Medial auditory thalamic stimulation as a conditioned stimulus for eyeblink conditioning in rats

The neural pathways that convey conditioned stimulus (CS) information to the cerebellum during eyeblink conditioning have not been fully delineated. It is well established that pontine mossy fiber inputs to the cerebellum convey CS-related stimulation for different sensory modalities (e.g., auditory, visual, tactile). Less is known about the sources of sensory input to the pons that are important for eyeblink conditioning. The first experiment of the current study was designed to determine whether electrical stimulation of the medial auditory thalamic nuclei is a sufficient CS for establishing eyeblink conditioning in rats. The second experiment used anterograde and retrograde tract tracing techniques to assess neuroanatomical connections between the medial auditory thalamus and pontine nuclei. Stimulation of the medial auditory thalamus was a very effective CS for eyeblink conditioning in rats, and the medial auditory thalamus has direct ipsilateral projections to the pontine nuclei. The results suggest that the medial auditory thalamic nuclei and their projections to the pontine nuclei are components of the auditory CS pathway in eyeblink conditioning.     

选择注意神经机制:前扣带皮层对躯体感觉输入的丘脑-皮层调制

本文阐述了认知神经科学关于选择注意发生在感知觉中枢信息流加工较早阶段以及前扣带皮层（ACC）在丘脑和初级感觉皮层水平调制躯体感觉输入的研究证据,揭示了ACC在感知觉信息加工早期的选择注意控制执行机能,以及实行该机能的神经途径。     

Lateral and anterior thalamic lesions impair independent memory systems

Damage to the medial region of the thalamus, both in clinical cases (e.g., patients with infarcts or the Korsakoff's syndrome) and animal lesion models, is associated with variable amnesic deficits. Some studies suggest that many of these memory deficits rely on the presence of lateral thalamic lesions (LT) that include the intralaminar nuclei, presumably by altering normal function between the striatum and frontal cortex. Other studies suggest that the anterior thalamic nuclei (AT) may be more critical, as a result of disruption to an extended hippocampal system. Here, highly selective LT and AT lesions were made to test the prediction that these two regions contribute to two different memory systems. Only LT lesions produced deficits on a preoperatively acquired response-related (egocentric) working memory task, tested in a cross-maze. Conversely, only AT lesions impaired postoperative acquisition of spatial working memory, tested in a radial maze. These findings provide the first direct evidence of a double dissociation between the LT and AT neural aggregates. As the lateral and the anterior medial thalamus influence parallel independent memory processing systems, they may each contribute to memory deficits, depending on lesion extent in clinical and experimental cases of thalamic amnesia.     

The role of the human thalamus in language and memory: evidence from electrophysiological studies

The data reviewed here indicate that electrical stimulation of the dominant ventrolateral thalamus can produce deficits in language processing that are not seen after similar stimulation of the nondominant ventrolateral thalamus. The nature of the language deficit produced varies, depending upon the rostrocaudal location of the stimulation site. Stimulation of the anterior left ventrolateral thalamus in right-handed patients resulted in production of a repeated erroneous word, stimulation of the medial ventrolateral thalamus evoked perseveration, and stimulation of the posterior ventrolateral thalamus and anterior pulvinar resulted in misnaming and omissions. Additional studies have examined the effect of electrical thalamic stimulation on verbal and nonverbal short-term memory. Left (but not right) ventrolateral thalamic stimulation during verbal memory input greatly decreased subsequent recall errors, while stimulation during verbal memory retrieval increased recall errors. This finding contrasted with those obtained from studies on nonverbal memory, in which right ventrolateral stimulation during memory input decreased recall errors, while left thalamic stimulation at the same stage increased recall errors. Left pulvinar stimulation disrupted verbal memory processing, while right pulvinar stimulation disrupted nonverbal memory processing. Limited evidence suggests that the effects of thalamic electrical stimulation on verbal memory may persist for several days after the stimulation has ended. The lateralization of thalamic functions also affects the motoric aspects of speech production. Left (but not right) ventrolateral thalamic stimulation disrupted speech articulation and increased the expiratory phase of respiration. The fact that these motor effects were evoked from the same general area of the thalamus that produced the language deficits discussed above raises the possibility that the thalamus is involved in coordinating the cognitive and motoric aspects of language production. A model of thalamic function is discussed in which defined regions of the thalamus operate as a "specific alerting response," increasing the input to memory of category-specific material while simultaneously inhibiting retrieval from memory.     

Attention versus consciousness in the visual brain: differences in conception, phenomenology, behavior, neuroanatomy, and physiology.

A common confound between consciousness and attention makes it difficult to think clearly about recent advances in the understanding of the visual brain. Visual consciousness involves phenomenal experience of the visual world, but visual attention is more plausibly treated as a function that selects and maintains the selection of potential conscious contents, often unconsciously. In the same sense, eye movements select conscious visual events, which are not the same as conscious visual experience. According to common sense, visual experience is consciousness, and selective processes are labeled as attention. The distinction is reflected in very different behavioral measures and in very different brain anatomy and physiology. Visual consciousness tends to be associated with the "what" stream of visual feature neurons in the ventral temporal lobe. In contrast, attentional selection and maintenance are mediated by other brain regions, ranging from superior colliculi to thalamus, prefrontal cortex, and anterior cingulate. The author applied the common-sense distinction between attention and consciousness to the theoretical positions of M. I. Posner (1992, 1994) and D. LaBerge (1997, 1998) to show how it helps to clarify the evidence. He concluded that clarity of thought is served by calling a thing by its proper name.     

A field theory of consciousness.

This article summarizes a variety of current as well as previous research in support of a new theory of consciousness. Evidence has been steadily accumulating that information about a stimulus complex is distributed to many neuronal populations dispersed throughout the brain and is represented by the departure from randomness of the temporal pattern of neural discharges within these large ensembles. Zero phase lag synchronization occurs between discharges of neurons in different brain regions and is enhanced by presentation of stimuli. This evidence further suggests that spatiotemporal patterns of coherence, which have been identified by spatial principal component analysis, may encode a multidimensional representation of a present or past event. How such distributed information is integrated into a holistic precept constitutes the binding problem. How a precept defined by a spatial distribution of nonrandomness can be subjectively experienced constitutes the problem of consciousness. Explanations based on a discrete connectionistic network cannot be reconciled with the relevant facts. Evidence is presented herein of invariant features of brain electrical activity found to change reversibly with loss and return of consciousness in a study of 176 patients anesthetized during surgical procedures. A review of relevant research areas, as well as the anesthesia data, leads to a postulation that consciousness is a property of quantum-like processes, within a brain field resonating within a core of structures, which may be the neural substrate of consciousness. This core includes regions of the prefrontal cortex, the frontal cortex, the pre- and paracentral cortex, thalamus, limbic system, and basal ganglia.     

Posterior parietal cortex as part of a neural network for directed attention in rats

A rodent model of directed attention has been developed based upon behavioral analysis of contralateral neglect, pharmacological manipulations, and anatomical analysis of neural circuitry. In each of these three domains the rodent model exhibits striking similarities to humans. We hypothesize that there is a specific thalamo-cortical-basal ganglia network that subserves spatial attentional functions. Key components of this network are medial agranular and posterior parietal cortex, dorsocentral striatum, and the lateral posterior thalamic nucleus. Several issues need to be addressed before we can hope to realistically understand or model the functions of this network. Among these are the roles of medial versus lateral posterior parietal cortex; cholinergic mechanisms in attention; interhemispheric interactions; the role of synchronous firing at the cortical, striatal, and thalamic levels; interactions between cortical and thalamic projections to the striatum; interactions between cortical and nigral inputs to the thalamus; the role of collicular inputs to the lateral posterior thalamic nucleus; the role of cerebral cortex versus superior colliculus in driving the motor output expressed as orienting behavior during directed attention; the extent to which the circuitry we describe for directed attention also plays a role in other forms of attention.     

Ontogenetic change in the auditory conditioned stimulus pathway for eyeblink conditioning

Two experiments examined the neural mechanisms underlying the ontogenetic emergence of auditory eyeblink conditioning. Previous studies found that the medial auditory thalamus is necessary for eyeblink conditioning with an auditory conditioned stimulus (CS) in adult rats. In experiment 1, stimulation of the medial auditory thalamus was used as a CS in rat pups trained on postnatal days (P) 17-18, 24-25, or 31-32. All three age groups showed significant acquisition relative to unpaired controls. However, there was an age-related increase in the rate of conditioning. Experiment 2 examined the effect of inactivating the medial auditory thalamus with muscimol on auditory eyeblink conditioning in rats trained on P17-18, 24-25, or 31-32. Rat pups trained on P24-25 and P31-32, but not P17-18, showed a significant reduction in conditioned responses following muscimol infusions. The findings suggest that the thalamic contribution to auditory eyeblink conditioning continues to develop through the first postnatal month.     

Epilepsy, consciousness and neurostimulation

Consciousness is often disrupted in epilepsy. This may involve altered responsiveness or changes in awareness of self and subjective experiences. Subcortical arousal systems and paralimbic fronto-parietal association cortices are thought to underpin current concepts of consciousness. The Network Inhibition Hypothesis proposes a common neuroanatomical substrate for impaired consciousness during absence, complex partial and tonic-clonic seizures. Neurostimulation in epilepsy remains in its infancy with vagal nerve stimulation (VNS) as the only firmly established technique and a series of other methods under investigation including deep brain stimulation (DBS), intracranial cortical stimulation and repetitive transcranial magnetic stimulation (rTMS). Many of these systems impact on the neural systems thought to be involved in consciousness as a continuous duty cycle although some adaptive (seizure triggered) techniques have been developed. Theoretically, fixed duty cycle neurostimulation could have profound effects on responsiveness, awareness of self and subjective experience. Animal studies suggest vagal nerve stimulation positively influences hippocampal long term potentiation. In humans, a chronic effect of increased alertness in VNS implanted subjects and acute effect on memory consolidation have been reported but convincing data on either improvements or deterioration in attention and memory is lacking. Thalamic deep brain stimulation (DBS) is perhaps the most interesting neurostimulation technique in the context of consciousness. Neither bilateral anterior or centromedian thalamic nucleus DBS seem to affect cognition. Unilateral globus pallidus internus DBS caused transient wakefulness in an anaesthetised individual. As intracranial neurostimulation, particularly thalamic DBS, becomes more established as a clinical intervention, the effects on consciousness and cognition with variations in stimulus parameters will need to be studied to understand whether these secondary effects of neurostimulation make a significant positive (or adverse) contribution to quality of life.     

A neural model of normal and abnormal learning and memory consolidation: adaptively timed conditioning,hippocampus, amnesia,neurotrophins, and consciousness

How do the hippocampus and amygdala interact with thalamocortical systems to regulate cognitive and cognitive-emotional learning? Why do lesions of thalamus, amygdala, hippocampus, and cortex have differential effects depending on the phase of learning when they occur? In particular, why is the hippocampus typically needed for trace conditioning, but not delay conditioning, and what do the exceptions reveal? Why do amygdala lesions made before or immediately after training decelerate conditioning while those made later do not? Why do thalamic or sensory cortical lesions degrade trace conditioning more than delay conditioning? Why do hippocampal lesions during trace conditioning experiments degrade recent but not temporally remote learning? Why do orbitofrontal cortical lesions degrade temporally remote but not recent or post-lesion learning? How is temporally graded amnesia caused by ablation of prefrontal cortex after memory consolidation? How are attention and consciousness linked during conditioning? How do neurotrophins, notably brain-derived neurotrophic factor (BDNF), influence memory formation and consolidation? Is there a common output path for learned performance? A neural model proposes a unified answer to these questions that overcome problems of alternative memory models.     

Contributions of volumetrics of the hippocampus and thalamus to verbal memory in temporal lobe epilepsy patients

Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However, dissociating the memory impairment that occurs following thalamic injury as distinguished from that following hippocampal injury has proven difficult. This study examined relationships between MRI volumetric measures of the hippocampus and thalamus and their contributions to prose and rote verbal memory functioning in 18 patients with intractable temporal lobe epilepsy (TLE). Results revealed that bilateral hippocampal and thalamic volume independently predicted delayed prose verbal memory functioning. However, bilateral hippocampal, but not thalamic, volume predicted delayed rote verbal memory functioning. Follow-up analyses indicated that bilateral thalamic volume independently predicted immediate prose, but not immediate rote, verbal recall, whereas bilateral hippocampal volume was not associated with any of these immediate memory measures. These findings underscore the cognitive significance of thalamic atrophy in chronic TLE, demonstrating that hippocampal and thalamic volume make quantitatively, and perhaps qualitatively, distinct contributions to episodic memory functioning in TLE patients. They are also consistent with theories proposing that the hippocampus supports long-term memory encoding and storage, whereas the thalamus is implicated in the executive aspects of episodic memory.     

The Functional Neuroanatomy of Awareness: With a Focus on the Role of Various Anatomical Systems in the Control of Intermodal Attention

This review considers a number of recent theories on the neural basis of consciousness, with particular attention to the theories of Bogen, Crick, Llinás, Newman, and Changeux. These theories allot different roles to various key brain areas, in particular the reticular and intralaminar nuclei of the thalamus and the cortex. Crick's hypothesis is that awareness is a function of reverberating corticothalamic loops and that the spotlight ofintramodalattention is controlled by the reticular nucleus of the thalamus. He also proposed different mechanisms for attention and intention (“will”). The current review presents a new hypothesis, based on elements from these hypotheses, includingintermodalattention and olfaction and pain, which may pose problems for Crick's original theory. This work reviews the possible role in awareness and intermodal attention and intention of the cholinergic system in the basal forebrain and the tegmentum; the reticular, the intralaminar, and the dorsomedial thalamic nuclei; the raphe and locus coeruleus; the reticular formation; the ventral striatum and extended amygdala; insula cortex, and other selected cortical areas. Both clinical and basic research data are covered. The conclusion is reached that the brain may work by largely nonlinear parallel processing and much intramodal shifts of attention may be effected by intracortical, or multiple corticothalamic mechanisms (small local “flashlights” rather than one major “searchlight”). But this is constrained by the functional anatomy of the circuits concerned and waking “awareness” is modulated by the many “nonspecific” systems (cholinergic from the basal forebrain, noradrenergic from the locus coeruleus, dopaminergic from the substantia nigra and ventral tegmentum, and serotoninergic from the raphe). But the principal agents for intermodal attention shifts, the “searchlight,” may be two key nuclei of the cholinergic system in the mesencephalon. Clinical loss of consciousness results from damage to these nuclei but not from damage to the cholinergic nucleus basalis of the basal forebrain.     

Neurocognitive correlates of stereotactic thalamotomy and thalamic stimulation in Parkinsonian patients

In the present paper we have reviewed five different studies that relate to neuropsychological consequences of stereotactic thalamotomy and thalamic stimulation in patients with Parkinson's disease. The neuropsychological results are in a strict sense confined to thalamotomy and thalamic stimulation, although the more general message of the importance of investigating cognitive functions before and after surgery applies to other stereotactic techniques for surgical treatment of movement disorders as well. It is argued in the paper that stereotactic thalamotomy provides a unique model for basic research on the neuropsychology of the thalamus, while in return, neuropsychological tests for cognitive dysfunction after surgery may be the most important clinical follow-up. Three general conclusions seem warranted from the data. (1) Parkinsonian patients are impaired on a range of cognitive functions, including language processing, memory, and executive functions. (2) Stereotactic thalamotomy does not further impair the patient; instead, we observed improvement on some tests, particularly verbal memory. (3) In general, there does not seem to be a laterality effect, depending on which side the thalamotomy lesion is applied. An exception to this are dichotically presented simple speech sounds and autonomic responses. In both instances, left-sided brain stimulation produced enhanced performance, while lesioning the left thalamus impaired dichotic listening performance. Finally, we present a new hypothesis for a mechanism behind the thalamotomy effect, based in part on changes in arousal thresholds.     

Radical embodiment: neural dynamics and consciousness

We propose a new approach to the neuroscience of consciousness, growing out of the ‘enactive’ viewpoint in cognitive science. This approach aims to map the neural substrates of consciousness at the level of large-scale, emergent and transient dynamical patterns of brain activity (rather than at the level of particular circuits or classes of neurons), and it suggests that the processes crucial for consciousness cut across the brain–body–world divisions, rather than being brain-bound neural events. Whereas standard approaches to the neural correlates of consciousness have assumed a one-way causal-explanatory relationship between internal neural representational systems and the contents of consciousness, our approach allows for theories and hypotheses about the two-way or reciprocal relationship between embodied conscious states and local neuronal activity.     

“Paradox of slow frequencies” – Are slow frequencies in upper cortical layers a neural predisposition of the level/state of consciousness (NPC)?

Consciousness research has much focused on faster frequencies like alpha or gamma while neglecting the slower ones in the infraslow (0.001–0.1 Hz) and slow (0.1–1 Hz) frequency range. These slower frequency ranges have a “bad reputation” though; their increase in power can observed during the loss of consciousness as in sleep, anesthesia, and vegetative state. However, at the same time, slower frequencies have been conceived instrumental for consciousness. The present paper aims to resolve this paradox which I describe as “paradox of slow frequencies”. I first show various data that suggest a central role of slower frequencies in integrating faster ones, i.e., “temporo-spatial integration and nestedness”. Such “temporo-spatial integration and nestedness” is disrupted during the loss of consciousness as in anesthesia and sleep leading to “temporo-spatial fragmentation and isolation” between slow and fast frequencies. Slow frequencies are supposedly mediated by neural activity in upper cortical layers in higher-order associative regions as distinguished from lower cortical layers that are related to faster frequencies. Taken together, slower and faster frequencies take on different roles for the level/state of consciousness. Faster frequencies by themselves are sufficient and thus a neural correlate of consciousness (NCC) while slower frequencies are a necessary non-sufficient condition of possible consciousness, e.g., a neural predisposition of the level/state of consciousness (NPC). This resolves the “paradox of slow frequencies” in that it assigns different roles to slower and faster frequencies in consciousness, i.e., NCC and NPC. Taken as NCC and NPC, fast and slow frequencies including their relation as in “temporo-spatial integration and nestedness” can be considered a first “building bloc” of a future “temporo-spatial theory of consciousness” (TTC) (Northoff, 2013; Northoff, 2014b; Northoff & Huang, 2017).     

The disunity of consciousness

Attempts to decode what has become known as the (singular) neural correlate of consciousness (NCC) suppose that consciousness is a single unified entity, a belief that finds expression in the term 'unity of consciousness'. Here, I propose that the quest for the NCC will remain elusive until we acknowledge that consciousness is not a unity, and that there are instead many consciousnesses that are distributed in time and space.     

Mesothalamic discharge in a chronic pain,allergy and fluid retention syndrome (case report)

A 32-year-old woman was bedridden for a year because of chronic pain and headaches. She had insomnia, depression, suicidal thoughts and a severe chemical allergy. She had been on steroid therapy for two years and became Cushingoid with striae in the arm pits, groins and abdomen. However, she had no hypertension, nor the buffalo fat and hirsutism. She was very edematous, with a weight gain from 112 to 180 lbs. The fluid retention did not conform to the syndrome of inappropriate antidiuretic hormone. Studies revealed abnormal scalp EEG discharges and high-voltage seizure discharges in the posterior thalamus. Electrothalamic stimulation suppressed the thalamic discharges and relieved the patient’s pelvic pain and headaches. After one month of several thalamic stimulations per day, she was able to get out of bed and ambulate. In addition, the patient no longer was edematous and was tolerating perfumes and floor detergents. Steroids were progressively reduced without complications of withdrawal. She went from a completely steroid dependent state to independent during the first 1-1/2 yrs of thalamic stimulation. With continued thalamic stimulation she has done well for 8-1/2 yrs, weighs 112 lbs, keeps house and drives a car. It’s speculated the illness is a chronic pain multiple system syndrome predominantly due to mesothalamic discharges and body infirmities. The mesothalamic discharge implicated neural networks, which represent biologic systems, i.e. pain, sleep, fluid retention, etc. Therapeutic stimulation attenuates the discharges and the neural networks return to their normal set points of homeostasis.     

The explanatory gap is still there

I argue that O'Regan & No?'s (O&N's) theory is in a no better position than any other theory to solve the "hard problem" of consciousness. Getting rid of the explanatory gap by exchanging sensorimotor contingencies for neural representations is an illusion.     

Consciousness, accessibility, and the mesh between psychology and neuroscience

How can we disentangle the neural basis of phenomenal consciousness from the neural machinery of the cognitive access that underlies reports of phenomenal consciousness? We see the problem in stark form if we ask how we can tell whether representations inside a Fodorian module are phenomenally conscious. The methodology would seem straightforward: Find the neural natural kinds that are the basis of phenomenal consciousness in clear cases--when subjects are completely confident and we have no reason to doubt their authority--and look to see whether those neural natural kinds exist within Fodorian modules. But a puzzle arises: Do we include the machinery underlying reportability within the neural natural kinds of the clear cases? If the answer is "Yes," then there can be no phenomenally conscious representations in Fodorian modules. But how can we know if the answer is "Yes"? The suggested methodology requires an answer to the question it was supposed to answer! This target article argues for an abstract solution to the problem and exhibits a source of empirical data that is relevant, data that show that in a certain sense phenomenal consciousness overflows cognitive accessibility. I argue that we can find a neural realizer of this overflow if we assume that the neural basis of phenomenal consciousness does not include the neural basis of cognitive accessibility and that this assumption is justified (other things being equal) by the explanations it allows.     

Can Studies of Autism Teach us About Consciousness of the Physical and the Mental?

Abstract

Most scientists and theorists concerned with the problem of consciousness focus on our consciousness of the physical world (our sensations, feelings, and awareness). In this paper I consider our consciousness of the mental world (our thoughts about thoughts, intentions, wishes, and emotions).The argument is made that these are two distinct forms of consciousness, the evidence for this deriving from studies of autism. Autism is a severe childhood psychiatric condition in which individuals may be conscious of the physical world but not of the mental world. Relevant experimental evidence is described, including some recent neuroimaging studies pointing towards the neural basis of our consciousness of the mental.