Neuromagnetic signatures of the spatiotemporal transformation for manual pointing.

Movement planning involves transforming the sensory signals into a command in motor coordinates. Surprisingly, the real-time dynamics of sensorimotor transformations at the whole brain level remain unknown, in part due to the spatiotemporal limitations of fMRI and neurophysiological recordings. Here, we used magnetoencephalography (MEG) during pro-/anti-wrist pointing to determine (1) the cortical areas involved in transforming visual signals into appropriate hand motor commands, and (2) how this transformation occurs in real time, both within and across the regions involved. We computed sensory, motor, and sensorimotor indices in 16 bilateral brain regions for direction coding based on hemispherically lateralized de/synchronization in the α (7-15 Hz) and ß (15-35 Hz) bands. We found a visuomotor progression, from pure sensory codes in 'early' occipital-parietal areas, to a temporal transition from sensory to motor coding in the majority of parietal-frontal sensorimotor areas, to a pure motor code, in both the α and ß bands. Further, the timing of these transformations revealed a top-down pro/anti cue influence that propagated 'backwards' from frontal through posterior cortical areas. These data directly demonstrate a progressive, real-time transformation both within and across the entire occipital-parietal-frontal network that follows specific rules of spatial distribution and temporal order.

The Vascular Behavioral and Cognitive Disorders criteria for vascular cognitive disorders: a validation study.

BACKGROUND AND PURPOSE: The Vascular Behavioral and Cognitive Disorders (VASCOG) criteria for vascular cognitive disorders were published in 2014, but their concurrent and predictive validity have not been examined. METHODS: Participants (N = 165, aged 49-86 years) were from Sydney Stroke Study, a longitudinal study of post-stroke cognitive impairment and dementia. Diagnoses using the National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN), the Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for vascular dementia (VaD) were made by consensus at multidisciplinary case conferences. Diagnoses for mild vascular cognitive disorder (mVCD) and VaD using VASCOG, DSM-5 and the Vascular Impairment of Cognition Classification Consensus Study (VICCCS) criteria were made by two study authors. Agreement levels between criteria sets were examined using Cohen's kappa (κ). The ability of VaD diagnoses to predict mortality over 10 years and of mVCD to predict dementia over 5 years was investigated. RESULTS: The VASCOG criteria yielded rates of mVCD slightly lower than for DSM-5 and VICCCS. VaD rates were similar for all criteria, although slightly lower for DSM-IV. Agreement between the VASCOG, VICCCS and DSM-5 criteria was excellent for VaD and mVCD (κ = 0.83-1.0), but lower for VaD between VASCOG and the other criteria (κ = 0.47-0.63). VaD-based mortality predictions were similar for the VASCOG, VICCCS and DSM-5 criteria, and higher than those for other criteria. The prediction of incident dementia within 5 years from mVCD was slightly lower with VASCOG criteria than with DSM-5 and VICCCS criteria. CONCLUSIONS: The VASCOG criteria have greater sensitivity, modest concurrent validity and better predictive validity than older criteria for VaD, but are comparable to DSM-5 and VICCCS criteria. Their operationalization and inclusion of a mild VCD category make them useful for clinical and research applications.

Functional magnetic resonance imaging adaptation reveals the cortical networks for processing grasp-relevant object properties.

Grasping behaviors require the selection of grasp-relevant object dimensions, independent of overall object size. Previous neuroimaging studies found that the intraparietal cortex processes object size, but it is unknown whether the graspable dimension (i.e., grasp axis between selected points on the object) or the overall size of objects triggers activation in that region. We used functional magnetic resonance imaging adaptation to investigate human brain areas involved in processing the grasp-relevant dimension of real 3-dimensional objects in grasping and viewing tasks. Trials consisted of 2 sequential stimuli in which the object's grasp-relevant dimension, its global size, or both were novel or repeated. We found that calcarine and extrastriate visual areas adapted to object size regardless of the grasp-relevant dimension during viewing tasks. In contrast, the superior parietal occipital cortex (SPOC) and lateral occipital complex of the left hemisphere adapted to the grasp-relevant dimension regardless of object size and task. Finally, the dorsal premotor cortex adapted to the grasp-relevant dimension in grasping, but not in viewing, tasks, suggesting that motor processing was complete at this stage. Taken together, our results provide a complete cortical circuit for progressive transformation of general object properties into grasp-related responses.

Impairment in instrumental activities of daily living with high cognitive demand is an early marker of mild cognitive impairment: the Sydney memory and ageing study.

BACKGROUND: Criteria for mild cognitive impairment (MCI) consider impairment in instrumental activities of daily living (IADL) as exclusionary, but cross-sectional studies suggest that some high-level functional deficits are present in MCI. This longitudinal study examines informant-rated IADL in MCI, compared with cognitively normal (CN) older individuals, and explores whether functional abilities, particularly those with high cognitive demand, are predictors of MCI and dementia over a 2-year period in individuals who were CN at baseline. METHOD: A sample of 602 non-demented community dwelling individuals (375 CN and 227 with MCI) aged 70-90 years underwent baseline and 24-month assessments that included cognitive and medical assessments and an interview with a knowledgeable informant on functional abilities with the Bayer Activities of Daily Living Scale. RESULTS: Significantly more deficits in informant-reported IADL with high cognitive demand were present in MCI compared with CN individuals at baseline and 2-year follow-up. Functional ability in CN individuals at baseline, particularly in activities with high cognitive demand, predicted MCI and dementia at follow-up. Difficulties with highly cognitively demanding activities specifically predicted amnestic MCI but not non-amnestic MCI whereas those with low cognitive demand did not predict MCI or dementia. Age, depressive symptoms, cardiovascular risk factors and the sex of the informant did not contribute to the prediction. CONCLUSIONS: IADL are affected in individuals with MCI, and IADL with a high cognitive demand show impairment predating the diagnosis of MCI. Subtle cognitive impairment is therefore likely to be a major hidden burden in society.

Prevalence and characteristics of depression in mild cognitive impairment: the Sydney Memory and Ageing Study.

OBJECTIVE: Depression might be a risk factor for dementia. However, little is known about the prevalence of depressive symptoms in mild cognitive impairment (MCI) and whether mood or motivation-related symptoms are predominant. METHOD: A total of 767 non-demented community-dwelling adults aged 70-90 years completed a comprehensive assessment, including neuropsychological testing, and a past psychiatric/medical history interview. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS) and Kessler Psychological Distress Scale (K10). Exploratory factor analysis was performed on the GDS and K10 to derive 'mood' and 'motivation' subscales. RESULTS: A total of 290 participants were classified as having MCI and 468 as cognitively normal (CN). Participants with MCI reported more depressive symptoms, and more MCI participants met the cut-off for clinically significant symptoms, relative to CN participants. Those with amnestic MCI (aMCI), but not non-amnestic MCI, had more depressive symptoms and were more likely to meet the cut-off for clinically significant depressive symptoms, relative to CN participants. Participants with MCI reported more mood-related symptoms than CN participants, while there were no differences between groups on motivation-related symptoms. CONCLUSION: Individuals with MCI, especially aMCI, endorse more depressive symptoms when compared with cognitively intact individuals. These findings highlight the importance of assessing and treating depressive symptoms in MCI.

Occipital and parietal cortex participate in a cortical network for transsaccadic discrimination of object shape and orientation.

Saccades change eye position and interrupt vision several times per second, necessitating neural mechanisms for continuous perception of object identity, orientation, and location. Neuroimaging studies suggest that occipital and parietal cortex play complementary roles for transsaccadic perception of intrinsic versus extrinsic spatial properties, e.g., dorsomedial occipital cortex (cuneus) is sensitive to changes in spatial frequency, whereas the supramarginal gyrus (SMG) is modulated by changes in object orientation. Based on this, we hypothesized that both structures would be recruited to simultaneously monitor object identity and orientation across saccades. To test this, we merged two previous neuroimaging protocols: 21 participants viewed a 2D object and then, after sustained fixation or a saccade, judged whether the shape or orientation of the re-presented object changed. We, then, performed a bilateral region-of-interest analysis on identified cuneus and SMG sites. As hypothesized, cuneus showed both saccade and feature (i.e., object orientation vs. shape change) modulations, and right SMG showed saccade-feature interactions. Further, the cuneus activity time course correlated with several other cortical saccade/visual areas, suggesting a 'functional network' for feature discrimination. These results confirm the involvement of occipital/parietal cortex in transsaccadic vision and support complementary roles in spatial versus identity updating.

Generation of torsional and vertical eye position signals by the interstitial nucleus of Cajal.

The neural integrator, which converts eye velocity signals into position signals, is central to oculomotor theory. Similar integrators are probably necessary in any neural system that changes and maintains muscular tension. The integrator for horizontal eye position is in the pons, but the locations of the vertical and torsional integrators have not been clearly defined. Recording three-dimensional eye movements in alert monkeys during microstimulation and pharmacological inactivation of midbrain sites showed that the interstitial nucleus of Cajal generates both the torsional and vertical eye position signals. Up and down signals are linked with clockwise signals in the right brain and counterclockwise signals in the left brain. This three-dimensional coordinate system achieves orthogonality and bilateral symmetry without redundancy and optimizes energy efficiency for horizontal visual scanning.

Lipolysis in homogenates of adipose tissue: an inhibitor found in fat from obese rats.

The presence of a lipidbound inhibitor in adipose tissue of rats with hypothalamic obesity may explain the failure of the tissue to release fatty acids on epinephrine stinmulation. Aqueous extracts of tissue from obese animals showed no deficiency of lipase activity, but when whole homogenates of epididymal fat from lean and obese animals were mixed, 25 percent tissue from obese animals reduced by 73 percent the release expected from tissue of lean controls.

Coordinate transformations for hand-guided saccades.

Relatively little is known about the role of proprioception in eye-hand coordination. In a previous article (Ren et al. J Neurophysiol 96:1464-1477, 2006), we observed anisotropic (direction-dependent) saccade overshoots to hand-held targets during active, but not passive hand movements. We hypothesized that these errors arose from a limb-centered anisotropic efference copy which was transformed (uncompensated) into head coordinates for saccade control. Here, we tested this hypothesis and the role of head orientation signals in this transformation, by dissociating limb coordinates from head coordinates. Twelve human subjects made saccades to hand-held targets actively placed at eight radial locations on a frontally placed table in a dark room with four conditions: (1) right hand (body and head centered), (2) left hand (body and head centered), (3) right hand (head tilted counter-clockwise), (4) right hand (head tilted clockwise). In condition 1, we observed the same anisotropic pattern of overshooting errors-approximately along the axis of the forearm-that we reported previously. Overall, these amplitude errors were much smaller for the left hand. However, the anisotropic pattern was observed for both hands, but reversed symmetrically between the right versus left hand. Head tilt did not cause any systematic errors in saccade direction. Moreover, during head tilt, the anisotropic amplitude errors-while showing some distortions-did not rotate with the head. These findings suggest that transformations of somatosensory information into oculomotor coordinates account for head orientation, and that the anisotropic amplitude errors in hand-guided saccades arise in limb coordinates.

Optic ataxia errors depend on remapped, not viewed, target location.

Optic ataxia is a disorder associated with posterior parietal lobe lesions, in which visually guided reaching errors typically occur for peripheral targets. It has been assumed that these errors are related to a faulty sensorimotor transformation of inputs from the 'ataxic visual field'. However, we show here that the errors observed in the contralesional field in optic ataxia depend on a dynamic gaze-centered internal representation of reach space.

Use of a potent, long acting agonist of gonadotropin-releasing hormone in the treatment of precocious puberty.

Studies utilizing the administration of GnRH in various GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting GnRH agonists (GnRHa), like continuous infusion of high doses of the native peptide, results in suppression of pituitary gonadotropin secretion. This selective and reversible suppression of gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of central precocious puberty (CPP), a disorder for which the previously available therapies lacked uniform efficacy and were associated with potential side effects. In our series, 74 children with CPP have been treated during the last 5 yr with the potent GnRH agonist, [D-Trp6, Pro9-ethylamide(NEt)]GnRH. Having selected a dose and route of administration that produced uniform suppression of spontaneous and stimulated pituitary gonadotropin secretion, GnRHa therapy resulted in a fall of gonadal sex steroid levels into the prepubertal range, a halting or regression of secondary sexual development, and a complete cessation of menses. Growth velocity slowed during therapy, with this slowing more pronounced during prolonged treatment periods and among those patients with more advanced chronological and skeletal ages. Skeletal maturation was retarded to a greater degree than linear growth, with resultant increases in the predictions for adult stature. Moreover, these benefits have been achieved in the absence of significant side effects. Complete reversal of the suppression of gonadarche has followed discontinuation of therapy; however, patterns of growth and skeletal maturation after discontinuation of GnRHa administration remain to be characterized. Thus, the impact of GnRHa therapy on final height must await further longitudinal study. The selective nature of GnRHa suppression of gonadarche also permits an investigation of the natural history of adrenarche and its discrete influences upon skeletal growth and maturation. In addition, GnRHa therapy of CPP provides a unique opportunity to study the effects of gonadal sex steroids on GH secretion and somatomedin-C (Sm-C) generation during sexual maturation. Finally, the detailed characterization of children with precocious puberty has helped to define more precisely a subset of patients whose precocity occurs in the absence of demonstrable gonadotropin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

The superior colliculus encodes gaze commands in retinal coordinates.

The superior colliculus (SC) has a topographic map of visual space, but the spatial nature of its output command for orienting gaze shifts remains unclear. Here we show that the SC codes neither desired gaze displacement nor gaze direction in space (as debated previously), but rather, desired gaze direction in retinal coordinates. Electrical micro-stimulation of the SC in two head-free (non-immobilized) monkeys evoked natural-looking, eye-head gaze shifts, with anterior sites producing small, fixed-vector movements and posterior sites producing larger, strongly converging movements. However, when correctly calculated in retinal coordinates, all of these trajectories became 'fixed-vector.' Moreover, our data show that this eye-centered SC command is then further transformed, as a function of eye and head position, by downstream mechanisms into the head- and body-centered commands for coordinated eye-head gaze shifts.

Partial target organ resistance to thyroid hormone.

An 8-year old boy with a small goiter, normal basal metabolic rate (BMR), and elevated serum thyroid hormone levels (thyroxine [T(4)] 19.5 mug per 100 ml, free T(4) 4 ng per 100 ml, triiodothyronine [T(3)] 505 ng per 100 ml) was studied. He had measurable serum thyroid-stimulating hormone (TSH) levels (average 5.5 muU per ml), and the thyroxine-binding proteins, hearing, and epiphyseal structures were normal. There was no parental consanguinity nor were there thyroid abnormalities either in the parents or six siblings.Methimazole, 50 mg daily, depressed thyroxine synthesis (T(4) 10.5, free T(4) 2.5) and caused a rise in TSH to 11 muU per ml. After discontinuation of treatment, TSH declined to 4.2 muU per ml and chemical hyperthyroidism returned (T(4) 21.0 mug per 100 ml, free T(4) 4.2, and total T(3) 475 ng per 100 ml, radioactive iodine [RAI] uptake 68%), but studies of BMR and insensible water loss showed the patient to be clinically euthyroid. Thyrotropin-releasing hormone (TRH), 200 mug i.v., caused a brisk rise in TSH to 28 muU per ml, with T(4) rising to 28 mug per 100 ml, free T(4) to 5.6, and T(3) to 730 ng per 100 ml, thus indicating that the pituitary-thyroid system was intact and that the patient's TSH was biologically active. The unusual sensitivity of the pituitary cells to TRH in spite of the markedly elevated serum thyroid hormone levels also suggested that the pituitary was insensitive to suppression by T(3) or T(4). Serum dilution studies gave immunochemical evidence that this patient's TSH was normal. Neither propranolol, 60 mg, chlorpromazine, 30 mg, nor prednisone, 15 mg daily, influenced thyroid indices. Steroid treatment, however, suppressed the pituitary response to TRH, T(3) in doses increased over a period of 12 days to as much as 150 mug daily caused a rise in serum T(3) to above 800 ng per 100 ml, a decline of T(4) to euthyroid levels (T(4) 9.5 mug per 100 ml, free T(4) 1.6 ng per 100 ml), suppression of the RAI uptake from 68% to 35%, and marked blunting of the responses to TRH, but the BMR and insensible water loss remained normal. The data suggest that the patient's disorder is due to partial resistance to thyroid hormone.

Adrenarche and skeletal maturation during luteinizing hormone releasing hormone analogue suppression of gonadarche.

During puberty the effects of adrenal androgens upon skeletal maturation are obscured by the influence of gonadal steroids. Suppression of gonadarche with an analogue of luteinizing hormone releasing hormone (LHRHa) affords an opportunity to examine the onset and progression of adrenarche in the absence of pubertal levels of gonadal steroids in a controlled fashion and to explore the relationship between adrenal androgens and the rate of epiphyseal maturation. In 29 children with central precocious puberty, gonadarche was suppressed with LHRHa administration for 1-4 yr. During LHRHa exposure, dehydroepiandrosterone sulfate (DHAS) levels, as an index of adrenal maturation, were constant or increased in an age-expected manner. The change in bone age for change in chronologic age decreased from 1.7 +/- 0.1 to 0.49 +/- 0.05 (P = 0.00005), indicating that the LHRHa-induced return to a prepubertal gonadal steroid environment was associated with a slowing of skeletal maturation. DHAS levels were correlated with the rate of skeletal advancement before (r = 0.57, P = 0.001) and during 12 to 48 mo of exposure to LHRHa (r = 0.52, P = 0.003). A negative correlation of DHAS values with subsequent increases in predicted mature height was observed (r = -0.49, P = 0.007). Thus, in children with central precocious puberty, adrenarche progressed normally during LHRHa suppression of gonadarche. In children with the onset of progression of adrenarche during maintenance of a prepubertal gonadal steroid milieu, there was less evidence than in preadrenarchal children of a restraint upon skeletal maturation. These data suggest that adrenal androgens contribute importantly to epiphyseal advancement during childhood.

Cortical Activation during Landmark-Centered vs. Gaze-Centered Memory of Saccade Targets in the Human: An FMRI Study.

A remembered saccade target could be encoded in egocentric coordinates such as gaze-centered, or relative to some external allocentric landmark that is independent of the target or gaze (landmark-centered). In comparison to egocentric mechanisms, very little is known about such a landmark-centered representation. Here, we used an event-related fMRI design to identify brain areas supporting these two types of spatial coding (i.e., landmark-centered vs. gaze-centered) for target memory during the Delay phase where only target location, not saccade direction, was specified. The paradigm included three tasks with identical display of visual stimuli but different auditory instructions: Landmark Saccade (remember target location relative to a visual landmark, independent of gaze), Control Saccade (remember original target location relative to gaze fixation, independent of the landmark), and a non-spatial control, Color Report (report target color). During the Delay phase, the Control and Landmark Saccade tasks activated overlapping areas in posterior parietal cortex (PPC) and frontal cortex as compared to the color control, but with higher activation in PPC for target coding in the Control Saccade task and higher activation in temporal and occipital cortex for target coding in Landmark Saccade task. Gaze-centered directional selectivity was observed in superior occipital gyrus and inferior occipital gyrus, whereas landmark-centered directional selectivity was observed in precuneus and midposterior intraparietal sulcus. During the Response phase after saccade direction was specified, the parietofrontal network in the left hemisphere showed higher activation for rightward than leftward saccades. Our results suggest that cortical activation for coding saccade target direction relative to a visual landmark differs from gaze-centered directional selectivity for target memory, from the mechanisms for other types of allocentric tasks, and from the directionally selective mechanisms for saccade planning and execution.

Neural control of three-dimensional eye and head movements.

Although the eyes and head can potentially rotate about any three-dimensional axis during orienting gaze shifts, behavioral recordings have shown that certain lawful strategies--such as Listing's law and Donders' law--determine which axis is used for a particular sensory input. Here, we review recent advances in understanding the neuromuscular mechanisms for these laws, the neural mechanisms that control three-dimensional head posture, and the neural mechanisms that coordinate three-dimensional eye orientation with head motion. Finally, we consider how the brain copes with the perceptual consequences of these motor acts.

Different Cortical Mechanisms for Spatial vs. Feature-Based Attentional Selection in Visual Working Memory.

The limited capacity of visual working memory (VWM) necessitates attentional mechanisms that selectively update and maintain only the most task-relevant content. Psychophysical experiments have shown that the retroactive selection of memory content can be based on visual properties such as location or shape, but the neural basis for such differential selection is unknown. For example, it is not known if there are different cortical modules specialized for spatial vs. feature-based mnemonic attention, in the same way that has been demonstrated for attention to perceptual input. Here, we used transcranial magnetic stimulation (TMS) to identify areas in human parietal and occipital cortex involved in the selection of objects from memory based on cues to their location (spatial information) or their shape (featural information). We found that TMS over the supramarginal gyrus (SMG) selectively facilitated spatial selection, whereas TMS over the lateral occipital cortex (LO) selectively enhanced feature-based selection for remembered objects in the contralateral visual field. Thus, different cortical regions are responsible for spatial vs. feature-based selection of working memory representations. Since the same regions are involved in terms of attention to external events, these new findings indicate overlapping mechanisms for attentional control over perceptual input and mnemonic representations.

Transformations of an auditory temporal code in the medulla of a sound-producing fish.

The fish auditory system provides important insights into the evolution and mechanisms of vertebrate hearing. Fish have relatively simple auditory systems, without a cochlea for mechanical frequency analysis. However, as in all vertebrates, the primary auditory afferents of fish represent sounds as stimulus-entrained spike trains. Thus, fish provide important models for studying how temporal spiking patterns are used in higher level neural computations. In this paper we demonstrate that one of the fundamental transformations of information in the auditory system of a sound-producing fish, Pollimyrus, takes place in the auditory medulla. We discovered a class of neurons in which evoked spiking patterns were relatively independent of the stimulus fine structure and appeared to reflect intrinsic properties of the neurons. These neurons generated sustained responses but were poorly phase-locked to tones compared with the primary afferents. The interval histograms showed that spike timing was regular. However, in contrast to primary afferents, the mode of the interspike interval distribution was independent of the period of tonal stimuli. The tuning of the neurons was broad, with best sensitivity in the same spectral region where these animals concentrate energy in their communication sounds. The physiology of these neurons was similar to that of the chopper neurons known in the auditory brainstem of mammals. Our findings suggest that this medullary transformation, from phase-locked afferent input to chopper-like physiology, is basic to vertebrate auditory processing, even within lineages that have not evolved a cochlea.

Curvature of visual space under vertical eye rotation: implications for spatial vision and visuomotor control.

Most models of spatial vision and visuomotor control reconstruct visual space by adding a vector representing the site of retinal stimulation to another vector representing gaze angle. However, this scheme fails to account for the curvatures in retinal projection produced by rotatory displacements in eye orientation. In particular, our simulations demonstrate that even simple vertical eye rotation changes the curvature of horizontal retinal projections with respect to eye-fixed retinal landmarks. We confirmed the existence of such curvatures by measuring target direction in eye coordinates in which the retinotopic representation of horizontally displaced targets curved obliquely as a function of vertical eye orientation. We then asked subjects to point (open loop) toward briefly flashed targets at various points along these lines of curvature. The vector-addition model predicted errors in pointing trajectory as a function of eye orientation. In contrast, with only minor exceptions, actual subjects showed no such errors, showing a complete neural compensation for the eye position-dependent geometry of retinal curvatures. Rather than bolstering the traditional model with additional corrective mechanisms for these nonlinear effects, we suggest that the complete geometry of retinal projection can be decoded through a single multiplicative comparison with three-dimensional eye orientation. Moreover, because the visuomotor transformation for pointing involves specific parietal and frontal cortical processes, our experiment implicates specific regions of cortex in such nonlinear transformations.

Task-dependent constraints in motor control: pinhole goggles make the head move like an eye.

In the 19th century, Donders observed that only one three-dimensional eye orientation is used for each gaze direction. Listing's law further specifies that the full set of eye orientation vectors forms a plane, whereas the equivalent Donders' law for the head, the Fick strategy, specifies a twisted two-dimensional range. Surprisingly, despite considerable research and speculation, the biological reasons for choosing one such range over another remain obscure. In the current study, human subjects performed head-free gaze shifts between visual targets while wearing pinhole goggles. During fixations, the head orientation range still obeyed Donders' law, but in most subjects, it immediately changed from the twisted Fick-like range to a flattened Listing-like range. Further controls showed that this was not attributable to loss of binocular vision or increased range of head motion, nor was it attributable to blocked peripheral vision; when subjects pointed a helmet-mounted laser toward targets (a task with goggle-like motor demands but normal vision), the head followed Listing's law even more closely. Donders' law of the head only broke down (in favor of a "minimum-rotation strategy") when head motion was dissociated from gaze. These behaviors could not be modeled using current "Donders' operators" but were readily simulated nonholonomically, i.e., by modulating head velocity commands as a function of position and task. We conclude that the gaze control system uses such velocity rules to shape Donders' law on a moment-to-moment basis, not primarily to satisfy perceptual or anatomic demands, but rather for motor optimization; the Fick strategy optimizes the role of the head as a platform for eye movement, whereas Listing's law optimizes rapid control of the eye (or head) as a gaze pointer.