Hemodynamic response function abnormalities in schizophrenia during a multisensory detection task

Functional magnetic resonance imaging (fMRI) of the blood oxygen level dependent (BOLD) response has commonly been used to investigate the neuropathology underlying cognitive and sensory deficits in patients with schizophrenia (SP) by examining the positive phase of the BOLD response, assuming a fixed shape for the hemodynamic response function (HRF). However, the individual phases (positive and post‐stimulus undershoot (PSU)) of the HRF may be differentially affected by a variety of underlying pathologies. The current experiment used a multisensory detection task with a rapid event‐related fMRI paradigm to investigate both the positive and PSU phases of the HRF in SP and healthy controls (HC). Behavioral results indicated no significant group differences during task performance. Analyses that examined the shape of the HRF indicated two distinct group differences. First, SP exhibited a reduced and/or prolonged PSU following normal task‐related positive BOLD activation in secondary auditory and visual sensory areas relative to HC. Second, SP did not show task‐induced deactivation in the anterior node of the default‐mode network (aDMN) relative to HC. In contrast, when performing traditional analyses that focus on the positive phase, there were no group differences. Interestingly, the magnitude of the PSU in secondary auditory and visual areas was positively associated with the magnitude of task‐induced deactivation within the aDMN, suggesting a possible common neural mechanism underlying both of these abnormalities (failure in neural inhibition). Results are consistent with recent views that separate neural processes underlie the two phases of the HRF and that they are differentially affected in SP. Hum Brain Mapp 37:745–755, 2016. © 2015 Wiley Periodicals, Inc.     

Visual reaction time as a function of locus,area, and complexity of stimulus

Summary Reaction time (RT) of normal subjects to square-wave gratings of two different frequencies were related to locus of presentation, area, and stimulus complexity. Each frequency was presented to either side of the horizontal meridian (half size stimulus) or both sides simultaneously (full size stimulus). The two different frequencies were also flashed simultaneously to both hemifields (compound stimulus). Stimulus position affected RT with the 1 c/deg stimulus, RT being faster for the lower hemifield. With presentation on both sides of the horizontal meridian simultaneously or of the two spatial frequencies, the resulting RT was equal to that of the faster component. Implications of the results for the functional organization of the visual system are discussed.     

Visual and auditory cue integration for the generation of saccadic eye movements in monkeys and lever pressing in humans

This study examined how effectively visual and auditory cues can be integrated in the brain for the generation of motor responses. The latencies with which saccadic eye movements are produced in humans and monkeys form, under certain conditions, a bimodal distribution, the first mode of which has been termed express saccades. In humans, a much higher percentage of express saccades is generated when both visual and auditory cues are provided compared with the single presentation of these cues [H. C. Hughes et al. (1994) J. Exp. Psychol. Hum. Percept. Perform., 20 , 131–153]. In this study, we addressed two questions: first, do monkeys also integrate visual and auditory cues for express saccade generation as do humans and second, does such integration take place in humans when, instead of eye movements, the task is to press levers with fingers? Our results show that (i) in monkeys, as in humans, the combined visual and auditory cues generate a much higher percentage of express saccades than do singly presented cues and (ii) the latencies with which levers are pressed by humans are shorter when both visual and auditory cues are provided compared with the presentation of single cues, but the distribution in all cases is unimodal; response latencies in the express range seen in the execution of saccadic eye movements are not obtained with lever pressing.     

The integration of parallel and serial processing mechanisms in visual search: evidence from eye movement recording

We examined timing and scanning paths of eye movements during a visual search task, in which subjects had to detect, as quickly as possible, the presence or absence of a target among distractors [Q-like element among O stimuli (QvsO) and vice-versa (OvsQ)]. According to an influential theory [Treisman, A. & Gelade, G. (1980) Cognitive Psychol, 12, 97--136; Treisman, A. & Sato, S. (1990) J. Exp. Psychol. Hum. Percept. Perform., 16, 459--478], only tasks yielding nonflat search functions (OvsQ) involve focal attention. Alternative models propose that all kinds of visual search are resolved by a biased competitive process, working in parallel across the visual field. Data show that QvsO and OvsQ tasks are characterized by quantitative rather than by qualitative differences in search strategy. No differences between the two tasks were found regarding either the percentage of saccades foveating single stimulus items or the timing of the button response with respect to the onset of the last foveation saccade within a trial. Furthermore, the number of saccades made during search predicted very accurately the time required to accomplish the task and fixation times were independent of the number of stimulus items. On the basis of our results there is no reason to postulate the occurrence of shifts of visuospatial attention, other than those associated with the executions of saccadic eye movements, which are driven by a parallel feature analysis of the visual scene, in both types of search tasks. A time-limited competitive model for attentive target identification, in which both parallel (competitive) and serial (attentive) processing mechanisms are integrated, can account for these findings, providing a unified conceptual framework for all kinds of visual search.     

Visual response characteristics of neurons in the second visual area of marmosets

The physiological characteristics of the marmoset second visual area (V2) are poorly understood compared with those of the primary visual area (V1). In this study, we observed the physiological response characteristics of V2 neurons in four healthy adult marmosets using intracortical tungsten microelectrodes. We recorded 110 neurons in area V2, with receptive fields located between 8° and 15° eccentricity. Most (88.2%) of these neurons were orientation selective, with half-bandwidths typically ranging between 10° and 30°. A significant proportion of neurons (28.2%) with direction selectivity had a direction index greater than 0.5. The vast majority of V2 neurons had separable spatial frequency and temporal frequency curves and, according to this criterion, they were not speed selective. The basic functional response characteristics of neurons in area V2 resemble those found in area V1. Our findings show that area V2 together with V1 are important in primate visual processing, especially in locating objects in space and in detecting an object’s direction of motion. The methods used in this study were approved by the Monash University Animal Ethics Committee, Australia (MARP 2009-2011) in 2009.

Chinese Library Classification No. R445; R339.14+6; S865.1+6     

Striatal grafts alleviate deficits in response execution in a lateralised reaction time task

It has been reported that homotopic neural transplants can ameliorate behavioural impairments induced by striatal lesions in a reaction time (RT) task. In the present study we seek to replicate and extend this observation in a new lateralised choice RT task based on the conventional Skinner box apparatus. Rats were trained to make rapid lateralised lever press responses to a visual stimulus presented on either the left or the right side of the animal. The RTs required to initiate and execute correct responses were recorded, along with other accuracy and performance indices. Following unilateral lesions of the dorsal striatum, the rats exhibited an increased number of error trials, a bias to respond towards the ipsilateral side, a decreased accuracy on the contralateral side, and an increase of the execution time to respond correctly to contralateral stimuli. Striatal grafts alleviated the lateralised response deficits, prevented the development of lateral disparity, and restored the speed of responding back to pre-lesion levels. Control grafts of cortical tissues also increased task accuracy and reduced the ipsilateral bias in responding, but were without effect on the RT deficit.     

Visual receptive field organization and cortico-cortical connections of the lateral intraparietal area (area LIP) in the macaque

The visual receptive field physiology and anatomical connections of the lateral intraparietal area (area LIP), a visuomotor area in the lateral bank of the inferior parietal lobule, were investigated in the cynomolgus monkey (Macaca fascicularis). Afferent input and physiological properties of area 5 neurons in the medial bank of the intraparietal sulcus (i.e., area PEa) were also determined. Area LIP is composed of two myeloarchitectonic zones: a ventral zone (LIPv), which is densely myelinated, and a lightly myelinated dorsal zone (LIPd) adjacent to visual area 7a. Previous single-unit recording studies in our laboratory have characterized visuomotor properties of area LIP neurons, including many neurons with powerful saccade-related activity. In the first part of the present study, single-unit recordings were used to map visual receptive fields from neurons in the two myeloarchitectonic zones of LIP. Receptive field size and eccentricity were compared to those in adjacent area 7a. The second part of the study investigated the cortico-cortical connections of area LIP neurons using tritiated amino acid injections and fluorescent retrograde tracers placed directly into different rostrocaudal and dorsoventral parts of area LIP. The approach to area LIP was through somatosensory area 5, which eliminated the possibility of diffusion of tracers into area 7a. Unlike many area 7a receptive fields, which are large and bilateral, area LIP receptive fields were much smaller and exclusively confined to the contralateral visual field. In area LIP, an orderly progression in visual receptive fields was evident as the recording electrode moved tangentially to the cortical surface and through the depths of area LIP. The overall visual receptive field organization, however, yielded only a rough topography with some duplications in receptive field representation within a given rostrocaudal or dorsoventral part of LIP. The central visual field representation was generally located more dorsally and the peripheral visual field more ventrally within the sulcus. The lower visual field was represented more anteriorly and the upper visual field more posteriorly. In LIP, receptive field size increased with eccentricity but with much variability with in the sample. Area LIPv was found to have reciprocal cortico-cortical connections with many extrastriate visual areas, including the parieto-occipital visual area PO; areas V3, V3A, and V4: the middle temporal area (MT); the middle superior temporal area (MST); dorsal prelunate area (DP); and area TEO (the occipital division of the intratemporal cortex). Area LIPv is also connected to area TF in the lateral posterior parahippocampal gyrus.(ABSTRACT TRUNCATED AT 400 WORDS)     

Arm movement and gap as factors influencing the reaction time of the second saccade in a double-step task

To guide our hand for reaching, we explore our visual environment by sequences of saccades. In the present paper, we studied the eye and hand movements of human subjects looking or looking and pointing at a target that is instantaneously displaced two times (double-step task). It was previously shown that the second saccade has a much longer reaction time than the first one [Feinstein & Williams (1972) Vision Res., 12, 33-44]. The second reaction time is even longer if the subject also has to point to the target with the hand [Lünenburger et al. (2000) Eur. J. Neurosci., 12, 4107-4116]. The conditions and objective for these effects are further examined in the present paper. It is shown that vision of the hand reduces the first and second saccadic reaction times in parallel. The second reaction time is prolonged for shorter delays between both target steps as well as for larger amplitudes of the second saccade. However, the long second reaction time does not reflect an absolute saccadic refractory period, because a gap before the second target step reduces the second reaction time to a value similar to the first. Hand response time and average hand velocity were increased when the second target step was larger. The response time for the eyes was about 30% of the response time of the hand. We argue that the observed effects reflect the coordination of eye and hand movement to allow a precise and efficient reaching behaviour.     

Methylphenidate effects of cognitive style and reaction time in four groups of children

Four groups of children referred for attention disorders, learning disorders, or both were blindly titrated at statistically equivalent dosage levels of methylphenidate and improved more or less equivalently on several measures of attentiveness (cognitive style tests and reaction time). Methylphenidate dosage needs, which vary considerably, appear more strongly related to indices of nervous system sensitivity than clinical diagnosis. Interactions of stimulus intensity, reward level, and drug condition on reaction time (RT) lend credence to the theoretical constructs of augmentation-reduction and nervous system sensitivity. Order of treatment (placebo before drug or drug before placebo) had an unexpected effect on RT, suggesting that on a boring, frustrating task, methylphenidate may enhance performance less as a function of number of exposures to the experience.     

Comparison of visual receptive fields in the dorsolateral prefrontal cortex and ventral intraparietal area in macaques

The concept of receptive field (RF) describes the responsiveness of neurons to sensory space. Neurons in the primate association cortices have long been known to be spatially selective but a detailed characterisation and direct comparison of RFs between frontal and parietal association cortices are missing. We sampled the RFs of a large number of neurons from two interconnected areas of the frontal and parietal lobes, the dorsolateral prefrontal cortex (dlPFC) and ventral intraparietal area (VIP), of rhesus monkeys by systematically presenting a moving bar during passive fixation. We found that more than half of neurons in both areas showed spatial selectivity. Single neurons in both areas could be assigned to five classes according to the spatial response patterns: few non‐uniform RFs with multiple discrete response maxima could be dissociated from the vast majority of uniform RFs showing a single maximum; the latter were further classified into full‐field and confined foveal, contralateral and ipsilateral RFs. Neurons in dlPFC showed a preference for the contralateral visual space and collectively encoded the contralateral visual hemi‐field. In contrast, VIP neurons preferred central locations, predominantly covering the foveal visual space. Putative pyramidal cells with broad‐spiking waveforms in PFC had smaller RFs than putative interneurons showing narrow‐spiking waveforms, but distributed similarly across the visual field. In VIP, however, both putative pyramidal cells and interneurons had similar RFs at similar eccentricities. We provide a first, thorough characterisation of visual RFs in two reciprocally connected areas of a fronto‐parietal cortical network.     

Distribution of neurofilament proteins in the lateral geniculate nucleus, primary visual cortex, and area MT of adult Cebus monkeys

We investigated the distribution pattern of SMI-32-immunopositive cells in the lateral geniculate nucleus (LGN) and in the primary (V1) and middle temporal (MT) cortical visual areas of the adult New World monkey Cebus apella. In the LGN, the reaction for SMI-32 labeled cells in both the magnocellular (M) and parvocellular (P) layers. However, the cellular label was heavier in M layers, which also showed a more intense labeling in the neuropil. In V1, the reaction showed a lamination pattern, with the heaviest labeling occurring in layer 4B and upper layer 6 (layers that project to area MT). Area MT shows a dense band of labeled neuropil and large pyramidal neurons in layer 3, large darkly labeled but less densely packed neurons in layer 5, and a population of small, lightly labeled cells in layer 6. These results resemble those found in other New and Old World monkeys, which suggest that the preferential labeling of projection neurons associated with fast-conducting pathways to the extrastriate dorsal stream is a common characteristic of simian primates. In the superficial layers of V1 in Cebus monkeys, however, SMI-32-labeled neurons are found in both cytochrome oxidase blobs and interblob regions. In this aspect, our results in Cebus are similar to those found in the Old World monkey Macaca and different from those described for squirrel monkey, a smaller New World Monkey. In Cebus, as well as in Macaca, there is no correlation between SMI-32 distribution and the blob pattern.     

Differences in muscle activity before, during, and after responding in a simple reaction time task: schizophrenics vs. normals.

Schizophrenics and normals were presented with a series of simple reaction time (RT) trials. Electromyographic techniques were used to partition RT into peripheral and central components. It was observed that contrary to the previously held assumption of "neuromuscular sameness," schizophrenics displayed a qualitatively different pattern of muscle activity in their motor responding. Differences of the observed sort could account, in part, for differences previously thought to be due solely to central dysfunction.     

Gamma-frequency fluctuations of the membrane potential and response selectivity in visual cortical neurons

Fluctuations at frequencies of 25-70 Hz is an inherent property of cortical activity. These rapid, gamma-range fluctuations are apparent in the local field potentials, in spiking of cells and cell groups, and in the membrane potential of neurons. To investigate stimulus dependence of the gamma-frequency fluctuations of the membrane potential, we have recorded intracellularly responses of cells in cat visual cortex to presentation of moving gratings. We found gamma-range fluctuations of the membrane potential in both simple and complex cells. The strength of the gamma-frequency fluctuations correlated with the stimulus optimality. Furthermore, the amplitude of the gamma-frequency fluctuations correlated with the phase of stimulus-imposed slow changes of the membrane potential. The combination of these features makes cortical neurons capable of encoding the slow changes in the visual world in a kind of amplitude modulation of the high frequency fluctuations. This assures reliable transformation of the membrane potential changes into spike responses without compromising the temporal resolution of visual information encoding in the low frequency range.     

Spatial and temporal frequency selectivity of neurons in the middle temporal visual area of new world monkeys (Callithrix jacchus)

Information about the responses of neurons to the spatial and temporal frequencies of visual stimuli is important for understanding the types of computations being performed in different visual areas. We characterized the spatiotemporal selectivity of neurons in the middle temporal area (MT), which is deemed central for the processing of direction and speed of motion. Recordings obtained in marmoset monkeys using high-contrast sine-wave gratings as stimuli revealed that the majority of neurons had bandpass spatial and temporal frequency tuning, and that the selectivity for these parameters was largely separable. Only in about one-third of the cells was inseparable spatiotemporal tuning detected, this typically being in the form of an increase in the optimal temporal frequency as a function of increasing grating spatial frequency. However, most of these interactions were weak, and only 10% of neurons showed spatial frequency-invariant representation of speed. Cells with inseparable spatiotemporal tuning were most commonly found in the infragranular layers, raising the possibility that they form part of the feedback from MT to caudal visual areas. While spatial frequency tuning curves were approximately scale-invariant on a logarithmic scale, temporal frequency tuning curves covering different portions of the spectrum showed marked and systematic changes. Thus, MT neurons can be reasonably described as similarly built spatial frequency filters, each covering a different dynamic range. The small proportion of speed-tuned neurons, together with the laminar position of these units, are compatible with the idea that an explicit neural representation of speed emerges from computations performed in MT.     

Visual attention in huntington''s disease: The effect of cueing on saccade latencies and manual reaction times

Studies of eye movements in patients with Huntington's disease (HD) have suggested that frontal lobe-basal ganglia structures are more involved in HD than the parietal lobes. To test this hypothesis further we compared the ability of HD patients and normal subjects to direct “covert” visual attention, using saccade latency and thumb press reaction time tasks that have been shown to be sensitive to parietal lobe dysfunction.

Subjects were instructed to move their eyes or to press a button when a peripheral target was illuminated. The peripheral stimulus appeared at various intervals after the appearance of a central arrow(s) that pointed in the direction of the target (valid cue), in the opposite direction (invalid cue), or pointed simultaneously in both directions (neutral cue). For both saccade and thumb press paradigms, the difference in the latencies for trials with invalid and valid cues was the same in HD patients and normals. These findings suggest that the ability to direct visual attention is normal in HD and are compatible with the hypothesis that in HD, frontal-basal ganglia circuits are more affected than parietal lobe pathways.     

Impairment of rapid repetitive finger movements and visual reaction time in patients with essential tremor

Background and purpose:  The question whether patients with essential tremor (ET) have slowed movements as part of their clinical manifestations is still a matter of controversy. We analyzed basic motor function in patients with ET and in healthy matched controls.
Methods:  We studied 61 patients with ET and 122 age- and sex-matched controls. Evaluation included four timed tests (pronation-supination, finger tapping and movement between two points, all with both hands, and walking test); and three tests performed on a personal computer (speed for pressing repetitively a key – frequency, visual reaction time and movement time, all with both hands).
Results:  Essential tremor patients showed higher mean values for right and left finger tapping, left movement between two points; and with right and left frequency and reaction time. In the logistic regression study, ET patients showed significantly higher values than controls for right and left finger tapping; mean, SD, maximum and rank values of right and left frequency; and mean, SD, minimum, maximum and rank values of right and left visual reaction time. Tremor severity was not correlated with the altered values.
Conclusions:  Patients with ET showed impaired motor performance, at least in some tasks, such as rapid repetitive finger movements (finger tapping and frequency) and visual reaction time (impairment was not related with tremor severity). This probably means that patients with ET have some degree of bradykinesia.     

Effects of age, intelligence and executive control function on saccadic reaction time in persons with intellectual disabilities

The current research aimed to clarify the influence of age, intelligence and executive control function on the central tendency and intraindividual variability of saccadic reaction time in persons with intellectual disabilities. Participants were 44 persons with intellectual disabilities aged between 13 and 57 years whose IQs were between 14 and 70. Executive control function was evaluated by a test of sustained simple motor action. To elicit saccades, a predictive visually guided saccade paradigm was used. Intelligence and executive control function were significantly associated with saccadic reaction time. The central tendency of saccadic reaction time was negatively correlated with intelligence. The more serious the degree of executive control dysfunction was, the larger the intraindividual variability of saccadic reaction time. It is thought that intelligence and executive control function have relatively independent influences on saccadic reaction time. However, there is a possibility that the increase of intraindividual variability in saccadic reaction time due to the problem of executive control function extends the central tendency of saccadic reaction time.     

Contrast-dependent, contextual response modulation in primary visual cortex and lateral geniculate nucleus of the cat

In the primary visual cortex (V1), the responses of neurons to stimuli presented in their classical receptive fields (CRFs) are modulated by another stimulus concurrently presented in their surround (receptive field surround, SRF). We studied the nature of the modulatory effects of SRF stimulation with respect to stimulus contrast in cat V1. In 51 V1 neurons studied, large SRF stimuli (40 degreesx30 degrees ) induced only the suppression of responses to CRF stimulation and the suppressive effects became stronger as the contrast for SRF stimulation increased. The contrast sensitivity of SRF suppression did not correlate with that of CRF responses. By independently controlling contrast of CRF and SRF stimuli, we studied whether SRF effects vary with CRF response magnitude. Increasing contrast for CRF stimulation caused an upward shift of the range of effective contrasts for SRF stimulation, indicating that a high contrast for SRF stimulation is required for suppressing strong responses to CRF stimulation at high contrasts. To assess the possible origin of the suppressive SRF effect on V1 neurons, we also investigated the contrast dependency of SRF effects in 28 neurons from the lateral geniculate nucleus. Our results suggest that SRF effects obtained at the subcortical level strongly contribute to those in V1. Taken together, we conclude that along the thalamocortical projections, SRF modulation exhibits a gain-control mechanism that scales the suppressive SRF effect depending on the contrast for CRF stimulation. In addition, SRF effects can be facilitatory at low stimulus contrasts potentially due to the enlargement of the summation field.