Biomedical subjects

A K Wiser

Publications and source records attributed to A K Wiser.

11 recordsLinked to original sources

PubMed2001

Neural basis of novel and well-learned recognition memory in schizophrenia: a positron emission tomography study.

The level of familiarity of a given stimulus plays an important role in memory processing. Indeed, the novelty/familiarity of learned material has been proven to affect the pattern of activations during recognition memory tasks. We used visually presented words to investigate the neural basis of recognition memory for relatively novel and familiar stimuli in schizophrenia. Subjects were 34 healthy volunteers and 19 schizophrenia spectrum patients. Two experimental cognitive conditions were used: 1 week and again 1 day prior to the PET imaging subjects had to thoroughly learn a list of 18 words (well-learned memory). Subjects were also asked to learn another set of 18 words presented 1 min before the PET experiment (novel memory). During the PET session, subjects had to recognize the list of 18 words among 22 new (distractor) words. Subjects also performed a control task (reading words). A nonparametric randomization test and a statistical t-mapping method were used to determine between- and within-group differences. In patients the recognition of novel material produced relatively less flow in several frontal areas, superior temporal gyrus, insular cortex, and parahippocampal areas, and relatively higher activity in parietal areas, visual cortex, and cerebellum, compared to controls. No significant differences in flow were seen when comparing well-learned memory activations between groups. These results suggest that different neural pathways are engaged during novel recognition memory in patients with schizophrenia compared to healthy individuals. During recognition of novel material, patients failed to activate frontal/limbic regions, recruiting a set of posterior perceptual brain regions instead.

Adult↗

PubMed2000

Novel vs. well-learned memory for faces: a positron emission tomography study.

Previous work has suggested that familiarity/novelty of learned materials affects the circuitry involved in memory, primarily in the size of activations rather than the pattern of activation. Although this work has examined both recall and recognition, it has been limited to verbal material. In this study, we set out to determine if the same result applies to nonverbal memory. We used the same experimental design, but used faces as the memory task. Healthy volunteers thoroughly learned a set of 18 faces a week prior to the Positron Emission Tomography (PET) experiment (well-learned memory) and were asked to remember another set of 18 faces, to which they were exposed 1 min before the PET experiment (novel memory). During the PET session, their task was to recognize the faces learned a week before and the faces seen a minute before; the "remembered faces" were interspersed among entirely new (distractor) faces. We found that, unlike for verbal material, the retention interval and the familiarity level of the faces affected both the pattern and the size of activations. Comparing the novel and well-learned recognition tasks revealed that novel memory for faces is primarily a frontal-lobe task, while well-learned recognition memory for faces utilizes a more distributed neural circuit, including visual areas, which appear to serve as memory-storage sites.

Adult↗

PubMed1999

Human frontal cortex: an MRI-based parcellation method.

The frontal lobe is not a single anatomical and functional brain region. Several lines of research have demonstrated that particular subregions within the frontal lobe are associated with specific motor and cognitive functions in the human being. Our main purpose is to develop a magnetic resonance image (MRI)-based parcellation method of the frontal lobe that permits us to explore plausible abnormalities in functionally relevant frontal subregions in brain illnesses. We describe a procedure using MRI for subdividing the entire frontal cortex into 11 subregions: supplementary motor area (SMA), rostral anterior cingulate gyrus (r-ACiG), caudal anterior cingulate gyrus (c-ACiG), superior cingulate gyrus (SCiG), medial frontal cortex (MFC), straight gyrus (SG), orbitofrontal cortex (OFC), precentral gyrus (PCG), superior frontal gyrus (SFG), inferior frontal gyrus (IFG), and middle frontal gyrus (MFG). Our method posits to conserve the topographic uniqueness of individual brains and is based on our ability to visualize both the three-dimensional (3D) rendered brain and the three orthogonal planes simultaneously. The reliability study for gray matter volume and surface area of each subregion was performed on a set of 10 MR scans by two raters. The intraclass R coefficients for gray matter volume of each subregion ranged between 0.86 and 0.99. We describe here a reproducible and reliable topography-based parcellation method of the frontal lobe that will allow us to use new approaches to understand the role of particular frontal cortical subregions in schizophrenia and other brain illnesses.

Brain Diseases↗

PubMed1999

Direct comparison of the neural substrates of recognition memory for words and faces.

For the purpose of identifying the relatively specific brain regions related to word and face recognition memory on the one hand and the regions common to both on the other, regional cerebral blood flow associated with different cognitive tasks for recognition memory was examined using [H215O]PET in healthy volunteers. The tasks consisted of recognizing two types of stimuli (faces and words) in two conditions (novel and familiar), and two baseline tasks (reading words and gender classification). The statistical analyses used to identify the specific regions consisted of three subtractions: novel words minus novel faces, familiar words minus familiar faces, and reading words minus gender classification. These analyses revealed relative differences in the brain circuitry used for recognizing words and for recognizing faces within a defined level of familiarity. In order to find the regions common to both face and word recognition, overlapping areas in four subtractions (novel words minus reading words, novel faces minus gender classification, familiar words minus reading words, and familiar faces minus gender classification) were identified. The results showed that the activation sites in word recognition tended to be lateralized to the left hemisphere and distributed as numerous small loci, and particularly included the posterior portion of the left middle and inferior temporal gyri. These regions may be related to lexical retrieval during written word recognition. In contrast, the activated regions for face recognition tended to be lateralized to the right hemisphere and located in a large aggregated area, including the right lingual and fusiform gyri. These findings suggest that strikingly different neural pathways are engaged during recognition memory for words and for faces, in which a critical role in discrimination is played by semantic cueing and perceptual loading, respectively. In addition, the investigation of the regions common to word and face recognition indicates that the anterior and posterior cingulate have dissociable functions in recognition memory that vary with familiarity, and that the cerebellum may serve as the co-ordinator of all four types of recognition memory processes.

Adult↗

PubMed1998

Dysfunctional cortico-cerebellar circuits cause 'cognitive dysmetria' in schizophrenia.

We examined regional cerebral blood flow (rCBF) during a long-term recognition memory task for words in schizophrenic patients and in healthy subjects using positron emission tomography (PET). The task was designed so that performance scores were similar in the patient and control subjects. This memory retrieval task did not increase rCBF in the patients' prefrontal cortex, precuneus and cerebellum as much as it did in the control group. These results point to a dysfunctional corticocerebellar circuit leading to poorly coordinated mental activity ('cognitive dysmetria'), which could explain the broad range of schizophrenic symptoms. In addition, other brain areas were more activated by the task in the patient group than in the control group and may form a compensatory network performing the memory retrieval task by assisting or replacing the dysfunctional cortico-cerebellar circuit.

Brain Mapping↗

PubMed1996

Contributions of individual layer 6 pyramidal neurons to local circuitry in macaque primary visual cortex.

We have studied the contributions of individual layer 6 pyramidal neurons in macaque primary visual cortex to local cortical circuitry by intracellular labeling and analysis of the morphologies of 58 neurons. These neurons are separated based on the laminar specificity of axonal and dendritic arbors into two classes, class I and class II, and into several types within these classes. Class I neurons project axons heavily and predominantly to layer 4C, whereas class II neurons have axonal projections primarily to layers other than 4C. Only 16 of the 58 neurons in our sample (28 percent) project to the white matter. Class I projection neurons are found at the top and bottom of layer 6, suggesting that they project to the lateral geniculate nucleus, whereas class II projection neurons are located in the middle of layer 6, suggesting that they project to the claustrum. The different types of class I neurons are distinguished from one another based on the sublaminar specificity of their axonal and dendritic arbors within layer 4, where they are biased toward compartments dominated by input from different functional streams. They are also distinct in their distributions within the depth of layer 6. The distinctive characteristics of the neuronal types we have identified suggest that each receives input from different sources and projects to a set of targets that is functionally appropriate. Thus, each type is likely to contribute uniquely to computations within V1 and extrinsically.

Animals↗

PubMed1995

Long-term potentiation disrupts auditory gating in the rat hippocampus.

The consequence of long-term potentiation (LTP) of hippocampal commissural inputs was investigated in an auditory gating paradigm. Auditory evoked potentials (AEPs) were recorded in the CA3b region of the hippocampus of rats anesthesitized with chloral hydrate. Two tones were delivered 0.5 sec apart; in this paradigm, the second AEP is diminished compared to the first. Electrical stimulation was applied to hippocampal commissural fibers to generate field potentials and population spikes which were recorded at the same site as the AEPs. LTP of the commissural input (initiated by three trains of 250 Hz/1 sec stimulation) was associated with changes in the AEPs: on average, the response to the first tone decreased and the response to the second tone increased, resulting in the disruption of auditory gating. When high-frequency stimulation of the commissural input failed to result in LTP, no effect on the AEPs was seen. If 3-(2-carboxypiperazin-4-yl)-propyl-L-phosphonic acid (CPP; 6 mg/kg, i.p.), an antagonist to the NMDA subclass of glutamate receptors, was administered prior to high-frequency stimulation, LTP induction was blocked and AEPs were not affected. Finally, reversal of LTP, achieved by high-frequency stimulation of CA3 input that was heterosynaptic to the particular commissural fibers at which the LTP was originally generated, caused disrupted auditory gating to return to normal. A model of reciprocal LTP and heterosynaptic depression of commissural and auditory input pathways is proposed to explain these findings.

Acoustic Stimulation↗

PubMed1991

Sensitivity of lateral hypothalamic neurons to glycemic level: possible involvement of an indirect adrenergic mechanism.

Most of the lateral hypothalamic neurons responding to moderate changes in blood glucose fail to be affected by direct glucose applications. Therefore their sensitivity to glycemic level must be mediated by an indirect mechanism. In order to test whether adrenergic afferents might be involved, the activity of lateral hypothalamic neurons was recorded during hyperglycemia and local glucose and epinephrine microiontophoresis. A majority of the recorded cells sensitive to local epinephrine responded to this substance with a decrease in activity. While no consistent correspondence was found between the responses of the same cells to local glucose and epinephrine ejections, almost all the neurons sensitive to glycemic alterations responded in the same direction to hyperglycemia and iontophorised epinephrine. These results support the view that the activity of lateral hypothalamic cells can be modulated in relation to changes in glycemic level through adrenergic signals released by some neurons which are sensitive to the blood glucose. The possible localization in the solitary tract area of such neurons projecting to the lateral hypothalamus is discussed.

Animals↗

PubMed1990

Local versus indirect action of glucose on the lateral hypothalamic neurons sensitive to glycemic level.

The neuronal activity in the lateral hypothalamus may be affected by moderate changes in blood glucose. The present study aimed to specify the direct or indirect origin of this sensitivity to glycemia, by recording the unit responses in this area to both local glucose application (by means of microelectrophoresis) and hyperglycemia (induced by an IV glucose injection). The activity of approximately 25% of the recorded LHA neurons was modified by topically ejected glucose. However, a large majority of these neurons sensitive to local glucose failed to respond to hyperglycemia. Conversely, only 1/3 of the glycemia-sensitive cells responded in the same direction to systemic and local glucose administration. Therefore, the response to IV glucose of the other 2/3 glycemia-sensitive cells could not result from the direct action of glucose molecules on these neurons, but probably involved an indirect afferent pathway conveying the glycemic cues from some central or peripheral glucose sensors to the cell under investigation.

Animals↗

PubMedDate not supplied

Contributions of individual layer 2-5 spiny neurons to local circuits in macaque primary visual cortex.

We studied excitatory local circuits in the macaque primary visual cortex (VI) to investigate their relationships to the magnocellular (M) and parvocellular (P) streams. Sixty-two intracellularly labeled spiny neurons in layers 2-5 were analyzed. We made detailed observations of the laminar and columnar specificity of axonal arbors and noted correlations with dendritic arbors. We find evidence for considerable mixing of M and P streams by the local circuitry in VI. Such mixing is provided by neurons in the primary geniculate recipient layer 4C, as well as by neurons in both the supragranular and infragranular layers. We were also interested in possible differences in the axonal projections of neurons with different dendritic morphologies. We found that layer 4B spiny stellate and pyramidal neurons have similar axonal arbors. However, we identified two types of layer 5 pyramidal neuron. The majority have a conventional pyramidal dendritic morphology, a dense axonal arbor in layers 2.4B, and do not project to the white matter. Layer 5 projection neurons have an unusual "backbranching" dendritic morphology (apical dendritic branches arc downward rather than upward) and weak or no axonal arborization in layers 2-4B, but have long horizontal axonal projections in layer 5B. We find no strong projection from layer 5 pyramidal neurons to layer 6. In macaque V1 there appears to be no single source of strong local input to layer 6; only a minority of cells in layers 2-5 have axonal branches in layer 6 and these are sparse. Our results suggest that local circuits in V1 mediate interactions between M and P input that are complex and not easily incorporated into a simple framework.

Animals↗

PubMedDate not supplied

Ocular dominance columns and local projections of layer 6 pyramidal neurons in macaque primary visual cortex.

To study the relationship between ocular dominance columns (ODCs) and axonal projections of individual layer 6 pyramidal neurons in the primary visual cortex, neurons were intracellularly labeled with biocytin in live slices prepared from macaque monkeys that had received an intravitreal injection of tetrodotoxin (TTX). The TTX injection indirectly causes a decrease in cytochrome oxidase (CO) expression in the cortical ODCs corresponding to the treated eye (Wong-Riley & Carroll, 1984). Sections from slices with labeled layer 6 neurons were double stained for biocytin and CO, to allow visualization of neuronal processes as well as ODCs. Twenty-seven layer 6 pyramidal neurons in ODC-labeled slices were analyzed. These neurons were classified according to the criteria of Wiser and Callaway (1996). Eight of these are class I neurons, which have dense axonal projections to the monocular layer 4C. The remaining 19 are class II neurons which project primarily to the binocular layers outside 4C. Among class I neurons, two have dense axonal arbors in layer 4C alpha (type I alpha), one in layer 4C beta (type I beta), and two throughout the depth of layer 4C (type IC). None of these neurons have ODC-specific axonal arbors. The remaining three class I neurons have focused axonal projections in layers 4C beta and 4A (type I beta A). All three appear to have axonal arbors predominantly within their home ODC in layer 4C. The axonal arbors of class II neurons do not appear to relate to ODCs in any specific fashion.

Animals↗