Amyloid plaques, one of the main hallmarks of Alzheimer's disease (AD), are classified into diffuse (associated with cognitive impairment) and dense-core types (a common finding in brains of people without Alzheimer's disease (non-AD) and without impaired cognitive function) based on their morphology. We tried to determine the usability of gray-level co-occurrence matrix (GLCM) texture parameters of homogeneity and heterogeneity for the differentiation of amyloid plaque images obtained from AD and non-AD individuals. Images of amyloid-β (Aβ) immunostained brain tissue samples were obtained from the Aging, Dementia and Traumatic Brain Injury Project. A total of 1,039 plaques were isolated from different brain regions of 69 AD and non-AD individuals and used for further GLCM analysis. Images of Aβ stained plaques show higher values of heterogeneity parameters and lower values of homogeneity parameters in AD patients, and vice versa in non-AD patients. Additionally, GLCM analysis shows differences in Aβ plaque texture between different brain regions in non-AD patients and correlates with variables that characterize patient's dementia status. The present study shows that GLCM texture analysis is an efficient method to discriminate between different types of amyloid plaques based on their morphology and thus can prove as a valuable tool in the neuropathological investigation of dementia.

There is some complementarity of models for the origin of the electroencephalogram (EEG) and neural network models for information storage in brainlike systems. From the EEG models of Freeman, of Nunez, and of the authors' group we argue that the wavelike processes revealed in the EEG exhibit linear and near-equilibrium dynamics at macroscopic scale, despite extremely nonlinear – probably chaotic – dynamics at microscopic scale. Simulations of cortical neuronal interactions at global and microscopic scales are then presented. The simulations depend on anatomical and physiological estimates of synaptic densities, coupling symmetries, synaptic gain, dendritic time constants, and axonal delays. It is shown that the frequency content, wave velocities, frequency/wavenumber spectra and response to cortical activation of the electrocorticogram (ECoG) can be reproduced by a “lumped” simulation treating small cortical areas as single-function units. The corresponding cellular neural network simulation has properties that include those of attractor neural networks proposed by Amit and by Parisi. Within the simulations at both scales, sharp transitions occur between low and high cell firing rates. These transitions may form a basis for neural interactions across scale. To maintain overall cortical dynamics in the normal low firing-rate range, interactions between the cortex and the subcortical systems are required to prevent runaway global excitation. Thus, the interaction of cortex and subcortex via corticostriatal and related pathways may partly regulate global dynamics by a principle analogous to adiabatic control of artificial neural networks.

Recent studies on neural pathways in a broad spectrum of vertebrates suggest that, in addition to migration and an increase in the number of certain select neurons, a significant aspect of neural evolution is a “parcellation” (segregation-isolation) process that involves the loss of selected connections by the new aggregates. A similar process occurs during ontogenetic development. These findings suggest that in many neuronal systems axons do not invade unknown territories during evolutionary or ontogenetic development but follow in their ancestors' paths to their ancestral targets; if the connection is later lost, it reflects the specialization of the circuitry.

The pattern of interspecific variability suggests (1) that overlap of circuits is a more common feature in primitive (generalized) than in specialized brain organizations and (2) that most projections, such as the retinal, thalamotelencephalic, corticotectal, and tectal efferent ones, were bilateral in the primitive condition. Specialization of these systems in some vertebrate groups has involved the selective loss of connections, resulting in greater isolation of functions. The parcellation process may also play an important role in cell diversification.

The parcellation process as described here is thought to be one of several underlying mechanisms of evolutionary and ontogenetic differentiation.

The proposition that declarative memory deficits are systematically related to smaller hippocampal volume was tested in a relatively large sample (n = 95) of U.S. military veterans with and without combat-related posttraumatic stress disorder. This correlative analysis was extended by including multiple measures of verbal and visual declarative memory and multiple memory-relevant regional brain volumes that had been shown to exhibit main effects of PTSD in prior work. Small-to-moderate effects were observed on verbal declarative memory in line with a recent meta-analysis; nevertheless, little or no evidence of systematic linear covariation between memory measures and brain volumes was observed. (JINS, 2009, 15, 830–839.)

Dolphin brain size with respect to body size ranks between that of apes and humans. The hypertrophic auditory structures, the large cerebrum with extended gyrification and the highly cognitive capabilities of toothed whales seem to be in paradoxical contrast to their thin neocortex with a plesiomorphic or paedomorphic cytoarchitecture. The total number of neurons in the delphinid neocortex is comparable to that of the chimpanzee (Primates), but, in relation to body weight, in the magnitude of the hedgehog (Insectivora) neocortex since cetaceans may be able to obtain larger body sizes than terrestrial mammals due to reduced gravitational effects in water. During evolution, dolphins may have increased the computational performance of their cytoarchitectonically ‘simple’ neocortex by a multiplication of relevant structures (resulting in a hypertrophic surface area) instead of increasing its complexity. Based on this hypothesis, I suggest that the evolution of the large dolphin brain was possible due to a combination of different prerequisites based on adaptations to the aquatic environment including the sonar system. The latter facilitated a successful feeding strategy to support an increased metabolic turnover of the brain and led to a hypertrophic auditory system. Moreover, the rudimentary pelvic girdle did not limit brain size at birth. These adaptations favoured the evolutionary size increase of the cerebral cortex in dolphins facilitating highly cognitive capabilities as well as precise and rapid sound processing using a ‘simple’ kind of neocortical cytoarchitecture.

Ethanol (EtOH) potentiates the locomotor effects of 3,4-methylenedioxymetamphetamine (MDMA) in rats. This potentiation might involve pharmacokinetic and/or pharmacodynamic mechanisms. We explored whether the latter could be local. Using a slice superfusion approach, we assessed the effects of MDMA (0.3, 3 μm) and/or EtOH (2‰, corresponding to 34.3 mm) on the spontaneous outflow and electrically evoked release of serotonin (5-HT), dopamine (DA) and acetylcholine (ACh) in the striatum, and for comparison, on 5-HT release in hippocampal and neocortical tissue. MDMA and less effectively EtOH, augmented the outflow of 5-HT in all regions. The electrically evoked 5-HT release was increased by MDMA at 3 μm in striatal slices only. With nomifensine throughout, EtOH significantly potentiated the 0.3 μm MDMA-induced outflow of 5-HT, but only in striatal slices. EtOH or MDMA also enhanced the spontaneous outflow of DA, but MDMA reduced the electrically evoked DA release. With fluvoxamine throughout superfusion, EtOH potentiated the effect of MDMA on the spontaneous outflow of DA. Finally, 3 μm MDMA diminished the electrically evoked release of ACh, an effect involving several receptors (D2, 5-HT2, NMDA, nicotinic, NK1), with some interactions with EtOH. Among other results, we show for the first time a local synergistic interaction of EtOH and MDMA on the spontaneous outflow of striatal DA and 5-HT, which could be relevant to the EtOH-induced potentiation of hyperlocomotion in MDMA-treated rats. These data do not preclude the contribution of other pharmacodynamic and/or pharmacokinetic mechanisms in vivo but support the hypothesis that EtOH may affect the abuse liability of MDMA.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD. (JINS, 2007, 13, 450–461.)

Brain evolution is a complex weave of species similarities and differences, bound by diverse rules and principles. This book is a detailed examination of these principles, using data from a wide array of vertebrates but minimizing technical details and terminology. It is written for advanced undergraduates, graduate students, and more senior scientists who already know something about “the brain,” but want a deeper understanding of how diverse brains evolved. The book's central theme is that evolutionary changes in absolute brain size tend to correlate with many other aspects of brain structure and function, including the proportional size of individual brain regions, their complexity, and their neuronal connections. To explain these correlations, the book delves into rules of brain development and asks how changes in brain structure impact function and behavior. Two chapters focus specifically on how mammal brains diverged from other brains and how Homo sapiens evolved a very large and “special” brain.

The absence epilepsies are characterized by recurrent episodes of loss of consciousness associated with generalized spike-and-wave discharges, with an abrupt onset and offset, in the thalamocortical system. In the absence of detailed neurophysiological studies in humans, many of the concepts regarding the pathophysiological basis of absence seizures are based on studies in animal models. Each of these models has its particular strengths and limitations, and the validity of findings from these models for the human condition cannot be assumed. Consequently, studies in different models have produced some conflicting findings and conclusions. A long-standing concept, based primarily from studies in vivo in cats and in vitro brain slices, is that these paroxysmal electrical events develop suddenly from sleep-related spindle oscillations. More specifically, it is proposed that the initial mechanisms that underlie absence-related spike-and-wave discharges are located in the thalamus, involving especially the thalamic reticular nucleus. By contrast, more recent studies in well-established, genetic models of absence epilepsy in rats demonstrate that spike-and-wave discharges originate in a cortical focus and develop from a wake-related natural corticothalamic sensorimotor rhythm. In this review we integrate recent findings showing that, in both the thalamus and the neocortex, genetically-determined, absence-related spike-and-wave discharges are the manifestation of hypersynchronized, cellular, rhythmic excitations and inhibitions that result from a combination of complex, intrinsic, synaptic mechanisms. Arguments are put forward supporting the hypothesis that layer VI corticothalamic neurons act as ‘drivers’ in the generation of spike-and-wave discharges in the somatosensory thalamocortical system that result in corticothalamic resonances particularly initially involving the thalamic reticular nucleus. However an important unresolved question is: what are the cellular and network mechanisms responsible for the switch from physiological, wake-related, natural oscillations into pathological spike-and-wave discharges? We speculate on possible answers to this, building particularly on recent findings from genetic models in rats.

Although a tremendous honour, it is with great sadness that this review is dedicated to Mircea's memory. Mircea has been, not only an inspiration throughout my career, but a generous and supportive friend whose kindly, incisive criticism has been a constant reminder that what we study in vitro must eventually be understood in the context of the whole system. Quoting from the Preface to his elegant monograph ‘The evolution of work on extremely simplified preparations has reached the point where some investigators are not shy to jump from single-cell properties to global brain functions, such as arousal and sleep, paroxysmal events of the epileptic type, and even conscious thinking.’ (Steriade, 2001). Bearing in mind that the properties both of single neurons and the connections between them might vary in different brain states and in different phases of cortical rhythms, in this review I summarize studies of the local circuitry of the thalamo-recipient layers 4 and 6 focussing on results obtained with dual intracellular recordings and biocytin-labelling in adult neocortical slices.

Mechanisms underlying seizure cessation remain elusive. The Lennox-Gastaut syndrome, a severe childhood epileptic disorder, is characterized by episodes of seizure with alternating epochs of spike-wave and fast run discharges. In a detailed computational model that incorporates extracellular potassium dynamics, we studied the dynamics of these state transitions between slow and fast oscillations. We show that dynamic modulation of synaptic transmission can cause termination of paroxysmal activity. An activity-dependent shift in the balance between synaptic excitation and inhibition towards more excitation caused seizure termination by favoring the slow oscillatory state, which permits recovery of baseline extracellular potassium concentration. We found that slow synaptic depression and change in chloride reversal potential can have similar effects on the seizure dynamics. Our results indicate a novel role for synaptic dynamics during epileptic neural activity patterns.

Intracellular recordings from thalamocortical (TC) neurons in the ventrolateral (VL) nucleus as well as paired intracellular recordings from TC-VL neurons and area 4 cortical neurons under ketamine-xylazine anesthesia were performed to study changes in hyperpolarization-rebound sequences evoked by successive stimuli to the dorsal thalamus at different frequencies and the impact of these changes at the cortical level. The cellular mechanisms of such changes in synaptic networks connecting TC with cortical neurons are relevant for short-term plasticity during low-frequency oscillatory activities. The progressive decrease in hyperpolarization of TC cells in response to single thalamic stimulus above a certain frequency (generally >1 Hz) and to pulse-trains at 10 Hz was mainly due to synaptic factors and not to mechanisms intrinsic to TC cells, as revealed by comparing responses evoked by synaptic volleys to those elicited by hyperpolarizing current pulses mimicking the synaptically evoked hyperpolarization-rebound sequence. The decreased hyperpolarization to repetitive synaptic volleys, leading to a decreased number of action potentials in the post-inhibitory spike-burst, had an impact on cortical activities, being matched by a decreased rebound depolarization of cortical cell during repetitive augmenting responses. The alterations in hyperpolarization-rebound sequences upon repetitive stimulation, probably resulting from the decreased efficacy of connections between thalamic reticular (RE) neurons to TC connections, results in the dampening of activities sustaining normal, and possibly paroxysmal, oscillations in the TC network. Our results suggest that this phenomenon should be taken into account when analyzing complex activities, such as physiological and pathological oscillations.

The visual cortex of freshwater turtles contains pyramidal cells, which have a regular spiking (RS) firing pattern, and several categories of aspiny, inhibitory interneurons. The interneurons show diverse firing patterns, including the fast spiking (FS) pattern. Postsynaptic potentials (PSPs) evoked in FS cells by visual stimulation of the retina reach their peak amplitudes as much as 200 ms before PSPs in RS cells (Mancilla et al., 1998). FS cells could, consequently, control the amplitudes of light-evoked PSPs in RS cells by producing disynaptic, feedforward inhibitory postsynaptic potentials (IPSPs) that overlap in time with geniculocortical excitatory postsynaptic potentials (EPSPs). Since FS cells receive recurrent, excitatory inputs from RS cells, they could also control the amplitudes of light-evoked PSPs in RS cells via polysynaptic, feedback inhibition. The in vitro geniculocortical preparation of Pseudemys scripta was used to characterize the temporal relationships of EPSPs and IPSPs produced in RS cells by electrical activation of geniculate afferents and by diffuse light flashes presented to the retina. GABAA receptor-mediated inhibition was blocked using extracellular application of bicuculline (3.5 mM) or intracellular perfusion of picrotoxin (1 μM) in individual RS cells. Electrical stimulation of thalamic afferents produced compound PSPs. Blockade of GABAA receptor-mediated IPSPs with either bicuculline or picrotoxin provided evidence for both early and late IPSPs in RS cells. Analysis of the apparent reversal potentials of light-evoked PSPs indicated the existence of early IPSPs during the first 140–300 ms following light onset. Light responses of cells perfused with picrotoxin diverged from control light responses at about 300 ms after light onset and had maximum amplitudes that were significantly different from control light responses. These experiments indicate that the responses of RS cells to both electrical and natural stimulation of geniculate afferents are controlled by both early and late IPSPs, consistent with activation of both feedforward and feedback pathways.

Sharp electrodes were used to record light-evoked postsynaptic potentials (PSPs) from neurons in turtle visual cortex in an in vitro preparation of the geniculocortical pathway. Neurons were placed into four groups based on the firing patterns produced by intracellular current injections: regular spiking (RS), fast spiking (FS), intrinsic bursting (IB), and chattering (CH) cells. RS cells have been shown to be pyramidal cells while FS cells are typically interneurons. Light stimuli were diffuse, 1-s flashes of 640-nm light with intensities (I) varying from 0 to 104 photons μm−2 s−1. The response (R) in each case was the maximal amplitude of the light-evoked depolarizing PSP. Cells of all four types showed sigmoidal intensity–response (IR) functions with a linear rising phase for stimuli above the intensity threshold followed by saturation at high light intensities. Responses at high intensities were variable and some cells showed indications of supersaturation. Light-evoked PSPs had longer latencies and times-to-peak response in RS cells than they did in FS cells. RS cells fired action potentials as much as 200 ms later than did FS cells. Since responses recorded in RS cells at light intensities just above threshold are unlikely to involve contributions from other pyramidal cells, these data indicate that the geniculocortical or feedforward pathway to pyramidal cells has a high gain. The fact that FS cells fire well before RS cells suggests that feedforward inhibition plays a role in controlling the gain of the geniculocortical pathway.