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Biomedical subjects

Matthew A Howard

Publications and source records attributed to Matthew A Howard.

11 recordsLinked to original sources

Electrophysiological correlates of reward prediction error recorded in the human prefrontal cortex.

Lesion and functional imaging studies have shown that the ventromedial prefrontal cortex is critically involved in the avoidance of risky choices. However, detailed descriptions of the mechanisms that underlie the establishment of such behaviors remain elusive, due in part to the spatial and temporal limitations of available research techniques. We investigated this issue by recording directly from prefrontal depth electrodes in a rare neurosurgical patient while he performed the Iowa Gambling Task, and we concurrently measured behavioral, autonomic, and electrophysiological responses. We found a robust alpha-band component of event-related potentials that reflected the mismatch between expected outcomes and actual outcomes in the task, correlating closely with the reward-related error obtained from a reinforcement learning model of the patient's choice behavior. The finding implicates this brain region in the acquisition of choice bias by means of a continuous updating of expectations about reward and punishment.

Choice Behavior↗

Intracortical responses in human and monkey primary auditory cortex support a temporal processing mechanism for encoding of the voice onset time phonetic parameter.

This study tests the hypothesis that temporal response patterns in primary auditory cortex are potentially relevant for voice onset time (VOT) encoding in two related experiments. The first experiment investigates whether temporal responses reflecting VOT are modulated in a way that can account for boundary shifts that occur with changes in first formant (F1) frequency, and by extension, consonant place of articulation. Evoked potentials recorded from Heschl's gyrus in a patient undergoing epilepsy surgery evaluation are examined. Representation of VOT varies in a manner that reflects the spectral composition of the syllables and the underlying tonotopic organization. Activity patterns averaged across extended regions of Heschl's gyrus parallel changes in the subject's perceptual boundaries. The second experiment investigates whether the physiological boundary for detecting the sequence of two acoustic elements parallels the psychoacoustic result of approximately 20 ms. Population responses evoked by two-tone complexes with variable tone onset times (TOTs) in primary auditory cortex of the monkey are examined. Onset responses evoked by both the first and second tones are detected at a TOT separation as short as 20 ms. Overall, parallels between perceptual and physiological results support the relevance of a population-based temporal processing mechanism for VOT encoding.

Animals↗

A functional connection between inferior frontal gyrus and orofacial motor cortex in human.

The inferior frontal gyrus (IFG) of humans is known to play a critical role in speech production. The IFG is a highly convoluted and cytoarchitectonically diverse structure, classically forming 3 subgyri. It is reasonable to speculate that during speaking the IFG, or some portion of it, influences by corticocortical connections the orofacial representational area of primary motor cortex. To test the hypothesis that such corticocortical connections exist, electrical-stimulation tract tracing experiments were performed intraoperatively on 14 human subjects undergoing surgical treatment of medically intractable epilepsy. Bipolar electrical stimulation was applied to sites on the IFG, while the resulting evoked potentials were recorded from orofacial motor cortex, using a multichannel recording array. Stimulation of the IFG evoked polyphasic waveforms on motor cortex of both language-dominant and -nondominant hemispheres. The evoked waveforms had consistent features across subjects. The responses were seen in discrete regions on precentral cortex. Stimulation of motor cortex also evoked responses on portions of IFG. The data provide evidence for a functional connection between the human IFG and orofacial motor cortex.

Adult↗

Effects of preparative parameters on the properties of chitosan hydrogel beads containing Candida rugosa lipase.

The influences of the pH, tripolyphosphate (TPP) concentration, and ionic strength of the gelling medium on the entrapment efficiency, release, and activity of lipase in chitosan hydrogel beads were studied. A solution of Candida rugosa lipase was prepared in a 1.5% w/v chitosan and 1% (v/v) acetic acid medium, and dropped into a TPP solution. Release of lipase in pH 7.2 Tris buffer was monitored over 36 h using the micro BCA protein assay. The activity of the entrapped enzyme was assayed using the Sigma lipase activity method. Following preliminary studies, an experimental design was followed to develop mathematical models that describe bead characteristics as functions of the pH and the TPP concentration in the gelling medium. The pH and the TPP concentration each had an effect on the entrapment, retention, and activity of lipase. Entrapped lipase retained a high degree of activity in multiple reactions. The ionic strength, in the range studied, exerted a minimal effect on bead characteristics. Statistical analysis allowed optimization within the factor space with respect to maximizing the enzyme entrapment efficiency and activity, and also minimizing the amount released after 36 h in the Tris buffer.

Candida↗

Extruded and spheronized beads containing no microcrystalline cellulose: influence of formulation and process variables.

The purposes of this study were to investigate the use of chitosan in the manufacture of beads by extrusion-spheronization without inclusion of microcrystalline cellulose, and to study the effect of formulation and process variables on the characteristics of the beads. Beads containing chitosan, fine particle ethylcellulose, hydroxypropyl methylcellulose (HPMC), and caffeine as the model drug were manufactured. Bead size, yield, shape, friability, density, porosity, and release studies were determined. Spherical beads with good mechanical properties could be manufactured without microcrystalline cellulose. Release studies showed that there was immediate release of drug from the beads. A five factor, half fraction screening design was employed to study the effect of formulation variables and process variables on the properties of the beads. Statistical analysis indicated that formulation variables such as the chitosan content, HPMC content, and water content, and process variables such as the spheronizer speed and extruder speed significantly affected the physical properties of the beads. The bead size decreased with an increase in chitosan content. Significant two-factor interactions exist between the variables for several of the measured responses. Beads with high percentage yield and high sphericity can be obtained at high chitosan content, and low HPMC content, water content, spheronizer speed, and extruder speed. Less friable beads can be obtained at high levels of studied formulation variables and low levels of studied process variables. Beads of high density and low porosity can be manufactured at high levels of the studied formulation and process variables. Regression equations were generated using Statgraphics Plus software that can be used to develop formulations with desired bead properties. Chitosan was useful to provide beads of acceptable physical properties using water as a granulating fluid in the extrusion-spheronization process.

Caffeine↗

Functional connections between auditory cortex on Heschl's gyrus and on the lateral superior temporal gyrus in humans.

Functional connections between auditory fields on Heschl's gyrus (HG) and the acoustically responsive posterior lateral superior temporal gyrus (field PLST) were studied using electrical stimulation and recording methods in patients undergoing diagnosis and treatment of intractable epilepsy. Averaged auditory (click-train) evoked potentials were recorded from multicontact subdural recording arrays chronically implanted over the lateral surface of the superior temporal gyrus (STG) and from modified depth electrodes inserted into HG. Biphasic electrical pulses (bipolar, constant current, 0.2 ms) were delivered to HG sites while recording from the electrode array over acoustically responsive STG cortex. Stimulation of sites along the mediolateral extent of HG resulted in complex waveforms distributed over posterolateral STG. These areas overlapped each other and field PLST. For any given HG stimulus site, the morphology of the electrically evoked waveform varied across the STG map. A characteristic waveform was recorded at the site of maximal amplitude of response to stimulation of mesial HG [presumed primary auditory field (AI)]. Latency measurements suggest that the earliest evoked wave resulted from activation of connections within the cortex. Waveforms changed with changes in rate of electrical HG stimulation or with shifts in the HG stimulus site. Data suggest widespread convergence and divergence of input from HG to posterior STG. Evidence is presented for a reciprocal functional projection, from posterolateral STG to HG. Results indicate that in humans there is a processing stream from AI on mesial HG to an associational auditory field (PLST) on the lateral surface of the superior temporal gyrus.

Acoustic Stimulation↗

Volume estimation of prefrontal cortical subfields using MRI and stereology.

The objective of this protocol was to provide a rapid, neurofunctionally relevant alternative to region-drawing or automated gyral/sulcal-based techniques. The Cavalieri method and point counting [e.g. Br. J. Radiol. 73 (2000) 679] were used in conjunction with a previously established parcellation methodology [Arch. Gen. Psychiatry 57 (2000) 761] to estimate the volumes of anatomically defined subfields of the prefrontal cortex (PFC) based on landmarks visible on T(1)-weighted magnetic resonance (MR) images. Ten participants (n=5 healthy adults; n=5 patients) were studied. Regional PFC volume estimates derived from point counting methods were reproducible between raters (Intraclass Correlations (ICC)=0.92-0.95) and repeatable within rater (ICC=0.93-0.99). Predicted coefficients of error for individual volume estimates were less than 5%. This protocol provides an efficient means of calculating unbiased volume estimates of the PFC with predictable precision for use in both cognitive and clinical studies.

Adolescent↗

A device for cooling localized regions of human cerebral cortex. Technical note.

Neurosurgeons use invasive mapping methods during surgery to understand the functional neuroanatomy of patients. Electrical stimulation methods are used routinely for the temporary disruption of focal regions of cerebral cortex so that the surgeon may infer the functional role of the brain site being stimulated. Although it is an efficient and useful method, modes of electrical stimulation mapping have significant limitations. Neuroscientists use focal cooling to effect a more controlled disruption of cortical functions in experimental animals, and in this report, the authors describe their experience using a device to achieve this same objective in patients undergoing neurosurgery. The cooling probe consists of a stainless steel chamber with thermocouples and electroencephalography (EEG) recording contacts. Active cooling is achieved by infusing chilled saline into the chamber when the cooling probe is positioned on the pial surface. Experiments were performed in 18 patients. Temperature gradient measurements indicate that the entire thickness of gray matter under the probe is cooled to temperatures that disrupt local synaptic activity. Statistically significant changes in spontaneous and stimulus-evoked EEG activity were consistently observed during cooling, providing clear evidence of reversible disruption of physiological functions. Preliminary findings during functional mapping of the Broca area demonstrated qualitative differences between the temporary neurological deficits induced by cooling and those caused by electrical stimulation. These findings indicate the safety and utility of the cooling probe as a neurosurgical research tool. Additional rigorously designed studies should be undertaken to correlate the effects of cooling, electrical stimulation, and focal lesioning.

Brain Mapping↗

Electrophysiological responses in the human amygdala discriminate emotion categories of complex visual stimuli.

The human amygdala has been shown to participate in processing emotionally salient stimuli related to threat, danger, and aversion, data that have come primarily from functional imaging and lesion studies. Recording intracranial field potentials from five amygdalas in four patients with chronically implanted depth electrodes, we analyzed responses in the gamma frequency range, a region of the power spectrum thought to reflect especially the contribution of neuronal activity to cognitive processes. Significant changes in the power amplitude of responses were obtained selectively to visual images judged to look aversive but not to those judged to look pleasant or neutral. Several possible confounds were addressed: all four patients had been carefully selected so that the amygdalas from which recordings were obtained were distal to epileptogenic foci, making it likely that we recorded from healthy tissue, and the observed responses could not be attributed to luminance or color differences between the stimuli. A further analysis of differences in power between the high and low gamma bands revealed an additional structure that discriminated those stimuli related to bodily injury from those related to disgust. Despite the increased power amplitude in the gamma range, there was no stimulus-locked phase coherence. The observed responses in the gamma frequency range may reflect the role of the amygdala in binding perceptual representations of the stimuli with memory, emotional response, and modulation of ongoing cognition, on the basis of the emotional significance of the stimuli.

Adult↗

Voxel-based morphometric comparison of hippocampal and extrahippocampal abnormalities in patients with left and right hippocampal atrophy.

We used voxel-based morphometry (VBM), an automatic whole-brain MR image analysis technique, to investigate gray matter abnormalities in patients with temporal lobe epilepsy (TLE), in whom hippocampal atrophy (HA) was demonstrated by application of the Cavalieri method of modern design stereology. VBM results (P < 0.05, corrected) indicated preferential gray matter concentration (GMC) reduction in anterior hippocampus in patients with left HA and posterior hippocampus in patients with right HA. GMC reduction was also found in right dorsal prefrontal cortex in left and right HA patients. Prefrontal atrophy may be due to epileptiform excitotoxic discharges from the reciprocally connected pathological hippocampus, and may be the underlying biological cause for executive dysfunction in patients with TLE. GMC excess in ipsilateral parahippocampal, cerebellar, and pericallosal regions was common to both left and right HA groups relative to controls, and is hypothesized to reflect diminished gray-white matter demarcation, underlying white matter atrophy, or structural displacement due to cerebrospinal fluid expansion. However, bilateral temporal lobe GMC excess was observed in left HA patients, while ipsilateral temporal lobe GMC excess was observed in right HA patients. This work demonstrates methodological consistency between automated VBM and manual stereological analysis of the hippocampus in group comparisons, indicates widespread extrahippocampal gray matter abnormalities in unilateral HA, and suggests that there may be inherent differences in the effect of TLE on temporal lobe structures depending on the side of HA.

Adolescent↗