This study explores different episodic memory domains, namely object, temporal and spatial memory... more This study explores different episodic memory domains, namely object, temporal and spatial memory, affected in patients with a clinical diagnosis of single domain amnestic mild cognitive impairment (aMCI). 15 aMCI patients and 25 healthy controls were recruited and tested. Object, spatial, and temporal memory were tested using computerized tasks and again in interactive, real-world tasks. Controls outperformed patients on the object computerized task and showed a trend toward significance for the computerized spatial and temporal tasks, but there was no difference in spatial and temporal memory when using the interactive tasks, indicating the employment of compensatory mechanisms in patients to overcome some of the memory impairments associated with aMCI. These findings highlight that aMCI patients might delay seeking help due to compensatory mechanisms which mask their deficits in real-world situations.
Journal of Clinical and Experimental Neuropsychology, Apr 7, 2011
We used functional magnetic resonance imaging (fMRI) to assess cortical involvement in a hidden p... more We used functional magnetic resonance imaging (fMRI) to assess cortical involvement in a hidden pattern task. The experimental and control conditions involved judgment of the presence/absence versus the position of a complex pattern. Activation specific to hidden pattern identification was concentrated on frontal, dorsal parietal, and mesolimbic cortex. This was consistent not only across individual subjects, but with hidden figures tasks used in previous fMRI investigations. Results suggest that pattern identification relies on a relatively stable neural network controlling selective attention. In combination with fMRI, hidden pattern tasks may be useful in neuropsychological assessment of visual search and object identification.
International Journal of Psychophysiology, Oct 1, 2007
We have previously used functional magnetic resonance imaging to assess specific anterolateral te... more We have previously used functional magnetic resonance imaging to assess specific anterolateral temporal regions involved in object recognition, providing a novel technique for evaluating functional status in temporal lobe epilepsy (i.e., a site directed approach). However, a method that combines high temporal resolution with spatial mapping is needed to isolate the specific processes associated with these regions (i.e., a process specific approach). In the current study, we evaluated the cognitive processes associated with object recognition and their relationship to the temporal lobe using high-density event-related potentials (ERPs). N300 and late positive component (LPC) responses were examined using a word-picture matching task, with three factors: congruity (match/mismatch), level of abstraction (basic/superordinate), and object category (natural/artificial). The N300 and LPC were analyzed in terms of their temporal characteristics as well as their spatial characteristics through source analysis. The results showed that the N300 primarily indexed processing of congruity and level of abstraction, whereas the LPC primarily indexed processing of object category. In agreement with previous functional imaging studies, N300 and LPC source analysis results confirmed temporal lobe involvement in object recognition. Importantly, LPC object category differences were detected in the anterior temporal lobe. Individual subject analyses revealed that these anterior temporal lobe differences were reliable--with greater activity for natural objects in 84% of subjects. The findings are discussed in terms of clinical applications that use spatiotemporal ERP differences to evaluate functional status of the temporal lobes.
Functional magnetic resonance imaging (fMRI) is increasingly being used for neurosurgical plannin... more Functional magnetic resonance imaging (fMRI) is increasingly being used for neurosurgical planning. One potential application relates to identifying eloquent cortex in regions immediately adjacent to epileptogenic foci in temporal lobe epilepsy (TLE). While medial temporal structures, such as the hippocampus and amygdala, are typically removed during surgery, it is often difficult to determine whether nearby cortical regions in the anterolateral temporal lobe should be spared. An essential first step is to identify a method of activating these regions in healthy individuals. The purpose of this study was to develop a site directed fMRI approach for evaluating functional status in the anterolateral temporal lobes. A picture-word matching task, with object category and level of abstraction factors, was used to characterize temporal lobe activation. Whole brain analysis at the group level confirmed the involvement of the temporal poles as well as adjacent superior, middle and inferior temporal gyri within a larger object recognition network. A region-of-interest analysis on the anterolateral temporal lobe demonstrated that activation varied across conditions and regions for individuals. Importantly, it was possible to detect activation in one or more conditions and/or regions for all individuals--demonstrating that it is possible to evaluate functional status. The findings provide the foundation for a novel fMRI approach in neurosurgical planning for TLE.
Annals of the New York Academy of Sciences, May 1, 1990
Animal studies regarding the antinociceptive effect of B vitamins have been reported only occasio... more Animal studies regarding the antinociceptive effect of B vitamins have been reported only occasionally and with contradictory results.'-3 It has been proposed that vitamins of the B group alleviate pain. In search of evidence for analgesic properties of these compounds, experiments have been recently carried out on rats.I4 These studies have indicated that administration of vitamin B compound (Neurobion, E-Merck) produced analgesia in clinical therapy and animal models of pain. The mechanism underlying this analgesic action is not known. Recent studies have also suggested that vitamin B, can directly suppress the responses of spinal neurons to nociceptive ~timulation.~.~ It has been suggested that this suppression might be involved in the analgesia in clinical therapy. Assuming that nociceptive activity conducted in ascending axons to the thalamus will cause a sensation of pain in man, it was of interest to observe what happens to the activity elicited in the thalamus by electrical stimulation of nociceptive afferents in the contralateral sciatic nerve when pyridoxine was administered parenterally. Activation of electrical stimulation was chosen to determine only central effects of pyridoxine in normal and pyridoxine-deficient rats.
Subjects were 20 learning‐disabled (LD) children who were matched for mean age and IQ against a g... more Subjects were 20 learning‐disabled (LD) children who were matched for mean age and IQ against a group of 20 non‐LD control children. A computer‐generated visual target identification task was used to assess visual selective attention capabilities. Subjects were asked to locate colored form targets (green squares) appearing amid an array of distractor stimuli. Distractors in disjunctive arrays shared no features with the target, whereas distractors in conjunctive arrays could share one feature—either color or form—with the target stimulus. LD children were faster than controls in correctly responding to targets, but no between‐group differences in accuracy were noted. Impulsive children — defined on the basis of performance in the Matching Familiar Figures (MFF) test —were significantly overrepresented in the LD group. Impulsive children were significantly less accurate at target identification for both array types than were reflective children. Both LD and impulsive children performed at normal levels in a test requiring the inhibitory modulation of motor output. Deficits in the automatic, preattentive processing of stimulus features are proposed to explain the performance impairments of impulsive children.
Using an automated apparatus modelled after that of DAVENPORT and ROGERS [lo], Irus monkeys were ... more Using an automated apparatus modelled after that of DAVENPORT and ROGERS [lo], Irus monkeys were progressively shaped to establish a cross-modal matching (CMM) set. The subjects were required to solve three novel haptic to visual matching problems. Two of the three problems were solved to criterion (80% correct for three successive days) within the allotted period. Learning rates were within-the limits normally reported for intramodal matching using touch and vision. Changes in the haptic features of the stimuli influenced the degree of difficulty associated with individual problems. CROSS-MODAL effects have been widely implicated as a necessary correlate of language skills in man [l-8]. GESCHWIND [l] argued that "the inability to acquire speech has as a prerequisite the ability to form cross-modal associations". Since that time, both crossmodal abilities [9, lo] and the capacity to acquire and manipulate language have been demonstrated in chimpanzees. More recently, the demonstration of cross-modal recognition in several monkey species [ll-131 has shown that earlier failures in experiments of this type [14] were due to inadequacies not of the animal subjects, but of the procedures used to test them. Meaningful research into the neural basis of cross-modal perception in primate species has awaited the development of a testing paradigm which would allow the simultaneous assessment of treatment effects and investigation of contributing neural processes. The procedure of cross-modal matching (CMM) as developed by DAVENPORT et al. [9, IO] has the advantage of allowing for repeated-trials analysis. Repetition in the context of matchingfrom-sample introduces confounding from reward contingencies, but permits the quantitative assessment of acquisition and retention rates. Likewise the trial to trial uniformity of the matching paradigm ensures an adequate sample of behaviour for electrophysiological analysis. This element is lacking in the otherwise elegant cross-modal recognition experiment devised by COWEY and WEISKRANTZ [5, 151. The use of an automated apparatus in the context of neurological research is desirable for several reasons. The experimenter gains precise control over the various temporal relationships between the subjects responses and the onset, sequence, duration and delay of stimuli and rewards. In addition, switch closures may be used, for example, to gather such measures as response latency, or to flag behavioural events for use in electrophysiological analysis such as evoked-potential averaging. The aim of the present study was to adapt the CMM paradigm for use with monkeys. A shaping program using successive approximations of the haptic to visual matching
Monkeys with either anterior or posterior lesions of area TE were tested on serial reversal of a ... more Monkeys with either anterior or posterior lesions of area TE were tested on serial reversal of a visual pattern discrimination problem. Compared with unoperated control subjects, both lesion groups took longer to learn the original problem. Reversal learning was impaired primarily in the anterior group. Dissociation of function within area TE was inferred from opposite effects of the lesions on the period of stationarity, which characterizes the presolution portion of the backward learning curve. Results are interpreted in terms of twoprocess models of extrastriate visual function.
Computerized electroencephalography and thalamic ventro-posterior lateral (VPL) unit activities w... more Computerized electroencephalography and thalamic ventro-posterior lateral (VPL) unit activities were recorded from pyridoxine-deficient and pair-fed pyridoxine-supplemented adult male rats. Pyridoxine-deficient animals exhibited slow electroencephalograms (EEG) represented by the dominance of delta activity and reduced seizure thresholds to local (VPL) application of either picrotoxin or pentylene tetrazole. Frequency and amplitude of thalamic VPL unit activity were significantly reduced in pyridoxine-deficient rats as compared to pyridoxine-supplemented controls. Pyridoxine-deficient rats exhibited irregular unit activity with frequent bursts and electrosilent periods in response to local (VPL) picrotoxin or pentylene tetrazole microinjections. They also exhibited severe seizure discharge activity of prolonged duration at any given dose of either picrotoxin or pentylene tetrazole. This was represented by significantly increased burst frequency, burst duration and reduced seizure latencies. Unit activity was transformed into burst discharge activity with intermittent electrosilent zones during picrotoxin or pentylene tetrazole epileptogenesis. Cerebral gamma aminobutyric acid (GABA) level was reduced and glutamate concentration increased in pyridoxine-deficient rats when compared with pyridoxine-supplemented controls. Local (VPL) microinjection of GABA or pyridoxine induced neuronal recovery in both convuisant-treated normal and pyridoxine-deficient rats. Neuronal recovery was however delayed in pyridoxine-deficient rats. Neuronal recovery was associated with a significant increase in EEG background frequency and reduction in delta frequencies in the EEG records of both normal and pyridoxine-deficient rats. Reduced seizure threshold and delayed neuronal recovery are related to the significantly reduced brain regional GABA and elevated glutamate levels in pyridoxine-deficient rats.
Transcortical evoked potentials (EP's) were collected while monkeys performed a haptic to visual ... more Transcortical evoked potentials (EP's) were collected while monkeys performed a haptic to visual matching task. EP's were sorted into "sample" groups, according to the haptic stimuli, "match" groups, according to the choice of a visual alternative, and "spatial" groups, depending upon the panel (right or left) pressed during the matching response. Electrodes in inferoparietal cortex yielded event-related activity due to the matching and spatial aspects ofresponding, but not to haptic sampling. A postcentral electrode yielded event-related differences due to haptic sampling and spatial response, and a smaller difference related to visual matching. Implications for the neural mediation of cross-modal operations are discussed. RECENT experiments Cl-43 have shown that monkeys share with men and apes [S, 61 the ability to solve cross-modal problems. The neural basis of this ability, however, remains a subject of controversy. Classically [7, S] the mediation of cross-modal operations in humans has been ascribed to the angular and supramarginal gyri-parietal areas that are without homology or at best poorly represented in monkeys. PETRIDES and IVERSEN [9, lo] have shown that lesions of periarcuate cortex in monkeys
Annals of the New York Academy of Sciences, May 1, 1990
Pyridoxal 5'-phosphate (PLP) is the major coenzymatic form of pyridoxine. There are over one hund... more Pyridoxal 5'-phosphate (PLP) is the major coenzymatic form of pyridoxine. There are over one hundred known pyridoxal 5'-phosphate-dependent reactions, most of which are involved in the metabolism of various amino acids. Pyridoxamine 5'-phosphate can function in aminotransf erase reactions by the cyclic regeneration of the two active phosphate forms. Pyridoxal 5'-phosphate-dependent reactions studied in the nervous system are involved in the catabolism of various amino acids. The putative neurotransmitters , dopamine, norepinephrine , serotonin , histamine , aminobutyric acid and taurine , as well as the sphingoiipids and poly amines are synthesized by PLP-dependent enzymes. Of these enzymes, three (glutamic acid decarboxylase , 5-hydroxytryptophan decarboxylase and crnithine decarboxylase) seem to have crucial roles (Fig. '). The clinical effects of pyridoxine deficiency can be explained on the basis of the known decreases in the activities of these enzymes (1). EXPERIMENTAL PYRIDOXINE DEFICIENCY IN THE NEONATE RAT Dakshinamurti and Stephens (2) first reported the production of congenital pyridoxine deficiency. Our observations extended the "chronic fetal distress" hypothesis of Gruenwald (3) to include effects on the development of the central nervous system. We later showed that a deficiency of pyridoxine in rat pups could be produced by depriving the dam of dietary pyridoxine during lactation (4). Such a deficiency has been characterized using biochemical and electrophysiological parameters. The electroencephalogram (EEG)
Quarterly Journal of Experimental Psychology Section B-comparative and Physiological Psychology, Feb 1, 2002
Three experiments investigated the conditions under which electrolytic lesions of the dorsolatera... more Three experiments investigated the conditions under which electrolytic lesions of the dorsolateral periaqueductal grey (dlPAG) facilitate conditioned defensive freezing in the rat (Rattus norvegicus). Experiment 1 found that dlPAG lesions placed before context-shock pairings facilitated conditioned defensive freezing with massed but not distributed shock. No such effect was found in Experiment 2, when the lesions were placed after context-shock pairings. Experiment 3 found that dlPAG lesions facilitated subsequent conditioning with massed but not a single shock. In addition, no differences in sensitivity to thermal or shock pain were evident in lesioned and unlesioned rats. Taken together, these results are consistent with the suggestion that dlPAG activation interferes with the processing of contextual cues during association formation. Although a number of experiments have investigated the neural substrates of defensive behaviour in the rat (for review, LeDoux, 1990, 1995), little is known about the brain mechanisms that allow rats to rapidly switch from one mode of defensive behaviour to another. When a rat is threatened, it defends itself in a manner appropriate to the level of threat (Bolles, 1970, 1975). How the current level of threat determines which particular response is selected is well described by predatory imminence theory (e.g., Fanselow & Lester, 1988). According to predatory imminence theory, defensive behaviour in the rat is divided into three categories: Pre-encounter, post-encounter, and circa-strike. Behaviours in the pre-encounter category Requests for reprints should be sent to Douglas A
Biochemical and biophysical research communications, Mar 25, 2018
Diabetes and obesity are commonly associated with Alzheimer's disease (AD). Accumulating evid... more Diabetes and obesity are commonly associated with Alzheimer's disease (AD). Accumulating evidence show that insulin signaling defects are protentional upstream driver of AD. However, the mechanism by which diabetes and insulin signaling defects contribute to AD remains unknown. Here we show that Fat mass and obesity-associated protein (FTO) is involved the insulin defects-associated AD. Defective insulin signaling in diabetes and obesity in human and mice activated Fto in the brain tissues. Lentivirus-mediated knockdown of Fto reduced the phosphorylation of Tau protein whereas overexpression of FTO promoted the level of phosphorylated Tau in neurons. Mechanism study demonstrated that FTO activated the phosphorylation of Tau in a mTOR-dependent manner because FTO activated mTOR and its downstream signaling and rapamycin blocked FTO-mediated phosphorylation of Tau. FTO promoted the activation of mTOR by increasing the mRNA level of TSC1 but not TSC2, the upstream inhibitor of mTOR...
This study explores different episodic memory domains, namely object, temporal and spatial memory... more This study explores different episodic memory domains, namely object, temporal and spatial memory, affected in patients with a clinical diagnosis of single domain amnestic mild cognitive impairment (aMCI). 15 aMCI patients and 25 healthy controls were recruited and tested. Object, spatial, and temporal memory were tested using computerized tasks and again in interactive, real-world tasks. Controls outperformed patients on the object computerized task and showed a trend toward significance for the computerized spatial and temporal tasks, but there was no difference in spatial and temporal memory when using the interactive tasks, indicating the employment of compensatory mechanisms in patients to overcome some of the memory impairments associated with aMCI. These findings highlight that aMCI patients might delay seeking help due to compensatory mechanisms which mask their deficits in real-world situations.
Conclusions: Limited activation patterns in ARND suggest problems in information processing along... more Conclusions: Limited activation patterns in ARND suggest problems in information processing along the ventral
Stimuli for Discrimination of Colours and Textures Each set of colour stimuli consisted of 4 Muns... more Stimuli for Discrimination of Colours and Textures Each set of colour stimuli consisted of 4 Munsell colour patches (2º visual angle) matched in luminance and chroma. Within each set, hue was systematically varied so that the patches were evenly spaced in the colour domains and steps in hue were equally spaced at 2.5 perceptual steps (range 2.5-7.5 steps). For the texture task, patches of marble-like textures from Brodatz's textures were employed. Due to the lack of a standard metric for textures, it was not possible to create equal perceptual steps for these stimuli.
This study explores different episodic memory domains, namely object, temporal and spatial memory... more This study explores different episodic memory domains, namely object, temporal and spatial memory, affected in patients with a clinical diagnosis of single domain amnestic mild cognitive impairment (aMCI). 15 aMCI patients and 25 healthy controls were recruited and tested. Object, spatial, and temporal memory were tested using computerized tasks and again in interactive, real-world tasks. Controls outperformed patients on the object computerized task and showed a trend toward significance for the computerized spatial and temporal tasks, but there was no difference in spatial and temporal memory when using the interactive tasks, indicating the employment of compensatory mechanisms in patients to overcome some of the memory impairments associated with aMCI. These findings highlight that aMCI patients might delay seeking help due to compensatory mechanisms which mask their deficits in real-world situations.
Journal of Clinical and Experimental Neuropsychology, Apr 7, 2011
We used functional magnetic resonance imaging (fMRI) to assess cortical involvement in a hidden p... more We used functional magnetic resonance imaging (fMRI) to assess cortical involvement in a hidden pattern task. The experimental and control conditions involved judgment of the presence/absence versus the position of a complex pattern. Activation specific to hidden pattern identification was concentrated on frontal, dorsal parietal, and mesolimbic cortex. This was consistent not only across individual subjects, but with hidden figures tasks used in previous fMRI investigations. Results suggest that pattern identification relies on a relatively stable neural network controlling selective attention. In combination with fMRI, hidden pattern tasks may be useful in neuropsychological assessment of visual search and object identification.
International Journal of Psychophysiology, Oct 1, 2007
We have previously used functional magnetic resonance imaging to assess specific anterolateral te... more We have previously used functional magnetic resonance imaging to assess specific anterolateral temporal regions involved in object recognition, providing a novel technique for evaluating functional status in temporal lobe epilepsy (i.e., a site directed approach). However, a method that combines high temporal resolution with spatial mapping is needed to isolate the specific processes associated with these regions (i.e., a process specific approach). In the current study, we evaluated the cognitive processes associated with object recognition and their relationship to the temporal lobe using high-density event-related potentials (ERPs). N300 and late positive component (LPC) responses were examined using a word-picture matching task, with three factors: congruity (match/mismatch), level of abstraction (basic/superordinate), and object category (natural/artificial). The N300 and LPC were analyzed in terms of their temporal characteristics as well as their spatial characteristics through source analysis. The results showed that the N300 primarily indexed processing of congruity and level of abstraction, whereas the LPC primarily indexed processing of object category. In agreement with previous functional imaging studies, N300 and LPC source analysis results confirmed temporal lobe involvement in object recognition. Importantly, LPC object category differences were detected in the anterior temporal lobe. Individual subject analyses revealed that these anterior temporal lobe differences were reliable--with greater activity for natural objects in 84% of subjects. The findings are discussed in terms of clinical applications that use spatiotemporal ERP differences to evaluate functional status of the temporal lobes.
Functional magnetic resonance imaging (fMRI) is increasingly being used for neurosurgical plannin... more Functional magnetic resonance imaging (fMRI) is increasingly being used for neurosurgical planning. One potential application relates to identifying eloquent cortex in regions immediately adjacent to epileptogenic foci in temporal lobe epilepsy (TLE). While medial temporal structures, such as the hippocampus and amygdala, are typically removed during surgery, it is often difficult to determine whether nearby cortical regions in the anterolateral temporal lobe should be spared. An essential first step is to identify a method of activating these regions in healthy individuals. The purpose of this study was to develop a site directed fMRI approach for evaluating functional status in the anterolateral temporal lobes. A picture-word matching task, with object category and level of abstraction factors, was used to characterize temporal lobe activation. Whole brain analysis at the group level confirmed the involvement of the temporal poles as well as adjacent superior, middle and inferior temporal gyri within a larger object recognition network. A region-of-interest analysis on the anterolateral temporal lobe demonstrated that activation varied across conditions and regions for individuals. Importantly, it was possible to detect activation in one or more conditions and/or regions for all individuals--demonstrating that it is possible to evaluate functional status. The findings provide the foundation for a novel fMRI approach in neurosurgical planning for TLE.
Annals of the New York Academy of Sciences, May 1, 1990
Animal studies regarding the antinociceptive effect of B vitamins have been reported only occasio... more Animal studies regarding the antinociceptive effect of B vitamins have been reported only occasionally and with contradictory results.'-3 It has been proposed that vitamins of the B group alleviate pain. In search of evidence for analgesic properties of these compounds, experiments have been recently carried out on rats.I4 These studies have indicated that administration of vitamin B compound (Neurobion, E-Merck) produced analgesia in clinical therapy and animal models of pain. The mechanism underlying this analgesic action is not known. Recent studies have also suggested that vitamin B, can directly suppress the responses of spinal neurons to nociceptive ~timulation.~.~ It has been suggested that this suppression might be involved in the analgesia in clinical therapy. Assuming that nociceptive activity conducted in ascending axons to the thalamus will cause a sensation of pain in man, it was of interest to observe what happens to the activity elicited in the thalamus by electrical stimulation of nociceptive afferents in the contralateral sciatic nerve when pyridoxine was administered parenterally. Activation of electrical stimulation was chosen to determine only central effects of pyridoxine in normal and pyridoxine-deficient rats.
Subjects were 20 learning‐disabled (LD) children who were matched for mean age and IQ against a g... more Subjects were 20 learning‐disabled (LD) children who were matched for mean age and IQ against a group of 20 non‐LD control children. A computer‐generated visual target identification task was used to assess visual selective attention capabilities. Subjects were asked to locate colored form targets (green squares) appearing amid an array of distractor stimuli. Distractors in disjunctive arrays shared no features with the target, whereas distractors in conjunctive arrays could share one feature—either color or form—with the target stimulus. LD children were faster than controls in correctly responding to targets, but no between‐group differences in accuracy were noted. Impulsive children — defined on the basis of performance in the Matching Familiar Figures (MFF) test —were significantly overrepresented in the LD group. Impulsive children were significantly less accurate at target identification for both array types than were reflective children. Both LD and impulsive children performed at normal levels in a test requiring the inhibitory modulation of motor output. Deficits in the automatic, preattentive processing of stimulus features are proposed to explain the performance impairments of impulsive children.
Using an automated apparatus modelled after that of DAVENPORT and ROGERS [lo], Irus monkeys were ... more Using an automated apparatus modelled after that of DAVENPORT and ROGERS [lo], Irus monkeys were progressively shaped to establish a cross-modal matching (CMM) set. The subjects were required to solve three novel haptic to visual matching problems. Two of the three problems were solved to criterion (80% correct for three successive days) within the allotted period. Learning rates were within-the limits normally reported for intramodal matching using touch and vision. Changes in the haptic features of the stimuli influenced the degree of difficulty associated with individual problems. CROSS-MODAL effects have been widely implicated as a necessary correlate of language skills in man [l-8]. GESCHWIND [l] argued that "the inability to acquire speech has as a prerequisite the ability to form cross-modal associations". Since that time, both crossmodal abilities [9, lo] and the capacity to acquire and manipulate language have been demonstrated in chimpanzees. More recently, the demonstration of cross-modal recognition in several monkey species [ll-131 has shown that earlier failures in experiments of this type [14] were due to inadequacies not of the animal subjects, but of the procedures used to test them. Meaningful research into the neural basis of cross-modal perception in primate species has awaited the development of a testing paradigm which would allow the simultaneous assessment of treatment effects and investigation of contributing neural processes. The procedure of cross-modal matching (CMM) as developed by DAVENPORT et al. [9, IO] has the advantage of allowing for repeated-trials analysis. Repetition in the context of matchingfrom-sample introduces confounding from reward contingencies, but permits the quantitative assessment of acquisition and retention rates. Likewise the trial to trial uniformity of the matching paradigm ensures an adequate sample of behaviour for electrophysiological analysis. This element is lacking in the otherwise elegant cross-modal recognition experiment devised by COWEY and WEISKRANTZ [5, 151. The use of an automated apparatus in the context of neurological research is desirable for several reasons. The experimenter gains precise control over the various temporal relationships between the subjects responses and the onset, sequence, duration and delay of stimuli and rewards. In addition, switch closures may be used, for example, to gather such measures as response latency, or to flag behavioural events for use in electrophysiological analysis such as evoked-potential averaging. The aim of the present study was to adapt the CMM paradigm for use with monkeys. A shaping program using successive approximations of the haptic to visual matching
Monkeys with either anterior or posterior lesions of area TE were tested on serial reversal of a ... more Monkeys with either anterior or posterior lesions of area TE were tested on serial reversal of a visual pattern discrimination problem. Compared with unoperated control subjects, both lesion groups took longer to learn the original problem. Reversal learning was impaired primarily in the anterior group. Dissociation of function within area TE was inferred from opposite effects of the lesions on the period of stationarity, which characterizes the presolution portion of the backward learning curve. Results are interpreted in terms of twoprocess models of extrastriate visual function.
Computerized electroencephalography and thalamic ventro-posterior lateral (VPL) unit activities w... more Computerized electroencephalography and thalamic ventro-posterior lateral (VPL) unit activities were recorded from pyridoxine-deficient and pair-fed pyridoxine-supplemented adult male rats. Pyridoxine-deficient animals exhibited slow electroencephalograms (EEG) represented by the dominance of delta activity and reduced seizure thresholds to local (VPL) application of either picrotoxin or pentylene tetrazole. Frequency and amplitude of thalamic VPL unit activity were significantly reduced in pyridoxine-deficient rats as compared to pyridoxine-supplemented controls. Pyridoxine-deficient rats exhibited irregular unit activity with frequent bursts and electrosilent periods in response to local (VPL) picrotoxin or pentylene tetrazole microinjections. They also exhibited severe seizure discharge activity of prolonged duration at any given dose of either picrotoxin or pentylene tetrazole. This was represented by significantly increased burst frequency, burst duration and reduced seizure latencies. Unit activity was transformed into burst discharge activity with intermittent electrosilent zones during picrotoxin or pentylene tetrazole epileptogenesis. Cerebral gamma aminobutyric acid (GABA) level was reduced and glutamate concentration increased in pyridoxine-deficient rats when compared with pyridoxine-supplemented controls. Local (VPL) microinjection of GABA or pyridoxine induced neuronal recovery in both convuisant-treated normal and pyridoxine-deficient rats. Neuronal recovery was however delayed in pyridoxine-deficient rats. Neuronal recovery was associated with a significant increase in EEG background frequency and reduction in delta frequencies in the EEG records of both normal and pyridoxine-deficient rats. Reduced seizure threshold and delayed neuronal recovery are related to the significantly reduced brain regional GABA and elevated glutamate levels in pyridoxine-deficient rats.
Transcortical evoked potentials (EP's) were collected while monkeys performed a haptic to visual ... more Transcortical evoked potentials (EP's) were collected while monkeys performed a haptic to visual matching task. EP's were sorted into "sample" groups, according to the haptic stimuli, "match" groups, according to the choice of a visual alternative, and "spatial" groups, depending upon the panel (right or left) pressed during the matching response. Electrodes in inferoparietal cortex yielded event-related activity due to the matching and spatial aspects ofresponding, but not to haptic sampling. A postcentral electrode yielded event-related differences due to haptic sampling and spatial response, and a smaller difference related to visual matching. Implications for the neural mediation of cross-modal operations are discussed. RECENT experiments Cl-43 have shown that monkeys share with men and apes [S, 61 the ability to solve cross-modal problems. The neural basis of this ability, however, remains a subject of controversy. Classically [7, S] the mediation of cross-modal operations in humans has been ascribed to the angular and supramarginal gyri-parietal areas that are without homology or at best poorly represented in monkeys. PETRIDES and IVERSEN [9, lo] have shown that lesions of periarcuate cortex in monkeys
Annals of the New York Academy of Sciences, May 1, 1990
Pyridoxal 5'-phosphate (PLP) is the major coenzymatic form of pyridoxine. There are over one hund... more Pyridoxal 5'-phosphate (PLP) is the major coenzymatic form of pyridoxine. There are over one hundred known pyridoxal 5'-phosphate-dependent reactions, most of which are involved in the metabolism of various amino acids. Pyridoxamine 5'-phosphate can function in aminotransf erase reactions by the cyclic regeneration of the two active phosphate forms. Pyridoxal 5'-phosphate-dependent reactions studied in the nervous system are involved in the catabolism of various amino acids. The putative neurotransmitters , dopamine, norepinephrine , serotonin , histamine , aminobutyric acid and taurine , as well as the sphingoiipids and poly amines are synthesized by PLP-dependent enzymes. Of these enzymes, three (glutamic acid decarboxylase , 5-hydroxytryptophan decarboxylase and crnithine decarboxylase) seem to have crucial roles (Fig. '). The clinical effects of pyridoxine deficiency can be explained on the basis of the known decreases in the activities of these enzymes (1). EXPERIMENTAL PYRIDOXINE DEFICIENCY IN THE NEONATE RAT Dakshinamurti and Stephens (2) first reported the production of congenital pyridoxine deficiency. Our observations extended the "chronic fetal distress" hypothesis of Gruenwald (3) to include effects on the development of the central nervous system. We later showed that a deficiency of pyridoxine in rat pups could be produced by depriving the dam of dietary pyridoxine during lactation (4). Such a deficiency has been characterized using biochemical and electrophysiological parameters. The electroencephalogram (EEG)
Quarterly Journal of Experimental Psychology Section B-comparative and Physiological Psychology, Feb 1, 2002
Three experiments investigated the conditions under which electrolytic lesions of the dorsolatera... more Three experiments investigated the conditions under which electrolytic lesions of the dorsolateral periaqueductal grey (dlPAG) facilitate conditioned defensive freezing in the rat (Rattus norvegicus). Experiment 1 found that dlPAG lesions placed before context-shock pairings facilitated conditioned defensive freezing with massed but not distributed shock. No such effect was found in Experiment 2, when the lesions were placed after context-shock pairings. Experiment 3 found that dlPAG lesions facilitated subsequent conditioning with massed but not a single shock. In addition, no differences in sensitivity to thermal or shock pain were evident in lesioned and unlesioned rats. Taken together, these results are consistent with the suggestion that dlPAG activation interferes with the processing of contextual cues during association formation. Although a number of experiments have investigated the neural substrates of defensive behaviour in the rat (for review, LeDoux, 1990, 1995), little is known about the brain mechanisms that allow rats to rapidly switch from one mode of defensive behaviour to another. When a rat is threatened, it defends itself in a manner appropriate to the level of threat (Bolles, 1970, 1975). How the current level of threat determines which particular response is selected is well described by predatory imminence theory (e.g., Fanselow & Lester, 1988). According to predatory imminence theory, defensive behaviour in the rat is divided into three categories: Pre-encounter, post-encounter, and circa-strike. Behaviours in the pre-encounter category Requests for reprints should be sent to Douglas A
Biochemical and biophysical research communications, Mar 25, 2018
Diabetes and obesity are commonly associated with Alzheimer's disease (AD). Accumulating evid... more Diabetes and obesity are commonly associated with Alzheimer's disease (AD). Accumulating evidence show that insulin signaling defects are protentional upstream driver of AD. However, the mechanism by which diabetes and insulin signaling defects contribute to AD remains unknown. Here we show that Fat mass and obesity-associated protein (FTO) is involved the insulin defects-associated AD. Defective insulin signaling in diabetes and obesity in human and mice activated Fto in the brain tissues. Lentivirus-mediated knockdown of Fto reduced the phosphorylation of Tau protein whereas overexpression of FTO promoted the level of phosphorylated Tau in neurons. Mechanism study demonstrated that FTO activated the phosphorylation of Tau in a mTOR-dependent manner because FTO activated mTOR and its downstream signaling and rapamycin blocked FTO-mediated phosphorylation of Tau. FTO promoted the activation of mTOR by increasing the mRNA level of TSC1 but not TSC2, the upstream inhibitor of mTOR...
This study explores different episodic memory domains, namely object, temporal and spatial memory... more This study explores different episodic memory domains, namely object, temporal and spatial memory, affected in patients with a clinical diagnosis of single domain amnestic mild cognitive impairment (aMCI). 15 aMCI patients and 25 healthy controls were recruited and tested. Object, spatial, and temporal memory were tested using computerized tasks and again in interactive, real-world tasks. Controls outperformed patients on the object computerized task and showed a trend toward significance for the computerized spatial and temporal tasks, but there was no difference in spatial and temporal memory when using the interactive tasks, indicating the employment of compensatory mechanisms in patients to overcome some of the memory impairments associated with aMCI. These findings highlight that aMCI patients might delay seeking help due to compensatory mechanisms which mask their deficits in real-world situations.
Conclusions: Limited activation patterns in ARND suggest problems in information processing along... more Conclusions: Limited activation patterns in ARND suggest problems in information processing along the ventral
Stimuli for Discrimination of Colours and Textures Each set of colour stimuli consisted of 4 Muns... more Stimuli for Discrimination of Colours and Textures Each set of colour stimuli consisted of 4 Munsell colour patches (2º visual angle) matched in luminance and chroma. Within each set, hue was systematically varied so that the patches were evenly spaced in the colour domains and steps in hue were equally spaced at 2.5 perceptual steps (range 2.5-7.5 steps). For the texture task, patches of marble-like textures from Brodatz's textures were employed. Due to the lack of a standard metric for textures, it was not possible to create equal perceptual steps for these stimuli.
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Papers by Bruce Bolster