Large-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems

Large-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems. J. Neurophysiol. 80: 3148-3162, 1998. Functional relations between specialized parts of the brain may be important determinants of learned behaviors. To study this, we examined the interrelations of the auditory system with several extraauditory structures in two groups of rats having different behavioral histories. Both groups were trained to associate a tone conditional stimulus (CS) with an aversive unconditional stimulus (US). For one group, a light presented with the tone predicted the absence of the US (group TL-). In the other group, the light was a neutral stimulus (group TL0). Fluorodeoxyglucose (FDG) incorporation was measured in the presence of the tone-light compound. Because the tone-light compound was physically identical for both groups, neural differences between groups reflected differences in the learned associative properties of the stimuli. Covariances of FDG uptake in the auditory system and extraauditory structures were examined using partial least squares. Three strong covariance or functional connectivity patterns were identified. The first pattern mainly reflected similarities between groups, with strong interrelations between the subcortical auditory system and the thalamocortical visual system, cerebellum, deep cerebellar nuclei, and midline thalamus. This pattern of interactions may represent part of a common circuit for relaying the associative value of the tone CS to the cerebellum and the midline thalamus. The external nucleus of the inferior colliculus and medial division of the medial geniculate nucleus were associated more strongly with this pattern for group TL-, which was interpreted as representing the change of the associative value of the tone by the light, mediated through extraauditory influences on these two regions. A second pattern involved midbrain auditory regions, superior colliculus, zona incerta, and subiculum and was stronger for group TL0. The relations between midbrain structures may represent the excitatory conditioned response (CR) evoked by the tone in this group. The final pattern was strongest in group TL- and involved interrelations of the thalamocortical auditory system with hippocampus, basolateral amygdala, and hypothalamus. This pattern may represent the learned inhibition of the CR to the tone in the presence of the light. These findings are consistent with behavioral studies suggesting that at least two types of associations are formed during associative learning. One is the sensory relation of the stimuli and another is the relation between the CS and the affective components of the US. These behavioral associations are mapped to the patterns of functional connectivity between auditory and extraauditory regions.     

A complexity measure for selective matching of signals by the brain

We have previously derived a theoretical measure of neural complexity (CN) in an attempt to characterize functional connectivity in the brain. CN measures the amount and heterogeneity of statistical correlations within a neural system in terms of the mutual information between subsets of its units. CN was initially used to characterize the functional connectivity of a neural system isolated from the environment. In the present paper, we introduce a related statistical measure, matching complexity (CM), which reflects the change in CN that occurs after a neural system receives signals from the environment. CM measures how well the ensemble of intrinsic correlations within a neural system fits the statistical structure of the sensory input. We show that CM is low when the intrinsic connectivity of a simulated cortical area is randomly organized. Conversely, CM is high when the intrinsic connectivity is modified so as to differentially amplify those intrinsic correlations that happen to be enhanced by sensory input. When the input is represented by an individual stimulus, a positive value of CM indicates that the limited mutual information between sensory sheets sampling the stimulus and the rest of the brain triggers a large increase in the mutual information between many functionally specialized subsets within the brain. In this way, a complex brain can deal with context and go "beyond the information given."     

The kininogen gene family in obstructive uropathy

Because many patients present themselves for treatment with both craniofacial and craniocervical pain, 2 questions arise: (1) What are the sensory and motor consequences of dysfunction in either of these areas on the other? (2) Do craniofacial and craniocervical pain have a similar cause? These questions formed the impetus for this review article. The phenomenon of concurrent pain in craniofacial and cervical structures is considered, and clinical reports and opinions are presented regarding theories of cervical-to-craniofacial and craniofacial-to-cervical pain referral. Because pain referral between these 2 areas requires anatomic and functional connectivity between trigeminally and cervically innervated structures, basic neurophysiologic and neuroanatomic literature is reviewed. The published data clearly demonstrate neurophysiologic and structural convergence of cervical sensory and muscle afferent inputs onto trigeminal subnucleus caudalis nociceptive and non-nociceptive neurons. Moreover, changes in metabolic activity and blood flow in the brainstem and cervical dorsal horn of the spinal cord in both monkeys and cats have been demonstrated after electric stimulation of the V1-innervated superior sagittal sinus. In conclusion, the animal experimental data support the findings of human empiric and experimental studies, which suggest that strong connectivity exists between trigeminal and cervical motor and sensory responses.     

The frontal eye field and attention.

Mammalian sensory systems must continuously select the events to be noticed from the ongoing stream of information, filtering out or habituating to the insignificant. This selective noticing is the province of central mechanisms of orientation and attention that are represented in structures along the neuraxis from brain stem to neocortex. One of the structures is the frontal eye field, long known to be implicated in visual attention through its involvement in horizontal movements of the eyes. The author reviews the relevant neuroanatomy and behavioral and electrophysiological research that decisively show that this small but complex region does more than regulate eye movements. Theories of frontal eye field function are considered, concluding with 2 contemporary views of attention, one based on arousal and the other on the processes of representation of stimulus input, that offer special promise for understanding the role of frontal cortex in the direction of attention. (5 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analog VLSI-based modeling of the primate oculomotor system

One way to understand a neurobiological system is by building a simulacrum that replicates its behavior in real time using similar constraints. Analog very large-scale integrated (VLSI) electronic circuit technology provides such an enabling technology. We here describe a neuromorphic system that is part of a long-term effort to understand the primate oculomotor system. It requires both fast sensory processing and fast motor control to interact with the world. A one-dimensional hardware model of the primate eye has been built that simulates the physical dynamics of the biological system. It is driven by two different analog VLSI chips, one mimicking cortical visual processing for target selection and tracking and another modeling brain stem circuits that drive the eye muscles. Our oculomotor plant demonstrates both smooth pursuit movements, driven by a retinal velocity error signal, and saccadic eye movements, controlled by retinal position error, and can reproduce several behavioral, stimulation, lesion, and adaptation experiments performed on primates.     

Cooperative formation of the ligand-binding site of the inositol 1,4, 5-trisphosphate receptor by two separable domains

According to Einstein's equivalence principle, inertial accelerations during translational motion are physically indistinguishable from gravitational accelerations experienced during tilting movements. Nevertheless, despite ambiguous sensory representation of motion in primary otolith afferents, primate oculomotor responses are appropriately compensatory for the correct translational component of the head movement. The neural computational strategies used by the brain to discriminate the two and to reliably detect translational motion were investigated in the primate vestibulo-ocular system. The experimental protocols consisted of either lateral translations, roll tilts, or combined translation-tilt paradigms. Results using both steady-state sinusoidal and transient motion profiles in darkness or near target viewing demonstrated that semicircular canal signals are necessary sensory cues for the discrimination between different sources of linear acceleration. When the semicircular canals were inactivated, horizontal eye movements (appropriate for translational motion) could no longer be correlated with head translation. Instead, translational eye movements totally reflected the erroneous primary otolith afferent signals and were correlated with the resultant acceleration, regardless of whether it resulted from translation or tilt. Therefore, at least for frequencies in which the vestibulo-ocular reflex is important for gaze stabilization (>0.1 Hz), the oculomotor system discriminates between head translation and tilt primarily by sensory integration mechanisms rather than frequency segregation of otolith afferent information. Nonlinear neural computational schemes are proposed in which not only linear acceleration information from the otolith receptors but also angular velocity signals from the semicircular canals are simultaneously used by the brain to correctly estimate the source of linear acceleration and to elicit appropriate oculomotor responses.     

Somatotopy in the human motor cortex hand area. A high-resolution functional MRI study

Fine-scale somatotopic encoding in brain areas devoted to sensorimotor processing has recently been questioned by functional neuroimaging studies which suggested its absence within the hand area of the human primary motor cortex. We re-examined this issue by addressing somatotopy both in terms of functional segregation and of cortical response preference using oxygenation-sensitive magnetic resonance imaging at high spatial resolution. In a first step, spatial representations of self-paced isolated finger movements were mapped by using motor rest as a control state. A subsequent experimental design studied the predominance of individual finger movements by using contrasting finger movements as the control task. While the first approach confirmed previous reports of extensive overlap in spatial representations, the second approach revealed foci of differential activation which displayed an orderly mediolateral progression in accordance with the classical cortical motor homunculus. We conclude that somatotopy within the hand area of the primary motor cortex does not present as qualitative functional segregation but as quantitative predominance of certain movement or digit representation embedded in an overall joint hand area.     

Eye movement as an indicator of sensory components in thought.

This study investigated a claim of the Neuro-Linguistic Programming (NLP) eye movement model, which states that specific eye movements are indicative of specific sensory components in thought. Forty-eight graduates and undergraduates were asked to concentrate on a single thought while their eye movements were videotaped. They were subsequently asked to report if their thoughts contained visual, auditory, or kinesthetic components. Two NLP-trained observers independently viewed silent videotapes of participants concentrating and recorded the presence or absence of eye movements posited by NLP theorists to indicate visual, auditory, or kinesthetic components in thought. Coefficients of agreement (Cohen's K) between participants' self-reports and trained observers' records indicate support for the visual (K?=?.81, p?p?p?     

Elucidating dynamic brain interactions with across-subjects correlational analyses of positron emission tomographic data: the functional connectivity of the amygdala and orbitofrontal cortex during olfactory tasks

Covariance analyses of positron emission tomography (PET) data are used increasingly to elucidate the functional connectivity between brain regions during different cognitive tasks. Functional connectivity may be estimated by examining the covariance between regions over time or across subjects. In functional brain-mapping studies, across-subjects covariance matrices derived from within-task (nonsubtracted) and between-task (subtracted) data characterize different, complementary aspects of functional interactions. The authors study amygdala-orbitofrontal interactions during three task conditions (aversive olfaction, odor detection, and resting with eyes closed) to illustrate the strengths and limitations of across-subjects covariance analyses based on subtracted and nonsubtracted data. This example underscores the dynamic nature of connectivity between the amygdalae and orbitofrontal cortices and highlights the importance of including data from resting conditions in covariance analyses.     

Vascularized bone flaps versus nonvascularized bone grafts for mandibular reconstruction: an outcome analysis of primary bony union and endosseous implant success

We present a patient with a lesion of the mesial frontal cortex, including the supplementary motor areas bilaterally, who on clinical examination revealed no spontaneous movements, although neurophysiological examination indicated integrity of the corticospinal tract to thenar and tibialis anterior muscles bilaterally. The patient was alert, speech was hesitant, and he was able to move his hands only on command. The role of the supplementary motor areas in planning, setting, and execution of skillful voluntary movements has been previously established by direct cortical electrical stimulation and studies of regional cerebral blood flow. The findings in our patient support the role of the supplementary motor areas in initiating movements. The presence of motor evoked potentials after acute insults to the brain is considered to be associated with a good functional outcome. This is in contrast to our patient who did not show improvement in motor performance, despite preserved motor evoked potentials. Hence, in the case of bilateral lesions to the supplementary motor areas sparing the corticospinal tract, the presence of motor evoked potentials may not predict functional recovery.     

Effect of horizontal vergence on the motor and sensory components of vertical fusion

PURPOSE: To compare motor and sensory capabilities for fusion of vertical disparities at different angles of horizontal vergence in healthy humans. METHODS: Eye movements were recorded from both eyes of 12 healthy subjects using three-axis search coils. The stimulus was a cross (+) (3.4 x 3.2 degrees , vertically and horizontally, respectively) presented to each eye with a stereoscopic display. Vertical disparities were introduced by adjusting the vertical position of the cross in front of one eye. The disparity was increased in small increments (0.08 degrees ) every 8 seconds. Viewing was defined as "near" if there was a horizontal disparity that elicited 6 degrees to 15 degrees convergence, depending on the subject's capability for horizontal fusion; viewing was defined as "far" at 1 degrees convergence. Maximum motor (measured), sensory (stimulus minus motor), and total (motor plus sensory) vertical fusion were compared. RESULTS: In 9 (75%) of 12 subjects the maximum total vertical fusion was more in near than in far viewing. The three who did not show this effect had relatively weak horizontal fusion. For the entire group, the motor component differed significantly between far (mean, 1.42 degrees ) and near (mean, 2.13 degrees). Total vertical fusion capability (motor plus sensory) also differed significantly between far (mean, 1.68 degrees ) and near (mean, 2.39 degrees ). For the sensory component there was no difference between between far (mean, 0.268 degrees ) and near (mean, 0.270 degrees ). As vertical disparity increased in a single trial, however, there was a small gradual increase of the contribution of the sensory component to vertical fusion. CONCLUSIONS: Vertical fusion capability usually increases with convergence. This increase is caused primarily by an increase in the motor component. There is a gradual but small increase in the sensory component as target disparity slowly increases.     

Microbial populations of Botrytis cinerea-inoculated strawberry fruit exposed to four volatile compounds

OBJECTIVE: The authors tested the hypothesis that eye tracking disorder in schizophrenia is associated with neurological signs. METHOD: The subjects were 93 normal comparison subjects and 59 schizophrenic patients. They were evaluated with the Neurological Evaluation Scale, a standardized rating instrument that assesses sensory integration, motor coordination, sequencing of complex motor acts, and other neurological signs. Also, the schizophrenic patients' smooth-pursuit eye movements were tested in response to a 0.3-Hz sinusoidal target by means of infrared oculography. They were divided into those with (N=18) and without (N=41) eye tracking disorder by using a previously described method, which was based on mixture analysis of the distribution of position root mean square error. RESULTS: The patients with eye tracking disorder had significantly worse performance than the patients without eye tracking disorder with respect to sensory integration, and the effect size was moderate to large. In comparison with the normal subjects, both patient subgroups had significantly worse performance on all of the Neurological Evaluation Scale subscales. CONCLUSIONS: Although neurological signs are present generally in schizophrenia, poor sensory integration is particularly pronounced in patients with eye tracking disorder. A review of the literature shows that the two abnormalities have strikingly similar patterns of validators, including 1) familial aggregation, 2) premorbid presence, 3) syndromal specificity, 4) trait status, and 5) association with the deficit syndrome. Poor sensory integration and eye tracking disorder in schizophrenia may be various manifestations of a common, underlying pathophysiological process.     

Inhibitory neural mechanisms in spatial orienting.

This talk reviews studies in normal and brain-injured humans which have revealed separate neural structures which control covert attention and others which regulate eye movements. These studies have also identified subcortical brain regions critical for reflexive orienting, and cortical regions important for endogenously controlled orienting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Integrative visuomotor behavior is associated with interregionally coherent oscillations in the human brain

Coherent electrical brain activity has been demonstrated to be associated with perceptual events in mammals. It is unclear whether or not it is also a mechanism instrumental in the performance of sensorimotor tasks requiring the continuous processing of information between primarily executive and receptive brain areas. In particular it is unknown whether or not interregional coherent activity detectable in electroencephalographic (EEG) recordings on the scalp reflects interareal functional cooperativity in humans. We studied patterns of changes in EEG-coherence associated with a visuomotor force-tracking task in seven subjects. Interregional coherence of EEG signals recorded from scalp regions overlying the visual and the motor cortex increased in comparison to a resting condition when subjects tracked a visual target by producing an isometric force with their right index finger. Coherence between visual and motor cortex decreased when the subjects produced a similar motor output in the presence of a visual distractor and was unchanged in a purely visual and purely motor task. Increases and decreases of coherence were best differentiated in the low beta frequency range (13-21 Hz). This observation suggests a special functional significance of low frequency oscillations in information processing in large-scale networks. These findings substantiate the view that coherent brain activity underlies integrative sensorimotor behavior.     

Prolonged studies of perfluorocarbon associated gas exchange and of the resumption of conventional mechanical ventilation

We applied functional magnetic resonance imaging (FMRI) to map the somatotopic organization of the primary motor cortex using voluntary movements of the hand, arm, and foot. Eight right-handed healthy subjects performed self-paced, repetitive, flexion/extension movements of the limbs while undergoing echo-planar imaging. Four subjects performed movements of the right fingers and toes, while the remaining subjects performed movements of the right fingers and elbow joint. There was statistically significant functional activity in the left primary motor cortex in all subjects. The pattern of functional activity followed a topographic representation: finger movements resulted in signal intensity changes over the convexity of the left motor cortex, whereas toe movements produced changes either at the interhemispheric fissure or on the dorsolateral surface adjacent to the interhemispheric fissure. Elbow movements overlapped the more medial signal intensity changes observed with finger movements. Functionally active regions were confined to the cortical ribbon and followed the gyral anatomy closely. These findings indicate that FMRI is capable of generating somatotopic maps of the primary motor cortex in individual subjects.     

Electrical stimulation of precentral cortical area in the treatment of central pain: electrophysiological and PET study

The clinical, electrophysiological and haemodynamic effects of precentral gyrus stimulation (PGS) as a treatment of refractory post-stroke pain were studied in 2 patients. The first patient had a right hemibody pain secondary to a left parietal infarct sparing the thalamus, while the second patient had left lower limb pain developed after a right mesencephalic infarct. In both cases, spontaneous pain was associated with hyperpathia, allodynia and hypoaesthesia in the painful territory involving both lemniscal and extra-lemniscal sensory modalities in patient 1, extra-lemniscal sensory modality only in patient 2. Both patients were treated with electrical PGS by means of a 4-pole electrode, the central sulcus being per-operatively located using the phase-reversal of the N20 wave of somatosensory evoked potentials. No sensory side effect, abnormal movement or epileptic seizure were observed during PGS. The analgesic effects were somatotopically distributed according to the localization of electrode on motor cortex. A satisfactory long-lasting pain control (60-70% on visual analog scale) as well as attenuation of nociceptive reflexes were obtained during PGS in the first patient. Pain relief was less marked and only transient (2 months) in patient 2, in spite of a similar operative procedure. In this patient, in whom PGS eventually evoked painful dysethesiae, no attenuation of nociceptive RIII reflex could be evidenced during PGS. Cerebral blood flow (CBF) was studied using emission tomography (PET) with O-labeled water. The sites of CBF increase during PGS were the same in both patients, namely the thalamus ipsilateral to PGS, cingulate gyrus, orbito-frontal cortex and brainstem. CBF increase in brainstem structures was greater and lasted longer in patient 1 while patient 2 showed a greater CBF increase in orbito-frontal and cingular regions. Our results suggest that PGS-induced analgesia is somatotopically mediated and does not require the integrity of somatosensory cortex and lemniscal system. PGS analgesic efficacy may be mainly related to increased synaptic activity in the thalamus and brainstem while changes in cingulate gyrus and orbito-frontal cortex may be rather related to attentional and/or emotional processes. The inhibitory control on pain would involve thalamic and/or brainstem relays on descending pathways down to the spinal cord segments, leading to a depression of nociceptive reflexes. Painful dysesthesiae during stimulation have to be distinguished from other innocuous sensory side effects, since they may compromise PGS efficacy.     

Coding of intention in the posterior parietal cortex

To look at or reach for what we see, spatial information from the visual system must be transformed into a motor plan. The posterior parietal cortex (PPC) is well placed to perform this function, because it lies between visual areas, which encode spatial information, and motor cortical areas. The PPC contains several subdivisions, which are generally conceived as high-order sensory areas. Neurons in area 7a and the lateral intraparietal area fire before and during visually guided saccades. Other neurons in areas 7a and 5 are active before and during visually guided arm movements. These areas are also active during memory tasks in which the animal remembers the location of a target for hundreds of milliseconds before making an eye or arm movement. Such activity could reflect either visual attention or the intention to make movements. This question is difficult to resolve, because even if the animal maintains fixation while directing attention to a peripheral location, the observed neuronal activity could reflect movements that are planned but not executed. To address this, we recorded from the PPC while monkeys planned either reaches or saccades to a single remembered location. We now report that, for most neurons, activity before the movement depended on the type of movement being planned. We conclude that PPC contains signals related to what the animal intends to do.     

A jitter after-effect reveals motion-based stabilization of vision

A shaky hand holding a video camera invariably turns a treasured moment into an annoying, jittery momento. More recent consumer cameras thoughtfully offer stabilization mechanisms to compensate for our unsteady grip. Our eyes face a similar challenge in that they are constantly making small movements even when we try to maintain a fixed gaze. What should be substantial, distracting jitter passes completely unseen. Position changes from large eye movements (saccades) seem to be corrected on the basis of extraretinal signals such as the motor commands sent to the eye muscle, and the resulting motion responses seem to be simply switched off. But this approach is impracticable for incessant, small displacements, and here we describe a novel visual illusion that reveals a compensation mechanism based on visual motion signals. Observers were adapted to a patch of dynamic random noise and then viewed a larger pattern of static random noise. The static noise in the unadapted regions then appeared to 'jitter' coherently in random directions. Several observations indicate that this visual jitter directly reflects fixational eye movements. We propose a model that accounts for this illusion as well as the stability of the visual world during small and/or slow eye movements such as fixational drift, smooth pursuit and low-amplitude mechanical vibrations of the eyes.     

Trigeminal disynaptic circuit mediating corneal afferent input to M. depressor palpebrae inferioris motoneurons in the pigeon (Columba livia)

Corneal afferent projections to the trigeminal brainstem nuclear complex (TBNC) and associated structures, as determined by transganglionic transport of various tracers, were found to be predominantly concentrated in two distinct patches in the dorsolateral medulla at periobex levels. One was in the external cuneate nucleus, and the other was in the ventralmost part of the ophthalmic division of the TBNC. The projections of putative second-order neurons in these regions, as determined by injections of wheat germ agglutinin conjugated to horseradish peroxidase into the dorsolateral medulla, were found to include the dorsal trigeminal motor nucleus (Vd), which innervates the M. depressor palpebrae inferioris. Electrical stimulation of Vd, which elicited lower eyelid movements, was then used to guide injections of tracer into Vd, which retrogradely labeled clusters of neurons in the corneal afferent recipient regions of the dorsolateral medulla. The lower eyelid of pigeons, unlike the nictitating membrane and upper lid, does not appear to be appreciably involved in either reflex blinking in response to relatively mild stimulation of the cornea (e.g., air puff), or in eye closure during the saccade-like head movements associated with walking, or in eye closure during pecking; but in response to a stimulus that makes corneal contact, an upward movement of the lower lid follows descent of the nictitating membrane and upper lid as part of a defensive eye-closing mechanism. The anatomical results thus appear to define a dedicated disynaptic trigeminal sensorimotor circuit for the control of lower eyelid motility in response to mechanical or noxious stimuli of the cornea. Injections of tracers into the lower and upper eyelids labeled palpebral sensory afferents that terminated predominantly in maxillary and ophthalmic portions, respectively, of the dorsal horn of upper cervical spinal segments. These terminal fields were therefore largely separate from those of corneal afferents. There were no specific corneal afferent projections upon accessory abducens motoneurons that innervate the two muscles controlling the nictitating membrane.     

Unilateral saccadic pursuit in patients with sensory stroke: sign of a pontine tegmentum lesion

BACKGROUND AND PURPOSE: Pure hemisensory syndrome can be caused by small strokes occurring in a number of regions, including the thalamus and pons. Differentiation of the pontine sensory syndrome from the thalamic sensory syndrome has generally been made on the basis of distribution of sensory loss and involvement of specific sensory modalities but not without uncertainties and difficulties. Because the pontine tegmentum plays a pivotal role in generating horizontal eye movement, we attempted to discriminate these 2 syndromes by analyzing horizontal eye movements in stroke patients with pure hemisensory syndrome. METHODS: Horizontal saccade, pursuit, vestibulo-ocular reflex (VOR), and VOR cancellation (VORC) were evaluated using electro-oculography in 6 patients with hemisensory syndromes, 3 due to pontine stroke and 3 due to thalamic stroke, and all were verified by MRI or CT. In addition, somatosensory evoked potentials (SEPs) were recorded. RESULTS: Smooth pursuit and VORC directed toward the side of the lesion were impaired unilaterally in patients with pontine sensory stroke, whereas those 2 movements were intact bilaterally in patients with thalamic sensory stroke. Saccade and VOR were preserved in all patients. SEPs were normal in all patients with pontine and thalamic sensory strokes. No difference was found in the pattern of sensory disturbance between the 2 types of stroke patients. CONCLUSIONS: Ipsilateral impairment of the smooth pursuit system may be a sign of a pontine lesion in patients with hemisensory stroke.