intrusion errors, and, rather than demonstrating a release from proactive inhibition, recalled fewer words outside the category. Groups differed in overall recall/recognition improvement (p = 0.015). CONCLUSIONS: Aged subjects preferentially retained internally generated material. However, among demented subjects, memory for internally generated words was influenced by the testing method used. PD+ subjects have poor internal recall, but excellent internal recognition. In pAD, memory for internally generated words may exceed external memory, but only when subjects are not explicitly trying to remember.

Cognitive and vestibulo-proprioceptive components of spatial ability in Parkinson's disease.

Visual-spatial deficits are often associated with Parkinson's Disease (PD). Recent theories suggest that frontal-basal ganglionic dysfunction affects cognition in PD. Although this hypothesis does not entirely explain spatial deficits in PD, the inappropriate utilization of cues associated with executive dysfunction may induce spatial deficits. Alternatively, the vestibular system is also involved in spatial cognition, and vestibular dysfunction may affect visual-spatial ability in PD. To test these hypotheses, we administered the Water Jar Test, while perturbing vestibulo-proprioceptive input. Non-demented PD patients were significantly less accurate than controls in judging horizontal, and appeared to inappropriately utilize cues. No group effect was found for head tilt. These findings suggest the visual-spatial difficulties seen in PD are related to executive dysfunction that is associated with a disruption of the frontal-basal ganglionic and frontal-parietal systems.

Attentional grasp in far extrapersonal space after thalamic infarction.

Studies of animals and humans with focal brain damage suggest that attention in near and far extrapersonal space may be mediated by anatomically separate systems. Thalamic lesions have been associated with spatial neglect, but whether asymmetric attention specific to near or far space occur after thalamic damage has not been explored. It is also unclear if thalamic injury can induce contralesional defective response inhibition. We tested a woman with a left thalamic infarction who reported that, when driving, she had a tendency to veer towards people or objects on the right side of the road. Our patient and four controls performed a line bisection task with a laser pointer in near and far extrapersonal space. The experimenter marked each bisection either from the right of the presented line (right-distractor, RD) or the left (left-distractor, LD). RD and LD trials were pseudo-randomized. Our patient performed similarly to controls (mean -0.7 mm, controls -0.6 mm) on the line bisection task in near space. In far space she erred significantly rightward compared to her performance in near space (p<0.001). Controls performed similarly in near and far space. The experimenter position did not affect our patient's performance on near line bisections, nor did controls demonstrate a distractor effect for the near condition. In the far condition, however, our patient showed a significant distractor effect (LD -3.3 mm, RD 35.3 mm, p<0.001). Controls also demonstrated a distractor effect in the far condition (LD -6.4 mm, RD 0.7 mm, p<0.01), though of much smaller magnitude. Our results suggest that frontal-thalamic systems regulating visual attention may be disrupted by thalamic infarction. Such damage may produce an attentional grasp specific to far extrapersonal space.

Ipsilesional intentional neglect and the effect of cueing.

BACKGROUND: Contralesional hemispatial neglect may be induced by an attentional deficit where patients are inattentive to or unaware of stimuli in contralesional hemispace, an intentional deficit where patients are unable to act in or towards contralesional hemispace, or both. The deficits associated with ipsilesional neglect have not been as well characterized. Because cueing may be used as a rehabilitative assistive device, we wanted to learn whether the efficacy of an attentional or intentional cue was related to the type of bias. METHODS: We studied a patient with a right frontotemporal stroke who had ipsilesional neglect by using a video apparatus that dissociates sensory-attentional and motor-intentional systems. We also performed a cueing experiment with primarily sensory-attentional cues (i.e., read the letter at the end of the line) and primarily motor-intentional cues (i.e., touch the end of the line). RESULTS AND CONCLUSIONS: Ipsilesional neglect was primarily a motor-intentional deficit with a motor-action bias to the left and a secondary sensory-attentional bias for stimuli to the right. With cueing we found a double dissociation: the rightwards motor-intentional cue improved the primary left-sided intentional bias and the leftwards sensory-attentional cue improved the secondary right-sided attentional bias. Effective rehabilitation strategies need to address both sensory-attentional and motor-intentional deficits in patients with neglect.

Crossed apraxia: implications for handedness.

Liepmann posited that right hand preference relates to left hemisphere dominance for learned skilled movements. Limb apraxia, impairment of skilled movement, typically occurs in individuals with left hemisphere (LH) lesions. The occurrence of apraxia in right-handed individuals following right-hemisphere lesions appears to refute Liepmann's hypothesis. We studied the apraxia of a right-handed man, RF, following a right frontal lesion to determine whether his apraxia paralleled the apraxia seen following LH lesions. Results of behavioral testing indicated that, like individuals with apraxia following left frontal lesions, RF was better at gesture recognition than gesture production which was significantly impaired across tasks. Kinematic motion analyses of movement linearity, planarity, and the coupling of temporospatial aspects of movements substantiated the parallel impairments in RF and patients with LH apraxia. The impairment seen in our patient with crossed apraxia provides evidence for the fractionation of systems underlying hand preference and skilled movement.

Pupillographic findings in neglect.

OBJECTIVES: Unilateral sensory neglect has been attributed to various defects, including a hemispatial attention-arousal deficit. However, support for this hypothesis has only been indirect. Therefore, the purpose of this study was to further test the hemispatial attentional-arousal hypothesis by measuring pupillary response as an index of arousal. METHODS: There were two experimental subjects with neglect and six matched controls. Stimuli (Arabic numbers) were presented on the right, left, and centre of a screen. The subjects were asked to look at the number in the centre, on the right, or left of the screen while their pupil diameter was measured. RESULTS: Unlike the control subjects, the subjects with neglect, who were aware of the left sided stimuli, did not show a pupillary dilatation when they looked at the stimulus on the left. CONCLUSIONS: Although this study provides support for the hemispatial attention-arousal hypotheses of neglect, it does not preclude the possibility that other mechanisms may also be important.

Adverse effect of dopamine agonist therapy in a patient with motor-intentional neglect.

Studies in animals and humans report dopamine agonists can improve neglect. Because dopamine deficit reduces intention to act, it has been suspected the dopamine agonist bromocriptine would improve deficient hemispatial intention. Thus, the effect of bromocriptine on line bisection was examined in a patient with neglect and failure of the action-intention system. The 58-year-old patient had left-sided neglect from a right cerebral infarction involving both cortical and subcortical (striatal) structures. It was determined that neglect on a line bisection task was attributable to a motor-intentional bias by testing under congruous and incongruous video monitoring. Testing sessions were held before starting bromocriptine, on 20 mg/d, and after stopping bromocriptine. The patient's ipsilesional bias increased on bromocriptine, and improved when bromocriptine was stopped. Bromocriptine may worsen neglect if putamenal receptors are damaged. Dopamine agonists may activate the normal hemisphere, increasing an intentional bias. Clinicians using dopaminergic pharmacotherapy should assess patients for this possible adverse effect.

Articulatory processes and phonologic dyslexia.

BACKGROUND/OBJECTIVE: Grapheme-to-phoneme conversion (GPC) allows the pronunciation of nonword letter strings and of real words with which the literate reader has no previous experience. Although cross-modal association between visual (orthographic) and auditory (phonemic-input) representations may contribute to GPC, many cases of deep or phonologic alexia result from injury to anterior perisylvian regions. Thus, GPC may rely upon associations between orthographic and articulatory (phonemic-output) representations. METHOD/RESULTS/CONCLUSION: Detailed analysis of a patient with phonologic alexia suggests that defective knowledge of the position and motion of the articulatory apparatus might contribute to impaired transcoding from letters to sounds.

Analysis of primary and secondary influences on spatial neglect.

When attempting to determine the middle of a line, patients with neglect deviate from true center. Deviation may be induced by perceptual-attentional bias, premotor-intentional bias, or both. Using a video-based apparatus, we decoupled perceptual from premotor influences on line bisection performance in patients with hemispatial neglect to examine (a) the relationship between primary and secondary bias and (b) the relationship of bias type to lesion location. The same video-based procedure was applied to target cancellation to determine if neglect type varied as a function of task. Primary attentional-perceptual bias was found using line bisection in 14/26 subjects, most of whom had lesions involving the posterior hemisphere. Primary premotor-intentional bias on line bisection was more often associated with lesions of frontal-subcortical structures. The neglect type determined by the bisection task agreed with the results of target cancellation in most cases. Secondary bias was determined based upon whether decoupling decreased the magnitude of bisection error (concordant), increased error (discordant), or produced no significant change. Most patients showed a secondary bias, with 12/26 in the discordant group and 11/26 in the concordant group. Discordant secondary bias was more common in premotor-intentional neglect (10/12) than in perceptual-attentional neglect (2/14), whereas concordant bias was more common in the latter group (10/14) compared to the former (1/12). The nonrandom relationship between primary and secondary bias may provide a more detailed description of ways in which anatomically separate components of a cortical network contribute to spatial processing under conditions of perceptuomotor incongruity.

Ipsilateral neglect: reversal of bias or exaggerated cross-over phenomenon?

When right brain injury produces contralesional neglect (CN), patients typically misbisect lines to the right. However, others demonstrate so-called "ipsilateral neglect" (IN) with misbisection to the left of midpoint. Paradoxically, most patients with CN also demonstrate a 'cross-over' phenomenon whereby they misbisect short lines to the left. It is not known whether patients with IN actually have a contralesional bias opposite the ipsilesional bias observed with CN, or if their performance reflects an exaggerated cross-over. These alternatives can be distinguished by power function analysis which evaluates the relationship between magnitude of perception and stimulus magnitude. Using line bisection tasks to derive a power function, an IN patient showed a reduced exponent (beta = 0.841), falling outside 95% confidence intervals (CI) for controls but within the CI for CN patients. The IN patient showed a greatly increased constant (K = 7.82), extending outside the CI for both controls and CN patients. The results suggest that the anomalous leftward misbisection with IN is associated with an exaggerated cross-over point and not simply reversal of spatial bias.

Dissociation of sensory-attentional from motor-intentional neglect.

OBJECTIVES: Spatial neglect may result from disruption of sensory-attentional systems that spatially allocate perceptual resources and the motor-intentional systems that direct exploration and action. Previous studies have suggested that the line bisection task is more sensitive to sensory-attentional disorders and the cancellation task to motor-intentional disorders. A new technique was developed that allows the dissociation of sensory-attentional and motor-intentional deficits in both tasks and thereby allows comparison of these tasks. METHODS: Ten patients with right hemispheric injury and hemispatial neglect performed line bisection and cancellation tasks while viewing stimuli on closed circuit TV. Direct view of the exploring hand and the target was precluded; the TV monitor guided performance. The direct condition made the direction of hand movement on the table (workspace) congruent with that on the monitor. Inverting the camera produced the indirect condition wherein the lateral movement in the workspace occurred in the opposite direction on the monitor. RESULTS: On the cancellation task, five patients marked targets in the right workspace in the direct condition but the left workspace in the indirect condition, indicating sensory-attentional neglect. However, four other patients cancelled targets only in the right workspace in both conditions, failing to explore the left workspace, suggesting motor-intentional neglect. A patient who performed ambiguously may have elements of both types of neglect. Only two out of five patients designated as sensory-attentional in cancellation tasks showed sensory neglect on line bisection. The other three patients, as well as patients defined as motor-intentional by cancellation performance, exhibited motor-intentional neglect on line bisection. CONCLUSION: The designation of sensory-attentional versus motor-intentional neglect therefore, in part, depends on task specific demands.

Cerebellar degeneration associated with human immunodeficiency virus infection.

Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. A primary cerebellar degeneration with HIV has not previously been reported. Ten patients were identified over an 8-year period at five medical centers. All patients had clinical, laboratory, and radiologic evaluations, and three had neuropathologic examinations. Patients presented with progressively unsteady gait, slurred speech, and limb clumsiness. Examination revealed gait ataxia, impaired limb coordination, dysarthria, and abnormal eye movements. Cognition, strength, and sensory function remained normal. CD4 lymphocyte counts varied between 10 and 437 cells/mm3. Neuroimaging studies showed prominent cerebellar atrophy. Neuropathology showed focal degeneration of the cerebellar granular cell layer and unusual focal axonal swellings in the brainstem and spinal cord. Cultures, histopathology, and immunochemical studies showed no conclusive evidence of infection. We report a syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection.

Dyssynchronous apraxia: failure to combine simultaneous preprogrammed movements.

Limb apraxia, a defect in skilled, learned purposive movement, may be related to impairment of either representational or innervatory components of praxis processing. Innervatory motor patterns, in turn, may involve on-line motor programs (visual feedback-controlled) or prepared movement programs (independent of continuous visual feedback). We evaluated movement abilities ofthe innervatory pattern system in TB,a 26-year-old patient with apraxia from a left dorsolateral frontal stroke. TB and four controls performed nonmeaningful single and multi-joint movements to command, with multi-joint movements combined sequentially (e.g. "open and close your hand and then bend your elbow") or simultaneously (e.g. "open and close your hand; keep doing that while bending your elbow"). TB showed no difference between single-joint (71.5% correct) and multi-joint movements in sequential combinations (68% correct), but she was significantly worse at simultaneous movement combinations (28.6% correct; P < .02). Controls performed consistently at > 90% mean accuracy. TB and four normals also performed the Fitts (1954) task, in which they alternately tapped with a pen between two target circles of varying size. TB was proportionately slower than controls on the larger Fitts circles, which call predominantly on prepared movement programs; her performance on the smaller circles (involving more on-line programs) was comparable to normals. We conclude that functional synchrony of one innervatory pattern subtype, prepared movement programs, may require late-level frontal processing, and that failure at this level can result in both apraxia and defective programming of nonmeaningful movements.

Anosognosia and confabulation during the Wada test.

Feinberg et al. proposed that right-hemisphere-damaged stroke patients with anosognosia for hemiplegia (AHP) confabulate seeing stimuli on the left side but those without AHP admit to having inadequate visual information. This study examines the relationship between AHP and confabulation using selective anesthesia of the cerebral hemispheres. Seventeen patients with intractable epilepsy were tested during intracarotid methohexital infusion. For half of the trials, subjects were stimulated on their paretic hand with a material (sandpaper, metal, or cloth), and for the remaining trials they were not stimulated. The subjects were trained to use a pointing response to indicate if they been stimulated and the type of material they had felt. Admission of uncertainty was defined as pointing to a question mark. Confabulation was defined as any material response to a no-touch trial. During anesthesia of either hemisphere, subjects with and without AHP confabulated responses. The AHP and non-AHP groups did not differ in admission of uncertainty. Our results support the postulate that confabulation and AHP are independent disorders, and therefore confabulation cannot fully account for AHP.

Gaze related enhancement of hemispheric blood flow in a stroke patient.

OBJECTIVE: A patient with a right posterior cerebral artery territory infarction and a left superior quadrantanopia exhibited improvement on various visual tasks including Goldmann perimetry during extreme right gaze. The phenomenon was investigated by functional imaging of cerebral blood flow. METHODS: [(99m)Tc]HMPAO SPECT was carried out while the patient gazed to the right and to the left at an 8 Hz flash stimulus. RESULTS: When compared with left gaze, photic stimulation during right gaze was associated with an up to 39.8% increase in regional cerebral blood flow in the damaged right hemisphere, including Brodmann's areas 3-1-2, 7, 21, 22, 39, and 40. CONCLUSIONS: These gaze related alterations in function and synaptic activity suggest the engagement of a novel arousal-like mechanism that may account in part for comparable findings in patients with neglect and other disorders, and may have relevance to rehabilitation.