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Masud Husain

Publications and source records attributed to Masud Husain.

At least 19 recordsLinked to original sources
PubMed2026

Research agenda to advance anhedonia assessment, understanding and treatment: an ECNP-GALENOS expert meeting report.

Anhedonia, broadly defined as a reduced ability to experience interest or pleasure, represents an important transdiagnostic neuropsychiatric symptom dimension which may benefit from targeted diagnostics and treatments. Different lines of research have proposed that it comprises multiple facets, including deficits in anticipatory ('wanting') and consummatory ('liking') reward processing as well as reward learning and affects different aspects of life (eg, social, physical, cognitive). Certain facets-more specifically anticipation, motivation and reward learning-likely involve blunted phasic dopaminergic signalling. However, recent meta-analytical evidence of human depression studies indicates that prodopaminergic antidepressants produce relatively small improvements in anhedonia symptoms and suggest that mechanisms beyond dopamine likely contribute to anhedonia. This stimulated an expert meeting to review the literature and define priorities for future research in anhedonia. A central key priority is developing a translational biologically-informed nomenclature and consensus that solves the current mismatch between constructs, paradigms and measures, and mechanisms, which separates discrete reward-related processes such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure. Clinical research priorities are improved multimodal measurement tools, integrating neurobiological frameworks (eg, neuroimaging, electrophysiology and liquid biomarkers capturing dopaminergic, glutamatergic, opioid and immunometabolic pathways) and transdiagnostic studies across neuropsychiatric disorders and developmental stages. Innovative trial designs that explicitly target anhedonic phenotypes as a primary outcome and test mechanism-based interventions are also needed. Translational research recommendations include back-translation strategies that begin with patient-relevant phenotypes followed by the development of comparable human and animal tasks that target reward-related processes, such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure, improve cross-species behavioural paradigms and enhance methodological rigour and reproducibility. Collectively, these recommendations will help refine the conceptualisation of anhedonia and advance its role within precision psychiatry as a mechanistically grounded target across multiple disorders.

Humans↗
PubMed2007

The hippocampus is required for short-term topographical memory in humans.

The hippocampus plays a crucial role within the neural systems for long-term memory, but little if any role in the short-term retention of some types of stimuli. Nonetheless, the hippocampus may be specialized for allocentric topographical processing, which impacts on short-term memory or even perception. To investigate this we developed performance-matched tests of perception (match-to-sample) and short-term memory (2 s delayed-match-to-sample) for the topography and for the nonspatial aspects of visual scenes. Four patients with focal hippocampal damage and one with more extensive damage, including right parahippocampal gyrus, were tested. All five patients showed impaired topographical memory and spared nonspatial processing in both memory and perception. Topographical perception was profoundly impaired in the patient with parahippocampal damage, mildly impaired in two of the hippocampal cases, and clearly preserved in the other two hippocampal cases (including one with dense amnesia). Our results suggest that the hippocampus supports allocentric topographical processing that is indispensable when appropriately tested after even very short delays, while the presence of the sample scene can allow successful topographical perception without it, possibly via a less flexible parahippocampal representation.

Adult↗
PubMed2006

Space and the parietal cortex.

Current views of the parietal cortex have difficulty accommodating the human inferior parietal lobe (IPL) within a simple dorsal versus ventral stream dichotomy. In humans, lesions of the right IPL often lead to syndromes such as hemispatial neglect that are seemingly in accord with the proposal that this region has a crucial role in spatial processing. However, recent imaging and lesion studies have revealed that inferior parietal regions have non-spatial functions, such as in sustaining attention, detecting salient events embedded in a sequence of events and controlling attention over time. Here, we review these findings and show that spatial processes and the visual guidance of action are only part of the repertoire of parietal functions. Although sub-regions in the human superior parietal lobe and intraparietal sulcus contribute to vision-for-action and spatial functions, more inferior parietal regions have distinctly non-spatial attributes that are neither conventionally 'dorsal' nor conventionally 'ventral' in nature.

Attention↗
PubMed2006

Role of the human supplementary eye field in the control of saccadic eye movements.

The precise function of the supplementary eye field (SEF) is poorly understood. Although electrophysiological and functional imaging studies are important for demonstrating when SEF neurones are active, lesion studies are critical to establish the functions for which the SEF is essential. Here we report a series of investigations performed on an extremely rare individual with a highly focal lesion of the medial frontal cortex. High-resolution structural imaging demonstrated that his lesion was confined to the region of the left paracentral sulcus, the anatomical locus of the SEF. Behavioural testing revealed that the patient was significantly impaired when required to switch between anti- and pro-saccades, when there were conflicting rules governing stimulus-response mappings for saccades. Similarly, the results of an arbitrary stimulus-response associative learning task demonstrated that he was impaired when required to select the appropriate saccade from conflicting eye movement responses, but not for limb movements on an analogous manual task. When making memory-guided saccadic sequences, the patient demonstrated hypometria, like patients with Parkinson's disease, but had no significant difficulties in reproducing the order of saccades correctly on a task that emphasized accuracy with a wide temporal segregation between responses. These findings are consistent with the hypothesis that the SEF plays a key role in implementing control when there is conflict between several, ongoing competing saccadic responses, but not when eye movements need to be made accurately in sequence.

Association Learning↗
PubMed2006

Visuomotor functions of the posterior parietal cortex.

In this special issue of Neuropsychologia leading experts in the field discuss controversies and advances in the role of the posterior parietal cortex (PPC) in visuomotor control. The papers are wide-ranging in their scope, covering monkey physiology and anatomy, functional imaging in humans and monkeys as well as transcranial magnetic stimulation and lesion studies in humans. The collection provides an important overview of the current state-of the-art in this area of research, including discussions on homologies between monkey and human parietal regions, the role of co-ordinate transformations and intermediate representations from vision to action, and reviews of controversial hot topics in this field.

Animals↗
PubMed2006

Space re-exploration in hemispatial neglect.

Exploration of the space around us is a fundamental part of human behaviour. When it breaks down there is an important opportunity to understand its underlying mechanisms. Here we show that many right-hemisphere patients with left neglect re-explore rightward locations, failing to keep track of them during search. Importantly, such re-exploration occurred despite leftward stimuli being indistinguishable in peripheral vision, so it is unlikely to result from implicit processing of neglected targets. Revisits generally occurred after visits to other targets and are therefore not immediate perseverations. Finally, manipulating the visual salience of found targets altered the degree of neglect, but not revisit rates. Space exploration appears to be modulated both by the ability to keep track of spatial locations and by stimulus salience.

Aged↗
PubMed2006

Noradrenergic modulation of space exploration in visual neglect.

Visual neglect after stroke is often associated with a failure to explore contralesional space. Here, we show that guanfacine, a noradrenergic agonist that modulates dorsolateral prefrontal cortex, improves leftward space exploration in selected right-hemisphere patients with neglect. The positive effects of guanfacine were associated with extended ability to maintain attention on task. The results suggest that neuropharmacological targeting of intact frontal areas might be one way to enhance cognitive function after damage to posterior brain regions in selected individuals.

Adrenergic alpha-Agonists↗
PubMed2006

The role of the posterior parietal lobe in prism adaptation: Failure to adapt to optical prisms in a patient with bilateral damage to posterior parietal cortex.

We studied a patient (J.J.) with bilateral damage to those regions of the posterior parietal cortex (PPC) thought to be involved in prism adaptation. We demonstrated, for the first time in a parietal patient, that J.J. was unable to adapt to the visual perturbation induced by the optical prisms with either hand within four times the number of trials required by healthy adult subjects. We offer a novel account for the role of the PPC in prism adaptation: that the reach direction to the veridical target location specified in extrinsic limb-based coordinates must be de-coupled from the gaze direction to the perceived target location specified by intrinsic oculocentric coordinates in order to produce spatially accurate movements. This spatial discrepancy between gaze direction and reach direction may provide the necessary training signal required by the cerebellum to update the current internal model used to maintain spatial congruency between visual and proprioceptive maps of peripersonal space. The hypothesis is discussed in relation to recent disconnectionist accounts of optic ataxia.

Adaptation, Physiological↗
PubMed2006

Disorders of visual attention and the posterior parietal cortex.

Traditionally, both the monkey and human posterior parietal cortex (PPC) have been considered to have a privileged role in spatial perception or action. Lesions to this region of the human brain, particularly of the right hemisphere, undoubtedly lead to spatially lateralised deficits such as visual extinction or neglect. However, although studies in monkeys have revealed much about the spatial functions of the parietal lobe, the monkey PPC may not be a good model system with which to understand fully the disorders of attention that follow damage to the human parietal cortex. Several lines of evidence, from functional imaging as well as investigations of patients with parietal damage, demonstrate that parts of the human inferior parietal lobe (IPL) have non-spatial functions. Here, we argue that it is important to distinguish spatially lateralised from spatial deficits. Both spatial and non-spatial impairments might, in principle, contribute to a spatially lateralised behavioural syndrome such as neglect. In this review, we discuss the evidence for such a proposal and suggest that a better understanding of human parietal syndromes may emerge from considering both the spatial and non-spatial functions of this region.

Animals↗
PubMed2006

Hemispatial neglect, balance and eye-movement control.

PURPOSE OF REVIEW: Disorders of spatial awareness and balance following stroke are common but often under-diagnosed. They lead to poor outcome and frequently coexist. Here we focus on recent progress in the understanding of the mechanisms underlying these disorders and potential therapeutic advances. RECENT FINDINGS: Right-hemisphere networks are important for both spatial attention and postural awareness. Neglect patients show multiple oculomotor impairments including reduced saccade amplitude and difficulty retaining spatial locations across saccades. There has been controversy regarding the brain regions associated with neglect, although most studies show the right inferior parietal lobe to be crucial and new imaging modalities have provided insight into neglect caused by subcortical stroke. The 'pusher syndrome' is a poorly understood balance disorder where patients push towards their paretic side, resulting in falls. It may involve impairment of subjective verticality but experimental studies have reported diverse findings. Advances in treatment for neglect include the successful use of prism adaptation and pilot data suggesting noradrenergic stimulation may improve search in selected patients. SUMMARY: New experimental techniques have provided insight into the debilitating disorders of spatial and postural awareness that often follow stroke. There are currently no widely used therapies for neglect but both new behavioural techniques and pharmacological methods are promising.

Animals↗
PubMed2006

Treatment of attention deficits in neurological disorders.

PURPOSE OF REVIEW: Recent work has revealed the impact of deficits of attention on patients with neurological disorders. Here we discuss therapeutic interventions that have been used across a range of conditions, highlighting common themes both in the nature of the attention deficits and the strategies employed to treat them. RECENT FINDINGS: Cholinesterase inhibitors improve attention, as well as memory, in several conditions including cortical Lewy body disease, Parkinson's disease dementia, traumatic brain injury and Alzheimer's disease. Recent studies suggest that cholinergic stimulation may boost attention further if more specific nicotinic cholinergic agonists are used, or if cholinesterase inhibitors are combined with other agents. Monoaminergic drugs have been shown to improve attention in traumatic brain injury, attention-deficit hyperactivity disorder and hemispatial neglect following right-hemisphere stroke. New compounds targeting other neurotransmitter systems are currently being tested, while several types of behavioural intervention have shown promise, particularly in stroke patients. SUMMARY: Pharmacological and behavioural interventions can improve attention in neurological patients. In the future, optimum therapy may depend on careful delineation of the components of attention that are impaired as well as assessment of the potential for surviving brain regions to compensate for attention deficits.

Attention↗
PubMed2005

Action control in visual neglect.

Patients with unilateral neglect show a variety of impairments when reaching towards objects in contralesional space. The basis of these deficits could be perceptual, motor or at one of the intermediate stages linking these processes. Here, we review studies of visually guided reaching in neglect and integrate these results with findings from normal human and monkey action control. We consider evidence which shows that neglect patients can be slow to initiate or execute reaches particularly to a contralesional target. We discuss the directional and spatial deficits that may interact to contribute to such reaching abnormalities and highlight the importance of effective target selection and on-line guidance, exploring the idea that deficits in these mechanisms underlie increased susceptibility to ipsilesional visual distraction in neglect. We also examine the relationship between optic ataxia and neglect by considering two illustrative cases, one with pure optic ataxia and the other with optic ataxia plus neglect, which reveal differences in the anatomical substrates of the two syndromes. We conclude that many patients with neglect make abnormal visually guided reaches, but the pattern of reaching deficits is highly variable, most likely reflecting heterogeneity of lesion location across subjects. Rather than being specific to the neglect syndrome, abnormalities of reaching in these patients may correspond to the extent of damage to the visuomotor control system which involves critical regions in both the parietal and frontal cortex, the white matter tracts connecting them and subcortical regions. Thus, the action control deficits in neglect may be conceptualised as a range of impairments affecting multiple stages in the visuomotor control process.

Attention↗
PubMed2005

Volition and conflict in human medial frontal cortex.

Controversy surrounds the role of human medial frontal cortex in controlling actions. Although damage to this area leads to severe difficulties in spontaneously initiating actions, the precise mechanisms underlying such "volitional" deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring and the control of voluntary action, suggesting that these key processes are functionally related or share neural substrates. Here, we combine a novel behavioral paradigm with functional imaging of the oculomotor system to reveal, for the first time, a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas that respond exclusively to either volition or conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict.

Adult↗
PubMed2005

Where the eye looks, the hand follows; limb-dependent magnetic misreaching in optic ataxia.

The posterior parietal cortex (PPC) is thought to play an important role in the sensorimotor transformations associated with reaching movements. In humans, damage to the PPC, particularly bilateral lesions, leads to impairments of visually guided reaching movements (optic ataxia). Recent accounts of optic ataxia based upon electrophysiological recordings in monkeys have proposed that this disorder arises because of a breakdown in the tuning fields of parietal neurons responsible for integrating spatially congruent retinal, eye, and hand position signals to produce coordinated eye and hand movements . We present neurological evidence that forces a reconceptualization of this view. We report a detailed case study of a patient with a limb-dependent form of optic ataxia who can accurately reach with either hand to objects that he can foveate (thereby demonstrating coordinated eye-hand movements) but who cannot effectively decouple reach direction from gaze direction for movements executed using his right arm. The demonstration that our patient's misreaching is confined to movements executed using his right limb, and only for movements that are directed to nonfoveal targets, rules out explanations based upon simple perceptual or motor deficits but indicates an impairment in the ability to dissociate the eye and limb visuomotor systems when appropriate.

Aged↗
PubMed2005

Spatial working memory capacity in unilateral neglect.

It has been proposed recently that a deficit in keeping track of spatial locations may contribute to the severity of unilateral neglect in some right hemisphere stroke patients. However, performance on traditional spatial working memory (SWM) tasks (e.g. Corsi blocks) might be confounded by failure to encode leftward locations, rather than a true deficit of maintaining locations in SWM. Here we introduced new procedures for circumventing this to measure SWM capacity in neglect. In a first experiment, 20 right hemisphere stroke patients (10 with and 10 without neglect) were tested on a computerized vertical variant of the Corsi task. Sequences of spatial locations in a vertical column were displayed and participants had to tap out the remembered sequence on a touchscreen. Patients with left neglect were impaired on this vertical SWM task compared with all control groups. However, poor performance on this task (as for Corsi blocks) might involve impaired memory for stimulus sequence, or poor visuomotor control of manual responding, rather than reduced SWM capacity per se. A second experiment therefore employed a purer measure of vertical SWM. After the displayed sequence, a single location was now probed visually, with observers judging verbally (yes/no) if it had been in the preceding sequence. Hence order no longer mattered, and no spatial motor response was required. Again, the neglect group was impaired relative to all others, now with very little overlap between the performances of individual neglect patients versus individuals in control groups. Poor performance on the second task, which provides a purer measure of SWM capacity, correlated with severity of left neglect on cancellation tasks (but not on line bisection), consistent with recent proposals that SWM deficits can exacerbate left neglect on visual search tasks when present conjointly. Lesion anatomy indicated that neglect patients with a SWM deficit were most likely to have damage to parietal white matter, plus, in the second experiment, to the insula also. These findings demonstrate that an impairment in SWM capacity can contribute to the neglect syndrome in patients with stroke involving regions within the right parietal lobe and insula.

Adult↗
PubMed2005

Neuropharmacological modulation of cognitive deficits after brain damage.

PURPOSE OF REVIEW: This review discusses recent studies that have implications for potential neuropharmacological interventions which target cognitive deficits resulting from traumatic brain injury or stroke. RECENT FINDINGS: An important new study concerning the activity of N-methyl-D-aspartate (NMDA) receptors after brain injury reveals that previous influential hypotheses about an increase in glutamate triggering neuronal death may need to be revised. Furthermore, the study suggests that cognitive function may be best preserved by stimulation of NMDA receptors with agonists rather than by the use of antagonists, as previously believed. Investigations of animal models of stroke and traumatic brain injury have further demonstrated the possibility of intervening in the acute and sub-acute stages to protect specific brain systems, such as preservation of the cholinergic system (via cholinesterase inhibitors) and hippocampal neurons (via a D2 agonist). Clinical trials in humans indicate it is also possible to target these neurotransmitter systems to enhance cognitive performance in patients with chronic deficits. In particular, recent studies demonstrated that it is possible to ameliorate the effects of two common cognitive syndromes, visual neglect and aphasia. SUMMARY: Cognitive deficits are an extremely common consequence of either traumatic brain injury or stroke. Recent studies demonstrate the potential for using neuropharmacological intervention after acquired brain injury to prevent or ameliorate the effects of cognitive impairments. These treatments, however, are still in their preliminary stages and further research is required to identify the most effective compounds.

Animals↗
PubMed2005

Revisiting previously searched locations in visual neglect: role of right parietal and frontal lesions in misjudging old locations as new.

Right-hemisphere patients with left neglect often demonstrate abnormal visual search, re-examining stimuli to the right while ignoring those to the left. But re-fixations alone do not reveal if patients misjudge whether they have searched a location before. Here, we not only tracked the eye movements of 16 neglect patients during search, but also asked them to click a response button only when they judged they were fixating a target for the very first time. ''Re-clicking'' on previously found targets would indicate that patients erroneously respond to these as new discoveries. Lesions were mapped with high-resolution MRI. Neglect patients with damage involving the right intraparietal sulcus or right inferior frontal lobe ''re-clicked'' on previously found targets on the right at a pathological rate, whereas those with medial occipito-temporal lesions did not. For the intraparietal sulcus patients, the probability of erroneous re-clicks on an old target increased with time since first discovering it; whereas for frontal patients it was independent of search time, suggesting different underlying mechanisms in these two types of patient. Re-click deficits correlated with degree of leftward neglect, mainly due to both being severe in intraparietal cases. These results demonstrate that misjudging previously searched locations for new ones can contribute to pathological search in neglect, with potentially different mechanisms being involved in intraparietal versus inferior frontal patients. When combined with a spatial bias to the right, such deficits might explain why many neglect patients often re-examine rightward locations, at the expense of items to their left.

Adult↗