Behaviorally relevant brain oscillations relate to each other in a specific manner to allow neuronal networks of different sizes with wide variety of connections to cooperate in a coordinated manner. For example, thalamo-cortical and hippocampal oscillations form numerous frequency bands, which follow a general rule. Specifically, the center frequencies and frequency ranges of oscillation bands with successively faster frequencies, from ultra-slow to ultra-fast frequency oscillations, form an arithmetic progression on the natural logarithmic scale. Due to mathematical properties of natural logarithm, the cycle lengths (periods) of oscillations, as an inverse of frequency, also form an arithmetic progression after natural logarithmic transformation. As a general rule, the neuronal excitability is larger during a certain phase of the oscillation period. Because the intervals between these activation phases and the temporal window of activation vary in proportion to the length of the oscillation period, lower frequency oscillations allow for an integration of neuronal effects with longer delays and larger variability in delays and larger areas of involvement. Neural representations based on these oscillations could therefore be complex. In contrast, high frequency oscillation bands allow for a more precise and spatially limited representation of information by incorporating synaptic events from closely located regions with short synaptic delays and limited variability. The large family of oscillation frequency bands with a constant relation may serve to overcome the information processing limitations imposed by the synaptic delays.

It may soon be possible to adapt the use of deep brain stimulation (DBS) technologies developed to treat movement disorders to improve the general cognitive function of brain-injured patients. We outline neurophysiological foundations for novel neuromodulation strategies to address these goals. Emphasis is placed on developing a rationale for targeting the intralaminar and related nuclei of the human thalamus for electrical stimulation. Recent anatomical and physiological studies are compared with original neurophysiological recordings obtained in an alert non-human primate. In this context we consider neuronal mechanisms that may underlie both clinical observations and cognitive rehabilitation maneuvers that provide theoretical support for open and closed-loop strategies to remediate acquired cognitive disability (ACD).

The intrinsic electrophysiological properties of medial geniculate body (MGB) neurons and their responses to noise bursts/pure tones were examined in the pentobarbital anesthetized guinea pig through intracellular recording. Discharge rate was calculated in the absence of acoustic stimuli over varied membrane potentials which were changed by intracellular injection of current or through automatic drifting. The non-acoustically-driven firing rate was 45.8 ± 23.3 Hz (mean ± S.D., n = 8) at membrane potentials of −45 mV, 30.6 ± 19.4 Hz (n = 14) at −50 mV, 18.0 ± 12.9 Hz (n = 14) at −55 mV, and significantly decreased to 5.7 ± 7.4 Hz at −60 mV, and to 0.7 ± 1.5 Hz (n = 10) at −65 mV (ANOVA, P < 0.001). The maximum non-acoustically-driven rate observed in the present study was 160 Hz. The auditory responsiveness of the MGB neurons was examined at membrane potentials over a range of −45 to −75 mV: the higher the membrane potential, the greater the responsiveness and vice versa. A putative non-low-threshold calcium spike (non-LTS) burst was observed in the present study. It showed significantly longer inter-spike intervals (11.6 ± 6.0 ms, P < 0.001, t-test) than those associated with the putative LTS bursts (6.7 ± 2.4 ms, P < 0.001, t-test). The dependence of the temporal structure of the spikes/spike bursts on the stimulus may provide insight into the temporal coding of sound information in the auditory system.

The ventral anterior (VA) nucleus of the thalamus is connected with prefrontal and premotor cortices and with the basal ganglia. Although classically associated with motor functions, recent evidence implicates the basal ganglia in cognition and emotion as well. Here, we used two complementary approaches to investigate whether the VA is a key link for pathways underlying cognitive and emotional processes through prefrontal cortices and the basal ganglia. After application of bidirectional tracers in functionally distinct lateral, medial, and orbitofrontal cortices, we found that projection neurons were embedded in much larger patches of axonal terminations found in the magnocellular part of VA (VAmc), and in the principal part of VA. Connections from medial prefrontal cortices occupied the dorsomedial and ventromedial VA, and orbitofrontal connections were found in ventrolateral VAmc. Moreover, about half of all projection neurons in orbitofrontal areas directed to the VA or VAmc were positive for calbindin but not parvalbumin, even though comparable populations of neurons were positive for each marker in the VA. We then applied tracers in VA and investigated simultaneously projections from all prefrontal areas, the internal segment of the globus pallidus (GPi), the substantia nigra reticulata (SNr), and the thalamic reticular nucleus. Projection neurons were most densely distributed in anterior cingulate areas 24 and 32, and dorsolateral areas 9 and 8, innervating the same VA sites that received projections from a large part of GPi and dorsal SNr. Nearly as many projection neurons originated from cortical layer V as from layer VI. There is evidence that cortical layer VI neurons innervate thalamic neurons that project focally to the middle cortical layers, whereas layer V neurons synapse with thalamic neurons projecting widely to cortical layer I. Projections from layer V to the VA may facilitate cortical recruitment for executive functions within a cognitive context through lateral prefrontal areas, and autonomic responses within an emotional context through anterior cingulate areas.

This paper provides an overview of the major organizational features of the basal ganglia and related thalamic centers, as delineated by the application of single-axon or single-cell labeling procedures in primates. These studies have revealed that the striatum, the external pallidum and the subthalamic nucleus harbor several types of projection neurons endowed with a highly collateralized axon that allows these neurons to interact with most components of the basal ganglia. In contrast, the internal pallidum, which is a major output structure of the basal ganglia, contains only two types of projection neurons. First, there is a minority of “limbic” pallidal neurons with a poorly branched axon that arborized profusely within the lateral habenula, which stands out as the most densely innervated pallidal target. Second, there is a majority of pallidal “motor” neurons with a long (total axonal length up to 27 cm) and highly branched axon that provides collaterals to the ventral tiers thalamic nuclei, the brainstem pedunculopontine nucleus and the centre médian/parafascicular thalamic complex. This type of axon allows internal pallidal neurons to send efferent copies of the same information to the thalamus and brainstem and hence influence various neuronal systems scattered throughout the neuraxis. Pallidal information is conveyed to the cerebral cortex and the striatum via the thalamus, while it is projected back to different components of the basal ganglia via the numerous reentrant pathways that arise from the pedunculopontine nucleus. Virtually all neurons in the centre médian thalamic nucleus innervate massively the striatum and less prominently the primary motor cortex, which in turn projects to the striatum directly or via a collateral from long-range corticofugal pyramidal axons. The results call for a reappraisal of our current concept of the anatomical and functional organization of basal ganglia, which play a crucial role in sensorimotor integration. Our data indicate that basal ganglia and related thalamic nuclei form a widely distributed neuronal network, whose elements are endowed with a highly patterned set of axon collaterals. This morphological feature allows a complex and exquisitely precise interaction between the various basal ganglia and related thalamic nuclei. The elucidation of this finely tuned network is needed to understand the complex spatiotemporal sequence of neural events that ensures the flow of cortical information through the basal ganglia and thalamus.

Broad amplitude variability and skewed distributions are characteristic features of quantal synaptic currents (minis) at central synapses. The relative contributions of the various underlying sources are still debated. Through computational models of thalamocortical neurons, we separated intra- from extra-synaptic sources. Our simulations indicate that the external factors of local input resistance and dendritic filtering generate equally small amounts of negatively skewed synaptic variability. The ability of these two factors to reduce positive skew increased as their contribution to variability increased, which in control trials for morphological, biophysical, and experimental parameters never exceeded 10% of the range. With these dendritic factors ruled out, we tested multiple release models, which led to distributions with clearly non-physiological multiple peaks. We conclude that intra-synaptic organization is the primary determinant of synaptic variability in thalamocortical neurons and, due to extra-synaptic mechanisms, is more potent than the data suggested. Thalamortical neurons, especially in rodents, constitute a remarkably favorable system for molecular genetic studies of synaptic variability and its functional consequence.

Erratum to “Neural basis of alertness and cognitive performance impairments during sleepiness II. Effects of 48 and 72 h of sleep deprivation on waking human regional brain activity”. [Thalamus & Related Systems 2 (2003) 199–229]doi of original article 10.1016/S 1472-9288(03)00020-7.